NOAEL Studies
Active Ingredient
Silver NOAEL Studies
INCI: SILVER
CAS: 7440-22-4
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip 63 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 125 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a40de15f-6f75-45d8-b8c0-f89ca0a80d08_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a40de15f-6f75-45d8-b8c0-f89ca0a80d08/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2010; basis=other:; key_result=false; entry_uuid=bda221be-e3dd-4a61-ab42-529f771fa24a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | <=40 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=gross pathology; key_result=true; upper_value=40; entry_uuid=13113a09-7ca3-4629-8a51-f72c9fceff4e |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 100 | mg/kg bw/day | rat | oral: gavage | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=7c5d12d0-6075-40ce-8f96-2452ee7506e6_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=7c5d12d0-6075-40ce-8f96-2452ee7506e6/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2013; basis=other:; key_result=false; entry_uuid=a63ec62d-b7ca-4333-a133-38834a3d7b39 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 30 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=5702541b-6b4d-4782-9447-1d1f3c845a4a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 4 | mg/kg bw/day | rat | oral: drinking water | - | developmental immunotoxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=53fbd963-9ec0-4add-a06b-a32c648f64d1_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=53fbd963-9ec0-4add-a06b-a32c648f64d1/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; basis=developmental immunotoxicity; key_result=false; entry_uuid=5a6b167e-a2ba-464b-820d-e6a8d54270b4 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 125 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a40de15f-6f75-45d8-b8c0-f89ca0a80d08_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a40de15f-6f75-45d8-b8c0-f89ca0a80d08/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2010; basis=other:; key_result=false; entry_uuid=bda221be-e3dd-4a61-ab42-529f771fa24a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | <=40 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=gross pathology; key_result=true; upper_value=40; entry_uuid=13113a09-7ca3-4629-8a51-f72c9fceff4e |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 100 | mg/kg bw/day | rat | oral: gavage | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=7c5d12d0-6075-40ce-8f96-2452ee7506e6_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=7c5d12d0-6075-40ce-8f96-2452ee7506e6/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2013; basis=other:; key_result=false; entry_uuid=a63ec62d-b7ca-4333-a133-38834a3d7b39 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 30 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=5702541b-6b4d-4782-9447-1d1f3c845a4a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 4 | mg/kg bw/day | rat | oral: drinking water | - | developmental immunotoxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=53fbd963-9ec0-4add-a06b-a32c648f64d1_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=53fbd963-9ec0-4add-a06b-a32c648f64d1/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; basis=developmental immunotoxicity; key_result=false; entry_uuid=5a6b167e-a2ba-464b-820d-e6a8d54270b4 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 125 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a40de15f-6f75-45d8-b8c0-f89ca0a80d08_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a40de15f-6f75-45d8-b8c0-f89ca0a80d08/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2010; basis=other:; key_result=false; entry_uuid=bda221be-e3dd-4a61-ab42-529f771fa24a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | <=40 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=gross pathology; key_result=true; upper_value=40; entry_uuid=13113a09-7ca3-4629-8a51-f72c9fceff4e |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 100 | mg/kg bw/day | rat | oral: gavage | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=7c5d12d0-6075-40ce-8f96-2452ee7506e6_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=7c5d12d0-6075-40ce-8f96-2452ee7506e6/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2013; basis=other:; key_result=false; entry_uuid=a63ec62d-b7ca-4333-a133-38834a3d7b39 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 30 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=5702541b-6b4d-4782-9447-1d1f3c845a4a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | LOAEL | 4 | mg/kg bw/day | rat | oral: drinking water | - | developmental immunotoxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=53fbd963-9ec0-4add-a06b-a32c648f64d1_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=53fbd963-9ec0-4add-a06b-a32c648f64d1/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; basis=developmental immunotoxicity; key_result=false; entry_uuid=5a6b167e-a2ba-464b-820d-e6a8d54270b4 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 30 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a40de15f-6f75-45d8-b8c0-f89ca0a80d08_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a40de15f-6f75-45d8-b8c0-f89ca0a80d08/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2010; basis=other:; key_result=false; entry_uuid=48984d7e-f823-49ce-b3a3-4bf6f85a8a06 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >=120 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=reproductive performance; key_result=true; entry_uuid=6043cd3d-2fcc-42b6-b4d3-315fe0559ae8 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | <=80 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=mortality; key_result=true; upper_value=80; entry_uuid=e5b3373d-d7f8-4aa7-a645-ae12e77c29b1 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 1000 | mg/kg bw/day | rat | oral: gavage | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=7c5d12d0-6075-40ce-8f96-2452ee7506e6_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=7c5d12d0-6075-40ce-8f96-2452ee7506e6/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2013; basis=other:; key_result=false; entry_uuid=51a310cc-e715-4f1e-a08c-3e180939a2a7 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 40 | mg/kg bw/day | - | - | - | one-generation reproductive toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=2793e30e-cc45-4336-95e9-ba6e2aa43c5a_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=2793e30e-cc45-4336-95e9-ba6e2aa43c5a/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=viability; key_result=true; entry_uuid=b67c323e-e6c0-4247-be61-787cb2b14789 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 36 | mg/kg bw/day | rat | oral: gavage | - | reproductive toxicity, other | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=45224929-0964-4198-9bb3-6a56c73607a3_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=45224929-0964-4198-9bb3-6a56c73607a3/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; ReportDate=2016-01-05; basis=reproductive function (oestrous cycle); key_result=false; entry_uuid=672e4573-a523-4809-aea4-e59ed6d7b6ab |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 10 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=75b5ad3b-0ba6-441c-8a8b-1e01c04a8ed1 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >100 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=ba234397-95ac-40c9-98ee-8537d725f3a4 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 250 | mg/kg bw/day | rat | oral: gavage | - | short-term repeated dose toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=74cd7dec-5947-469b-b89a-399a41103b2c_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=74cd7dec-5947-469b-b89a-399a41103b2c/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2013; basis=behaviour (functional findings); key_result=false; entry_uuid=9fc5b01b-3ad9-4c97-95b3-221fc2dd6b02 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 515.3 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=41423335-e331-428d-9c14-508ea04c6705_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=41423335-e331-428d-9c14-508ea04c6705/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2015; basis=other:; key_result=false; entry_uuid=63f0531c-9456-4b77-805c-9303e34e2475 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 200 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=527a3468-ba4c-43d0-aedd-78a2dae66ca9_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=527a3468-ba4c-43d0-aedd-78a2dae66ca9/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2016; basis=body weight and weight gain; key_result=false; entry_uuid=37a4d648-2dc3-4a16-8f98-d621eb45b97e |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 0.4 | mg/kg bw/day | rat | oral: drinking water | - | developmental immunotoxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=53fbd963-9ec0-4add-a06b-a32c648f64d1_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=53fbd963-9ec0-4add-a06b-a32c648f64d1/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; basis=developmental immunotoxicity; key_result=false; entry_uuid=0f16d377-f882-428a-91a4-56d4a56dd914 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 400 | mg/kg bw/day | rat | oral: gavage | - | reproductive toxicity, other | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=ab5a4c13-e2ff-4345-8065-b3400132d1bc_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=ab5a4c13-e2ff-4345-8065-b3400132d1bc/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; ReportDate=2016-01-05; basis=reproductive function (oestrous cycle); key_result=true; entry_uuid=672e4573-a523-4809-aea4-e59ed6d7b6ab |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 4 | mg/kg bw/day | rat | oral: drinking water | - | one-generation reproductive toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=5ce70463-4834-4f3e-bf7a-e5ee571a6c07_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=5ce70463-4834-4f3e-bf7a-e5ee571a6c07/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2017; basis=water consumption and compound intake; key_result=false; entry_uuid=7154c810-e2a6-4716-a56d-ae658d63ab2a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 150 | mg/kg bw/day | rat | other: | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a70ce4c1-768c-4e7c-a8ce-4f165144e43f_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a70ce4c1-768c-4e7c-a8ce-4f165144e43f/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1998; basis=other:; key_result=false; entry_uuid=c3fa1e8c-92ed-4f82-bb57-d4455010eb49 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >=320 | mg/kg bw/day | rat | oral: feed | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=b12e4eed-7842-46ca-bb6f-24539b65f881_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=b12e4eed-7842-46ca-bb6f-24539b65f881/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2022; ReportDate=2022-02-07; basis=body weight and weight gain; key_result=false; entry_uuid=e44000cd-bb6c-4b29-89ec-aa85473846d9 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 30 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a40de15f-6f75-45d8-b8c0-f89ca0a80d08_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a40de15f-6f75-45d8-b8c0-f89ca0a80d08/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2010; basis=other:; key_result=false; entry_uuid=48984d7e-f823-49ce-b3a3-4bf6f85a8a06 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >=120 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=reproductive performance; key_result=true; entry_uuid=6043cd3d-2fcc-42b6-b4d3-315fe0559ae8 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | <=80 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=mortality; key_result=true; upper_value=80; entry_uuid=e5b3373d-d7f8-4aa7-a645-ae12e77c29b1 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 1000 | mg/kg bw/day | rat | oral: gavage | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=7c5d12d0-6075-40ce-8f96-2452ee7506e6_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=7c5d12d0-6075-40ce-8f96-2452ee7506e6/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2013; basis=other:; key_result=false; entry_uuid=51a310cc-e715-4f1e-a08c-3e180939a2a7 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 40 | mg/kg bw/day | - | - | - | one-generation reproductive toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=2793e30e-cc45-4336-95e9-ba6e2aa43c5a_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=2793e30e-cc45-4336-95e9-ba6e2aa43c5a/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=viability; key_result=true; entry_uuid=b67c323e-e6c0-4247-be61-787cb2b14789 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 36 | mg/kg bw/day | rat | oral: gavage | - | reproductive toxicity, other | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=45224929-0964-4198-9bb3-6a56c73607a3_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=45224929-0964-4198-9bb3-6a56c73607a3/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; ReportDate=2016-01-05; basis=reproductive function (oestrous cycle); key_result=false; entry_uuid=672e4573-a523-4809-aea4-e59ed6d7b6ab |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 10 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=75b5ad3b-0ba6-441c-8a8b-1e01c04a8ed1 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >100 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=ba234397-95ac-40c9-98ee-8537d725f3a4 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 250 | mg/kg bw/day | rat | oral: gavage | - | short-term repeated dose toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=74cd7dec-5947-469b-b89a-399a41103b2c_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=74cd7dec-5947-469b-b89a-399a41103b2c/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2013; basis=behaviour (functional findings); key_result=false; entry_uuid=9fc5b01b-3ad9-4c97-95b3-221fc2dd6b02 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 515.3 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=41423335-e331-428d-9c14-508ea04c6705_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=41423335-e331-428d-9c14-508ea04c6705/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2015; basis=other:; key_result=false; entry_uuid=63f0531c-9456-4b77-805c-9303e34e2475 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 200 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=527a3468-ba4c-43d0-aedd-78a2dae66ca9_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=527a3468-ba4c-43d0-aedd-78a2dae66ca9/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2016; basis=body weight and weight gain; key_result=false; entry_uuid=37a4d648-2dc3-4a16-8f98-d621eb45b97e |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 0.4 | mg/kg bw/day | rat | oral: drinking water | - | developmental immunotoxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=53fbd963-9ec0-4add-a06b-a32c648f64d1_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=53fbd963-9ec0-4add-a06b-a32c648f64d1/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; basis=developmental immunotoxicity; key_result=false; entry_uuid=0f16d377-f882-428a-91a4-56d4a56dd914 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 400 | mg/kg bw/day | rat | oral: gavage | - | reproductive toxicity, other | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=ab5a4c13-e2ff-4345-8065-b3400132d1bc_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=ab5a4c13-e2ff-4345-8065-b3400132d1bc/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; ReportDate=2016-01-05; basis=reproductive function (oestrous cycle); key_result=true; entry_uuid=672e4573-a523-4809-aea4-e59ed6d7b6ab |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 4 | mg/kg bw/day | rat | oral: drinking water | - | one-generation reproductive toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=5ce70463-4834-4f3e-bf7a-e5ee571a6c07_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=5ce70463-4834-4f3e-bf7a-e5ee571a6c07/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2017; basis=water consumption and compound intake; key_result=false; entry_uuid=7154c810-e2a6-4716-a56d-ae658d63ab2a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 150 | mg/kg bw/day | rat | other: | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a70ce4c1-768c-4e7c-a8ce-4f165144e43f_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a70ce4c1-768c-4e7c-a8ce-4f165144e43f/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1998; basis=other:; key_result=false; entry_uuid=c3fa1e8c-92ed-4f82-bb57-d4455010eb49 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >=320 | mg/kg bw/day | rat | oral: feed | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=b12e4eed-7842-46ca-bb6f-24539b65f881_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=b12e4eed-7842-46ca-bb6f-24539b65f881/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2022; ReportDate=2022-02-07; basis=body weight and weight gain; key_result=false; entry_uuid=e44000cd-bb6c-4b29-89ec-aa85473846d9 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 30 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a40de15f-6f75-45d8-b8c0-f89ca0a80d08_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a40de15f-6f75-45d8-b8c0-f89ca0a80d08/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2010; basis=other:; key_result=false; entry_uuid=48984d7e-f823-49ce-b3a3-4bf6f85a8a06 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >=120 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=reproductive performance; key_result=true; entry_uuid=6043cd3d-2fcc-42b6-b4d3-315fe0559ae8 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | <=80 | mg/kg bw/day | - | - | - | extended one-generation reproductive toxicity - with both developmental neuro- and immunotoxicity (Cohorts 1A, 1B without extension, 2A, 2B, and 3) | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=811bf8a2-190e-4265-834a-a7ca4986af5d_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=811bf8a2-190e-4265-834a-a7ca4986af5d/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=mortality; key_result=true; upper_value=80; entry_uuid=e5b3373d-d7f8-4aa7-a645-ae12e77c29b1 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 1000 | mg/kg bw/day | rat | oral: gavage | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=7c5d12d0-6075-40ce-8f96-2452ee7506e6_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=7c5d12d0-6075-40ce-8f96-2452ee7506e6/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2013; basis=other:; key_result=false; entry_uuid=51a310cc-e715-4f1e-a08c-3e180939a2a7 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 40 | mg/kg bw/day | - | - | - | one-generation reproductive toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=2793e30e-cc45-4336-95e9-ba6e2aa43c5a_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=2793e30e-cc45-4336-95e9-ba6e2aa43c5a/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; basis=viability; key_result=true; entry_uuid=b67c323e-e6c0-4247-be61-787cb2b14789 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 36 | mg/kg bw/day | rat | oral: gavage | - | reproductive toxicity, other | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=45224929-0964-4198-9bb3-6a56c73607a3_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=45224929-0964-4198-9bb3-6a56c73607a3/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; ReportDate=2016-01-05; basis=reproductive function (oestrous cycle); key_result=false; entry_uuid=672e4573-a523-4809-aea4-e59ed6d7b6ab |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 10 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=75b5ad3b-0ba6-441c-8a8b-1e01c04a8ed1 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >100 | mg/kg bw/day | - | - | - | developmental toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=aebdb00a-784e-4199-9d5c-031056926532_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=aebdb00a-784e-4199-9d5c-031056926532/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=DevelopmentalToxicityTeratogenicity; basis=other:; key_result=false; entry_uuid=ba234397-95ac-40c9-98ee-8537d725f3a4 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 250 | mg/kg bw/day | rat | oral: gavage | - | short-term repeated dose toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=74cd7dec-5947-469b-b89a-399a41103b2c_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=74cd7dec-5947-469b-b89a-399a41103b2c/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2013; basis=behaviour (functional findings); key_result=false; entry_uuid=9fc5b01b-3ad9-4c97-95b3-221fc2dd6b02 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 515.3 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=41423335-e331-428d-9c14-508ea04c6705_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=41423335-e331-428d-9c14-508ea04c6705/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2015; basis=other:; key_result=false; entry_uuid=63f0531c-9456-4b77-805c-9303e34e2475 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 200 | mg/kg bw/day | rat | oral: gavage | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=527a3468-ba4c-43d0-aedd-78a2dae66ca9_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=527a3468-ba4c-43d0-aedd-78a2dae66ca9/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2016; basis=body weight and weight gain; key_result=false; entry_uuid=37a4d648-2dc3-4a16-8f98-d621eb45b97e |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 0.4 | mg/kg bw/day | rat | oral: drinking water | - | developmental immunotoxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=53fbd963-9ec0-4add-a06b-a32c648f64d1_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=53fbd963-9ec0-4add-a06b-a32c648f64d1/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; basis=developmental immunotoxicity; key_result=false; entry_uuid=0f16d377-f882-428a-91a4-56d4a56dd914 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 400 | mg/kg bw/day | rat | oral: gavage | - | reproductive toxicity, other | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=ab5a4c13-e2ff-4345-8065-b3400132d1bc_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=ab5a4c13-e2ff-4345-8065-b3400132d1bc/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2016; ReportDate=2016-01-05; basis=reproductive function (oestrous cycle); key_result=true; entry_uuid=672e4573-a523-4809-aea4-e59ed6d7b6ab |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 4 | mg/kg bw/day | rat | oral: drinking water | - | one-generation reproductive toxicity | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=5ce70463-4834-4f3e-bf7a-e5ee571a6c07_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=5ce70463-4834-4f3e-bf7a-e5ee571a6c07/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=2017; basis=water consumption and compound intake; key_result=false; entry_uuid=7154c810-e2a6-4716-a56d-ae658d63ab2a |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | 150 | mg/kg bw/day | rat | other: | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=a70ce4c1-768c-4e7c-a8ce-4f165144e43f_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=a70ce4c1-768c-4e7c-a8ce-4f165144e43f/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1998; basis=other:; key_result=false; entry_uuid=c3fa1e8c-92ed-4f82-bb57-d4455010eb49 |
| ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip | NOAEL | >=320 | mg/kg bw/day | rat | oral: feed | - | sub-chronic toxicity: oral | dossier=a842c2ff-dd8f-473d-bb15-a27046511baa.i6z; document=b12e4eed-7842-46ca-bb6f-24539b65f881_a842c2ff-dd8f-473d-bb15-a27046511baa.i6d; document_key=b12e4eed-7842-46ca-bb6f-24539b65f881/a842c2ff-dd8f-473d-bb15-a27046511baa; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=2022; ReportDate=2022-02-07; basis=body weight and weight gain; key_result=false; entry_uuid=e44000cd-bb6c-4b29-89ec-aa85473846d9 |
EPA_IRIS_iris_rfd_systems.csv 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| EPA_IRIS_iris_rfd_systems.csv | LOAEL | =0.014 | mg/kg/day | - | oral | chronic | IRIS chronic oral RfD system PoD | row_hash=e7fe64cc0849a8c9; file=iris_rfd_systems.csv; kind=point_of_departure; raw_column=point_of_departure; raw_value=LOAEL : 1.4e-2 mg/kg-day; system=Dermal; basis=Argyria; point_of_departure=LOAEL : 1.4e-2 mg/kg-day; composite_uf=3; confidence=Low; dtxsid=DTXSID4024305; detail_url=https://iris.epa.gov/ChemicalLanding/&substance_nmbr=99; rfd_last_updated=12/01/1991; rfd_pdf_url=https://iris.epa.gov/static/pdfs/0099_summary.pdf |
| EPA_IRIS_iris_rfd_systems.csv | RfD | =0.005 | mg/kg/day | - | oral | chronic | IRIS chronic oral RfD system | row_hash=6ddb65163759785e; file=iris_rfd_systems.csv; kind=reference_value; raw_column=rfd_mg_per_kg_day; raw_value=5e-3; system=Dermal; basis=Argyria; point_of_departure=LOAEL : 1.4e-2 mg/kg-day; composite_uf=3; confidence=Low; dtxsid=DTXSID4024305; detail_url=https://iris.epa.gov/ChemicalLanding/&substance_nmbr=99; rfd_last_updated=12/01/1991; rfd_pdf_url=https://iris.epa.gov/static/pdfs/0099_summary.pdf |
ICH Q3D(R2) 18 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ICH Q3D(R2) | ICH Q3D PDE | 150 | ug/day | - | oral | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"oral_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 15 | ug/day | - | parenteral | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"parenteral_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 7 | ug/day | - | inhalation | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"inhalation_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 150 | ug/day | - | oral | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"oral_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 15 | ug/day | - | parenteral | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"parenteral_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 7 | ug/day | - | inhalation | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"inhalation_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 150 | ug/day | - | oral | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"oral_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 15 | ug/day | - | parenteral | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"parenteral_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D PDE | 7 | ug/day | - | inhalation | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"inhalation_pde_ug_day"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 15 | ug/g | - | oral concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"oral_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 1.5 | ug/g | - | parenteral concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"parenteral_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 0.7 | ug/g | - | inhalation concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"inhalation_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 15 | ug/g | - | oral concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"oral_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 1.5 | ug/g | - | parenteral concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"parenteral_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 0.7 | ug/g | - | inhalation concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"inhalation_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 15 | ug/g | - | oral concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"oral_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 1.5 | ug/g | - | parenteral concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"parenteral_concentration_ug_g"} |
| ICH Q3D(R2) | ICH Q3D concentration limit | 0.7 | ug/g | - | inhalation concentration | - | ICH Q3D elemental impurity limit | {"element_symbol":"Ag","guideline":"ICH Q3D(R2) Guideline for Elemental Impurities","ich_class":"2B","row_hash":"8635a0e898ecd273ee89b8cb7ffcfa8eda60eab1b6e5518162e60bf4b5df3eb7","source_file":"C:\\BENDA_PROJECT\\DOWNLOADS_NEW\\ich_q3d_elemental_impurities.pdf","source_page":26,"source_sha256":"940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75","source_table":"ich_pde_limits","source_table_name":"Table A.2.1","value_column":"inhalation_concentration_ug_g"} |
NTP_ICE_acute_inhalation 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_acute_inhalation | LC50 | >5.16 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=2403; Record_ID=acute_inhalation_681; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID4024305; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response_Modifier=>; Response=5.16; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/3/3/?documentUUID=09aba99a-f123-4c51-a470-12b999f56520; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4024305; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID4024305 |
| NTP_ICE_acute_inhalation | LC50 | >0.0008 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=2404; Record_ID=acute_inhalation_682; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID4024305; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response_Modifier=>; Response=0.0008; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/3/3/?documentUUID=34c0b076-8c2e-4f59-91d4-fedbaa60dee5; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID4024305; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID4024305 |
SCCS_vision_codex 172 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested.","effect":"ver the ATSDR concludes that ‘existing evidence’ does not point to a strong effect of the silver ion on reproduction and no historical evidence to indicate an effect of silver on reproduction in humans. While subcutaneous injection of silver nitrate has been reported to cause reversible damage to the testes in rats (Hoey, 1966), no effects on spermatozoa or fertility were observed in a drinking water study. A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested. Indications of slight maternal toxicity were observed at this dose level; more severe maternal toxicity was observed at a dose level of 160 mg/kg bw/d in a screening study. Published data (Shavlovsky et al., 1995) indicate an effect of silver on development at maternally toxic dose levels and secondary to copper deficiency caused by the displacement of copper by silver from ceruloplasmin. 3.3.9. Toxicokinetics 3.3.9.1. Absorption Stu","page":15,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.00056 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","effect":"r-bound estimate and orders of magnitude higher than those measured in vitro with intact or mildly damaged human skin (Larese et al. 2009). Reference values All published reviews concur that the relevant (critical) effect of silver exposure is argyria. Toxicological reference values for silver have been derived by the EPA, WHO and EFSA. The US EPA uses a systemic lifetime (systemic) exposure of 1 g silver as starting point1; 1 The EPA (1989) used the study of Gaul & Staud to derive a minimal (lifetime exposure) NOAEL of 1 g silver (systemic). This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","page":21,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_002"} |
| SCCS_vision_codex | NOAEL | =0.0065 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg.","effect":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg. Based on the epidemiological and pharmacokinetic data, WHO (2003) derives a human NOAEL (lifetime oral intake) for silver of 10 g, corresponding to 0.39 mg Ag/person/day or 0.0065 mg/kg bw/d. Assuming a gastrointestinal absorption of silver of 5%, this is equivalent to a systemic reference value of 0.000325 mg/kg bw/d (0.325 µg/kg bw/d). EFSA has evaluated silver-based preservatives for use in food-contact materials on the basis of human and animal data and has derived a group restriction limit of 0.05 mg Ag/kg food, which corresponds to a worst-case exposure of 0.05 mg Ag/person/day or 0.00083 mg/k","page":22,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_003"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 9-year | repeated dose toxicity | {"dose":"The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.","effect":"e deposited in numerous organs and tissues and liver was identified as the principal organ for Silver deposition. The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).","page":25,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | - | - | developmental | repeated dose toxicity | {"dose":"Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","effect":"as done in the current assessment appropriately protects for the reproductive and developmental toxicity endpoint. SCCS comment For an overview and description of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/p","page":27,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_003"} |
| SCCS_vision_codex | NOAEL | =70 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_007"} |
| SCCS_vision_codex | NOAEL | =25500 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | - | human | oral | - | NOAEL study | {"effect":"ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_009"} |
| SCCS_vision_codex | NOAEL | =0.05 | mg/kg | human | oral | - | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"y Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine in","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_010"} |
| SCCS_vision_codex | NOAEL | =13 | % | human | oral | 64 years | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine injection therapy and a biospectrometric analysis of 10 cases of generalized argyria classified according to the quantity of Silver present. In this i.v. study, data were presented for 10 male (23-64 years old) and for tw","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_011"} |
| SCCS_vision_codex | NOAEL | =0.2 | % | rat | oral | chronic | carcinogenicity | {"dose":"The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment.","effect":"___________________________________________________________________________________ 34 Human data Several regulatory agencies (WHO, EFSA, US EPA) have established human reference doses based on argyria as the human-relevant effect caused by chronic exposure to Silver via, respectively, drinking water, food / food contact material or medication. The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment. Instead, the SCCS will use the NOAEL derived from a chronic combined toxicity and carcinogenicity study on Silver zinc zeolite in rats. Special investigations / 4. CONCLUSION (1) In light of the data provided and taking under consideration the classification as toxic for reproduction Cat. 2, does the SCCS consider micron-sized particulate Silver safe when used up to a maximum concentration of 0.2 % in rinse-off and 0.3 % in leave-on cosmetic products? In light of the data provided and taking under consideration the classification as toxic for r","page":34,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_021"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver...","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver containing active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_022"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.","effect":"taining active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-chronic studies 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_023"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rat | oral | 90-day | NOAEL study | {"dose":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.","effect":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2010 in ECHA, 2022)/ KL2 90-day gavage study in Sprague Dawley rats (6 males); OECD TG 408, PVP capped nanoparticles 0, 50, 100, 200 mg/kg bw/day At 200 and 100 mg/kg bw/day non-significant increase in epididymis and testis weight was observed. At 200 mg/kg bw/day, decrease sperm viability was observed. At 50 mg/kg bw/day, decrease in food intake was observed. At 50 and 100 mg/kg bw/day significant increase in sperm anomalies were observed. LOAEL: 50 mg Silver/kg bw/day (Lafue","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_024"} |
| SCCS_vision_codex | NOAEL | =1665 | - | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL:","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_025"} |
| SCCS_vision_codex | NOAEL | =0.5 | % | rat | oral | 30-day | repeated dose toxicity | {"dose":"ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No tre...","effect":"nd lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No treatment related adverse effects at any dose level NOAEL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NO","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_026"} |
| SCCS_vision_codex | NOAEL | =95 | - | rat | oral | Sub-chronic | repeated dose toxicity | {"effect":"EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_027"} |
| SCCS_vision_codex | NOAEL | =12500 | ppm | rat | oral | 9 months | repeated dose toxicity | {"dose":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exp...","effect":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exposed for 6 months, the rest for 12 months) SCAS Sub-chronic studies 14-week oral study 0, 1000, 6250, At 2 and 6 mg Silver/kg bw/day NOAEL: (Study report in Sprague-Dawley and 12500 ppm effects on behaviour/activity, 0.65 mg Silver/ 2001 in ECHA rat (10/sex/group); of Silver zinc pigmentation of pancreas, kg bw/day RAC, 2022;","page":42,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_028"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg | dog | oral | 90-day | NOAEL study | {"dose":"(Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 43 Similar to OECD TG zeolite thymus, the mandibular lymph ECHA RAC, 408; AgION approximately 0, node, changes in clinical 2015)/ KL1 Antimicrobial Type 0.65, 2.0, and chemistry and haematology AK (Silver zinc 6.0 mg Silver/kg were observed zeolite) bw/day 90-day oral gavage 0, 10, 50, and At 5.1 mg Silver/kg bw/day NOAEL: (Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_029"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg | rat | oral | 90-day | NOAEL study | {"dose":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At 9.5 mg Silver/kg bw/day, NOAEL: (ECHA RAC, CD rats; similar to 1000 mg/kg relative heart weight was 0.29 mg 2022)/ KL2 OECD TG 408; Silver bw/day of Silver increased in males. Silver/kg sodium zirconium sodium zirconium At 9.5 and 2.9 mg Silver/kg bw/day hydrogen hydrogen bw/day, increased ALP levels, phosphate phosphate discoloration of pancreas and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_030"} |
| SCCS_vision_codex | NOAEL | =0 | - | - | oral | 90-day | NOAEL study | {"effect":"s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_031"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | developmental | reproductive toxicity | {"dose":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats:","effect":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0,","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_032"} |
| SCCS_vision_codex | NOAEL | =52 | - | rat | oral | 52 days | reproductive toxicity | {"dose":"2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose.","effect":"opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_033"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","effect":"se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_035"} |
| SCCS_vision_codex | NOAEL | =26 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","effect":"vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_037"} |
| SCCS_vision_codex | NOAEL | =20000 | ppm | rat | oral | 10 weeks | reproductive toxicity | {"dose":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_040"} |
| SCCS_vision_codex | NOAEL | =87 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"At 72/87 mg/kg bw/day, reduced thymus weight in males.","effect":"al changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg Silver/kg bw/day, increased stillbirth index, decreased live birth index, body weights, reduced organ weights (brain, thymus, spleen). At 72/87 mg/kg bw/day, reduced thymus weight in males. LOAEL (systemic- F0 and F1): 1.5 mg Silver/kg bw/day NOAEL (reproduction, F0 and F1): 1.5 mg Silver/kg bw/day. LOAEL (developmental toxicity (F1 and F2): 1.5 mg Silver/kg bw/day (Schroeder, 2002 ECHA RAC, 2015; SCCS, 2023)/KL 1","page":48,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_046"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | Prenatal | developmental toxicity | {"dose":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal):","effect":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal): Charehsaz, developmental citrate-capped histopathological findings in 0.2 mg Silver/kg et al., 2016 toxicity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopec","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_047"} |
| SCCS_vision_codex | NOAEL | =25 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:","effect":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and r","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_050"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,","page":30,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_054"} |
| SCCS_vision_codex | NOAEL | =40 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_055"} |
| SCCS_vision_codex | NOAEL | =41 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_059"} |
| SCCS_vision_codex | NOAEL | =9 | - | rat | oral | 28-day | NOAEL study | {"effect":"Unlabeled table on page 41: 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate | 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) | At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed | LOAEL: 9 mg Silver/ kg bw/day | (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_060"} |
| SCCS_vision_codex | NOAEL | =78 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_061"} |
| SCCS_vision_codex | NOAEL | =43 | - | - | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_065"} |
| SCCS_vision_codex | NOAEL | =45 | - | - | oral | - | NOAEL study | {"effect":"Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_067"} |
| SCCS_vision_codex | NOAEL | =46 | - | - | - | - | reproductive toxicity | {"dose":"AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation.","effect":"Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_068"} |
| SCCS_vision_codex | NOAEL | =63.7 | % | rat | oral | 10 weeks | reproductive toxicity | {"dose":"Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"Unlabeled table on page 47: One generation drinking water reproductive toxicity study in Sprague-Dawley rats, according to FDA CFSAN Redbook; Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 | At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed | NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day | (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_069"} |
| SCCS_vision_codex | NOAEL | =64.6 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022;","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver acetate (64.6% Silver) | 0, 10, 30, 100 mg Silver acetate/kg bw/day equivalent to 6.5, 19, and 65 mg Silver/kg bw/day GD 6-19, by gavage | At 65 mg Silver/kg bw/day: Dams Piloerection, alopecia was observed in foetuses Increase percentage litters with late, foetal deaths (10%), reduced male bodyweight/litter (5%), foetal bodyweight/litter (5%). At 65 mg Silver/kg bw: increased skeletal variations | NOAEL (maternal and developmental): 19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022; ECHA, 2022)/ KL1-2","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_073"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/...","effect":"Unlabeled table on page 50: Prenatal developmental toxicity- DRF study, Sprague Dawley rats, OECD Guideline 414 (8 female/group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC< 2022)/KL2","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_076"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24:","effect":"cientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 25 3.4.3 Acute toxicity 1 2 See SCCS/1665/24. 3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24: 7 The SCCS has reservations regarding the Applicant's choice of the PoD of 0.014 mg Silver/kg 8 bw/day. This is further explained in 3.5 (Safety evaluation) of the SCCS/1665/24 Opinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation.","effect":"pinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion equivalents, derived from a study 19 with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). 20 This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity 21 study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment 22 in this Opinion. 23 24 3.4.6 Mutagenicity / genotoxicity 25 26 Taken and abridged from SCCS/1665/24: 27 The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not 28","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_003"} |
| SCCS_vision_codex | NOAEL | =1687 | - | human | oral | - | repeated dose toxicity | {"dose":"3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity):","effect":"SCCS/1687/25 Preliminary Scientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 26 3.4.9 Human data 1 2 See SCCS/1665/24. 3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity): 10 4.5 μg/kg bw/day. 11 For the respective aggregate SED’s, see: 3.3 Calculation of the SED. 12 13 Dermally applied products: 14 MoS = NOAELadj / aggregate SED = 4.5 / 0.0024 = 1875 15 16 Orally applied products: 17 MoS = NOAELadj / aggregate SED = 4.5 / 0.0052 = 865 18 19 Pump based spray products: 20 MoS = NOAELadj / aggregate SED = 4.5 / 0.009 = 500 21 22 Margin of Safety (MoS): 23 (conservatively) aggregated over all","page":26,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested.","effect":"ver the ATSDR concludes that ‘existing evidence’ does not point to a strong effect of the silver ion on reproduction and no historical evidence to indicate an effect of silver on reproduction in humans. While subcutaneous injection of silver nitrate has been reported to cause reversible damage to the testes in rats (Hoey, 1966), no effects on spermatozoa or fertility were observed in a drinking water study. A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested. Indications of slight maternal toxicity were observed at this dose level; more severe maternal toxicity was observed at a dose level of 160 mg/kg bw/d in a screening study. Published data (Shavlovsky et al., 1995) indicate an effect of silver on development at maternally toxic dose levels and secondary to copper deficiency caused by the displacement of copper by silver from ceruloplasmin. 3.3.9. Toxicokinetics 3.3.9.1. Absorption Stu","page":15,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.00056 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","effect":"r-bound estimate and orders of magnitude higher than those measured in vitro with intact or mildly damaged human skin (Larese et al. 2009). Reference values All published reviews concur that the relevant (critical) effect of silver exposure is argyria. Toxicological reference values for silver have been derived by the EPA, WHO and EFSA. The US EPA uses a systemic lifetime (systemic) exposure of 1 g silver as starting point1; 1 The EPA (1989) used the study of Gaul & Staud to derive a minimal (lifetime exposure) NOAEL of 1 g silver (systemic). This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","page":21,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_002"} |
| SCCS_vision_codex | NOAEL | =0.0065 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg.","effect":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg. Based on the epidemiological and pharmacokinetic data, WHO (2003) derives a human NOAEL (lifetime oral intake) for silver of 10 g, corresponding to 0.39 mg Ag/person/day or 0.0065 mg/kg bw/d. Assuming a gastrointestinal absorption of silver of 5%, this is equivalent to a systemic reference value of 0.000325 mg/kg bw/d (0.325 µg/kg bw/d). EFSA has evaluated silver-based preservatives for use in food-contact materials on the basis of human and animal data and has derived a group restriction limit of 0.05 mg Ag/kg food, which corresponds to a worst-case exposure of 0.05 mg Ag/person/day or 0.00083 mg/k","page":22,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_003"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested.","effect":"ver the ATSDR concludes that ‘existing evidence’ does not point to a strong effect of the silver ion on reproduction and no historical evidence to indicate an effect of silver on reproduction in humans. While subcutaneous injection of silver nitrate has been reported to cause reversible damage to the testes in rats (Hoey, 1966), no effects on spermatozoa or fertility were observed in a drinking water study. A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested. Indications of slight maternal toxicity were observed at this dose level; more severe maternal toxicity was observed at a dose level of 160 mg/kg bw/d in a screening study. Published data (Shavlovsky et al., 1995) indicate an effect of silver on development at maternally toxic dose levels and secondary to copper deficiency caused by the displacement of copper by silver from ceruloplasmin. 3.3.9. Toxicokinetics 3.3.9.1. Absorption Stu","page":15,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.00056 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","effect":"r-bound estimate and orders of magnitude higher than those measured in vitro with intact or mildly damaged human skin (Larese et al. 2009). Reference values All published reviews concur that the relevant (critical) effect of silver exposure is argyria. Toxicological reference values for silver have been derived by the EPA, WHO and EFSA. The US EPA uses a systemic lifetime (systemic) exposure of 1 g silver as starting point1; 1 The EPA (1989) used the study of Gaul & Staud to derive a minimal (lifetime exposure) NOAEL of 1 g silver (systemic). This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","page":21,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_002"} |
| SCCS_vision_codex | NOAEL | =0.0065 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg.","effect":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg. Based on the epidemiological and pharmacokinetic data, WHO (2003) derives a human NOAEL (lifetime oral intake) for silver of 10 g, corresponding to 0.39 mg Ag/person/day or 0.0065 mg/kg bw/d. Assuming a gastrointestinal absorption of silver of 5%, this is equivalent to a systemic reference value of 0.000325 mg/kg bw/d (0.325 µg/kg bw/d). EFSA has evaluated silver-based preservatives for use in food-contact materials on the basis of human and animal data and has derived a group restriction limit of 0.05 mg Ag/kg food, which corresponds to a worst-case exposure of 0.05 mg Ag/person/day or 0.00083 mg/k","page":22,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_003"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 9-year | repeated dose toxicity | {"dose":"The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.","effect":"e deposited in numerous organs and tissues and liver was identified as the principal organ for Silver deposition. The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).","page":25,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | - | - | developmental | repeated dose toxicity | {"dose":"Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","effect":"as done in the current assessment appropriately protects for the reproductive and developmental toxicity endpoint. SCCS comment For an overview and description of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/p","page":27,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_003"} |
| SCCS_vision_codex | NOAEL | =70 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_007"} |
| SCCS_vision_codex | NOAEL | =25500 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | - | human | oral | - | NOAEL study | {"effect":"ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_009"} |
| SCCS_vision_codex | NOAEL | =0.05 | mg/kg | human | oral | - | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"y Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine in","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_010"} |
| SCCS_vision_codex | NOAEL | =13 | % | human | oral | 64 years | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine injection therapy and a biospectrometric analysis of 10 cases of generalized argyria classified according to the quantity of Silver present. In this i.v. study, data were presented for 10 male (23-64 years old) and for tw","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_011"} |
| SCCS_vision_codex | NOAEL | =0.2 | % | rat | oral | chronic | carcinogenicity | {"dose":"The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment.","effect":"___________________________________________________________________________________ 34 Human data Several regulatory agencies (WHO, EFSA, US EPA) have established human reference doses based on argyria as the human-relevant effect caused by chronic exposure to Silver via, respectively, drinking water, food / food contact material or medication. The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment. Instead, the SCCS will use the NOAEL derived from a chronic combined toxicity and carcinogenicity study on Silver zinc zeolite in rats. Special investigations / 4. CONCLUSION (1) In light of the data provided and taking under consideration the classification as toxic for reproduction Cat. 2, does the SCCS consider micron-sized particulate Silver safe when used up to a maximum concentration of 0.2 % in rinse-off and 0.3 % in leave-on cosmetic products? In light of the data provided and taking under consideration the classification as toxic for r","page":34,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_021"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver...","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver containing active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_022"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.","effect":"taining active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-chronic studies 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_023"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rat | oral | 90-day | NOAEL study | {"dose":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.","effect":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2010 in ECHA, 2022)/ KL2 90-day gavage study in Sprague Dawley rats (6 males); OECD TG 408, PVP capped nanoparticles 0, 50, 100, 200 mg/kg bw/day At 200 and 100 mg/kg bw/day non-significant increase in epididymis and testis weight was observed. At 200 mg/kg bw/day, decrease sperm viability was observed. At 50 mg/kg bw/day, decrease in food intake was observed. At 50 and 100 mg/kg bw/day significant increase in sperm anomalies were observed. LOAEL: 50 mg Silver/kg bw/day (Lafue","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_024"} |
| SCCS_vision_codex | NOAEL | =1665 | - | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL:","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_025"} |
| SCCS_vision_codex | NOAEL | =0.5 | % | rat | oral | 30-day | repeated dose toxicity | {"dose":"ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No tre...","effect":"nd lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No treatment related adverse effects at any dose level NOAEL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NO","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_026"} |
| SCCS_vision_codex | NOAEL | =95 | - | rat | oral | Sub-chronic | repeated dose toxicity | {"effect":"EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_027"} |
| SCCS_vision_codex | NOAEL | =12500 | ppm | rat | oral | 9 months | repeated dose toxicity | {"dose":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exp...","effect":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exposed for 6 months, the rest for 12 months) SCAS Sub-chronic studies 14-week oral study 0, 1000, 6250, At 2 and 6 mg Silver/kg bw/day NOAEL: (Study report in Sprague-Dawley and 12500 ppm effects on behaviour/activity, 0.65 mg Silver/ 2001 in ECHA rat (10/sex/group); of Silver zinc pigmentation of pancreas, kg bw/day RAC, 2022;","page":42,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_028"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg | dog | oral | 90-day | NOAEL study | {"dose":"(Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 43 Similar to OECD TG zeolite thymus, the mandibular lymph ECHA RAC, 408; AgION approximately 0, node, changes in clinical 2015)/ KL1 Antimicrobial Type 0.65, 2.0, and chemistry and haematology AK (Silver zinc 6.0 mg Silver/kg were observed zeolite) bw/day 90-day oral gavage 0, 10, 50, and At 5.1 mg Silver/kg bw/day NOAEL: (Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_029"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg | rat | oral | 90-day | NOAEL study | {"dose":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At 9.5 mg Silver/kg bw/day, NOAEL: (ECHA RAC, CD rats; similar to 1000 mg/kg relative heart weight was 0.29 mg 2022)/ KL2 OECD TG 408; Silver bw/day of Silver increased in males. Silver/kg sodium zirconium sodium zirconium At 9.5 and 2.9 mg Silver/kg bw/day hydrogen hydrogen bw/day, increased ALP levels, phosphate phosphate discoloration of pancreas and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_030"} |
| SCCS_vision_codex | NOAEL | =0 | - | - | oral | 90-day | NOAEL study | {"effect":"s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_031"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | developmental | reproductive toxicity | {"dose":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats:","effect":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0,","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_032"} |
| SCCS_vision_codex | NOAEL | =52 | - | rat | oral | 52 days | reproductive toxicity | {"dose":"2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose.","effect":"opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_033"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","effect":"se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_035"} |
| SCCS_vision_codex | NOAEL | =26 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","effect":"vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_037"} |
| SCCS_vision_codex | NOAEL | =20000 | ppm | rat | oral | 10 weeks | reproductive toxicity | {"dose":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_040"} |
| SCCS_vision_codex | NOAEL | =87 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"At 72/87 mg/kg bw/day, reduced thymus weight in males.","effect":"al changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg Silver/kg bw/day, increased stillbirth index, decreased live birth index, body weights, reduced organ weights (brain, thymus, spleen). At 72/87 mg/kg bw/day, reduced thymus weight in males. LOAEL (systemic- F0 and F1): 1.5 mg Silver/kg bw/day NOAEL (reproduction, F0 and F1): 1.5 mg Silver/kg bw/day. LOAEL (developmental toxicity (F1 and F2): 1.5 mg Silver/kg bw/day (Schroeder, 2002 ECHA RAC, 2015; SCCS, 2023)/KL 1","page":48,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_046"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | Prenatal | developmental toxicity | {"dose":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal):","effect":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal): Charehsaz, developmental citrate-capped histopathological findings in 0.2 mg Silver/kg et al., 2016 toxicity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopec","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_047"} |
| SCCS_vision_codex | NOAEL | =25 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:","effect":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and r","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_050"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,","page":30,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_054"} |
| SCCS_vision_codex | NOAEL | =40 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_055"} |
| SCCS_vision_codex | NOAEL | =41 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_059"} |
| SCCS_vision_codex | NOAEL | =9 | - | rat | oral | 28-day | NOAEL study | {"effect":"Unlabeled table on page 41: 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate | 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) | At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed | LOAEL: 9 mg Silver/ kg bw/day | (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_060"} |
| SCCS_vision_codex | NOAEL | =78 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_061"} |
| SCCS_vision_codex | NOAEL | =43 | - | - | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_065"} |
| SCCS_vision_codex | NOAEL | =45 | - | - | oral | - | NOAEL study | {"effect":"Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_067"} |
| SCCS_vision_codex | NOAEL | =46 | - | - | - | - | reproductive toxicity | {"dose":"AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation.","effect":"Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_068"} |
| SCCS_vision_codex | NOAEL | =63.7 | % | rat | oral | 10 weeks | reproductive toxicity | {"dose":"Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"Unlabeled table on page 47: One generation drinking water reproductive toxicity study in Sprague-Dawley rats, according to FDA CFSAN Redbook; Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 | At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed | NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day | (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_069"} |
| SCCS_vision_codex | NOAEL | =64.6 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022;","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver acetate (64.6% Silver) | 0, 10, 30, 100 mg Silver acetate/kg bw/day equivalent to 6.5, 19, and 65 mg Silver/kg bw/day GD 6-19, by gavage | At 65 mg Silver/kg bw/day: Dams Piloerection, alopecia was observed in foetuses Increase percentage litters with late, foetal deaths (10%), reduced male bodyweight/litter (5%), foetal bodyweight/litter (5%). At 65 mg Silver/kg bw: increased skeletal variations | NOAEL (maternal and developmental): 19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022; ECHA, 2022)/ KL1-2","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_073"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/...","effect":"Unlabeled table on page 50: Prenatal developmental toxicity- DRF study, Sprague Dawley rats, OECD Guideline 414 (8 female/group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC< 2022)/KL2","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_076"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 9-year | repeated dose toxicity | {"dose":"The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.","effect":"e deposited in numerous organs and tissues and liver was identified as the principal organ for Silver deposition. The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).","page":25,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | - | - | developmental | repeated dose toxicity | {"dose":"Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","effect":"as done in the current assessment appropriately protects for the reproductive and developmental toxicity endpoint. SCCS comment For an overview and description of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/p","page":27,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_003"} |
| SCCS_vision_codex | NOAEL | =70 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_007"} |
| SCCS_vision_codex | NOAEL | =25500 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | - | human | oral | - | NOAEL study | {"effect":"ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_009"} |
| SCCS_vision_codex | NOAEL | =0.05 | mg/kg | human | oral | - | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"y Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine in","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_010"} |
| SCCS_vision_codex | NOAEL | =13 | % | human | oral | 64 years | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine injection therapy and a biospectrometric analysis of 10 cases of generalized argyria classified according to the quantity of Silver present. In this i.v. study, data were presented for 10 male (23-64 years old) and for tw","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_011"} |
| SCCS_vision_codex | NOAEL | =0.2 | % | rat | oral | chronic | carcinogenicity | {"dose":"The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment.","effect":"___________________________________________________________________________________ 34 Human data Several regulatory agencies (WHO, EFSA, US EPA) have established human reference doses based on argyria as the human-relevant effect caused by chronic exposure to Silver via, respectively, drinking water, food / food contact material or medication. The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment. Instead, the SCCS will use the NOAEL derived from a chronic combined toxicity and carcinogenicity study on Silver zinc zeolite in rats. Special investigations / 4. CONCLUSION (1) In light of the data provided and taking under consideration the classification as toxic for reproduction Cat. 2, does the SCCS consider micron-sized particulate Silver safe when used up to a maximum concentration of 0.2 % in rinse-off and 0.3 % in leave-on cosmetic products? In light of the data provided and taking under consideration the classification as toxic for r","page":34,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_021"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver...","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver containing active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_022"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.","effect":"taining active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-chronic studies 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_023"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rat | oral | 90-day | NOAEL study | {"dose":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.","effect":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2010 in ECHA, 2022)/ KL2 90-day gavage study in Sprague Dawley rats (6 males); OECD TG 408, PVP capped nanoparticles 0, 50, 100, 200 mg/kg bw/day At 200 and 100 mg/kg bw/day non-significant increase in epididymis and testis weight was observed. At 200 mg/kg bw/day, decrease sperm viability was observed. At 50 mg/kg bw/day, decrease in food intake was observed. At 50 and 100 mg/kg bw/day significant increase in sperm anomalies were observed. LOAEL: 50 mg Silver/kg bw/day (Lafue","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_024"} |
| SCCS_vision_codex | NOAEL | =1665 | - | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL:","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_025"} |
| SCCS_vision_codex | NOAEL | =0.5 | % | rat | oral | 30-day | repeated dose toxicity | {"dose":"ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No tre...","effect":"nd lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No treatment related adverse effects at any dose level NOAEL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NO","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_026"} |
| SCCS_vision_codex | NOAEL | =95 | - | rat | oral | Sub-chronic | repeated dose toxicity | {"effect":"EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_027"} |
| SCCS_vision_codex | NOAEL | =12500 | ppm | rat | oral | 9 months | repeated dose toxicity | {"dose":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exp...","effect":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exposed for 6 months, the rest for 12 months) SCAS Sub-chronic studies 14-week oral study 0, 1000, 6250, At 2 and 6 mg Silver/kg bw/day NOAEL: (Study report in Sprague-Dawley and 12500 ppm effects on behaviour/activity, 0.65 mg Silver/ 2001 in ECHA rat (10/sex/group); of Silver zinc pigmentation of pancreas, kg bw/day RAC, 2022;","page":42,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_028"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg | dog | oral | 90-day | NOAEL study | {"dose":"(Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 43 Similar to OECD TG zeolite thymus, the mandibular lymph ECHA RAC, 408; AgION approximately 0, node, changes in clinical 2015)/ KL1 Antimicrobial Type 0.65, 2.0, and chemistry and haematology AK (Silver zinc 6.0 mg Silver/kg were observed zeolite) bw/day 90-day oral gavage 0, 10, 50, and At 5.1 mg Silver/kg bw/day NOAEL: (Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_029"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg | rat | oral | 90-day | NOAEL study | {"dose":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At 9.5 mg Silver/kg bw/day, NOAEL: (ECHA RAC, CD rats; similar to 1000 mg/kg relative heart weight was 0.29 mg 2022)/ KL2 OECD TG 408; Silver bw/day of Silver increased in males. Silver/kg sodium zirconium sodium zirconium At 9.5 and 2.9 mg Silver/kg bw/day hydrogen hydrogen bw/day, increased ALP levels, phosphate phosphate discoloration of pancreas and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_030"} |
| SCCS_vision_codex | NOAEL | =0 | - | - | oral | 90-day | NOAEL study | {"effect":"s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_031"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | developmental | reproductive toxicity | {"dose":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats:","effect":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0,","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_032"} |
| SCCS_vision_codex | NOAEL | =52 | - | rat | oral | 52 days | reproductive toxicity | {"dose":"2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose.","effect":"opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_033"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","effect":"se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_035"} |
| SCCS_vision_codex | NOAEL | =26 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","effect":"vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_037"} |
| SCCS_vision_codex | NOAEL | =20000 | ppm | rat | oral | 10 weeks | reproductive toxicity | {"dose":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_040"} |
| SCCS_vision_codex | NOAEL | =87 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"At 72/87 mg/kg bw/day, reduced thymus weight in males.","effect":"al changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg Silver/kg bw/day, increased stillbirth index, decreased live birth index, body weights, reduced organ weights (brain, thymus, spleen). At 72/87 mg/kg bw/day, reduced thymus weight in males. LOAEL (systemic- F0 and F1): 1.5 mg Silver/kg bw/day NOAEL (reproduction, F0 and F1): 1.5 mg Silver/kg bw/day. LOAEL (developmental toxicity (F1 and F2): 1.5 mg Silver/kg bw/day (Schroeder, 2002 ECHA RAC, 2015; SCCS, 2023)/KL 1","page":48,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_046"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | Prenatal | developmental toxicity | {"dose":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal):","effect":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal): Charehsaz, developmental citrate-capped histopathological findings in 0.2 mg Silver/kg et al., 2016 toxicity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopec","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_047"} |
| SCCS_vision_codex | NOAEL | =25 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:","effect":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and r","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_050"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,","page":30,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_054"} |
| SCCS_vision_codex | NOAEL | =40 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_055"} |
| SCCS_vision_codex | NOAEL | =41 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_059"} |
| SCCS_vision_codex | NOAEL | =9 | - | rat | oral | 28-day | NOAEL study | {"effect":"Unlabeled table on page 41: 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate | 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) | At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed | LOAEL: 9 mg Silver/ kg bw/day | (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_060"} |
| SCCS_vision_codex | NOAEL | =78 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_061"} |
| SCCS_vision_codex | NOAEL | =43 | - | - | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_065"} |
| SCCS_vision_codex | NOAEL | =45 | - | - | oral | - | NOAEL study | {"effect":"Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_067"} |
| SCCS_vision_codex | NOAEL | =46 | - | - | - | - | reproductive toxicity | {"dose":"AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation.","effect":"Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_068"} |
| SCCS_vision_codex | NOAEL | =63.7 | % | rat | oral | 10 weeks | reproductive toxicity | {"dose":"Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"Unlabeled table on page 47: One generation drinking water reproductive toxicity study in Sprague-Dawley rats, according to FDA CFSAN Redbook; Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 | At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed | NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day | (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_069"} |
| SCCS_vision_codex | NOAEL | =64.6 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022;","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver acetate (64.6% Silver) | 0, 10, 30, 100 mg Silver acetate/kg bw/day equivalent to 6.5, 19, and 65 mg Silver/kg bw/day GD 6-19, by gavage | At 65 mg Silver/kg bw/day: Dams Piloerection, alopecia was observed in foetuses Increase percentage litters with late, foetal deaths (10%), reduced male bodyweight/litter (5%), foetal bodyweight/litter (5%). At 65 mg Silver/kg bw: increased skeletal variations | NOAEL (maternal and developmental): 19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022; ECHA, 2022)/ KL1-2","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_073"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/...","effect":"Unlabeled table on page 50: Prenatal developmental toxicity- DRF study, Sprague Dawley rats, OECD Guideline 414 (8 female/group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC< 2022)/KL2","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_076"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24:","effect":"cientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 25 3.4.3 Acute toxicity 1 2 See SCCS/1665/24. 3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24: 7 The SCCS has reservations regarding the Applicant's choice of the PoD of 0.014 mg Silver/kg 8 bw/day. This is further explained in 3.5 (Safety evaluation) of the SCCS/1665/24 Opinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation.","effect":"pinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion equivalents, derived from a study 19 with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). 20 This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity 21 study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment 22 in this Opinion. 23 24 3.4.6 Mutagenicity / genotoxicity 25 26 Taken and abridged from SCCS/1665/24: 27 The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not 28","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_003"} |
| SCCS_vision_codex | NOAEL | =1687 | - | human | oral | - | repeated dose toxicity | {"dose":"3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity):","effect":"SCCS/1687/25 Preliminary Scientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 26 3.4.9 Human data 1 2 See SCCS/1665/24. 3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity): 10 4.5 μg/kg bw/day. 11 For the respective aggregate SED’s, see: 3.3 Calculation of the SED. 12 13 Dermally applied products: 14 MoS = NOAELadj / aggregate SED = 4.5 / 0.0024 = 1875 15 16 Orally applied products: 17 MoS = NOAELadj / aggregate SED = 4.5 / 0.0052 = 865 18 19 Pump based spray products: 20 MoS = NOAELadj / aggregate SED = 4.5 / 0.009 = 500 21 22 Margin of Safety (MoS): 23 (conservatively) aggregated over all","page":26,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_005"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24:","effect":"cientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 25 3.4.3 Acute toxicity 1 2 See SCCS/1665/24. 3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24: 7 The SCCS has reservations regarding the Applicant's choice of the PoD of 0.014 mg Silver/kg 8 bw/day. This is further explained in 3.5 (Safety evaluation) of the SCCS/1665/24 Opinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation.","effect":"pinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion equivalents, derived from a study 19 with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). 20 This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity 21 study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment 22 in this Opinion. 23 24 3.4.6 Mutagenicity / genotoxicity 25 26 Taken and abridged from SCCS/1665/24: 27 The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not 28","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_003"} |
| SCCS_vision_codex | NOAEL | =1687 | - | human | oral | - | repeated dose toxicity | {"dose":"3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity):","effect":"SCCS/1687/25 Preliminary Scientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 26 3.4.9 Human data 1 2 See SCCS/1665/24. 3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity): 10 4.5 μg/kg bw/day. 11 For the respective aggregate SED’s, see: 3.3 Calculation of the SED. 12 13 Dermally applied products: 14 MoS = NOAELadj / aggregate SED = 4.5 / 0.0024 = 1875 15 16 Orally applied products: 17 MoS = NOAELadj / aggregate SED = 4.5 / 0.0052 = 865 18 19 Pump based spray products: 20 MoS = NOAELadj / aggregate SED = 4.5 / 0.009 = 500 21 22 Margin of Safety (MoS): 23 (conservatively) aggregated over all","page":26,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested.","effect":"ver the ATSDR concludes that ‘existing evidence’ does not point to a strong effect of the silver ion on reproduction and no historical evidence to indicate an effect of silver on reproduction in humans. While subcutaneous injection of silver nitrate has been reported to cause reversible damage to the testes in rats (Hoey, 1966), no effects on spermatozoa or fertility were observed in a drinking water study. A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested. Indications of slight maternal toxicity were observed at this dose level; more severe maternal toxicity was observed at a dose level of 160 mg/kg bw/d in a screening study. Published data (Shavlovsky et al., 1995) indicate an effect of silver on development at maternally toxic dose levels and secondary to copper deficiency caused by the displacement of copper by silver from ceruloplasmin. 3.3.9. Toxicokinetics 3.3.9.1. Absorption Stu","page":15,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.00056 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","effect":"r-bound estimate and orders of magnitude higher than those measured in vitro with intact or mildly damaged human skin (Larese et al. 2009). Reference values All published reviews concur that the relevant (critical) effect of silver exposure is argyria. Toxicological reference values for silver have been derived by the EPA, WHO and EFSA. The US EPA uses a systemic lifetime (systemic) exposure of 1 g silver as starting point1; 1 The EPA (1989) used the study of Gaul & Staud to derive a minimal (lifetime exposure) NOAEL of 1 g silver (systemic). This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","page":21,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_002"} |
| SCCS_vision_codex | NOAEL | =0.0065 | mg/kg bw/d | human | oral | 70 years | NOAEL study | {"dose":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg.","effect":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg. Based on the epidemiological and pharmacokinetic data, WHO (2003) derives a human NOAEL (lifetime oral intake) for silver of 10 g, corresponding to 0.39 mg Ag/person/day or 0.0065 mg/kg bw/d. Assuming a gastrointestinal absorption of silver of 5%, this is equivalent to a systemic reference value of 0.000325 mg/kg bw/d (0.325 µg/kg bw/d). EFSA has evaluated silver-based preservatives for use in food-contact materials on the basis of human and animal data and has derived a group restriction limit of 0.05 mg Ag/kg food, which corresponds to a worst-case exposure of 0.05 mg Ag/person/day or 0.00083 mg/k","page":22,"pdf":"sccs_o_198.pdf","row_type":"noael_study","study_id":"sccs_o_198_noael_003"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 9-year | repeated dose toxicity | {"dose":"The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.","effect":"e deposited in numerous organs and tissues and liver was identified as the principal organ for Silver deposition. The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).","page":25,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | - | - | developmental | repeated dose toxicity | {"dose":"Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","effect":"as done in the current assessment appropriately protects for the reproductive and developmental toxicity endpoint. SCCS comment For an overview and description of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/p","page":27,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_003"} |
| SCCS_vision_codex | NOAEL | =70 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_007"} |
| SCCS_vision_codex | NOAEL | =25500 | - | human | oral | 500 days | NOAEL study | {"dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","effect":"weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | - | human | oral | - | NOAEL study | {"effect":"ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_009"} |
| SCCS_vision_codex | NOAEL | =0.05 | mg/kg | human | oral | - | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"y Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine in","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_010"} |
| SCCS_vision_codex | NOAEL | =13 | % | human | oral | 64 years | NOAEL study | {"dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","effect":"0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine injection therapy and a biospectrometric analysis of 10 cases of generalized argyria classified according to the quantity of Silver present. In this i.v. study, data were presented for 10 male (23-64 years old) and for tw","page":29,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_011"} |
| SCCS_vision_codex | NOAEL | =0.2 | % | rat | oral | chronic | carcinogenicity | {"dose":"The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment.","effect":"___________________________________________________________________________________ 34 Human data Several regulatory agencies (WHO, EFSA, US EPA) have established human reference doses based on argyria as the human-relevant effect caused by chronic exposure to Silver via, respectively, drinking water, food / food contact material or medication. The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment. Instead, the SCCS will use the NOAEL derived from a chronic combined toxicity and carcinogenicity study on Silver zinc zeolite in rats. Special investigations / 4. CONCLUSION (1) In light of the data provided and taking under consideration the classification as toxic for reproduction Cat. 2, does the SCCS consider micron-sized particulate Silver safe when used up to a maximum concentration of 0.2 % in rinse-off and 0.3 % in leave-on cosmetic products? In light of the data provided and taking under consideration the classification as toxic for r","page":34,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_021"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver...","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver containing active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_022"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.","effect":"taining active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-chronic studies 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_023"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg bw/day | rat | oral | 90-day | NOAEL study | {"dose":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.","effect":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2010 in ECHA, 2022)/ KL2 90-day gavage study in Sprague Dawley rats (6 males); OECD TG 408, PVP capped nanoparticles 0, 50, 100, 200 mg/kg bw/day At 200 and 100 mg/kg bw/day non-significant increase in epididymis and testis weight was observed. At 200 mg/kg bw/day, decrease sperm viability was observed. At 50 mg/kg bw/day, decrease in food intake was observed. At 50 and 100 mg/kg bw/day significant increase in sperm anomalies were observed. LOAEL: 50 mg Silver/kg bw/day (Lafue","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_024"} |
| SCCS_vision_codex | NOAEL | =1665 | - | rat | oral | Sub-acute | repeated dose toxicity | {"dose":"Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL:","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_025"} |
| SCCS_vision_codex | NOAEL | =0.5 | % | rat | oral | 30-day | repeated dose toxicity | {"dose":"ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No tre...","effect":"nd lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No treatment related adverse effects at any dose level NOAEL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NO","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_026"} |
| SCCS_vision_codex | NOAEL | =95 | - | rat | oral | Sub-chronic | repeated dose toxicity | {"effect":"EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_027"} |
| SCCS_vision_codex | NOAEL | =12500 | ppm | rat | oral | 9 months | repeated dose toxicity | {"dose":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exp...","effect":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exposed for 6 months, the rest for 12 months) SCAS Sub-chronic studies 14-week oral study 0, 1000, 6250, At 2 and 6 mg Silver/kg bw/day NOAEL: (Study report in Sprague-Dawley and 12500 ppm effects on behaviour/activity, 0.65 mg Silver/ 2001 in ECHA rat (10/sex/group); of Silver zinc pigmentation of pancreas, kg bw/day RAC, 2022;","page":42,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_028"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg | dog | oral | 90-day | NOAEL study | {"dose":"(Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 43 Similar to OECD TG zeolite thymus, the mandibular lymph ECHA RAC, 408; AgION approximately 0, node, changes in clinical 2015)/ KL1 Antimicrobial Type 0.65, 2.0, and chemistry and haematology AK (Silver zinc 6.0 mg Silver/kg were observed zeolite) bw/day 90-day oral gavage 0, 10, 50, and At 5.1 mg Silver/kg bw/day NOAEL: (Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_029"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg | rat | oral | 90-day | NOAEL study | {"dose":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","effect":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At 9.5 mg Silver/kg bw/day, NOAEL: (ECHA RAC, CD rats; similar to 1000 mg/kg relative heart weight was 0.29 mg 2022)/ KL2 OECD TG 408; Silver bw/day of Silver increased in males. Silver/kg sodium zirconium sodium zirconium At 9.5 and 2.9 mg Silver/kg bw/day hydrogen hydrogen bw/day, increased ALP levels, phosphate phosphate discoloration of pancreas and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_030"} |
| SCCS_vision_codex | NOAEL | =0 | - | - | oral | 90-day | NOAEL study | {"effect":"s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_031"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | developmental | reproductive toxicity | {"dose":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats:","effect":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0,","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_032"} |
| SCCS_vision_codex | NOAEL | =52 | - | rat | oral | 52 days | reproductive toxicity | {"dose":"2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose.","effect":"opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_033"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","effect":"se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_035"} |
| SCCS_vision_codex | NOAEL | =26 | - | - | - | developmental | reproductive toxicity | {"dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","effect":"vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_037"} |
| SCCS_vision_codex | NOAEL | =20000 | ppm | rat | oral | 10 weeks | reproductive toxicity | {"dose":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_040"} |
| SCCS_vision_codex | NOAEL | =87 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"At 72/87 mg/kg bw/day, reduced thymus weight in males.","effect":"al changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg Silver/kg bw/day, increased stillbirth index, decreased live birth index, body weights, reduced organ weights (brain, thymus, spleen). At 72/87 mg/kg bw/day, reduced thymus weight in males. LOAEL (systemic- F0 and F1): 1.5 mg Silver/kg bw/day NOAEL (reproduction, F0 and F1): 1.5 mg Silver/kg bw/day. LOAEL (developmental toxicity (F1 and F2): 1.5 mg Silver/kg bw/day (Schroeder, 2002 ECHA RAC, 2015; SCCS, 2023)/KL 1","page":48,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_046"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | Prenatal | developmental toxicity | {"dose":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal):","effect":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal): Charehsaz, developmental citrate-capped histopathological findings in 0.2 mg Silver/kg et al., 2016 toxicity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopec","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_047"} |
| SCCS_vision_codex | NOAEL | =25 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:","effect":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and r","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_050"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,","page":30,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_054"} |
| SCCS_vision_codex | NOAEL | =40 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating","page":40,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_055"} |
| SCCS_vision_codex | NOAEL | =41 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_059"} |
| SCCS_vision_codex | NOAEL | =9 | - | rat | oral | 28-day | NOAEL study | {"effect":"Unlabeled table on page 41: 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate | 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) | At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed | LOAEL: 9 mg Silver/ kg bw/day | (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_060"} |
| SCCS_vision_codex | NOAEL | =78 | - | rat | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_061"} |
| SCCS_vision_codex | NOAEL | =43 | - | - | oral | 90-day | NOAEL study | {"effect":"Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,","page":43,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_065"} |
| SCCS_vision_codex | NOAEL | =45 | - | - | oral | - | NOAEL study | {"effect":"Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020","page":45,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_067"} |
| SCCS_vision_codex | NOAEL | =46 | - | - | - | - | reproductive toxicity | {"dose":"AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation.","effect":"Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...","page":46,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_068"} |
| SCCS_vision_codex | NOAEL | =63.7 | % | rat | oral | 10 weeks | reproductive toxicity | {"dose":"Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","effect":"Unlabeled table on page 47: One generation drinking water reproductive toxicity study in Sprague-Dawley rats, according to FDA CFSAN Redbook; Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 | At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed | NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day | (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2","page":47,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_069"} |
| SCCS_vision_codex | NOAEL | =64.6 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022;","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver acetate (64.6% Silver) | 0, 10, 30, 100 mg Silver acetate/kg bw/day equivalent to 6.5, 19, and 65 mg Silver/kg bw/day GD 6-19, by gavage | At 65 mg Silver/kg bw/day: Dams Piloerection, alopecia was observed in foetuses Increase percentage litters with late, foetal deaths (10%), reduced male bodyweight/litter (5%), foetal bodyweight/litter (5%). At 65 mg Silver/kg bw: increased skeletal variations | NOAEL (maternal and developmental): 19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022; ECHA, 2022)/ KL1-2","page":49,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_073"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | Prenatal | developmental toxicity | {"dose":"Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/...","effect":"Unlabeled table on page 50: Prenatal developmental toxicity- DRF study, Sprague Dawley rats, OECD Guideline 414 (8 female/group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC< 2022)/KL2","page":50,"pdf":"sccs_o_288.pdf","row_type":"noael_study","study_id":"sccs_o_288_noael_076"} |
| SCCS_vision_codex | NOAEL | =0.0045 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24:","effect":"cientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 25 3.4.3 Acute toxicity 1 2 See SCCS/1665/24. 3 4 3.4.4 Repeated dose toxicity 5 6 Taken and abridged from SCCS/1665/24: 7 The SCCS has reservations regarding the Applicant's choice of the PoD of 0.014 mg Silver/kg 8 bw/day. This is further explained in 3.5 (Safety evaluation) of the SCCS/1665/24 Opinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_001"} |
| SCCS_vision_codex | NOAEL | =0.25 | mg/kg bw/d | rat | oral | 12 months | repeated dose toxicity | {"dose":"9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation.","effect":"pinion. 9 The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- 10 ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived 11 from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 12 2021, SCCS/1650/23). 13 14 3.4.5 Reproductive toxicity 15 16 Taken and abridged from SCCS/1665/24: 17 From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity 18 the most conservative NOAEL at 0.25 mg/kg bw/d silver ion equivalents, derived from a study 19 with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). 20 This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity 21 study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment 22 in this Opinion. 23 24 3.4.6 Mutagenicity / genotoxicity 25 26 Taken and abridged from SCCS/1665/24: 27 The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not 28","page":25,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_003"} |
| SCCS_vision_codex | NOAEL | =1687 | - | human | oral | - | repeated dose toxicity | {"dose":"3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity):","effect":"SCCS/1687/25 Preliminary Scientific Advice Scientific advice on Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products _________________________________________________________________________________ 26 3.4.9 Human data 1 2 See SCCS/1665/24. 3 3.4.10 Special investigations 4 5 / 6 7 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) 8 9 NOAEL for silver ions, adjusted for oral absorption (see 3.4.4 Repeated Dose Toxicity): 10 4.5 μg/kg bw/day. 11 For the respective aggregate SED’s, see: 3.3 Calculation of the SED. 12 13 Dermally applied products: 14 MoS = NOAELadj / aggregate SED = 4.5 / 0.0024 = 1875 15 16 Orally applied products: 17 MoS = NOAELadj / aggregate SED = 4.5 / 0.0052 = 865 18 19 Pump based spray products: 20 MoS = NOAELadj / aggregate SED = 4.5 / 0.009 = 500 21 22 Margin of Safety (MoS): 23 (conservatively) aggregated over all","page":26,"pdf":"sccs_o_309.pdf","row_type":"noael_study","study_id":"sccs_o_309_noael_005"} |
ToxValDB_ECHA_IUCLID 12 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_ECHA_IUCLID | LOAEL | =125 | mg/kg bw/day | Rat | oral | subchronic; 13 weeks | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacb3e4b0a7c65d1c0640; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11913/7/6/2?documentUUID=23950611-8c31-4047-bbd0-b9d313a1d2da; YEAR=1979; ORIGINAL_YEAR=1979; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15837406_15839949_15846439_15850224_15850225_15850226:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ade1d8e758dcb5d37ae295befc708ca3 |
| ToxValDB_ECHA_IUCLID | LOAEL | >=40 | mg/kg bw/day | Rat | oral | subchronic; 12 weeks | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaee2e4b0a7c65d1cb6bb; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/6/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; TOXICOLOGICAL_EFFECT=serum/plasma biochemistry; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry; STUDY_GROUP=ECHA IUCLID:15849820:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_3967796cb24d57bc237dfe8ae9379032 |
| ToxValDB_ECHA_IUCLID | LOAEL | =4 | mg/kg bw/day | Rat | oral | - | developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eab59e4b0a7c65d1b9cb5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/9/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; TOXICOLOGICAL_EFFECT=F1: developmental immunotoxicity; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ECHA IUCLID:15858559:M/F:F1-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_795d3e5e6b4b73fcaf4c773930b998ba |
| ToxValDB_ECHA_IUCLID | NOAEC | >=0.061 | mg/m3 | Rat | inhalation | short-term; 4 weeks | short-term | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/6/3?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; STUDY_GROUP=ECHA IUCLID:15827227:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_69a80685b830ceac32b217d24accdd70 |
| ToxValDB_ECHA_IUCLID | NOAEC | >=0.115 | mg/m3 | Rat | inhalation | short-term; 4 weeks | short-term | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/6/3?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; STUDY_GROUP=ECHA IUCLID:15827470:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_b8cfd0ec42e3d99d61e0c36adb418f8a |
| ToxValDB_ECHA_IUCLID | NOAEL | =200 | mg/kg bw/day | Rat | oral | subchronic; 90 days | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaee2e4b0a7c65d1cb6d2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/6/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; TOXICOLOGICAL_EFFECT=body weight and weight gain|histopathology: non-neoplastic|organ weights and organ / body weight ratios; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|nonneoplastic histopathology|organ weight; STUDY_GROUP=ECHA IUCLID:15849821:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_162babb58875705a566458202ef95ee9 |
| ToxValDB_ECHA_IUCLID | NOAEL | =30 | mg/kg bw/day | Rat | oral | subchronic; 13 weeks | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eae5ae4b0a7c65d1c8e11; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5603/7/6/2?documentUUID=de2eca6c-217e-4af6-b0cb-50d9f7b88e62; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15837406_15839949_15846439_15850224_15850225_15850226:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_0c270400410ab9921458da1f0207c290 |
| ToxValDB_ECHA_IUCLID | NOAEL | =36 | mg/kg bw/day | Rat | oral | subchronic; 13 weeks | subchronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaee2e4b0a7c65d1cb6ea; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/6/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; TOXICOLOGICAL_EFFECT=clinical biochemistry|clinical signs|haematology|histopathology: neoplastic|histopathology: non-neoplastic; TOXICOLOGICAL_EFFECT_CATEGORY=cancer|clinical chemistry|clinical signs|hematology|nonneoplastic histopathology; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15850909_15850988_15851026:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_4aa6df0a67c9f75c3b7619eff4f2f2fb |
| ToxValDB_ECHA_IUCLID | NOAEL | =250 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eab59e4b0a7c65d1b9cbb; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/9/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15856209_15857684:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0dfe25e61d8460bdb1e2fa7c5d424e68 |
| ToxValDB_ECHA_IUCLID | NOAEL | =80 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c93ee4b0a7c65d21c232; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/9/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; TOXICOLOGICAL_EFFECT=P0: mortality; TOXICOLOGICAL_EFFECT_CATEGORY=mortality/survival; STUDY_GROUP=ECHA IUCLID:15857011:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_e7a41b63f09f4f46ee3d748589fa1bbe |
| ToxValDB_ECHA_IUCLID | NOAEL | =0.4 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eab59e4b0a7c65d1b9cb8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/9/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; TOXICOLOGICAL_EFFECT=F1: viability|F1: body weight and weight gain; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|reproduction; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15858310_15858752_15858785:M/F:F1-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_246fe45d48c73813240e68b59c494f08 |
| ToxValDB_ECHA_IUCLID | NOAEL | =4 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eab59e4b0a7c65d1b9cb8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16155/7/9/2?documentUUID=a842c2ff-dd8f-473d-bb15-a27046511baa; YEAR=1977; ORIGINAL_YEAR=1977; TOXICOLOGICAL_EFFECT=F1: test mat.|F1: mortality|F1: organ weights and organ / body weight ratios; TOXICOLOGICAL_EFFECT_CATEGORY=mortality/survival|organ weight|other; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15858310_15858752_15858785:M/F:F1-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_4c8b3de8a5a0b88381e389acd0b144ba |
ToxValDB_ECOTOX 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_ECOTOX | LOEL | =250 | mg/L | Rat | oral | short-term; 21 days | short-term | LONG_REF=Comp. Biochem. Physiol. C Comp. Pharmacol.81(1): 131-132 Abdel Rahim,A.G. The Effects of Dietary L-Ascorbic Acid on the Absorption and Utilization of Na75SeO3 of Silver-Treated Rats 1985; TITLE=The Effects of Dietary L-Ascorbic Acid on the Absorption and Utilization of Na75SeO3 of Silver-Treated Rats; AUTHOR=Abdel Rahim,A.G.; DOI=10.1016/0742-8413(85)90103-3; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=105678; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1985; ORIGINAL_YEAR=1985; TOXICOLOGICAL_EFFECT=Physiology: Selenium uptake; STUDY_GROUP=ECOTOX:15596126:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=c6687cc7eb6bf0172b61c19c89bf9120 |
ToxValDB_EPA_TSCA_8e 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_EPA_TSCA_8e | LEL | =2 | mg/m3 | Rat | inhalation | short-term; 5 days | short-term | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=8EHQ-17-20957_Combined.pdf; TOXICOLOGICAL_EFFECT=increased total white blood cell, neutrophil and lymphocyte counts, increased lung weights, increased bronchoalveolar lavage neutrophil, lymphocyte, monocyte counts, proteins, chemoattractants, enzymes, and osteopontin levels, pulmonary inflammation, granular material, and hypertrophy/hyperplasia of the bronchiolar-alveolar junction; STUDY_GROUP=EPA TSCA 8e_dup_-_15957590_15957591_15957592:M:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_e625844411f4653bea002a26900f10e4 |
| ToxValDB_EPA_TSCA_8e | LEL | =0.8 | mg/m3 | Rat | inhalation | short-term; 5 days | short-term | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=8EHQ-17-20957_Combined.pdf; TOXICOLOGICAL_EFFECT=increased bronchoalveolar lavage neutrophil, lymphocyte, monocyte counts, proteins, chemoattractants, enzymes, and osteopontin levels, pulmonary inflammation, granular material, and hypertrophy/hyperplasia of the bronchiolar-alveolar junction; STUDY_GROUP=EPA TSCA 8e_dup_-_15957590_15957591_15957592:M:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_9a44d4aef5ad8920b966f85b4d77a0f8 |
| ToxValDB_EPA_TSCA_8e | LEL | =10.2 | mg/m3 | Rat | inhalation | short-term; 5 days | short-term | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=090225268023f448_8EHQ-16-20231_Section 8 (e)_N_2076 EPA No Confidentiality Letter CDX.pdf; TOXICOLOGICAL_EFFECT=changes to hematology and clinical chemistry parameters and chemistry and respiratory tract; STUDY_GROUP=EPA TSCA 8e:15957593:M:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_183bed40d6b245dc5a45b8b933148c3d |
| ToxValDB_EPA_TSCA_8e | NEL | =0.2 | mg/m3 | Rat | inhalation | short-term; 5 days | short-term | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=8EHQ-17-20957_Combined.pdf; TOXICOLOGICAL_EFFECT=no effects; STUDY_GROUP=EPA TSCA 8e_dup_-_15957590_15957591_15957592:M:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_d26438981772cc90a55234573ba9e0ef |
ToxValDB_GESTIS_DNEL 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_GESTIS_DNEL | DNEL local | =0.008 | mg/m3 | Human | inhalation | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15634633_15634634:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_7ac70fe0dc022ba81c8a0bf6a1bf50e1 |
ToxValDB_IRIS 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_IRIS | LOAEL | =0.014 | mg/kg bw/day | Human | oral | - | clinical | LONG_REF=Gaul, L.E. and A.H. Staud. 1935. Clinical spectroscopy. Seventy cases of generalized argyrosis following organic and colloidal silver medication. J. Am. Med. Assoc. 104: 1387-1390.; TITLE=Clinical spectroscopy. Seventy cases of generalized argyrosis following organic and colloidal silver medication; AUTHOR=Gaul, L.E. and A.H. Staud; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/652e8a2ce4b045b9ff7a4d76; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/iris; SUBSOURCE_URL=https://iris.epa.gov/ChemicalLanding/&substance_nmbr=99; TOXICOLOGICAL_EFFECT=argyria; TOXICOLOGICAL_EFFECT_CATEGORY=clinical signs; STUDY_GROUP=IRIS:15645400:M/F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_011f178d6c24c293703452998bb84177 |
| ToxValDB_IRIS | RfD | =0.005 | mg/kg bw/day | Human | oral | - | Toxicity Value | LONG_REF=Gaul, L.E. and A.H. Staud. 1935. Clinical spectroscopy. Seventy cases of generalized argyrosis following organic and colloidal silver medication. J. Am. Med. Assoc. 104: 1387-1390.; TITLE=Clinical spectroscopy. Seventy cases of generalized argyrosis following organic and colloidal silver medication; AUTHOR=Gaul, L.E. and A.H. Staud; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/652e8a2ce4b045b9ff7a4d76; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/iris; SUBSOURCE_URL=https://iris.epa.gov/ChemicalLanding/&substance_nmbr=99; TOXICOLOGICAL_EFFECT=argyria; STUDY_GROUP=IRIS:15645401:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_5e624646d97320469738582bd32245af |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 80 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.00056 | mg/kg bw/d | human | oral | 70 years | - | SOURCE_SUBDIR=sccs_o_198; REPORT_TITLE=OPINION ON preservative EcoG+; OPINION_NUMBER=SCCS/1577/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 6 October 2016; VALUE_TEXT=0.00056; DOSE=This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3; EFFECT=r-bound estimate and orders of magnitude higher than those measured in vitro with intact or mildly damaged human skin (Larese et al. 2009). Reference values All published reviews concur that the relevant (critical) effect of silver exposure is argyria. Toxicological reference values for silver have been derived by the EPA, WHO and EFSA. The US EPA uses a systemic lifetime (systemic) exposure of 1 g silver as starting point1; 1 The EPA (1989) used the study of Gaul & Staud to derive a minimal (lifetime exposure) NOAEL of 1 g silver (systemic). This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","duration":"70 years","effect":"r-bound estimate and orders of magnitude higher than those measured in vitro with intact or mildly damaged human skin (Larese et al. 2009). Reference values All published reviews concur that the relevant (critical) effect of silver exposure is argyria. Toxicological reference values for silver have been derived by the EPA, WHO and EFSA. The US EPA uses a systemic lifetime (systemic) exposure of 1 g silver as starting point1; 1 The EPA (1989) used the study of Gaul & Staud to derive a minimal (lifetime exposure) NOAEL of 1 g silver (systemic). This level of systemic exposure is calculated to be equivalent to an oral reference dose (RfD) of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) following correction for the extent of oral absorption (5 %), bodyweight (70 kg), exposure over a lifetime of 70 years (25500 days) and an uncertainty factor of 3","endpoint":"","ingredient":"intended to be released into the cosmetic product is the silver","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.00056","page":21,"route":"oral","species":"human","study_id":"sccs_o_198_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.0065 | mg/kg bw/d | human | oral | 70 years | - | SOURCE_SUBDIR=sccs_o_198; REPORT_TITLE=OPINION ON preservative EcoG+; OPINION_NUMBER=SCCS/1577/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 6 October 2016; VALUE_TEXT=0.0065; DOSE=SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg.; EFFECT=SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg. Based on the epidemiological and pharmacokinetic data, WHO (2003) derives a human NOAEL (lifetime oral intake) for silver of 10 g, corresponding to 0.39 mg Ag/person/day or 0.0065 mg/kg bw/d. Assuming a gastrointestinal absorption of silver of 5%, this is equivalent to a systemic reference value of 0.000325 mg/kg bw/d (0.325 µg/kg bw/d). EFSA has evaluated silver-based preservatives for use in food-contact materials on the basis of human and animal data and has derived a group restriction limit of 0.05 mg Ag/kg food, which corresponds to a worst-case exposure of 0.05 mg Ag/person/day or 0.00083 mg/k; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg.","duration":"70 years","effect":"SCCS/1577/16 Final version of the Opinion on Eco G+ 22 this is calculated to be equivalent to a systemic exposure level of 0.00056 mg/kg bw/d (0.56 μg/kg bw/d) assuming a lifetime of 70 years and a bodyweight of 70 kg. Based on the epidemiological and pharmacokinetic data, WHO (2003) derives a human NOAEL (lifetime oral intake) for silver of 10 g, corresponding to 0.39 mg Ag/person/day or 0.0065 mg/kg bw/d. Assuming a gastrointestinal absorption of silver of 5%, this is equivalent to a systemic reference value of 0.000325 mg/kg bw/d (0.325 µg/kg bw/d). EFSA has evaluated silver-based preservatives for use in food-contact materials on the basis of human and animal data and has derived a group restriction limit of 0.05 mg Ag/kg food, which corresponds to a worst-case exposure of 0.05 mg Ag/person/day or 0.00083 mg/k","endpoint":"","ingredient":"intended to be released into the cosmetic product is the silver","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0065","page":22,"route":"oral","species":"human","study_id":"sccs_o_198_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 70 | - | human | oral | 500 days | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu; DOSE=Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.; EFFECT=and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","duration":"500 days","effect":"and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:and dividing by 70 kg (adult body weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance valu","page":29,"route":"oral","species":"human","study_id":"sccs_o_288_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25500 | - | human | oral | 500 days | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S; DOSE=Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.; EFFECT=weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver.","duration":"500 days","effect":"weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:weight) and 25,500 days (a lifetime, or 70 years) [(1000/0.04)/ (70*25500) = 0.014]. Further, to account for differences in the individuals, an uncertainty factor (UF) of 3 is also used (0.014/3=0.0047 rounded to 0.005 mg Silver/kg bw/day) The above derived value of 0.005 mg Silver/kg bw/day has been used by the US EPA as the chronic reference dose for Silver. In its original assessment, the WHO (1993) considered a ‘total lifetime’ oral intake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for S","page":29,"route":"oral","species":"human","study_id":"sccs_o_288_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 10 | - | human | oral | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive; EFFECT=ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"","effect":"ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:ntake of about 10 g of Silver as the human no observed adverse effect level (NOAEL) corresponding to 0.39 mg Silver/person/day or 0.0065 mg Silver/kg bw/day based on the toxicological dataset provided, considering argyria as sign of Silver overload. This is also based on the present epidemiological and pharmacokinetic knowledge with scientific references ranging from 1935 to 1989. However, a recent draft background document for the development of WHO Guidelines for Silver in drinking water suggested that the above NOAEL of 10 g of Silver is inappropriate to derive the formal guidance value for Silver and considered the derivation of formal guidance value as unnecessary (WHO, 2020). In this report, the WHO considered a LOAEL of 0.6 mg Silver/kg bw/day from a case study report by Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derive","page":29,"route":"oral","species":"human","study_id":"sccs_o_288_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.05 | mg/kg | human | oral | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.05; DOSE=Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).; EFFECT=y Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derived from the WHO "Guidelines for drinking water quality". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","duration":"","effect":"y Kim et al., 2009 to derive the bounding value for Silver. EFSA has evaluated Silver-based preservatives for use in food-contact materials on the basis of human and animal data and derived a group restriction limit of 0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine in","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg","noael_value":"0.05","page":29,"route":"oral","species":"human","study_id":"sccs_o_288_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 13 | % | human | oral | 64 years | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=13; DOSE=Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).; EFFECT=0.05 mg Silver/kg food. This is derived from the WHO "Guidelines for drinking water quality". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine injection therapy and a biospectrometric analysis of 10 cases of generalized argyria classified according to the quantity of Silver present. In this i.v. study, data were presented for 10 male (23-64 years old) and for tw; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food).","duration":"64 years","effect":"0.05 mg Silver/kg food. This is derived from the WHO \"Guidelines for drinking water quality\". According to these Guidelines a total lifetime oral intake of about 10 g of Silver (equal to 0.39 mg/day/person) can be considered on the basis of epidemiological and pharmacokinetic knowledge as the human NOAEL. Using the default food-contact material exposure scenario (European Commission, 2001), the restriction of 0.05 mg/kg of food (as Silver) limits the intake from food contact plastics to less than 13% of the human NOAEL of 0.39 mg/person/day (i.e., 0.39*0.13=0.05 mg/kg food). From Applicant: Clinical study. Gaul and Staud (1935) reported 70 cases of generalized argyria following organic and colloidal Silver medication, including 13 cases of generalised argyria following intravenous (i.v.) Silver arsphenamine injection therapy and a biospectrometric analysis of 10 cases of generalized argyria classified according to the quantity of Silver present. In this i.v. study, data were presented for 10 male (23-64 years old) and for tw","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"13","page":29,"route":"oral","species":"human","study_id":"sccs_o_288_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.0045 | mg/kg bw/d | rat | oral | 12 months | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine).; EFFECT=SCCS-rejected applicant NOAEL: poses. In addition, the Applicant states that, when performing an RfD-based safety assessment, the MoS should at least be 1 to conclude no safety concern for the respective ingredient (SCCS, 2021; Position paper on MoS). SCCS comment The SCCS does not agree with this approach. The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine). Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23), The Margins of Safety (MoS), based on this NOAEL divided by the Systemic Exposure Doses (SED) calculated by the SCCS as shown in Table 6 (section 3.3.2), are presented below in Table 7.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine).","duration":"12 months","effect":"SCCS-rejected applicant NOAEL: poses. In addition, the Applicant states that, when performing an RfD-based safety assessment, the MoS should at least be 1 to conclude no safety concern for the respective ingredient (SCCS, 2021; Position paper on MoS). SCCS comment The SCCS does not agree with this approach. The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine). Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23), The Margins of Safety (MoS), based on this NOAEL divided by the Systemic Exposure Doses (SED) calculated by the SCCS as shown in Table 6 (section 3.3.2), are presented below in Table 7.","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":30,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.0045 | mg/kg bw/d | rat | oral | 12 months | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine).; EFFECT=SCCS-rejected applicant NOAEL: be 1 to conclude no safety concern for the respective ingredient (SCCS, 2021; Position paper on MoS). SCCS comment The SCCS does not agree with this approach. The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine). Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23), The Margins of Safety (MoS), based on this NOAEL divided by the Systemic Exposure Doses (SED) calculated by the SCCS as shown in Table 6 (section 3.3.2), are presented below in Table 7.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine).","duration":"12 months","effect":"SCCS-rejected applicant NOAEL: be 1 to conclude no safety concern for the respective ingredient (SCCS, 2021; Position paper on MoS). SCCS comment The SCCS does not agree with this approach. The data on which this reference dose is based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine). Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23), The Margins of Safety (MoS), based on this NOAEL divided by the Systemic Exposure Doses (SED) calculated by the SCCS as shown in Table 6 (section 3.3.2), are presented below in Table 7.","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":30,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.0045 | mg/kg bw/d | rat | oral | 12 months | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation.; EFFECT=based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine). Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23), The Margins of Safety (MoS), based on this NOAEL divided by the Systemic Exposure Doses (SED) calculated by the SCCS as shown in Table 6 (section 3.3.2), are presented below in Table 7.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation.","duration":"12 months","effect":"based are old (1935) and derived from a study describing clinical symptoms after intravenous injections of a Silver–arsenic compound as medication (Silver arsphenamine). Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23), The Margins of Safety (MoS), based on this NOAEL divided by the Systemic Exposure Doses (SED) calculated by the SCCS as shown in Table 6 (section 3.3.2), are presented below in Table 7.","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":30,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.0045 | mg/kg bw/d | - | oral | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=Margin of Safety (MoS) for the separate product categories, based on the systemic Exposure Doses (SED) calculated by the SCCS (see section 3.3.2) and the NOAEL of 0.0045 mg/kg bw/d.; EFFECT=SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 31 Table 7. Margin of Safety (MoS) for the separate product categories, based on the systemic Exposure Doses (SED) calculated by the SCCS (see section 3.3.2) and the NOAEL of 0.0045 mg/kg bw/d. For oral products, a bioavailabilty of 0.01% (see section 3.2.2) has been taken into account. Product category Product sub- types Eproduct (mg/kg bw Intended use level Retention day) (%) SED MoS Dermal exposure Face cream1 1 25.67 0.2 0.00110 4.1 Face cream1 face tonic 1 25.67 0.1 0.00055 8.2 Face cream1 anti-redness 1 25.67 0.2 0.00110 4.1 face cream Face cream1 1 25.67 0.2 0.00110 4.1 Anti-pimple Skin care face cream 4 Face cream1 face refresh 1 25.67 0.1 0.00055 8.2 spray Hand; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Margin of Safety (MoS) for the separate product categories, based on the systemic Exposure Doses (SED) calculated by the SCCS (see section 3.3.2) and the NOAEL of 0.0045 mg/kg bw/d.","duration":"","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 31 Table 7. Margin of Safety (MoS) for the separate product categories, based on the systemic Exposure Doses (SED) calculated by the SCCS (see section 3.3.2) and the NOAEL of 0.0045 mg/kg bw/d. For oral products, a bioavailabilty of 0.01% (see section 3.2.2) has been taken into account. Product category Product sub- types Eproduct (mg/kg bw Intended use level Retention day) (%) SED MoS Dermal exposure Face cream1 1 25.67 0.2 0.00110 4.1 Face cream1 face tonic 1 25.67 0.1 0.00055 8.2 Face cream1 anti-redness 1 25.67 0.2 0.00110 4.1 face cream Face cream1 1 25.67 0.2 0.00110 4.1 Anti-pimple Skin care face cream 4 Face cream1 face refresh 1 25.67 0.1 0.00055 8.2 spray Hand","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":31,"route":"oral","species":"","study_id":"sccs_o_288_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 200 | mg/kg bw/day | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=200; DOSE=408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.; EFFECT=408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2010 in ECHA, 2022)/ KL2 90-day gavage study in Sprague Dawley rats (6 males); OECD TG 408, PVP capped nanoparticles 0, 50, 100, 200 mg/kg bw/day At 200 and 100 mg/kg bw/day non-significant increase in epididymis and testis weight was observed. At 200 mg/kg bw/day, decrease sperm viability was observed. At 50 mg/kg bw/day, decrease in food intake was observed. At 50 and 100 mg/kg bw/day significant increase in sperm anomalies were observed. LOAEL: 50 mg Silver/kg bw/day (Lafue; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.","duration":"90-day","effect":"408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2010 in ECHA, 2022)/ KL2 90-day gavage study in Sprague Dawley rats (6 males); OECD TG 408, PVP capped nanoparticles 0, 50, 100, 200 mg/kg bw/day At 200 and 100 mg/kg bw/day non-significant increase in epididymis and testis weight was observed. At 200 mg/kg bw/day, decrease sperm viability was observed. At 50 mg/kg bw/day, decrease in food intake was observed. At 50 and 100 mg/kg bw/day significant increase in sperm anomalies were observed. LOAEL: 50 mg Silver/kg bw/day (Lafue","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":40,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 250 | mg/kg | dog | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=250; DOSE=(Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;; EFFECT=in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 43 Similar to OECD TG zeolite thymus, the mandibular lymph ECHA RAC, 408; AgION approximately 0, node, changes in clinical 2015)/ KL1 Antimicrobial Type 0.65, 2.0, and chemistry and haematology AK (Silver zinc 6.0 mg Silver/kg were observed zeolite) bw/day 90-day oral gavage 0, 10, 50, and At 5.1 mg Silver/kg bw/day NOAEL: (Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"(Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","duration":"90-day","effect":"in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 43 Similar to OECD TG zeolite thymus, the mandibular lymph ECHA RAC, 408; AgION approximately 0, node, changes in clinical 2015)/ KL1 Antimicrobial Type 0.65, 2.0, and chemistry and haematology AK (Silver zinc 6.0 mg Silver/kg were observed zeolite) bw/day 90-day oral gavage 0, 10, 50, and At 5.1 mg Silver/kg bw/day NOAEL: (Study study in Beagle 250 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg","noael_value":"250","page":43,"route":"oral","species":"dog","study_id":"sccs_o_288_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1000 | mg/kg | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=1000; DOSE=50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;; EFFECT=50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At 9.5 mg Silver/kg bw/day, NOAEL: (ECHA RAC, CD rats; similar to 1000 mg/kg relative heart weight was 0.29 mg 2022)/ KL2 OECD TG 408; Silver bw/day of Silver increased in males. Silver/kg sodium zirconium sodium zirconium At 9.5 and 2.9 mg Silver/kg bw/day hydrogen hydrogen bw/day, increased ALP levels, phosphate phosphate discoloration of pancreas and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed;","duration":"90-day","effect":"50 mg/kg changes in clinical signs, 1 mg Silver/kg report, dogs (4/sex/group); bw/day of Silver haematology and clinical bw/day 2003 in Similar to OECD TG zinc zeolite chemistry was observed; ECHA RAC, 409; approximately 0, Histopathological 2022; ECHA Silver zinc zeolite 0.2, 1.0, and examinations revealed RAC, 2015; 5.1 mg Silver/kg discoloration of the pancreas SCCS, bw/day and gastro-intestinal tract and 2023)/KL1 changes in the kidney 90-day oral study in 0, 30, 300, and At 9.5 mg Silver/kg bw/day, NOAEL: (ECHA RAC, CD rats; similar to 1000 mg/kg relative heart weight was 0.29 mg 2022)/ KL2 OECD TG 408; Silver bw/day of Silver increased in males. Silver/kg sodium zirconium sodium zirconium At 9.5 and 2.9 mg Silver/kg bw/day hydrogen hydrogen bw/day, increased ALP levels, phosphate phosphate discoloration of pancreas and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":43,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_030"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0 | - | - | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,; EFFECT=s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"90-day","effect":"s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:s and equivalent to 0, the Harderian gland, increase 0.29, 2.9, and 9.5 in RBCs and cholesterol (males mg Silver/kg only) and changes in organ bw/day weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. 90-day oral study in 0, 200, 400, and At 20 mg Silver/kg bw/day one NOAEL: (ECHA RAC,","page":43,"route":"oral","species":"","study_id":"sccs_o_288_noael_031"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:/day decreased body weights, further significant decrease in the number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1; EFFECT=/day decreased body weights, further significant decrease in the number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"","effect":"/day decreased body weights, further significant decrease in the number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:/day decreased body weights, further significant decrease in the number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1","page":47,"route":"","species":"","study_id":"sccs_o_288_noael_043"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:e number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1; EFFECT=e number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"","effect":"e number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:e number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1","page":47,"route":"","species":"","study_id":"sccs_o_288_noael_044"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1; EFFECT=in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"","effect":"in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus weight was recorded. At 9.9 mg Silver/kg bw/day, reduced thymus weight in females was recorded. NOAEL (parental toxicity) (F0 and F1): 1.9 mg Silver/kg bw/day NOAEL (reproduction) (F0 and F1): 9.9 mg Silver/kg bw/day NOAEL (foetal toxicity) (F1 and F2): 1.9 mg Silver/kg bw/day (Wood, 2002 in ECHA RAC, 2022; US EPA, 2003)/KL1","page":47,"route":"","species":"","study_id":"sccs_o_288_noael_045"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.0045 | mg/kg bw/d | - | oral | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d; EFFECT=Unlabeled table on page 30: Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d","duration":"","effect":"Unlabeled table on page 30: Instead, the SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":30,"route":"oral","species":"","study_id":"sccs_o_288_noael_053"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 30 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,; EFFECT=Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 30: Silver-ion equivalents for the safety evaluation. This NOAEL is the most conservative value,","page":30,"route":"","species":"","study_id":"sccs_o_288_noael_054"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating; EFFECT=Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 40: Study type, Species | Doses | Key findings | NOAEL | Reference/ KL rating","page":40,"route":"","species":"","study_id":"sccs_o_288_noael_055"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1000 | mg/kg bw/day | rat | oral | 28-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=1000; DOSE=OECD TG 407, Silver nanoparticles (60 nm) | 0, 30, 300, and 1000 mg/kg bw/day | At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.; EFFECT=Unlabeled table on page 40: 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) | 0, 30, 300, and 1000 mg/kg bw/day | At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals | NOAEL: 30 mg Silver/ kg bw/day | (Kim et al., 2008 in ECHA, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"OECD TG 407, Silver nanoparticles (60 nm) | 0, 30, 300, and 1000 mg/kg bw/day | At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.","duration":"28-day","effect":"Unlabeled table on page 40: 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) | 0, 30, 300, and 1000 mg/kg bw/day | At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals | NOAEL: 30 mg Silver/ kg bw/day | (Kim et al., 2008 in ECHA, 2022)/ KL2","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":40,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_056"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 500 | mg/kg bw/day | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=500; DOSE=OECD TG 408 Silver nanoparticles (60 nm) | 0, 30, 125, and 500 mg/kg bw/day | At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.; EFFECT=Unlabeled table on page 40: 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) | 0, 30, 125, and 500 mg/kg bw/day | At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. | NOAEL: 30 mg Silver/ kg bw/day | (Kim et al., 2010 in ECHA, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"OECD TG 408 Silver nanoparticles (60 nm) | 0, 30, 125, and 500 mg/kg bw/day | At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage.","duration":"90-day","effect":"Unlabeled table on page 40: 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) | 0, 30, 125, and 500 mg/kg bw/day | At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose- dependent accumulation of Silver in all tissues examined. Further, Right kidney weights were significantly decreased without dose-relation. | NOAEL: 30 mg Silver/ kg bw/day | (Kim et al., 2010 in ECHA, 2022)/ KL2","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"500","page":40,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_057"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.5 | % | rat | oral | 30-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.5; DOSE=30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) | 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) | No treatment related a...; EFFECT=Unlabeled table on page 41: 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) | 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) | No treatment related adverse effects at any dose level | NOAEL: 95 mg Silver/ kg bw/day | (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) | 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) | No treatment related a...","duration":"30-day","effect":"Unlabeled table on page 41: 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) | 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) | No treatment related adverse effects at any dose level | NOAEL: 95 mg Silver/ kg bw/day | (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"0.5","page":41,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_058"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 41 | - | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2; EFFECT=Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"90-day","effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_059"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 9 | - | rat | oral | 28-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=LOAEL: 9 mg Silver/ kg bw/day; EFFECT=Unlabeled table on page 41: 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate | 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) | At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed | LOAEL: 9 mg Silver/ kg bw/day | (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"28-day","effect":"Unlabeled table on page 41: 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate | 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) | At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed | LOAEL: 9 mg Silver/ kg bw/day | (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"LOAEL: 9 mg Silver/ kg bw/day","page":41,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_060"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 78 | - | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females; EFFECT=Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"90-day","effect":"Unlabeled table on page 41: 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate | 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) | At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females | NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females | (Study report, 2022 in ECHA, 2022)/ KL2","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females","page":41,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_061"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 12500 | ppm | rat | oral | 14-week | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=12500; DOSE=14-week oral study in Sprague-Dawley rat (10/sex/group); | 0, 1000, 6250, and 12500 ppm of Silver zinc | At 2 and 6 mg Silver/kg bw/day effects on behaviour/activity, pigmentation of pancreas, | NOAEL:; EFFECT=Unlabeled table on page 42: 14-week oral study in Sprague-Dawley rat (10/sex/group); | 0, 1000, 6250, and 12500 ppm of Silver zinc | At 2 and 6 mg Silver/kg bw/day effects on behaviour/activity, pigmentation of pancreas, | NOAEL: 0.65 mg Silver/ kg bw/day | (Study report 2001 in ECHA RAC, 2022;; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"14-week oral study in Sprague-Dawley rat (10/sex/group); | 0, 1000, 6250, and 12500 ppm of Silver zinc | At 2 and 6 mg Silver/kg bw/day effects on behaviour/activity, pigmentation of pancreas, | NOAEL:","duration":"14-week","effect":"Unlabeled table on page 42: 14-week oral study in Sprague-Dawley rat (10/sex/group); | 0, 1000, 6250, and 12500 ppm of Silver zinc | At 2 and 6 mg Silver/kg bw/day effects on behaviour/activity, pigmentation of pancreas, | NOAEL: 0.65 mg Silver/ kg bw/day | (Study report 2001 in ECHA RAC, 2022;","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"ppm","noael_value":"12500","page":42,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_062"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 250 | mg/kg bw/day | dog | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=250; DOSE=Silver zinc zeolite | 0, 10, 50, and 250 mg/kg bw/day of Silver zinc zeolite approximately 0, 0.2, 1.0, and 5.1 mg Silver/kg bw/day | At 5.1 mg Silver/kg bw/day changes in clinical signs, haematology and clinical chemistry was observed;; EFFECT=Unlabeled table on page 43: 90-day oral gavage study in Beagle dogs (4/sex/group); Similar to OECD TG 409; Silver zinc zeolite | 0, 10, 50, and 250 mg/kg bw/day of Silver zinc zeolite approximately 0, 0.2, 1.0, and 5.1 mg Silver/kg bw/day | At 5.1 mg Silver/kg bw/day changes in clinical signs, haematology and clinical chemistry was observed; Histopathological examinations revealed discoloration of the pancreas and gastro-intestinal tract and changes in the kidney | NOAEL: 1 mg Silver/kg bw/day | (Study report, 2003 in ECHA RAC, 2022; ECHA RAC, 2015; SCCS, 2023)/KL1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver zinc zeolite | 0, 10, 50, and 250 mg/kg bw/day of Silver zinc zeolite approximately 0, 0.2, 1.0, and 5.1 mg Silver/kg bw/day | At 5.1 mg Silver/kg bw/day changes in clinical signs, haematology and clinical chemistry was observed;","duration":"90-day","effect":"Unlabeled table on page 43: 90-day oral gavage study in Beagle dogs (4/sex/group); Similar to OECD TG 409; Silver zinc zeolite | 0, 10, 50, and 250 mg/kg bw/day of Silver zinc zeolite approximately 0, 0.2, 1.0, and 5.1 mg Silver/kg bw/day | At 5.1 mg Silver/kg bw/day changes in clinical signs, haematology and clinical chemistry was observed; Histopathological examinations revealed discoloration of the pancreas and gastro-intestinal tract and changes in the kidney | NOAEL: 1 mg Silver/kg bw/day | (Study report, 2003 in ECHA RAC, 2022; ECHA RAC, 2015; SCCS, 2023)/KL1","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":43,"route":"oral","species":"dog","study_id":"sccs_o_288_noael_063"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1000 | mg/kg bw/day | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=1000; DOSE=Silver sodium zirconium hydrogen phosphate | 0, 30, 300, and 1000 mg/kg bw/day of Silver sodium zirconium hydrogen phosphate equivalent to 0, 0.29, 2.9, and 9.5 mg Silver/kg bw/day | At 9.5 mg Silver/kg bw/day, relative heart weight was increased in males.; EFFECT=Unlabeled table on page 43: 90-day oral study in CD rats; similar to OECD TG 408; Silver sodium zirconium hydrogen phosphate | 0, 30, 300, and 1000 mg/kg bw/day of Silver sodium zirconium hydrogen phosphate equivalent to 0, 0.29, 2.9, and 9.5 mg Silver/kg bw/day | At 9.5 mg Silver/kg bw/day, relative heart weight was increased in males. At 9.5 and 2.9 mg Silver/kg bw/day, increased ALP levels, discoloration of pancreas and the Harderian gland, increase in RBCs and cholesterol (males only) and changes in organ weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. | NOAEL: 0.29 mg Silver/kg bw/day | (ECHA RAC, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver sodium zirconium hydrogen phosphate | 0, 30, 300, and 1000 mg/kg bw/day of Silver sodium zirconium hydrogen phosphate equivalent to 0, 0.29, 2.9, and 9.5 mg Silver/kg bw/day | At 9.5 mg Silver/kg bw/day, relative heart weight was increased in males.","duration":"90-day","effect":"Unlabeled table on page 43: 90-day oral study in CD rats; similar to OECD TG 408; Silver sodium zirconium hydrogen phosphate | 0, 30, 300, and 1000 mg/kg bw/day of Silver sodium zirconium hydrogen phosphate equivalent to 0, 0.29, 2.9, and 9.5 mg Silver/kg bw/day | At 9.5 mg Silver/kg bw/day, relative heart weight was increased in males. At 9.5 and 2.9 mg Silver/kg bw/day, increased ALP levels, discoloration of pancreas and the Harderian gland, increase in RBCs and cholesterol (males only) and changes in organ weights. The absolute weights of testes and epididymides were reduced (for epididymides this reduction was only statistically significant for the right organ). In the absence of histopathological findings, the significance of these effects is unclear. | NOAEL: 0.29 mg Silver/kg bw/day | (ECHA RAC, 2022)/ KL2","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":43,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_064"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 43 | - | - | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,; EFFECT=Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"90-day","effect":"Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 43: 90-day oral study in | 0, 200, 400, and | At 20 mg Silver/kg bw/day one | NOAEL: | (ECHA RAC,","page":43,"route":"oral","species":"","study_id":"sccs_o_288_noael_065"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 45 | - | - | oral | - | - | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020; EFFECT=Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020","endpoint":"","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 45: One-generation dietary | 0, 4, 40, 80, 160, and 320 mg | F0 Generation: At 208 mg Silver/kg bw/day overall body | NOAEL: Not established | (Study report 2020","page":45,"route":"oral","species":"","study_id":"sccs_o_288_noael_067"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 0.2 | % | rat | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.2; DOSE=The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment.; EFFECT=___________________________________________________________________________________ 34 Human data Several regulatory agencies (WHO, EFSA, US EPA) have established human reference doses based on argyria as the human-relevant effect caused by chronic exposure to Silver via, respectively, drinking water, food / food contact material or medication. The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment. Instead, the SCCS will use the NOAEL derived from a chronic combined toxicity and carcinogenicity study on Silver zinc zeolite in rats. Special investigations / 4. CONCLUSION (1) In light of the data provided and taking under consideration the classification as toxic for reproduction Cat. 2, does the SCCS consider micron-sized particulate Silver safe when used up to a maximum concentration of 0.2 % in rinse-off and 0.3 % in leave-on cosmetic products? In light of the data provided and taking under consideration the classification as toxic for r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment.","duration":"chronic","effect":"___________________________________________________________________________________ 34 Human data Several regulatory agencies (WHO, EFSA, US EPA) have established human reference doses based on argyria as the human-relevant effect caused by chronic exposure to Silver via, respectively, drinking water, food / food contact material or medication. The SCCS will not accept the Applicant’s proposal to use a medication-based reference dose for its point of departure for risk-assessment. Instead, the SCCS will use the NOAEL derived from a chronic combined toxicity and carcinogenicity study on Silver zinc zeolite in rats. Special investigations / 4. CONCLUSION (1) In light of the data provided and taking under consideration the classification as toxic for reproduction Cat. 2, does the SCCS consider micron-sized particulate Silver safe when used up to a maximum concentration of 0.2 % in rinse-off and 0.3 % in leave-on cosmetic products? In light of the data provided and taking under consideration the classification as toxic for r","endpoint":"carcinogenicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"0.2","page":34,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 87 | mg/kg bw/day | - | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=87; DOSE=At 72/87 mg/kg bw/day, reduced thymus weight in males.; EFFECT=al changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg Silver/kg bw/day, increased stillbirth index, decreased live birth index, body weights, reduced organ weights (brain, thymus, spleen). At 72/87 mg/kg bw/day, reduced thymus weight in males. LOAEL (systemic- F0 and F1): 1.5 mg Silver/kg bw/day NOAEL (reproduction, F0 and F1): 1.5 mg Silver/kg bw/day. LOAEL (developmental toxicity (F1 and F2): 1.5 mg Silver/kg bw/day (Schroeder, 2002 ECHA RAC, 2015; SCCS, 2023)/KL 1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"At 72/87 mg/kg bw/day, reduced thymus weight in males.","duration":"developmental","effect":"al changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg Silver/kg bw/day, increased stillbirth index, decreased live birth index, body weights, reduced organ weights (brain, thymus, spleen). At 72/87 mg/kg bw/day, reduced thymus weight in males. LOAEL (systemic- F0 and F1): 1.5 mg Silver/kg bw/day NOAEL (reproduction, F0 and F1): 1.5 mg Silver/kg bw/day. LOAEL (developmental toxicity (F1 and F2): 1.5 mg Silver/kg bw/day (Schroeder, 2002 ECHA RAC, 2015; SCCS, 2023)/KL 1","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"87","page":48,"route":"","species":"","study_id":"sccs_o_288_noael_046"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 20 | mg/kg bw/day | rat | - | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=20; DOSE=_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal):; EFFECT=_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal): Charehsaz, developmental citrate-capped histopathological findings in 0.2 mg Silver/kg et al., 2016 toxicity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopec; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal):","duration":"Prenatal","effect":"_________ _________________________________________________________________________________________ 49 APPENDIX D Study type, species Doses Critical effects Dose descriptor Reference/ KL rating Nano-size Silver metal particles Prenatal 0, 0.2, 2, 20 mg Increased frequency of LOAEL (maternal): Charehsaz, developmental citrate-capped histopathological findings in 0.2 mg Silver/kg et al., 2016 toxicity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopec","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":49,"route":"","species":"rat","study_id":"sccs_o_288_noael_047"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 20 | mg/kg bw/day | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=20; DOSE=2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day:; EFFECT=icity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopecia was developmental): ECHA RAC, Dawley rats, equivalent to 6.5, observed in foetuses 19 mg Silver 2022; ECHA, OECD Guideline 19, and 65 mg Increase percentage litters with mg/kg bw/day 2022)/ 414 (25 female/ Silver/kg bw/day late, foetal deaths (10%), KL1-2 group); Silver GD 6-19, by reduced male bodyweight/litter acetate (64.6% gavage (5%), foetal bodyweight/litter Silver) (5%). At 65 m; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day:","duration":"developmental","effect":"icity, Sprague Silver brain and liver of dams with bw/day in ECHA Dawley rats, no nanoparticles (55 neuronal loss event NOAEL RAC, Guideline (10 nm) (hippocampal sclerosis) and (developmental): 2022/KL2 female/ group); hepatocellular vacuolation at all 20 mg/kg bw/day Silver dose levels. nanoparticles No treatment related changes and Silver nitrate on histopathology of brain, heart, liver, kidney and lung tissues of the offspring Silver salts Prenatal 0, 10, 30, 100 mg At 65 mg Silver/kg bw/day: NOAEL (maternal (Price et al., developmental Silver acetate/kg Dams and 2002 in toxicity, Sprague bw/day Piloerection, alopecia was developmental): ECHA RAC, Dawley rats, equivalent to 6.5, observed in foetuses 19 mg Silver 2022; ECHA, OECD Guideline 19, and 65 mg Increase percentage litters with mg/kg bw/day 2022)/ 414 (25 female/ Silver/kg bw/day late, foetal deaths (10%), KL1-2 group); Silver GD 6-19, by reduced male bodyweight/litter acetate (64.6% gavage (5%), foetal bodyweight/litter Silver) (5%). At 65 m","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":49,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_048"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 13 | % | rat | oral | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=13; DOSE=7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:; EFFECT=SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:","duration":"Prenatal","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"13","page":50,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_049"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 25 | % | rat | oral | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=25; DOSE=__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:; EFFECT=__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw:","duration":"Prenatal","effect":"__________________________________________________________________________ _________________________________________________________________________________________ 50 Silver nitrate hepatocellular vacuolation SCAS Prenatal 0, 200, 700, 2000 At 29 mg Silver/kg bw mg/kg bw: NOAEL (maternal): (Study developmental mg/kg bw/day increase mortality (1/20) 10 mg Silver/kg report, 1990 toxicity, Sprague equivalent to 0, 3, Decreased body weight (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and r","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"25","page":50,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_050"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 1000 | mg/kg | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=1000; DOSE=Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day...; EFFECT=ght (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, study, Sprague to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/kg 2021; ECHA Dawley rats, 25 mg Silver/kg bw/day RAC< OECD Guideline bw/day gestation 2022)/KL2 414 (8 day (GD) 6-15, by female/group); gavage Silver sodium zirconium hydrogenphosp hate (10% Silver) Prenatal 0, 100, 300, and No treatment-related e; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day...","duration":"developmental","effect":"ght (13%) bw/day; in ECHA Dawley rats, 10 and 29 mg and bodyweight gain (25%) NOAEL RAC; US OECD Guideline Silver/kg bw GD 6- and clinical signs: sedation, void (developmental): EPA, 414 (30 female/ 15, by gavage faeces, urogenital discharge, 29 mg Silver/kg 1991)/KL1 group); Silver thinness. bw/day copper zeolite No treatment related effects Study type, species Doses Critical effects Dose descriptor Reference/ KL rating were observed in foetuses Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, study, Sprague to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/kg 2021; ECHA Dawley rats, 25 mg Silver/kg bw/day RAC< OECD Guideline bw/day gestation 2022)/KL2 414 (8 day (GD) 6-15, by female/group); gavage Silver sodium zirconium hydrogenphosp hate (10% Silver) Prenatal 0, 100, 300, and No treatment-related e","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":50,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_051"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 1000 | mg/kg | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=1000; DOSE=(Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, study, Sprague to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/kg 2021;; EFFECT=(Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, study, Sprague to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/kg 2021; ECHA Dawley rats, 25 mg Silver/kg bw/day RAC< OECD Guideline bw/day gestation 2022)/KL2 414 (8 day (GD) 6-15, by female/group); gavage Silver sodium zirconium hydrogenphosp hate (10% Silver) Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity, Sprague bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, Dawley rats, to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/ kg 2021; ECHA OECD Guideline 25 mg Silver/kg bw/day RAC, 2022)/ 414 (25 female/ bw/day GD 6-15, KL2 group); Silver by gavage sodium zirconium hydrogenphosp hate (10% Silver); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"(Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, study, Sprague to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/kg 2021;","duration":"developmental","effect":"(Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity- DRF bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, study, Sprague to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/kg 2021; ECHA Dawley rats, 25 mg Silver/kg bw/day RAC< OECD Guideline bw/day gestation 2022)/KL2 414 (8 day (GD) 6-15, by female/group); gavage Silver sodium zirconium hydrogenphosp hate (10% Silver) Prenatal 0, 100, 300, and No treatment-related effects in NOAEL (maternal (Study developmental 1000 mg/kg either dams or foetuses up to and report, 1999 toxicity, Sprague bw/day equivalent the highest tested dose of 25 mg developmental): in EU CAR, Dawley rats, to 0, 2.5, 7.4 and Silver/kg bw/day >25 mg Silver/ kg 2021; ECHA OECD Guideline 25 mg Silver/kg bw/day RAC, 2022)/ 414 (25 female/ bw/day GD 6-15, KL2 group); Silver by gavage sodium zirconium hydrogenphosp hate (10% Silver)","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":50,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_052"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 20 | mg/kg bw/day | rat | - | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=20; DOSE=Silver nanoparticles and Silver nitrate | 0, 0.2, 2, 20 mg citrate-capped Silver nanoparticles (55 nm) | Increased frequency of histopathological findings in brain and liver of dams with neuronal loss event (hippocampal sclerosis) and hepatocellular vacuolation at all dose levels.; LOAEL_VALUE=20 mg/kg bw/day; EFFECT=Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, no Guideline (10 female/ group); Silver nanoparticles and Silver nitrate | 0, 0.2, 2, 20 mg citrate-capped Silver nanoparticles (55 nm) | Increased frequency of histopathological findings in brain and liver of dams with neuronal loss event (hippocampal sclerosis) and hepatocellular vacuolation at all dose levels. No treatment related changes on histopathology of brain, heart, liver, kidney and lung tissues of the offspring | LOAEL (maternal): 0.2 mg Silver/kg bw/day NOAEL (developmental): 20 mg/kg bw/day | Charehsaz, et al., 2016 in ECHA RAC, 2022/KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver nanoparticles and Silver nitrate | 0, 0.2, 2, 20 mg citrate-capped Silver nanoparticles (55 nm) | Increased frequency of histopathological findings in brain and liver of dams with neuronal loss event (hippocampal sclerosis) and hepatocellular vacuolation at all dose levels.","duration":"Prenatal","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, no Guideline (10 female/ group); Silver nanoparticles and Silver nitrate | 0, 0.2, 2, 20 mg citrate-capped Silver nanoparticles (55 nm) | Increased frequency of histopathological findings in brain and liver of dams with neuronal loss event (hippocampal sclerosis) and hepatocellular vacuolation at all dose levels. No treatment related changes on histopathology of brain, heart, liver, kidney and lung tissues of the offspring | LOAEL (maternal): 0.2 mg Silver/kg bw/day NOAEL (developmental): 20 mg/kg bw/day | Charehsaz, et al., 2016 in ECHA RAC, 2022/KL2","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"20 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"20","page":49,"route":"","species":"rat","study_id":"sccs_o_288_noael_072"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 64.6 | % | rat | oral | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=64.6; DOSE=19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022;; EFFECT=Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver acetate (64.6% Silver) | 0, 10, 30, 100 mg Silver acetate/kg bw/day equivalent to 6.5, 19, and 65 mg Silver/kg bw/day GD 6-19, by gavage | At 65 mg Silver/kg bw/day: Dams Piloerection, alopecia was observed in foetuses Increase percentage litters with late, foetal deaths (10%), reduced male bodyweight/litter (5%), foetal bodyweight/litter (5%). At 65 mg Silver/kg bw: increased skeletal variations | NOAEL (maternal and developmental): 19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022; ECHA, 2022)/ KL1-2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022;","duration":"Prenatal","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver acetate (64.6% Silver) | 0, 10, 30, 100 mg Silver acetate/kg bw/day equivalent to 6.5, 19, and 65 mg Silver/kg bw/day GD 6-19, by gavage | At 65 mg Silver/kg bw/day: Dams Piloerection, alopecia was observed in foetuses Increase percentage litters with late, foetal deaths (10%), reduced male bodyweight/litter (5%), foetal bodyweight/litter (5%). At 65 mg Silver/kg bw: increased skeletal variations | NOAEL (maternal and developmental): 19 mg Silver mg/kg bw/day | (Price et al., 2002 in ECHA RAC, 2022; ECHA, 2022)/ KL1-2","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"64.6","page":49,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_073"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 250 | mg/kg bw/day | rat | - | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=250; DOSE=Silver chloride | 0, 50 mg/day (250 mg/kg bw/day; equivalent to 188 mg Silver/kg bw/day) (5 females were treated during GD 7-15 and 20 females during gestation days 1- 20) | At 188 mg Silver/kg bw/day Dams:; EFFECT=Unlabeled table on page 49: Prenatal developmental toxicity, albino rats, Guideline not specified (5- 36 female/ group); Silver chloride | 0, 50 mg/day (250 mg/kg bw/day; equivalent to 188 mg Silver/kg bw/day) (5 females were treated during GD 7-15 and 20 females during gestation days 1- 20) | At 188 mg Silver/kg bw/day Dams: Decreased ceruloplasmin Foetuses: (treated during GD 1- 20), increased post- implantation deaths (26%), cryptorchidism (33%), hydronephrosis (25%) decreased ceruloplasmin, bodyweight (22%) and viability index (100% deaths) | LOAEL: (maternal/ developmental): 188 mg Silver/kg bw/day | (Shavlovski et al.,1995 in EU CAR, 2021; ECHA RAC, 2022)/ KL2-3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver chloride | 0, 50 mg/day (250 mg/kg bw/day; equivalent to 188 mg Silver/kg bw/day) (5 females were treated during GD 7-15 and 20 females during gestation days 1- 20) | At 188 mg Silver/kg bw/day Dams:","duration":"Prenatal","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, albino rats, Guideline not specified (5- 36 female/ group); Silver chloride | 0, 50 mg/day (250 mg/kg bw/day; equivalent to 188 mg Silver/kg bw/day) (5 females were treated during GD 7-15 and 20 females during gestation days 1- 20) | At 188 mg Silver/kg bw/day Dams: Decreased ceruloplasmin Foetuses: (treated during GD 1- 20), increased post- implantation deaths (26%), cryptorchidism (33%), hydronephrosis (25%) decreased ceruloplasmin, bodyweight (22%) and viability index (100% deaths) | LOAEL: (maternal/ developmental): 188 mg Silver/kg bw/day | (Shavlovski et al.,1995 in EU CAR, 2021; ECHA RAC, 2022)/ KL2-3","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":49,"route":"","species":"rat","study_id":"sccs_o_288_noael_074"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 20 | - | rat | - | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=LOAEL (maternal): 20 mg Silver/kg bw/day; DOSE=Prenatal developmental toxicity, Sprague Dawley rats, no Guideline (10 female/ group); | 20 mg Silver/kg bw/day as Silver nitrate | Reduced body weight in treated dams.; EFFECT=Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, no Guideline (10 female/ group); | 20 mg Silver/kg bw/day as Silver nitrate | Reduced body weight in treated dams. Increased frequency of histopathological findings in brain and liver of dams with neuronal loss event (type 2 hippocampal sclerosis) and | LOAEL (maternal): 20 mg Silver/kg bw/day | Charehsaz, et al., 2016 in ECHA RAC, 2022/KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Prenatal developmental toxicity, Sprague Dawley rats, no Guideline (10 female/ group); | 20 mg Silver/kg bw/day as Silver nitrate | Reduced body weight in treated dams.","duration":"Prenatal","effect":"Unlabeled table on page 49: Prenatal developmental toxicity, Sprague Dawley rats, no Guideline (10 female/ group); | 20 mg Silver/kg bw/day as Silver nitrate | Reduced body weight in treated dams. Increased frequency of histopathological findings in brain and liver of dams with neuronal loss event (type 2 hippocampal sclerosis) and | LOAEL (maternal): 20 mg Silver/kg bw/day | Charehsaz, et al., 2016 in ECHA RAC, 2022/KL2","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"LOAEL (maternal): 20 mg Silver/kg bw/day","page":49,"route":"","species":"rat","study_id":"sccs_o_288_noael_075"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 10 | % | rat | oral | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=10; DOSE=Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/...; EFFECT=Unlabeled table on page 50: Prenatal developmental toxicity- DRF study, Sprague Dawley rats, OECD Guideline 414 (8 female/group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC< 2022)/KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/...","duration":"Prenatal","effect":"Unlabeled table on page 50: Prenatal developmental toxicity- DRF study, Sprague Dawley rats, OECD Guideline 414 (8 female/group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day gestation day (GD) 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC< 2022)/KL2","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"10","page":50,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_076"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 10 | % | rat | oral | Prenatal | developmental toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=10; DOSE=Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day GD 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/ kg bw/day | (St...; EFFECT=Unlabeled table on page 50: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day GD 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/ kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day GD 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/ kg bw/day | (St...","duration":"Prenatal","effect":"Unlabeled table on page 50: Prenatal developmental toxicity, Sprague Dawley rats, OECD Guideline 414 (25 female/ group); Silver sodium zirconium hydrogenphosp hate (10% Silver) | 0, 100, 300, and 1000 mg/kg bw/day equivalent to 0, 2.5, 7.4 and 25 mg Silver/kg bw/day GD 6-15, by gavage | No treatment-related effects in either dams or foetuses up to the highest tested dose of 25 mg Silver/kg bw/day | NOAEL (maternal and developmental): >25 mg Silver/ kg bw/day | (Study report, 1999 in EU CAR, 2021; ECHA RAC, 2022)/ KL2","endpoint":"developmental toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"10","page":50,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_077"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | rat | oral | 9-year | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.; EFFECT=e deposited in numerous organs and tissues and liver was identified as the principal organ for Silver deposition. The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.","duration":"9-year","effect":"e deposited in numerous organs and tissues and liver was identified as the principal organ for Silver deposition. The NOAELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":25,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | rat | oral | 9-year | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=AELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.; EFFECT=AELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"AELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine.","duration":"9-year","effect":"AELs based on the repeated dose oral toxicity studies were significantly higher than the PoD of 0.014 mg Silver/kg bw/day which was based on 2- to 9-year period clinical study in humans with Silver arsphenamine. SCCS comment The SCCS has reservations regarding the applicant's choice of the PoD of 0.014 mg Silver/kg bw/day. This is further explained in 3.5 (Safety evaluation). The SCCS will use a NOAEL (corrected for oral bioavailability) of 0.0045 mg/kg bw/d Silver- ion equivalents for the safety evaluation. This NOAEL is the most conservative value, derived from a long-term (> 12 months) study on Silver zinc zeolite in rats (Takizawa 1992, EU CAR 2021, SCCS/1650/23).","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":25,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.25 | mg/kg bw/d | - | - | developmental | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.25; DOSE=Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).; EFFECT=as done in the current assessment appropriately protects for the reproductive and developmental toxicity endpoint. SCCS comment For an overview and description of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/p; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","duration":"developmental","effect":"as done in the current assessment appropriately protects for the reproductive and developmental toxicity endpoint. SCCS comment For an overview and description of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/p","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.25","page":27,"route":"","species":"","study_id":"sccs_o_288_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | - | - | Developmental | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).; EFFECT=on of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/pup mortality) and to some extent with Silver sodium zirconium hydrogen phosphate. One plausible mechanism for these instances of developmental toxicity involv; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","duration":"Developmental","effect":"on of all the studies see ECHA – RAC 2022. Fertility/reproduction: While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, the SCCS will set for fertility the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) that will be used for the overall risk-assessment in this Opinion. Developmental: ECHA-RAC 2022 is of the opinion that clear developmental toxicity has been observed with Silver salts such as Silver chloride, Silver acetate, Silver zinc zeolite (e.g., foetal/pup mortality) and to some extent with Silver sodium zirconium hydrogen phosphate. One plausible mechanism for these instances of developmental toxicity involv","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":27,"route":"","species":"","study_id":"sccs_o_288_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.25 | mg/kg bw/d | - | - | developmental | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.25; DOSE=or these instances of developmental toxicity involves Silver interfering with copper binding to ceruloplasmin and thereby reducing the availability of copper, iron or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range-...; EFFECT=or these instances of developmental toxicity involves Silver interfering with copper binding to ceruloplasmin and thereby reducing the availability of copper, iron or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range- finder study (2021) and the main EOGRTS study (2022). From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment in this Opinion. 3.4.6 Mutagenicity / genotoxicity Applicant's assessment of the relevance and conclusions of available genotoxicity studies for MicroSilver BG. Taking into account the overall weight of t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"or these instances of developmental toxicity involves Silver interfering with copper binding to ceruloplasmin and thereby reducing the availability of copper, iron or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range-...","duration":"developmental","effect":"or these instances of developmental toxicity involves Silver interfering with copper binding to ceruloplasmin and thereby reducing the availability of copper, iron or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range- finder study (2021) and the main EOGRTS study (2022). From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment in this Opinion. 3.4.6 Mutagenicity / genotoxicity Applicant's assessment of the relevance and conclusions of available genotoxicity studies for MicroSilver BG. Taking into account the overall weight of t","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.25","page":27,"route":"","species":"","study_id":"sccs_o_288_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | - | - | developmental | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=on or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range- finder study (2021) and the main EOGRTS study (2022).; EFFECT=on or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range- finder study (2021) and the main EOGRTS study (2022). From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment in this Opinion. 3.4.6 Mutagenicity / genotoxicity Applicant's assessment of the relevance and conclusions of available genotoxicity studies for MicroSilver BG. Taking into account the overall weight of the evidence suggesting Silver to be non-genotoxic and the poor and slow-release kinetics of Silver from MicroSilver BG under physiological conditions as a result; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"on or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range- finder study (2021) and the main EOGRTS study (2022).","duration":"developmental","effect":"on or perhaps both metals to the foetus (supported by the copper analysis of F2 pups in the Silver zinc zeolite study and copper and ceruloplasmin analysis in both the EOGRTS dose range- finder study (2021) and the main EOGRTS study (2022). From the RAC evaluation of developmental toxicity, the SCCS will set for reproductive toxicity the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando et al. (2016) cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study (see 3.4.4: Repeated dose toxicity) which will be used for the overall risk-assessment in this Opinion. 3.4.6 Mutagenicity / genotoxicity Applicant's assessment of the relevance and conclusions of available genotoxicity studies for MicroSilver BG. Taking into account the overall weight of the evidence suggesting Silver to be non-genotoxic and the poor and slow-release kinetics of Silver from MicroSilver BG under physiological conditions as a result","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":27,"route":"","species":"","study_id":"sccs_o_288_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | rat | - | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=Repeated dose toxicity The NOAEL used in this evaluation (0.0045 mg/kg bw/d) is derived from a combined chronic (up to 24 months) toxicity/carcinogenicity study in mice and rats that were fed with a Silver zinc zeolite containing 2.3% Silver and is based on pigmentation as a critical effect from Silver release.; EFFECT=Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 33 Skin sensitisation Following its Opinions on a Silver-containing packaging material and on Silver Zinc Zeolite (SCCS/1577/16, SCCS/1650/23), the SCCS regards the risk of sensitisation from exposure to Silver as negligible. Repeated dose toxicity The NOAEL used in this evaluation (0.0045 mg/kg bw/d) is derived from a combined chronic (up to 24 months) toxicity/carcinogenicity study in mice and rats that were fed with a Silver zinc zeolite containing 2.3% Silver and is based on pigmentation as a critical effect from Silver release. (Takizawa 1992). Reproductive toxicity While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Repeated dose toxicity The NOAEL used in this evaluation (0.0045 mg/kg bw/d) is derived from a combined chronic (up to 24 months) toxicity/carcinogenicity study in mice and rats that were fed with a Silver zinc zeolite containing 2.3% Silver and is based on pigmentation as a critical effect from Silver release.","duration":"chronic","effect":"Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 33 Skin sensitisation Following its Opinions on a Silver-containing packaging material and on Silver Zinc Zeolite (SCCS/1577/16, SCCS/1650/23), the SCCS regards the risk of sensitisation from exposure to Silver as negligible. Repeated dose toxicity The NOAEL used in this evaluation (0.0045 mg/kg bw/d) is derived from a combined chronic (up to 24 months) toxicity/carcinogenicity study in mice and rats that were fed with a Silver zinc zeolite containing 2.3% Silver and is based on pigmentation as a critical effect from Silver release. (Takizawa 1992). Reproductive toxicity While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":33,"route":"","species":"rat","study_id":"sccs_o_288_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.25 | mg/kg bw/d | rat | oral | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.25; DOSE=Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).; EFFECT=ity study in mice and rats that were fed with a Silver zinc zeolite containing 2.3% Silver and is based on pigmentation as a critical effect from Silver release. (Takizawa 1992). Reproductive toxicity While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","duration":"chronic","effect":"ity study in mice and rats that were fed with a Silver zinc zeolite containing 2.3% Silver and is based on pigmentation as a critical effect from Silver release. (Takizawa 1992). Reproductive toxicity While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxi","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.25","page":33,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | rat | oral | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).; EFFECT=se. (Takizawa 1992). Reproductive toxicity While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxicity The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not warranted. In its opinion on a Silver-releasing packaging material; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","duration":"chronic","effect":"se. (Takizawa 1992). Reproductive toxicity While the SCCS will follow the proposal by ECHA-RAC 2022 to classify Silver for adverse effects on sexual function and fertility as a Category 2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxicity The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not warranted. In its opinion on a Silver-releasing packaging material","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":33,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | rat | oral | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).; EFFECT=2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxicity The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not warranted. In its opinion on a Silver-releasing packaging material (SCCS/1577/16) the SCCS concluded that the genotoxicity of Ag+ ions was investigated for all the three endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy, a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","duration":"chronic","effect":"2 reproductive toxicant, it will not use the data from the studies with the nano-forms. Instead, regarding fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxicity The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not warranted. In its opinion on a Silver-releasing packaging material (SCCS/1577/16) the SCCS concluded that the genotoxicity of Ag+ ions was investigated for all the three endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy, a","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":33,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.0045 | mg/kg bw/d | rat | oral | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.0045; DOSE=g fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).; EFFECT=g fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxicity The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not warranted. In its opinion on a Silver-releasing packaging material (SCCS/1577/16) the SCCS concluded that the genotoxicity of Ag+ ions was investigated for all the three endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy, although results from mammalian cell gene mutation tests were not provided. The available tests were not al; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"g fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022).","duration":"chronic","effect":"g fertility in this Opinion, the SCCS will set the most conservative NOAEL at 0.25 mg/kg bw/d Silver ion equivalents, derived from a study with Silver acetate (Sprando 2017, also cited in ECHA-RAC 2022). This is well above the NOAEL of 0.0045 mg/kg bw/d, derived from the long-term toxicity study in rats (see 3.4.4: Repeated dose toxicity), which will be used for the overall risk-assessment in this Opinion. The NOAEL derived from the chronic oral toxicity study (which is used in the current assessment) is below the NOAEL for reproductive and developmental effects. Mutagenicity / genotoxicity The SCCS concurs with ECHA – RAC (2022) that a classification for mutagenicity is not warranted. In its opinion on a Silver-releasing packaging material (SCCS/1577/16) the SCCS concluded that the genotoxicity of Ag+ ions was investigated for all the three endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy, although results from mammalian cell gene mutation tests were not provided. The available tests were not al","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0045","page":33,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1000 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=1000; DOSE=7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver...; EFFECT=SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver containing active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver...","duration":"Sub-acute","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 40 APPENDIX B Applicant's overview of repeated dose toxicity studies with Silver nanoforms of Silver, Silver salts and SCAS (Silver containing active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":40,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 500 | mg/kg bw/day | rat | oral | Sub-acute | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=500; DOSE=OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.; EFFECT=taining active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-chronic studies 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels.","duration":"Sub-acute","effect":"taining active substances). Study type, Species Doses Key findings NOAEL or LOAEL Reference/ KL rating Nano-size Silver metal Sub-acute studies 28-day gavage study in Sprague- Dawley rats (10 rats/group); OECD TG 407, Silver nanoparticles (60 nm) 0, 30, 300, and 1000 mg/kg bw/day At 300 mg/kg bw/day and above, dose-related increases in alkaline phosphatase, cholesterol and total protein levels. Increased incidences of bile duct hyperplasia around the central vein were observed in livers of male and female animals NOAEL: 30 mg Silver/ kg bw/day (Kim et al., 2008 in ECHA, 2022)/ KL2 Sub-chronic studies 90-day gavage study in Fisher 344 rats (10 rats/group); OECD TG 408 Silver nanoparticles (60 nm) 0, 30, 125, and 500 mg/kg bw/day At and above 125 mg/kg bw/day, dose-related changes were found in alkaline phosphatase and cholesterol levels indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"500","page":40,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1665 | - | rat | oral | Sub-acute | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA; DOSE=Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL:; EFFECT=SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL:","duration":"Sub-acute","effect":"SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1665/24 Final version Opinion on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products ______________________________________________________________________________ _________________________________________________________________________________________ 41 Sub-acute studies 28-day, gavage study in WI(Han) rats (5/sex/group); OECD TG 407; Silver 0, 20, 50, and 100 mg Silver nitrate/kg bw/day (equivalent to 0, No treatment related adverse effects at any dose level NOAEL: 64 mg Silver/ kg bw/day (ECHA RAC, 2022)/ KL1 nitrate 13, 32, and 64 mg Silver/kg bw/day) 28-day, gavage study in Wistar Hannover Galas rats (8 females); no guideline; Silver acetate 0, and 14 mg Silver acetate/kg bw/day (equivalent to 9 mg Silver/kg bw/day) At 9 mg Silver/kg bw/day lower body weight gain, an increase in alkaline phosphatase and a decrease in urea concentrations in plasma and lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA","page":41,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 0.5 | % | rat | oral | 30-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=0.5; DOSE=ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No tre...; EFFECT=nd lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No treatment related adverse effects at any dose level NOAEL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NO; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No tre...","duration":"30-day","effect":"nd lower absolute and relative thymus weight was observed LOAEL: 9 mg Silver/ kg bw/day (Hadrup et al., 2012 in ECHA, 2022; ECHA RAC, 2022/ KL2 30-day oral swab study in Fischer 344 rats (4/sex/group); according to standard methods that comply with the guidelines of the OECD as summarised in Mosberg and Hayes (1989); antismoking mouthwash (0.5% Silver nitrate) 0, 1.5, 15, and 150 mg Silver nitrate/kg bw/day (equivalent to 0.95, 9.5, and 95 mg Silver/kg bw/day) No treatment related adverse effects at any dose level NOAEL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NO","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"0.5","page":41,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 95 | - | rat | oral | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2; EFFECT=EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"","duration":"Sub-chronic","effect":"EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:EL: 95 mg Silver/ kg bw/day (Tamimi et al., 1998 in ECHA, 2022; ECHA RAC, 2022)/ KL2 Sub-chronic studies 90-day dietary study in Crl: WI(Han) rats (10/sex/group); OECD TG 408; Silver acetate 0, 40, 120, and 320 mg Silver acetate/kg bw/day (equivalent to 0, 26, 78, and 208 mg Silver/kg bw/day) At 208 mg Silver/kg bw/day, reduced body weight, body weight gain and food consumption were observed during the study. However, effects on food consumption and body weight were considered adverse for males and not for females NOAEL: 78 mg Silver/ kg bw/day for males; 208 mg Silver/ kg bw/day in females (Study report, 2022 in ECHA, 2022)/ KL2","page":41,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_027"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 12500 | ppm | rat | oral | 9 months | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=12500; DOSE=ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exp...; EFFECT=ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exposed for 6 months, the rest for 12 months) SCAS Sub-chronic studies 14-week oral study 0, 1000, 6250, At 2 and 6 mg Silver/kg bw/day NOAEL: (Study report in Sprague-Dawley and 12500 ppm effects on behaviour/activity, 0.65 mg Silver/ 2001 in ECHA rat (10/sex/group); of Silver zinc pigmentation of pancreas, kg bw/day RAC, 2022;; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exp...","duration":"9 months","effect":"ilver particles 141 mg al., 1981 in study in albino (stated to be in the outer aspect of the Silver/ kg ECHA RAC, Wistar rats; no 222 mg/kg ciliary epithelium basement bw/day 2022)/ KL2 guideline specified; bw/day membrane of eyes Silver nitrate (equivalent to 141 mg Silver/kg bw/day) 9 months (after 10 weeks half of the animals were further exposed for 6 months, the rest for 12 months) SCAS Sub-chronic studies 14-week oral study 0, 1000, 6250, At 2 and 6 mg Silver/kg bw/day NOAEL: (Study report in Sprague-Dawley and 12500 ppm effects on behaviour/activity, 0.65 mg Silver/ 2001 in ECHA rat (10/sex/group); of Silver zinc pigmentation of pancreas, kg bw/day RAC, 2022;","endpoint":"repeated dose toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"ppm","noael_value":"12500","page":42,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_198; REPORT_TITLE=OPINION ON preservative EcoG+; OPINION_NUMBER=SCCS/1577/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 6 October 2016; VALUE_TEXT=100; DOSE=A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested.; EFFECT=ver the ATSDR concludes that ‘existing evidence’ does not point to a strong effect of the silver ion on reproduction and no historical evidence to indicate an effect of silver on reproduction in humans. While subcutaneous injection of silver nitrate has been reported to cause reversible damage to the testes in rats (Hoey, 1966), no effects on spermatozoa or fertility were observed in a drinking water study. A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested. Indications of slight maternal toxicity were observed at this dose level; more severe maternal toxicity was observed at a dose level of 160 mg/kg bw/d in a screening study. Published data (Shavlovsky et al., 1995) indicate an effect of silver on development at maternally toxic dose levels and secondary to copper deficiency caused by the displacement of copper by silver from ceruloplasmin. 3.3.9. Toxicokinetics 3.3.9.1. Absorption Stu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested.","duration":"developmental","effect":"ver the ATSDR concludes that ‘existing evidence’ does not point to a strong effect of the silver ion on reproduction and no historical evidence to indicate an effect of silver on reproduction in humans. While subcutaneous injection of silver nitrate has been reported to cause reversible damage to the testes in rats (Hoey, 1966), no effects on spermatozoa or fertility were observed in a drinking water study. A high-quality developmental toxicity study performed in the rat with silver acetate (NTP, 2002) concludes a NOAEL for developmental toxicity of 100 mg/kg bw/d, the highest dose level tested. Indications of slight maternal toxicity were observed at this dose level; more severe maternal toxicity was observed at a dose level of 160 mg/kg bw/d in a screening study. Published data (Shavlovsky et al., 1995) indicate an effect of silver on development at maternally toxic dose levels and secondary to copper deficiency caused by the displacement of copper by silver from ceruloplasmin. 3.3.9. Toxicokinetics 3.3.9.1. Absorption Stu","endpoint":"reproductive toxicity","ingredient":"intended to be released into the cosmetic product is the silver","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"100","page":15,"route":"oral","species":"rat","study_id":"sccs_o_198_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 250 | mg/kg bw/day | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=250; DOSE=productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats:; EFFECT=productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats:","duration":"developmental","effect":"productive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0,","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":45,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_032"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 52 | - | rat | oral | 52 days | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and; DOSE=2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose.; EFFECT=opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose.","duration":"52 days","effect":"opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:opsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2 Silver salts One-generation dietary 0, 4, 40, 80, 160, and 320 mg F0 Generation: At 208 mg Silver/kg bw/day overall body NOAEL: Not established (Study report 2020 Study type, species Doses Critical effects Dose descriptor Reference/KL rating reproductive toxicity study, Wistar rats, no guideline; Silver acetate (dose range finding (DRF) study for EOGRTS) Silver acetate/kg bw/day (equivalent to 0, 0.65, 2.6, 26, 52, 104, 208 mg Silver /kg bw/d ay) weight gain was low; pigment was observed in Kupffer cells and to a lesser extent in hepatocytes and in the vascular walls of the liver of males administered 104 and 208 mg Silver/kg bw/day and","page":45,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_033"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 0 | - | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:y; changes in F0/F1 red blood cell parameters at all dose levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximat; DOSE=y; changes in F0/F1 red blood cell parameters at all dose levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed.; EFFECT=y; changes in F0/F1 red blood cell parameters at all dose levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"y; changes in F0/F1 red blood cell parameters at all dose levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed.","duration":"developmental","effect":"y; changes in F0/F1 red blood cell parameters at all dose levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximat","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:y; changes in F0/F1 red blood cell parameters at all dose levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximat","page":46,"route":"","species":"","study_id":"sccs_o_288_noael_034"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1 | - | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo; DOSE=5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo; EFFECT=se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","duration":"developmental","effect":"se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:se levels; changes in F1 offspring survival at 78 mg Silver/kg bw/day was observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. mo","page":46,"route":"","species":"","study_id":"sccs_o_288_noael_035"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 52 | - | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:as observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; DOSE=5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; EFFECT=as observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","duration":"developmental","effect":"as observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:as observed. At 52 mg Silver/kg bw/day in F1, changes in neurobehavioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"route":"","species":"","study_id":"sccs_o_288_noael_036"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 26 | - | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; DOSE=5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; EFFECT=vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","duration":"developmental","effect":"vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:vioral/ sensory function, sperm morphology and effect on histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"route":"","species":"","study_id":"sccs_o_288_noael_037"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 26 | - | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; DOSE=5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; EFFECT=histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","duration":"developmental","effect":"histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:histopathology of brain was observed. At 26 mg Silver/kg/day, systemic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"route":"","species":"","study_id":"sccs_o_288_noael_038"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1 | - | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:mic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; DOSE=5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; EFFECT=mic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","duration":"developmental","effect":"mic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:mic toxicity in F1 adults reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait and brain LOAEL (F0- systemic toxicity): 26 mg Silver/kg bw/day NOAEL (F1- systemic toxicity): 26 mg Silver /kg bw/day NOAEL (F0- mating performanc e and fertility): 78 mg Silver /kg bw/day NOAEL (F1- offspring survival and growth): 52 mg Silver /kg bw/day NOAEL (developmental toxicity): 52 mg Silver/kg bw/day; NOAEL (developmental neurotoxicity in F1): 26 mg Silver /kg bw/day; NOAEL (developme ntal immunotoxi city): 78 mg Silver/kg bw/day. 5 (Renaut, 2022 in ECHA, 2022)/KL1 Study type, species Doses Critical effects Dose descriptor Reference/KL rating welfare grounds at approximately 10 weeks of age rather than 13- 14 weeks of age. morphometry was observed.","page":46,"route":"","species":"","study_id":"sccs_o_288_noael_039"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 20000 | ppm | rat | oral | 10 weeks | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=20000; DOSE=4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.; EFFECT=4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","duration":"10 weeks","effect":"4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"ppm","noael_value":"20000","page":47,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_040"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 20000 | ppm | rat | oral | 10 weeks | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=20000; DOSE=ent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.; EFFECT=ent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At 40 mg Silver/kg bw/day increase in spleen weig; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"ent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","duration":"10 weeks","effect":"ent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At 40 mg Silver/kg bw/day increase in spleen weig","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"ppm","noael_value":"20000","page":47,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_041"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 20000 | ppm | rat | oral | 10 weeks | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=20000; DOSE=Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data:; EFFECT=ay. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At 40 mg Silver/kg bw/day increase in spleen weight, relative brain weight and a decrease in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data:","duration":"10 weeks","effect":"ay. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2 SCAS Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females F0 data: At 40 mg Silver/kg bw/day increase in spleen weight, relative brain weight and a decrease in","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"ppm","noael_value":"20000","page":47,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_042"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 250 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=250; DOSE=Combined repeat dose toxicity with reproductive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) | 0, 62.5, 125 and 250 mg/kg bw/day Male rats:; EFFECT=Unlabeled table on page 45: Combined repeat dose toxicity with reproductive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) | 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation | No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. | NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day | (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Combined repeat dose toxicity with reproductive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) | 0, 62.5, 125 and 250 mg/kg bw/day Male rats:","duration":"developmental","effect":"Unlabeled table on page 45: Combined repeat dose toxicity with reproductive developmental toxicity screening study, OECD TG 422; citrate-capped Silver nanoparticles (8 nm) | 0, 62.5, 125 and 250 mg/kg bw/day Male rats: 14 days before mating, 14 days during the mating period and 14 days of post-mating until necropsy (daily). Female rats (maximum of 52 days): 2 weeks before mating, during the mating and gestation period, and during 4 days of lactation | No treatment related adverse effects were observed on any reproductive/ developmental parameter evaluated up to highest tested dose. | NOAEL (reproductive/ developmental) toxicity: 250 mg Silver/kg bw/day | (Hong et al., 2014 in ECHA RAC, 2022; ECHA, 2022)/KL2","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":45,"route":"","species":"rat","study_id":"sccs_o_288_noael_066"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 46 | - | - | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=unclear:Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...; DOSE=AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation.; EFFECT=Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation.","duration":"","effect":"Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 46: Extended one generation reproductive toxicity study (EOGRTS), Sprague-Dawley, OECD TG 443; Silver acetate Trade name: AG(I) Acetate T2 HSTDP Silver(I) acetate | 0, 40, 80 and 120 mg Silver acetate/kg bw/day (equivalent to 0, 26, 52 and 78 mg Silver/kg bw/day) females were treated for ten weeks before pairing, throughout pairing up to necropsy on Day 28 of lactation. The F1 generation was treated from weaning to their scheduled termination (relevant to each cohort) at the same dose levels and volume- dose as the F0 generation, with exception on animals at 120 mg Silver acetate/kg bw/day in Cohorts 1A and 1B which were terminated prematurely on | Significant decrease in cauda epididymis and testicular weight and at all dose levels, testicular and cauda epididymal total spermatid and sperm counts were low. At 78 mg Silver/kg bw/day mortality in F1, changes in neurobehavioral/sensory function, effect on sperm counts and sperm morphology was observed. At 26, 52 and 78 mg Silver /kg/ bw/day effects such as; F1 mortality at 78 mg Silver/kg bw/day; changes in F...","page":46,"route":"","species":"","study_id":"sccs_o_288_noael_068"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 63.7 | % | rat | oral | 10 weeks | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=63.7- 65.5; DOSE=Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.; EFFECT=Unlabeled table on page 47: One generation drinking water reproductive toxicity study in Sprague-Dawley rats, according to FDA CFSAN Redbook; Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 | At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed | NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day | (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day.","duration":"10 weeks","effect":"Unlabeled table on page 47: One generation drinking water reproductive toxicity study in Sprague-Dawley rats, according to FDA CFSAN Redbook; Silver acetate (63.7- 65.5% Silver), non-GLP | 0, 0.4, 4 and 40 mg Silver acetate/kg bw/day equivalent to 0, 0.25, 2.5 and 25 Silver mg/kg bw/day. Parental animals were exposed 10 weeks prior to mating. The F1-pups were sacrificed on postnatal day (PND) 26 | At 25 mg Silver/kg bw/day reduced fertility and the number of litters and decrease in stomach weigh and reduction in fluid consumption was observed. At 2.5 mg Silver/kg bw/day lower male and female pup weight, decrease in right kidney weight and heart, increase in right epididymal weight in male pups was observed | NOAEL (systemic) F0: 0.25 mg Silver/kg bw/day. NOAEL (fertility) F0: 2.5 mg Silver/kg bw/; NOAEL (develop- mental): 0.25 mg Silver/kg bw/day | (Sprando et al., 2017 in ECHA, 2022; ECHA RAC, 2022)/ KL2","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"%","noael_value":"63.7- 65.5","page":47,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_069"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 20000 | ppm | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=20000; DOSE=Silver sodium zirconium hydrogen phosphate | 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females | F0 data:; EFFECT=Unlabeled table on page 47: Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate | 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females | F0 data: At 40 mg Silver/kg bw/day increase in spleen weight, relative brain weight and a decrease in the thymus, adrenals, kidneys weight and darkened or discoloured pancreas was observed. At 9.9 mg Silver/kg bw/day increased pigmentation of pancreas and increase in spleen weight was observed. F1 generation: At 40 mg Silver/kg bw/day decreased body weights, further significant decrease in the number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver sodium zirconium hydrogen phosphate | 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females | F0 data:","duration":"","effect":"Unlabeled table on page 47: Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver sodium zirconium hydrogen phosphate | 0, 1000, 5000 and 20000 ppm correspondin g to 0, 72.5/78.2, 363/400 and 1465/1612 mg sodium zirconium hydrogen phosphate/kg bw/day or 0, 1.9, 9.9 and 40 mg Silver /kg bw/day in females | F0 data: At 40 mg Silver/kg bw/day increase in spleen weight, relative brain weight and a decrease in the thymus, adrenals, kidneys weight and darkened or discoloured pancreas was observed. At 9.9 mg Silver/kg bw/day increased pigmentation of pancreas and increase in spleen weight was observed. F1 generation: At 40 mg Silver/kg bw/day decreased body weights, further significant decrease in the number born and in live litter size on Day 1 postpartum in F1 dams and darkened or discoloured pancreas decreased absolute weight of seminal vesicles/coagulating gland and changes in semen parameters was observed. F2 generation: At 40 mg Silver/kg bw/day, reduced litter size, reduced group mean litter and individual weights, number of pups born, and thymus...","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"ppm","noael_value":"20000","page":47,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_070"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 12500 | ppm | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_288; REPORT_TITLE=OPINION on the safety of Silver (CAS/EC No. 7440-22-4/231-131-3) used in cosmetic products; OPINION_NUMBER=SCCS/1665/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=20 June 2024; VALUE_TEXT=12500; DOSE=Silver zinc zeolite | 0, 1000, 6250, 12500 ppm (equivalent to 0, 72/87, 472/548, 984/1109 mg Silver zinc zeolite/kg bw/day (premating) correspondin g to approximatel y 0, 1.5/1.8, 9.8/11.3; and 20.3/22.9 mg Silver/kg bw/day in males and females, respectively | F0 data:; EFFECT=Unlabeled table on page 48: Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver zinc zeolite | 0, 1000, 6250, 12500 ppm (equivalent to 0, 72/87, 472/548, 984/1109 mg Silver zinc zeolite/kg bw/day (premating) correspondin g to approximatel y 0, 1.5/1.8, 9.8/11.3; and 20.3/22.9 mg Silver/kg bw/day in males and females, respectively | F0 data: At 20.3/22.9 and 9.8/11.3 mg Silver/kg bw/day in males and females, increase in mortality, reduced bodyweight, bodyweight gain, and food consumption increase in mortality, decrease in bodyweight, bodyweight gain, and food consumption and histopathological changes of kidney were observed. F1 generation: At 20.3/22.9 and 9.8/11.3 mg Silver/kg bw/day in males and females, mortality, decrease in bodyweight, bodyweight gain, histopathological changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg S...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"7440-22-4","citation":"","dose":"Silver zinc zeolite | 0, 1000, 6250, 12500 ppm (equivalent to 0, 72/87, 472/548, 984/1109 mg Silver zinc zeolite/kg bw/day (premating) correspondin g to approximatel y 0, 1.5/1.8, 9.8/11.3; and 20.3/22.9 mg Silver/kg bw/day in males and females, respectively | F0 data:","duration":"","effect":"Unlabeled table on page 48: Two generation dietary reproductive toxicity in Sprague Dawley rats, OECD TG 416; Silver zinc zeolite | 0, 1000, 6250, 12500 ppm (equivalent to 0, 72/87, 472/548, 984/1109 mg Silver zinc zeolite/kg bw/day (premating) correspondin g to approximatel y 0, 1.5/1.8, 9.8/11.3; and 20.3/22.9 mg Silver/kg bw/day in males and females, respectively | F0 data: At 20.3/22.9 and 9.8/11.3 mg Silver/kg bw/day in males and females, increase in mortality, reduced bodyweight, bodyweight gain, and food consumption increase in mortality, decrease in bodyweight, bodyweight gain, and food consumption and histopathological changes of kidney were observed. F1 generation: At 20.3/22.9 and 9.8/11.3 mg Silver/kg bw/day in males and females, mortality, decrease in bodyweight, bodyweight gain, histopathological changes in organs were observed. Further, there were also effects, such as a higher percentage of abnormal sperm increase on the day of the vaginal opening was observed F2 generation: At 20.3/22.9 mg Silver/kg bw/day, no pups due to high toxicity in parents. At 9.8/11.3 mg S...","endpoint":"reproductive toxicity","ingredient":"codes ........................................................... 12","loael_value":"","noael_unit":"ppm","noael_value":"12500","page":48,"route":"oral","species":"rat","study_id":"sccs_o_288_noael_071"} |
ich_q3d_elemental_impurities.pdf 12 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ich_q3d_elemental_impurities.pdf | LOAEL | silver nitrate drinking-water study; 64% silver20 | mg Ag/kg | mouse | oral | 125 days | drinking water study | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=oral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=PDE = 20 mg/kg x 50 kg / (12 x 10 x 5 x 1 x 10) = 167 ug/day A factor 10 was chosen for F5 because the LOAEL was used |
| ich_q3d_elemental_impurities.pdf | LOAEL | PDF says inadequate to set parenteral PDE1 | g metallic silver cumulative | human | parenteral | 2 to 9.75 years | intravenous case series | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=parenteral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=the lowest cumulative dose of silver resulting in argyria was 1 g metallic silver. Argyria was reported in other patients at higher cumulative doses of silver. Using this study, the US EPA (2003) identified this dose as a LOAEL |
| ich_q3d_elemental_impurities.pdf | LOAEL | silver nitrate drinking-water study; 64% silver20 | mg Ag/kg | mouse | oral | 125 days | drinking water study | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=oral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=PDE = 20 mg/kg x 50 kg / (12 x 10 x 5 x 1 x 10) = 167 ug/day A factor 10 was chosen for F5 because the LOAEL was used |
| ich_q3d_elemental_impurities.pdf | LOAEL | PDF says inadequate to set parenteral PDE1 | g metallic silver cumulative | human | parenteral | 2 to 9.75 years | intravenous case series | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=parenteral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=the lowest cumulative dose of silver resulting in argyria was 1 g metallic silver. Argyria was reported in other patients at higher cumulative doses of silver. Using this study, the US EPA (2003) identified this dose as a LOAEL |
| ich_q3d_elemental_impurities.pdf | LOAEL | silver nitrate drinking-water study; 64% silver20 | mg Ag/kg | mouse | oral | 125 days | drinking water study | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=oral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=PDE = 20 mg/kg x 50 kg / (12 x 10 x 5 x 1 x 10) = 167 ug/day A factor 10 was chosen for F5 because the LOAEL was used |
| ich_q3d_elemental_impurities.pdf | LOAEL | PDF says inadequate to set parenteral PDE1 | g metallic silver cumulative | human | parenteral | 2 to 9.75 years | intravenous case series | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=parenteral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=the lowest cumulative dose of silver resulting in argyria was 1 g metallic silver. Argyria was reported in other patients at higher cumulative doses of silver. Using this study, the US EPA (2003) identified this dose as a LOAEL |
| ich_q3d_elemental_impurities.pdf | LOAEL | silver nitrate drinking-water study; 64% silver20 | mg Ag/kg | mouse | oral | 125 days | drinking water study | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=oral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=PDE = 20 mg/kg x 50 kg / (12 x 10 x 5 x 1 x 10) = 167 ug/day A factor 10 was chosen for F5 because the LOAEL was used |
| ich_q3d_elemental_impurities.pdf | LOAEL | PDF says inadequate to set parenteral PDE1 | g metallic silver cumulative | human | parenteral | 2 to 9.75 years | intravenous case series | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=parenteral; source_page=65; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=the lowest cumulative dose of silver resulting in argyria was 1 g metallic silver. Argyria was reported in other patients at higher cumulative doses of silver. Using this study, the US EPA (2003) identified this dose as a LOAEL |
| ich_q3d_elemental_impurities.pdf | TLV | US DoL TLV0.01 | mg/m3 | - | inhalation | occupational | occupational exposure limit | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=inhalation; source_page=66; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=Using the Threshold Limit Value (TLV) of 0.01 mg/m3 for silver metal and soluble compounds |
| ich_q3d_elemental_impurities.pdf | TLV | US DoL TLV0.01 | mg/m3 | - | inhalation | occupational | occupational exposure limit | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=inhalation; source_page=66; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=Using the Threshold Limit Value (TLV) of 0.01 mg/m3 for silver metal and soluble compounds |
| ich_q3d_elemental_impurities.pdf | TLV | US DoL TLV0.01 | mg/m3 | - | inhalation | occupational | occupational exposure limit | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=inhalation; source_page=66; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=Using the Threshold Limit Value (TLV) of 0.01 mg/m3 for silver metal and soluble compounds |
| ich_q3d_elemental_impurities.pdf | TLV | US DoL TLV0.01 | mg/m3 | - | inhalation | occupational | occupational exposure limit | ICH Q3D(R2) Guideline for Elemental Impurities; Appendix 3; pde_route=inhalation; source_page=66; source_sha256=940176418af05c88ed33416a5d5e719a4ab7fe1d31cf1cd56ed331749b649c75; source_quote=Using the Threshold Limit Value (TLV) of 0.01 mg/m3 for silver metal and soluble compounds |
openFDA substances 8 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | Q3A5NLA4B5 | UNII | - | - | - | specifiedSubstanceG1 | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"specifiedSubstanceG1","unii_code":"Q3A5NLA4B5"} |
| openFDA substances | FDA UNII substance identifier | 3M4G523W1G | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"Ag","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3M4G523W1G"} |
| openFDA substances | FDA UNII substance identifier | Q3A5NLA4B5 | UNII | - | - | - | specifiedSubstanceG1 | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"specifiedSubstanceG1","unii_code":"Q3A5NLA4B5"} |
| openFDA substances | FDA UNII substance identifier | Q3A5NLA4B5 | UNII | - | - | - | specifiedSubstanceG1 | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"specifiedSubstanceG1","unii_code":"Q3A5NLA4B5"} |
| openFDA substances | FDA UNII substance identifier | 3M4G523W1G | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"Ag","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3M4G523W1G"} |
| openFDA substances | FDA UNII substance identifier | 3M4G523W1G | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"Ag","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3M4G523W1G"} |
| openFDA substances | FDA UNII substance identifier | Q3A5NLA4B5 | UNII | - | - | - | specifiedSubstanceG1 | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"specifiedSubstanceG1","unii_code":"Q3A5NLA4B5"} |
| openFDA substances | FDA UNII substance identifier | 3M4G523W1G | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"Ag","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3M4G523W1G"} |