NOAEL Studies
Active Ingredient
Zinc Pyrithione NOAEL Studies
INCI: ZINC PYRITHIONE
CAS: 13463-41-7
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
COSMOS DB 7 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| COSMOS DB | LOAEL | 1 | mg/kg bw/day | rat | oral | 90 day | Subchronic | REACH; study report |
| COSMOS DB | LOAEL | 1.39999997616 | mg/kg bw/day | rat | oral | 2 year | Chronic | REACH; study report |
| COSMOS DB | LOAEL | 1.5 | mg/kg bw/day | rat | oral | 2 year | Chronic | REACH; study report |
| COSMOS DB | LOAEL | 22 | mg/kg bw/day | primate | oral | 28 day | Subchronic | REACH; study report |
| COSMOS DB | NOAEL | 0.20000000298 | mg/kg bw/day | rat | oral | 90 day | Subchronic | REACH; study report |
| COSMOS DB | NOAEL | 0.5 | mg/kg bw/day | rat | oral | 2 year | Chronic | REACH; study report |
| COSMOS DB | NOAEL | 11 | mg/kg bw/day | primate | oral | 28 day | Subchronic | REACH; study report |
NTP ICE acute dermal 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE acute dermal | EPA classification | 3 | unitless | Rat | Dermal | - | In Vivo; Rat Acute Dermal Toxicity | sheet=Data; excel_row=1752; Record_ID=acute_dermal_11; Data_Type=In Vivo; Formulation_ID=MIX11; Formulation_Name=Acticide SR 8213 C; Percent_Active_Ingredient=5.0; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Rat Acute Dermal Toxicity; Endpoint=EPA classification; Response=3.0; Response_Unit=Unitless; Species=Rat; Route=Dermal; Reference=FIFRA data; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute dermal | GHS classification | 5 | unitless | Rat | Dermal | - | In Vivo; Rat Acute Dermal Toxicity | sheet=Data; excel_row=1754; Record_ID=acute_dermal_11; Data_Type=In Vivo; Formulation_ID=MIX11; Formulation_Name=Acticide SR 8213 C; Percent_Active_Ingredient=5.0; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Rat Acute Dermal Toxicity; Endpoint=GHS classification; Response=5.0; Response_Unit=Unitless; Species=Rat; Route=Dermal; Reference=FIFRA data; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute dermal | LD50 | >2000 | mg/kg | Rat | Dermal | - | In Vivo; Rat Acute Dermal Toxicity | sheet=Data; excel_row=1751; Record_ID=acute_dermal_11; Data_Type=In Vivo; Formulation_ID=MIX11; Formulation_Name=Acticide SR 8213 C; Percent_Active_Ingredient=5.0; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Rat Acute Dermal Toxicity; Endpoint=LD50; Response_Modifier=>; Response=2000.0; Response_Unit=mg/kg; Species=Rat; Route=Dermal; Reference=FIFRA data; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
NTP ICE acute inhalation 7 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE acute inhalation | EPA Classification | 4 | unitless | - | Inhalation | - | In Vivo; AcuteInhal6pack; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=3991; Record_ID=acute_inhalation_417; Data_Type=In Vivo; Internal_Data_Source=AcuteInhal6pack; Formulation_ID=MIX611; Formulation_Name=Trilux 44 - White; Percent_Active_Ingredient=4.12; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Rat Acute Inhalation Toxicity; Endpoint=EPA Classification; Response=4; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute inhalation | GHS Classification | 5 | unitless | - | Inhalation | - | In Vivo; AcuteInhal6pack; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=3989; Record_ID=acute_inhalation_417; Data_Type=In Vivo; Internal_Data_Source=AcuteInhal6pack; Formulation_ID=MIX611; Formulation_Name=Trilux 44 - White; Percent_Active_Ingredient=4.12; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Rat Acute Inhalation Toxicity; Endpoint=GHS Classification; Response=5; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute inhalation | LC50 | 0.14 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=3992; Record_ID=acute_inhalation_2812; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response=0.14; Response_Unit=mg/L; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute inhalation | LC50 | 0.84 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=3988; Record_ID=acute_inhalation_1680; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response=0.84; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/3/3/?documentUUID=831c8bad-7c57-408a-b280-e48301764ab7; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute inhalation | LC50 | 1.03 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=3987; Record_ID=acute_inhalation_1683; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response=1.03; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/3/3/?documentUUID=831c8bad-7c57-408a-b280-e48301764ab7; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute inhalation | LC50 | 1.34 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=3990; Record_ID=acute_inhalation_1676; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response=1.34; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/3/3/?documentUUID=831c8bad-7c57-408a-b280-e48301764ab7; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE acute inhalation | LC50 | >5.15 | mg/L | - | Inhalation | - | In Vivo; AcuteInhal6pack; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=3986; Record_ID=acute_inhalation_417; Data_Type=In Vivo; Internal_Data_Source=AcuteInhal6pack; Formulation_ID=MIX611; Formulation_Name=Trilux 44 - White; Percent_Active_Ingredient=4.12; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response_Modifier=>; Response=5.15; Response_Unit=mg/L; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
NTP ICE acute oral 10 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE acute oral | EPA classification | =3 | Unitless | Rat | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_13257; row=11997; data_type=In Vivo; mixture=Mixture; formulation_id=MIX711; formulation_name=Shelter Island Plus - White; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.0; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | EPA classification | =3 | Unitless | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_12197; row=11999; data_type=In Vivo; mixture=Mixture; formulation_id=MIX11; formulation_name=Acticide SR 8213 C; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=5.0; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | EPA classification | =3 | Unitless | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_12975; row=12000; data_type=In Vivo; mixture=Mixture; formulation_id=MIX449; formulation_name=Shelter Island Plus; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.0; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | EPA classification | =3 | Unitless | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_13058; row=12003; data_type=In Vivo; mixture=Mixture; formulation_id=MIX611; formulation_name=Trilux 44 - White; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.12; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | GHS classification | =4 | Unitless | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_12197; row=12001; data_type=In Vivo; mixture=Mixture; formulation_id=MIX11; formulation_name=Acticide SR 8213 C; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=5.0; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | GHS classification | =4 | Unitless | Rat | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_13257; row=12005; data_type=In Vivo; mixture=Mixture; formulation_id=MIX711; formulation_name=Shelter Island Plus - White; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.0; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | GHS classification | =5 | Unitless | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_12975; row=12002; data_type=In Vivo; mixture=Mixture; formulation_id=MIX449; formulation_name=Shelter Island Plus; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.0; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | GHS classification | =5 | Unitless | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_13058; row=12004; data_type=In Vivo; mixture=Mixture; formulation_id=MIX611; formulation_name=Trilux 44 - White; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.12; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | LD50 | >2000 | mg/kg bw | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_13058; row=11996; data_type=In Vivo; mixture=Mixture; formulation_id=MIX611; formulation_name=Trilux 44 - White; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.12; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
| NTP ICE acute oral | LD50 | >2000 | mg/kg bw | Rat (Female) | oral | acute | Rat Acute Oral Toxicity | Studies submitted to EPA in support of pesticide registration applications (undated); record_id=acute_oral_12975; row=11998; data_type=In Vivo; mixture=Mixture; formulation_id=MIX449; formulation_name=Shelter Island Plus; chemical_name=Pyrithione zinc; preferred_name=Zinc pyrithione; percent_active_ingredient=4.0; dtxsid=DTXSID7026314; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID7026314; source_file=acute_oral.xlsx |
NTP ICE dart 6 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE dart | LOEL | 1.5 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, Reproductive performance | sheet=Data; excel_row=109476; Record_ID=dart_17370; Data_Type=In Vivo; DTXSID=DTXSID7026314; Assay=DART, Reproductive performance; Endpoint=LOEL; Response=1.5; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0035150;CUI;Reproduction|UMLS;C4086749;CUI;Post-implantation Loss Percent; Reference=ToxRefDB v2 , ID = 1753; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE dart | LOEL | 1.5 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=109477; Record_ID=dart_17375; Data_Type=In Vivo; DTXSID=DTXSID7026314; Assay=DART, In life observation; Endpoint=LOEL; Response=1.5; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C2983605;CUI;Food Consumption|UMLS;C3540840;CUI;Sign or Symptom|UMLS;C2983605;CUI;Food Consumption; Reference=ToxRefDB v2 , ID = 1753; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE dart | LOEL | 1.5 | mg/kg bw/day | Rabbit | Oral | - | In Vivo; DART, Offspring survival early | sheet=Data; excel_row=109478; Record_ID=dart_17377; Data_Type=In Vivo; DTXSID=DTXSID7026314; Assay=DART, Offspring survival early; Endpoint=LOEL; Response=1.5; Response_Unit=mg/kg/day; Species=Rabbit; Strain=New Zealand White; Sex=Male/Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0015954;CUI;Fetal Viability|UMLS;C4086644;CUI;Number of Live Fetuses; Reference=ToxRefDB v2 , ID = 1753; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE dart | LOEL | 3 | mg/kg bw/day | Rat | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=109479; Record_ID=dart_17566; Data_Type=In Vivo; DTXSID=DTXSID7026314; Assay=DART, In life observation; Endpoint=LOEL; Response=3; Response_Unit=mg/kg/day; Species=Rat; Strain=Sprague Dawley (CD); Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0013132;CUI;Drooling; Reference=ToxRefDB v2 , ID = 1754; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE dart | LOEL | 3 | mg/kg bw/day | Rat | Oral | - | In Vivo; DART, Developmental malformation | sheet=Data; excel_row=109480; Record_ID=dart_17572; Data_Type=In Vivo; DTXSID=DTXSID7026314; Assay=DART, Developmental malformation; Endpoint=LOEL; Response=3; Response_Unit=mg/kg/day; Species=Rat; Strain=Sprague Dawley (CD); Sex=Male/Female; Life_Stage=Fetal; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0000768;CUI;Congenital Abnormality|UMLS;C0265509;CUI;Congenital anomaly of skeletal bone|UMLS;C0699952;CUI;Fused; Reference=ToxRefDB v2 , ID = 1754; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE dart | LOEL | 3 | mg/kg bw/day | Rat | Oral | - | In Vivo; DART, In life observation | sheet=Data; excel_row=109481; Record_ID=dart_17505; Data_Type=In Vivo; DTXSID=DTXSID7026314; Assay=DART, In life observation; Endpoint=LOEL; Response=3; Response_Unit=mg/kg/day; Species=Rat; Strain=Sprague Dawley (CD); Sex=Female; Life_Stage=Adult; Route=Oral; Critical_Effect=Yes; Unified_Medical_Language_System=UMLS;C0005910;CUI;Body Weight|UMLS;C3540840;CUI;Sign or Symptom|UMLS;C0043094;CUI;Weight Gain; Reference=ToxRefDB v2 , ID = 1754; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
NTP ICE endocrine 7 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE endocrine | AC50 | 0.246652718 | uM | - | - | - | ARPathway2016; AR Pathway Model, Agonist | sheet=Integrated_approaches; excel_row=16372; RecordID=ARPathway2016_64; DatasetName=ARPathway2016; DTXSID=DTXSID7026314; Assay=AR Pathway Model, Agonist; Endpoint=AC50; Response=0.246652718; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE endocrine | AC50 | 2.04176096879569 | uM | - | - | - | ERPathway2016; ER Pathway Model, Agonist | sheet=Integrated_approaches; excel_row=16378; RecordID=ERPathway2016_101; DatasetName=ERPathway2016; DTXSID=DTXSID7026314; Assay=ER Pathway Model, Agonist; Endpoint=AC50; Response=2.04176096879569; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE endocrine | ACC | 0.190148851 | uM | - | - | - | ARPathway2016; AR Pathway Model, Agonist | sheet=Integrated_approaches; excel_row=16373; RecordID=ARPathway2016_64; DatasetName=ARPathway2016; DTXSID=DTXSID7026314; Assay=AR Pathway Model, Agonist; Endpoint=ACC; Response=0.190148851; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE endocrine | ACC | 1.85188882209664 | uM | - | - | - | ERPathway2016; ER Pathway Model, Agonist | sheet=Integrated_approaches; excel_row=16379; RecordID=ERPathway2016_101; DatasetName=ERPathway2016; DTXSID=DTXSID7026314; Assay=ER Pathway Model, Agonist; Endpoint=ACC; Response=1.85188882209664; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE endocrine | Model Score | 0 | unitless | - | - | - | ARPathway2016; AR Pathway Model, Agonist | sheet=Integrated_approaches; excel_row=16375; RecordID=ARPathway2016_64; DatasetName=ARPathway2016; DTXSID=DTXSID7026314; Assay=AR Pathway Model, Agonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE endocrine | Model Score | 0.237 | unitless | - | - | - | ERPathway2016; ER Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=16381; RecordID=ERPathway2016_101; DatasetName=ERPathway2016; DTXSID=DTXSID7026314; Assay=ER Pathway Model, Antagonist; Endpoint=Model Score; Response=0.237; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE endocrine | Model Score | 0.645 | unitless | - | - | - | ARPathway2016; AR Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=16374; RecordID=ARPathway2016_64; DatasetName=ARPathway2016; DTXSID=DTXSID7026314; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0.645; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
NTP ICE eye irritation 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE eye irritation | EPA Classification | 1 | unitless | Rabbit | Ocular | - | In Vivo; Draize Eye Irritation/Corrosion Test | sheet=Data; excel_row=2071; Record_ID=eye_irritation_1018; Data_Type=In Vivo; Formulation_ID=EyeIrritation6pack_PID871; Formulation_Name=Shelter Island Plus; Percent_Active_Ingredient=4.0; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Draize Eye Irritation/Corrosion Test; Endpoint=EPA Classification; Response=1; Response_Unit=Unitless; Species=Rabbit; Reference=FIFRA data; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
NTP ICE skin irritation 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE skin irritation | EPA classification | 3 | unitless | Rabbit | Dermal | - | In Vivo; Draize Skin Irritation/Corrosion Test | sheet=Data_invivo; excel_row=1372; Record_ID=skin_irritation_invivo_523; Data_Type=In Vivo; Formulation_ID=MIX11; Formulation_Name=Acticide SR 8213 C; Percent_Active_Ingredient=5; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Draize Skin Irritation/Corrosion Test; Endpoint=EPA classification; Response=3; Response_Unit=Unitless; Species=Rabbit; Reference=FIFRA (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE skin irritation | EPA classification | 3 | unitless | Rabbit | Dermal | - | In Vivo; Draize Skin Irritation/Corrosion Test | sheet=Data_invivo; excel_row=1374; Record_ID=skin_irritation_invivo_857; Data_Type=In Vivo; Formulation_ID=MIX11; Formulation_Name=Acticide SR 8213 C; Percent_Active_Ingredient=5; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Draize Skin Irritation/Corrosion Test; Endpoint=EPA classification; Response=3; Response_Unit=Unitless; Species=Rabbit; Reported_Strain=New Zealand White; Strain=New Zealand White; Reference=FIFRA (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE skin irritation | EPA classification | 4 | unitless | Rabbit | Dermal | - | In Vivo; Draize Skin Irritation/Corrosion Test | sheet=Data_invivo; excel_row=1373; Record_ID=skin_irritation_invivo_614; Data_Type=In Vivo; Formulation_ID=MIX449; Formulation_Name=Shelter Island Plus; Percent_Active_Ingredient=4; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Draize Skin Irritation/Corrosion Test; Endpoint=EPA classification; Response=4; Response_Unit=Unitless; Species=Rabbit; Reference=FIFRA (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE skin irritation | EPA classification | 4 | unitless | Rabbit | Dermal | - | In Vivo; Draize Skin Irritation/Corrosion Test | sheet=Data_invivo; excel_row=1376; Record_ID=skin_irritation_invivo_943; Data_Type=In Vivo; Formulation_ID=MIX449; Formulation_Name=Shelter Island Plus; Percent_Active_Ingredient=4; Mixture=Mixture; DTXSID=DTXSID7026314; Assay=Draize Skin Irritation/Corrosion Test; Endpoint=EPA classification; Response=4; Response_Unit=Unitless; Species=Rabbit; Reported_Strain=New Zealand white; Strain=New Zealand White; Sex=Male; Reference=FIFRA (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
NTP ICE skin sensitization 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE skin sensitization | Incidence of positive responses | 0 | % | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test | sheet=Data_invivo; excel_row=4833; Record_ID=skin_sensitization_invivo_1159; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Human Repeat Insult Patch Test; Endpoint=Incidence of positive responses; Response=0; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE skin sensitization | Induction dose per skin area | 852.5 | ug/cm2 | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test | sheet=Data_invivo; excel_row=4831; Record_ID=skin_sensitization_invivo_1159; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=852.5; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE skin sensitization | Induction dose per skin area | 2093 | ug/cm2 | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test | sheet=Data_invivo; excel_row=4847; Record_ID=skin_sensitization_invivo_1163; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=3.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=2093; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
| NTP ICE skin sensitization | Relative reliability score | 3 | unitless | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test | sheet=Data_invivo; excel_row=4821; Record_ID=skin_sensitization_invivo_1155; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=3.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID7026314; Assay=Human Repeat Insult Patch Test; Endpoint=Relative reliability score; Response=3; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1973; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7026314; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7026314 |
SCCNFP Opinion 16 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCNFP Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater the animals usually died without developing a paralysis. The dose/time response with respect to paralysis is not yet completely understood, since it is complicated by several variables that are discussed below. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 µg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two year study period. Hind-limb Paralysis Several studies have been conducted to determine the dose range that produces paralysis, the reversibility of this effect, and the ultrastructural cellular changes involved. The results of these studies have been fully considered as part of the safety evaluation of ZPT. In many of the studies reported, ZPT was added to the diet of th","page":8,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_001"} |
| SCCNFP Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater the animals usually died without developing a paralysis. The dose/time response with respect to paralysis is not yet completely understood, since it is complicated by several variables that are discussed below. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 µg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two year study period. Hind-limb Paralysis Several studies have been conducted to determine the dose range that produces paralysis, the reversibility of this effect, and the ultrastructural cellular changes involved. The results of these studies have been fully considered as part of the safety evaluation of ZPT. In many of the studies reported, ZPT was added to the diet of th","page":8,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_001"} |
| SCCNFP Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater the animals usually died without developing a paralysis. The dose/time response with respect to paralysis is not yet completely understood, since it is complicated by several variables that are discussed below. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 µg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two year study period. Hind-limb Paralysis Several studies have been conducted to determine the dose range that produces paralysis, the reversibility of this effect, and the ultrastructural cellular changes involved. The results of these studies have been fully considered as part of the safety evaluation of ZPT. In many of the studies reported, ZPT was added to the diet of th","page":8,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_001"} |
| SCCNFP Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater the animals usually died without developing a paralysis. The dose/time response with respect to paralysis is not yet completely understood, since it is complicated by several variables that are discussed below. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 µg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two year study period. Hind-limb Paralysis Several studies have been conducted to determine the dose range that produces paralysis, the reversibility of this effect, and the ultrastructural cellular changes involved. The results of these studies have been fully considered as part of the safety evaluation of ZPT. In many of the studies reported, ZPT was added to the diet of th","page":8,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_001"} |
| SCCNFP Opinion | NOAEL | =0.6 | mg/kg/d | rat | oral | chronic | NOAEL study | {"dose":"Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten.","effect":"produced mild or no neurologic deficit or electrophysiologic changes prior to death. Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten. The work by Chrisman and Ross (1978) is especially important in that it confirmed the no-effect level [10 ppm (0.6mg/kg/d) of ZPT in diet] determined by Larson (1958) in the chronic feeding study summarised below. In addition to confirming the NOEL, the work also serves to point out the sensitivity of the rat to the neurologic effects of ZPT (see also Sahenk and Mendell (1980)).","page":11,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_002"} |
| SCCNFP Opinion | NOAEL | =0.6 | mg/kg/d | rat | oral | chronic | NOAEL study | {"dose":"Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten.","effect":"produced mild or no neurologic deficit or electrophysiologic changes prior to death. Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten. The work by Chrisman and Ross (1978) is especially important in that it confirmed the no-effect level [10 ppm (0.6mg/kg/d) of ZPT in diet] determined by Larson (1958) in the chronic feeding study summarised below. In addition to confirming the NOEL, the work also serves to point out the sensitivity of the rat to the neurologic effects of ZPT (see also Sahenk and Mendell (1980)).","page":11,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_002"} |
| SCCNFP Opinion | NOAEL | =0.6 | mg/kg/d | rat | oral | chronic | NOAEL study | {"dose":"Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten.","effect":"produced mild or no neurologic deficit or electrophysiologic changes prior to death. Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten. The work by Chrisman and Ross (1978) is especially important in that it confirmed the no-effect level [10 ppm (0.6mg/kg/d) of ZPT in diet] determined by Larson (1958) in the chronic feeding study summarised below. In addition to confirming the NOEL, the work also serves to point out the sensitivity of the rat to the neurologic effects of ZPT (see also Sahenk and Mendell (1980)).","page":11,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_002"} |
| SCCNFP Opinion | NOAEL | =0.6 | mg/kg/d | rat | oral | chronic | NOAEL study | {"dose":"Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten.","effect":"produced mild or no neurologic deficit or electrophysiologic changes prior to death. Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten. The work by Chrisman and Ross (1978) is especially important in that it confirmed the no-effect level [10 ppm (0.6mg/kg/d) of ZPT in diet] determined by Larson (1958) in the chronic feeding study summarised below. In addition to confirming the NOEL, the work also serves to point out the sensitivity of the rat to the neurologic effects of ZPT (see also Sahenk and Mendell (1980)).","page":11,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_002"} |
| SCCNFP Opinion | NOAEL | =100 | mg/kg/d | human | oral | chronic | carcinogenicity | {"dose":"No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"or after practical application to humans. Thus the scientific evaluation of the submission, the results of these investigations on ZPT have been separated as to (i) ingredient based data, (ii) product based data and, where applicable, to the mode of application. As to probable neurotoxicological properties of ZPT the results of investigations in several species can be summarized as follows: In chronic toxicity experiments it was shown that an oral application of 500 µg/kg/d applied over (~ 18 m) can be regarded as NOAEL. No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_003"} |
| SCCNFP Opinion | NOAEL | =100 | mg/kg/d | human | oral | chronic | carcinogenicity | {"dose":"No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"or after practical application to humans. Thus the scientific evaluation of the submission, the results of these investigations on ZPT have been separated as to (i) ingredient based data, (ii) product based data and, where applicable, to the mode of application. As to probable neurotoxicological properties of ZPT the results of investigations in several species can be summarized as follows: In chronic toxicity experiments it was shown that an oral application of 500 µg/kg/d applied over (~ 18 m) can be regarded as NOAEL. No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_003"} |
| SCCNFP Opinion | NOAEL | =100 | mg/kg/d | human | oral | chronic | carcinogenicity | {"dose":"No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"or after practical application to humans. Thus the scientific evaluation of the submission, the results of these investigations on ZPT have been separated as to (i) ingredient based data, (ii) product based data and, where applicable, to the mode of application. As to probable neurotoxicological properties of ZPT the results of investigations in several species can be summarized as follows: In chronic toxicity experiments it was shown that an oral application of 500 µg/kg/d applied over (~ 18 m) can be regarded as NOAEL. No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_003"} |
| SCCNFP Opinion | NOAEL | =100 | mg/kg/d | human | oral | chronic | carcinogenicity | {"dose":"No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"or after practical application to humans. Thus the scientific evaluation of the submission, the results of these investigations on ZPT have been separated as to (i) ingredient based data, (ii) product based data and, where applicable, to the mode of application. As to probable neurotoxicological properties of ZPT the results of investigations in several species can be summarized as follows: In chronic toxicity experiments it was shown that an oral application of 500 µg/kg/d applied over (~ 18 m) can be regarded as NOAEL. No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_003"} |
| SCCNFP Opinion | NOAEL | =400 | mg/kg/day | rat | oral | - | reproductive toxicity | {"dose":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological studies 2.5 mg/kg/day applied orally to rats was the NOAEL maternally, no reproductive effects were observed in rabbits and rats when ZPT was topically administered up to 400 mg/kg/day. Toxicokinetic investigations revealed : * percutaneous absorption of ZPT varies from approximately 0.03 to 3.4% * the distribution of radioactivity in tissues after oral administration of labelled ZPT showed that the radioactivity rapidly disappeared from the blood, and the primary route of excretion was via the urine. The residual radioactivity was low (4.5% of dose), ZPT was distributed","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_004"} |
| SCCNFP Opinion | NOAEL | =400 | mg/kg/day | rat | oral | - | reproductive toxicity | {"dose":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological studies 2.5 mg/kg/day applied orally to rats was the NOAEL maternally, no reproductive effects were observed in rabbits and rats when ZPT was topically administered up to 400 mg/kg/day. Toxicokinetic investigations revealed : * percutaneous absorption of ZPT varies from approximately 0.03 to 3.4% * the distribution of radioactivity in tissues after oral administration of labelled ZPT showed that the radioactivity rapidly disappeared from the blood, and the primary route of excretion was via the urine. The residual radioactivity was low (4.5% of dose), ZPT was distributed","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_004"} |
| SCCNFP Opinion | NOAEL | =400 | mg/kg/day | rat | oral | - | reproductive toxicity | {"dose":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological studies 2.5 mg/kg/day applied orally to rats was the NOAEL maternally, no reproductive effects were observed in rabbits and rats when ZPT was topically administered up to 400 mg/kg/day. Toxicokinetic investigations revealed : * percutaneous absorption of ZPT varies from approximately 0.03 to 3.4% * the distribution of radioactivity in tissues after oral administration of labelled ZPT showed that the radioactivity rapidly disappeared from the blood, and the primary route of excretion was via the urine. The residual radioactivity was low (4.5% of dose), ZPT was distributed","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_004"} |
| SCCNFP Opinion | NOAEL | =400 | mg/kg/day | rat | oral | - | reproductive toxicity | {"dose":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","effect":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological studies 2.5 mg/kg/day applied orally to rats was the NOAEL maternally, no reproductive effects were observed in rabbits and rats when ZPT was topically administered up to 400 mg/kg/day. Toxicokinetic investigations revealed : * percutaneous absorption of ZPT varies from approximately 0.03 to 3.4% * the distribution of radioactivity in tissues after oral administration of labelled ZPT showed that the radioactivity rapidly disappeared from the blood, and the primary route of excretion was via the urine. The residual radioactivity was low (4.5% of dose), ZPT was distributed","page":31,"pdf":"out225_en.pdf","row_type":"noael_study","study_id":"out225_en_noael_004"} |
SCCS Opinion 100 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"uration) Oral studies Summary taken from SCCNFP/0671/03 Concerning ZPT: No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater, the animals usually died without developing paralysis. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 μg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two-year study period. Concerning shampoo formulations containing ZPT: Orally administered ZPT in a shampoo formulation produces a reversible paralysis in rats and rabbits within one to two weeks at levels of 10 mg/kg/day. A dose level of 10 mg/kg/day of ZPT in shampoo was used in a monkey gavage study which lasted 16 weeks. No adverse effects were observed. Because of the e","page":32,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_001"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/d | - | oral | chronic | NOAEL study | {"dose":"From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived.","effect":"ppm diet. Ratios of organ weights to body weights did not differ significantly among the surviving groups at termination. Histopathologic examinations did not reveal any lesions that appeared to be attributable to the administration of ZPT. These observations included careful attention to retina, optic nerve, cerebral cortex, and other parts of the central and peripheral nervous systems. There were no significant differences in the rate of frequency of neoplasms between any of the groups. From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived. Further data Two oral chronic studies performed with ZPT are mentioned at ECHA's website (http://echa.europa.eu/), one is apparently the study by Larson (1958) already evaluated for SCCNFP 0671/03. According to the Batch number given, the second study must have been performed with NaPT although not specifically stated on ECHA's website. Data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule af","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_008"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg bw/d | rat | - | chronic | carcinogenicity | {"citation":"Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0","dose":"Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose.","effect":"were no toxicologically relevant treatment-related findings. Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose. The effects were also observed to a lesser degree at 1.5 mg/kg bw/d. The incidence of neoplastic findings was not influenced by substance treatment. Under the conditions of this study, NaPT was not carcinogenic to rats. Based on the non- neoplastic findings observed, a NOAEL of 0.5 mg/kg bw/d can be derived from this study. Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0.5 and 1.3 mg/kg (satellite) 20 per sex for the chronic study at the highest dose (satellite) Controls: 56 males and females for the carcinogenic study (main group) 12 males and females for the chronic study (satellite) Test substance: Natrium Pyrion 40% LSG Batch: 99072150 Purity:","page":41,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_009"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"uration) Oral studies Summary taken from SCCNFP/0671/03 Concerning ZPT: No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater, the animals usually died without developing paralysis. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 μg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two-year study period. Concerning shampoo formulations containing ZPT: Orally administered ZPT in a shampoo formulation produces a reversible paralysis in rats and rabbits within one to two weeks at levels of 10 mg/kg/day. A dose level of 10 mg/kg/day of ZPT in shampoo was used in a monkey gavage study which lasted 16 weeks. No adverse effects were observed. Because of the e","page":32,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_001"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/d | - | oral | chronic | NOAEL study | {"dose":"From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived.","effect":"ppm diet. Ratios of organ weights to body weights did not differ significantly among the surviving groups at termination. Histopathologic examinations did not reveal any lesions that appeared to be attributable to the administration of ZPT. These observations included careful attention to retina, optic nerve, cerebral cortex, and other parts of the central and peripheral nervous systems. There were no significant differences in the rate of frequency of neoplasms between any of the groups. From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived. Further data Two oral chronic studies performed with ZPT are mentioned at ECHA's website (http://echa.europa.eu/), one is apparently the study by Larson (1958) already evaluated for SCCNFP 0671/03. According to the Batch number given, the second study must have been performed with NaPT although not specifically stated on ECHA's website. Data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule af","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_008"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg bw/d | rat | - | chronic | carcinogenicity | {"citation":"Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0","dose":"Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose.","effect":"were no toxicologically relevant treatment-related findings. Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose. The effects were also observed to a lesser degree at 1.5 mg/kg bw/d. The incidence of neoplastic findings was not influenced by substance treatment. Under the conditions of this study, NaPT was not carcinogenic to rats. Based on the non- neoplastic findings observed, a NOAEL of 0.5 mg/kg bw/d can be derived from this study. Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0.5 and 1.3 mg/kg (satellite) 20 per sex for the chronic study at the highest dose (satellite) Controls: 56 males and females for the carcinogenic study (main group) 12 males and females for the chronic study (satellite) Test substance: Natrium Pyrion 40% LSG Batch: 99072150 Purity:","page":41,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_009"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"uration) Oral studies Summary taken from SCCNFP/0671/03 Concerning ZPT: No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater, the animals usually died without developing paralysis. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 μg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two-year study period. Concerning shampoo formulations containing ZPT: Orally administered ZPT in a shampoo formulation produces a reversible paralysis in rats and rabbits within one to two weeks at levels of 10 mg/kg/day. A dose level of 10 mg/kg/day of ZPT in shampoo was used in a monkey gavage study which lasted 16 weeks. No adverse effects were observed. Because of the e","page":32,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_001"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/d | - | oral | chronic | NOAEL study | {"dose":"From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived.","effect":"ppm diet. Ratios of organ weights to body weights did not differ significantly among the surviving groups at termination. Histopathologic examinations did not reveal any lesions that appeared to be attributable to the administration of ZPT. These observations included careful attention to retina, optic nerve, cerebral cortex, and other parts of the central and peripheral nervous systems. There were no significant differences in the rate of frequency of neoplasms between any of the groups. From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived. Further data Two oral chronic studies performed with ZPT are mentioned at ECHA's website (http://echa.europa.eu/), one is apparently the study by Larson (1958) already evaluated for SCCNFP 0671/03. According to the Batch number given, the second study must have been performed with NaPT although not specifically stated on ECHA's website. Data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule af","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_008"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg bw/d | rat | - | chronic | carcinogenicity | {"citation":"Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0","dose":"Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose.","effect":"were no toxicologically relevant treatment-related findings. Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose. The effects were also observed to a lesser degree at 1.5 mg/kg bw/d. The incidence of neoplastic findings was not influenced by substance treatment. Under the conditions of this study, NaPT was not carcinogenic to rats. Based on the non- neoplastic findings observed, a NOAEL of 0.5 mg/kg bw/d can be derived from this study. Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0.5 and 1.3 mg/kg (satellite) 20 per sex for the chronic study at the highest dose (satellite) Controls: 56 males and females for the carcinogenic study (main group) 12 males and females for the chronic study (satellite) Test substance: Natrium Pyrion 40% LSG Batch: 99072150 Purity:","page":41,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_009"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | rat | oral | 14 days | NOAEL study | {"dose":"No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","effect":"uration) Oral studies Summary taken from SCCNFP/0671/03 Concerning ZPT: No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater, the animals usually died without developing paralysis. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 μg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two-year study period. Concerning shampoo formulations containing ZPT: Orally administered ZPT in a shampoo formulation produces a reversible paralysis in rats and rabbits within one to two weeks at levels of 10 mg/kg/day. A dose level of 10 mg/kg/day of ZPT in shampoo was used in a monkey gavage study which lasted 16 weeks. No adverse effects were observed. Because of the e","page":32,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_001"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/d | - | oral | chronic | NOAEL study | {"dose":"From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived.","effect":"ppm diet. Ratios of organ weights to body weights did not differ significantly among the surviving groups at termination. Histopathologic examinations did not reveal any lesions that appeared to be attributable to the administration of ZPT. These observations included careful attention to retina, optic nerve, cerebral cortex, and other parts of the central and peripheral nervous systems. There were no significant differences in the rate of frequency of neoplasms between any of the groups. From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived. Further data Two oral chronic studies performed with ZPT are mentioned at ECHA's website (http://echa.europa.eu/), one is apparently the study by Larson (1958) already evaluated for SCCNFP 0671/03. According to the Batch number given, the second study must have been performed with NaPT although not specifically stated on ECHA's website. Data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule af","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_008"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg bw/d | rat | - | chronic | carcinogenicity | {"citation":"Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0","dose":"Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose.","effect":"were no toxicologically relevant treatment-related findings. Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose. The effects were also observed to a lesser degree at 1.5 mg/kg bw/d. The incidence of neoplastic findings was not influenced by substance treatment. Under the conditions of this study, NaPT was not carcinogenic to rats. Based on the non- neoplastic findings observed, a NOAEL of 0.5 mg/kg bw/d can be derived from this study. Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0.5 and 1.3 mg/kg (satellite) 20 per sex for the chronic study at the highest dose (satellite) Controls: 56 males and females for the carcinogenic study (main group) 12 males and females for the chronic study (satellite) Test substance: Natrium Pyrion 40% LSG Batch: 99072150 Purity:","page":41,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_009"} |
| SCCS Opinion | NOAEL | =0.75 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test","dose":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose.","effect":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose. At 3.0 mg/kg bw/d, a slight increase in the incidence of fetal malformations and a less pronounced increase in mean postimplantation loss compared to controls were observed. However, as fetal effects occur at dosages where maternal toxicity is observed, the test article is not considered as a developmental toxicant. A NOAEL of 0.75 mg/kg/d is derived from the study for maternal and developmental toxicity. Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test substance: Zinc Omadine ®, 48 % aqueous solution Batch: 33-22902781 Purity: 52.2 % Vehicle: deionised water Dose levels: 0.5, 2.0, 4.0, 8.0 and 12.0 mg/kg bw/d Exposure: oral, gavage, once daily on GD 6 - 18 GLP statement: yes Date: 1993 Dose lev","page":56,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_019"} |
| SCCS Opinion | NOAEL | =0.75 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test","dose":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose.","effect":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose. At 3.0 mg/kg bw/d, a slight increase in the incidence of fetal malformations and a less pronounced increase in mean postimplantation loss compared to controls were observed. However, as fetal effects occur at dosages where maternal toxicity is observed, the test article is not considered as a developmental toxicant. A NOAEL of 0.75 mg/kg/d is derived from the study for maternal and developmental toxicity. Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test substance: Zinc Omadine ®, 48 % aqueous solution Batch: 33-22902781 Purity: 52.2 % Vehicle: deionised water Dose levels: 0.5, 2.0, 4.0, 8.0 and 12.0 mg/kg bw/d Exposure: oral, gavage, once daily on GD 6 - 18 GLP statement: yes Date: 1993 Dose lev","page":56,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_019"} |
| SCCS Opinion | NOAEL | =0.75 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test","dose":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose.","effect":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose. At 3.0 mg/kg bw/d, a slight increase in the incidence of fetal malformations and a less pronounced increase in mean postimplantation loss compared to controls were observed. However, as fetal effects occur at dosages where maternal toxicity is observed, the test article is not considered as a developmental toxicant. A NOAEL of 0.75 mg/kg/d is derived from the study for maternal and developmental toxicity. Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test substance: Zinc Omadine ®, 48 % aqueous solution Batch: 33-22902781 Purity: 52.2 % Vehicle: deionised water Dose levels: 0.5, 2.0, 4.0, 8.0 and 12.0 mg/kg bw/d Exposure: oral, gavage, once daily on GD 6 - 18 GLP statement: yes Date: 1993 Dose lev","page":56,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_019"} |
| SCCS Opinion | NOAEL | =0.75 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | {"citation":"Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test","dose":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose.","effect":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose. At 3.0 mg/kg bw/d, a slight increase in the incidence of fetal malformations and a less pronounced increase in mean postimplantation loss compared to controls were observed. However, as fetal effects occur at dosages where maternal toxicity is observed, the test article is not considered as a developmental toxicant. A NOAEL of 0.75 mg/kg/d is derived from the study for maternal and developmental toxicity. Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test substance: Zinc Omadine ®, 48 % aqueous solution Batch: 33-22902781 Purity: 52.2 % Vehicle: deionised water Dose levels: 0.5, 2.0, 4.0, 8.0 and 12.0 mg/kg bw/d Exposure: oral, gavage, once daily on GD 6 - 18 GLP statement: yes Date: 1993 Dose lev","page":56,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_019"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg/d | rat | - | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"the top dose. There were no effects on the success or duration of gestation, number of live births, viability, lactation and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_016"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa","dose":"At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females.","effect":"parental animals and offspring from two generations: in parental animals, a reduction in body weight gain, atrophy of hind limb muscles, hindlimb paralysis, impaired movement and adverse effects on F0 generation fertility and mating performance were observed. In the offspring, there was evidence of a slight retardation of development during lactation. At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females. From the results of this study, a parental NOAEL of 1.5 mg/kg bw/d can be derived. For the offspring, NOAELs of 1.5 and 0.5 mg/kg bw/d can be derived for male and female animals, respectively. Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa.europa.eu/). This study is not available for evaluation: - a 2-generation study performed according to EPA OPPTS 870.3800 in male and female Sprague-Dawley rats receiving 0, 0.7, 1.4, and 2.8 mg/kg/d aqueous substance by gavage. For parental animals, NOAELs of 1.4 and 0.7 mg/kg/d were","page":52,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_018"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg/d | rat | - | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"the top dose. There were no effects on the success or duration of gestation, number of live births, viability, lactation and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_016"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa","dose":"At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females.","effect":"parental animals and offspring from two generations: in parental animals, a reduction in body weight gain, atrophy of hind limb muscles, hindlimb paralysis, impaired movement and adverse effects on F0 generation fertility and mating performance were observed. In the offspring, there was evidence of a slight retardation of development during lactation. At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females. From the results of this study, a parental NOAEL of 1.5 mg/kg bw/d can be derived. For the offspring, NOAELs of 1.5 and 0.5 mg/kg bw/d can be derived for male and female animals, respectively. Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa.europa.eu/). This study is not available for evaluation: - a 2-generation study performed according to EPA OPPTS 870.3800 in male and female Sprague-Dawley rats receiving 0, 0.7, 1.4, and 2.8 mg/kg/d aqueous substance by gavage. For parental animals, NOAELs of 1.4 and 0.7 mg/kg/d were","page":52,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_018"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg/d | rat | - | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"the top dose. There were no effects on the success or duration of gestation, number of live births, viability, lactation and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_016"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa","dose":"At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females.","effect":"parental animals and offspring from two generations: in parental animals, a reduction in body weight gain, atrophy of hind limb muscles, hindlimb paralysis, impaired movement and adverse effects on F0 generation fertility and mating performance were observed. In the offspring, there was evidence of a slight retardation of development during lactation. At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females. From the results of this study, a parental NOAEL of 1.5 mg/kg bw/d can be derived. For the offspring, NOAELs of 1.5 and 0.5 mg/kg bw/d can be derived for male and female animals, respectively. Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa.europa.eu/). This study is not available for evaluation: - a 2-generation study performed according to EPA OPPTS 870.3800 in male and female Sprague-Dawley rats receiving 0, 0.7, 1.4, and 2.8 mg/kg/d aqueous substance by gavage. For parental animals, NOAELs of 1.4 and 0.7 mg/kg/d were","page":52,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_018"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg/d | rat | - | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"the top dose. There were no effects on the success or duration of gestation, number of live births, viability, lactation and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_016"} |
| SCCS Opinion | NOAEL | =1.5 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa","dose":"At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females.","effect":"parental animals and offspring from two generations: in parental animals, a reduction in body weight gain, atrophy of hind limb muscles, hindlimb paralysis, impaired movement and adverse effects on F0 generation fertility and mating performance were observed. In the offspring, there was evidence of a slight retardation of development during lactation. At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females. From the results of this study, a parental NOAEL of 1.5 mg/kg bw/d can be derived. For the offspring, NOAELs of 1.5 and 0.5 mg/kg bw/d can be derived for male and female animals, respectively. Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa.europa.eu/). This study is not available for evaluation: - a 2-generation study performed according to EPA OPPTS 870.3800 in male and female Sprague-Dawley rats receiving 0, 0.7, 1.4, and 2.8 mg/kg/d aqueous substance by gavage. For parental animals, NOAELs of 1.4 and 0.7 mg/kg/d were","page":52,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_018"} |
| SCCS Opinion | NOAEL | =2 | mg/kg/d | - | oral | 28 days | NOAEL study | {"citation":"Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B","dose":"Electrocardiograms of the high dose group were essentially normal.","effect":"mistry and urinalysis. Electrocardiograms of the high dose group were essentially normal. No abnormal findings were noted following gross and histopathological examination. Relative kidney weights in the intermediate and high dose were reduced compared to control, which was attributed to high kidney weights in the control animals. Relative uterus weight was reduced in a dose-related manner at 2.0 and 8.0 mg/kg/d and was associated with apparent immaturity of the uteri. From this study, a LOAEL of 2.0 mg/kg/d and a NOAEL of 0.5 mg/kg/d can be derived. Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B.7 Species/strain/sex: Monkey / Cynomolgus / both sexes Group size: 4 per sex /dose at 5.5 and 11.0 mg/kg/d, 6 per sex /dose at 22.0 mg/kg/d Controls: 6 male, 6 female Test substance: Zinc Omadine ® powder Batch: 9204084481 Purity: 96.3 % Vehicle: Dose levels: 0, 5.5, 11.0, 22.0 mg/kg/d Exposure: oral, gelatine capsules, once daily for 28 days GLP statement: yes Date: 1992 Stability statement: it was confirmed by the spon","page":33,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_002"} |
| SCCS Opinion | NOAEL | =2 | % | human | - | - | irritation | {"dose":"With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism:","effect":"ing grounds: With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism: (1) it results from the concomitant use of rinse-off shampoo in combination with leave-on tonic, (2) it is a value, to which 1 standard deviation has been added in order to cope for more extended periods of application and (3) it results from the upper boundary of internal exposure determined in the human clinical study. With respect to the TD part: (1) the previously derived NOAEL of 500 µg/kg bw/d has been converted to a LOAEL based on the occurrence of some effects which could not be retraced further due to unavailability of data. (2) ZPT has been used as an anti-dandruff active in shampoo formulations at levels of 1.0 and 2.0% since the 1940’s. During this time there has been little evidence of any serious adverse effects from this usage, and those few effects that have been recorded are limited to eye and skin irritation as can be expected for surfactant-based formulations. Therefore a","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_030"} |
| SCCS Opinion | NOAEL | =2 | mg/kg/d | - | oral | 28 days | NOAEL study | {"citation":"Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B","dose":"Electrocardiograms of the high dose group were essentially normal.","effect":"mistry and urinalysis. Electrocardiograms of the high dose group were essentially normal. No abnormal findings were noted following gross and histopathological examination. Relative kidney weights in the intermediate and high dose were reduced compared to control, which was attributed to high kidney weights in the control animals. Relative uterus weight was reduced in a dose-related manner at 2.0 and 8.0 mg/kg/d and was associated with apparent immaturity of the uteri. From this study, a LOAEL of 2.0 mg/kg/d and a NOAEL of 0.5 mg/kg/d can be derived. Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B.7 Species/strain/sex: Monkey / Cynomolgus / both sexes Group size: 4 per sex /dose at 5.5 and 11.0 mg/kg/d, 6 per sex /dose at 22.0 mg/kg/d Controls: 6 male, 6 female Test substance: Zinc Omadine ® powder Batch: 9204084481 Purity: 96.3 % Vehicle: Dose levels: 0, 5.5, 11.0, 22.0 mg/kg/d Exposure: oral, gelatine capsules, once daily for 28 days GLP statement: yes Date: 1992 Stability statement: it was confirmed by the spon","page":33,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_002"} |
| SCCS Opinion | NOAEL | =2 | % | human | - | - | irritation | {"dose":"With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism:","effect":"ing grounds: With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism: (1) it results from the concomitant use of rinse-off shampoo in combination with leave-on tonic, (2) it is a value, to which 1 standard deviation has been added in order to cope for more extended periods of application and (3) it results from the upper boundary of internal exposure determined in the human clinical study. With respect to the TD part: (1) the previously derived NOAEL of 500 µg/kg bw/d has been converted to a LOAEL based on the occurrence of some effects which could not be retraced further due to unavailability of data. (2) ZPT has been used as an anti-dandruff active in shampoo formulations at levels of 1.0 and 2.0% since the 1940’s. During this time there has been little evidence of any serious adverse effects from this usage, and those few effects that have been recorded are limited to eye and skin irritation as can be expected for surfactant-based formulations. Therefore a","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_030"} |
| SCCS Opinion | NOAEL | =2 | mg/kg/d | - | oral | 28 days | NOAEL study | {"citation":"Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B","dose":"Electrocardiograms of the high dose group were essentially normal.","effect":"mistry and urinalysis. Electrocardiograms of the high dose group were essentially normal. No abnormal findings were noted following gross and histopathological examination. Relative kidney weights in the intermediate and high dose were reduced compared to control, which was attributed to high kidney weights in the control animals. Relative uterus weight was reduced in a dose-related manner at 2.0 and 8.0 mg/kg/d and was associated with apparent immaturity of the uteri. From this study, a LOAEL of 2.0 mg/kg/d and a NOAEL of 0.5 mg/kg/d can be derived. Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B.7 Species/strain/sex: Monkey / Cynomolgus / both sexes Group size: 4 per sex /dose at 5.5 and 11.0 mg/kg/d, 6 per sex /dose at 22.0 mg/kg/d Controls: 6 male, 6 female Test substance: Zinc Omadine ® powder Batch: 9204084481 Purity: 96.3 % Vehicle: Dose levels: 0, 5.5, 11.0, 22.0 mg/kg/d Exposure: oral, gelatine capsules, once daily for 28 days GLP statement: yes Date: 1992 Stability statement: it was confirmed by the spon","page":33,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_002"} |
| SCCS Opinion | NOAEL | =2 | % | human | - | - | irritation | {"dose":"With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism:","effect":"ing grounds: With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism: (1) it results from the concomitant use of rinse-off shampoo in combination with leave-on tonic, (2) it is a value, to which 1 standard deviation has been added in order to cope for more extended periods of application and (3) it results from the upper boundary of internal exposure determined in the human clinical study. With respect to the TD part: (1) the previously derived NOAEL of 500 µg/kg bw/d has been converted to a LOAEL based on the occurrence of some effects which could not be retraced further due to unavailability of data. (2) ZPT has been used as an anti-dandruff active in shampoo formulations at levels of 1.0 and 2.0% since the 1940’s. During this time there has been little evidence of any serious adverse effects from this usage, and those few effects that have been recorded are limited to eye and skin irritation as can be expected for surfactant-based formulations. Therefore a","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_030"} |
| SCCS Opinion | NOAEL | =2 | mg/kg/d | - | oral | 28 days | NOAEL study | {"citation":"Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B","dose":"Electrocardiograms of the high dose group were essentially normal.","effect":"mistry and urinalysis. Electrocardiograms of the high dose group were essentially normal. No abnormal findings were noted following gross and histopathological examination. Relative kidney weights in the intermediate and high dose were reduced compared to control, which was attributed to high kidney weights in the control animals. Relative uterus weight was reduced in a dose-related manner at 2.0 and 8.0 mg/kg/d and was associated with apparent immaturity of the uteri. From this study, a LOAEL of 2.0 mg/kg/d and a NOAEL of 0.5 mg/kg/d can be derived. Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B.7 Species/strain/sex: Monkey / Cynomolgus / both sexes Group size: 4 per sex /dose at 5.5 and 11.0 mg/kg/d, 6 per sex /dose at 22.0 mg/kg/d Controls: 6 male, 6 female Test substance: Zinc Omadine ® powder Batch: 9204084481 Purity: 96.3 % Vehicle: Dose levels: 0, 5.5, 11.0, 22.0 mg/kg/d Exposure: oral, gelatine capsules, once daily for 28 days GLP statement: yes Date: 1992 Stability statement: it was confirmed by the spon","page":33,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_002"} |
| SCCS Opinion | NOAEL | =2 | % | human | - | - | irritation | {"dose":"With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism:","effect":"ing grounds: With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism: (1) it results from the concomitant use of rinse-off shampoo in combination with leave-on tonic, (2) it is a value, to which 1 standard deviation has been added in order to cope for more extended periods of application and (3) it results from the upper boundary of internal exposure determined in the human clinical study. With respect to the TD part: (1) the previously derived NOAEL of 500 µg/kg bw/d has been converted to a LOAEL based on the occurrence of some effects which could not be retraced further due to unavailability of data. (2) ZPT has been used as an anti-dandruff active in shampoo formulations at levels of 1.0 and 2.0% since the 1940’s. During this time there has been little evidence of any serious adverse effects from this usage, and those few effects that have been recorded are limited to eye and skin irritation as can be expected for surfactant-based formulations. Therefore a","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_030"} |
| SCCS Opinion | NOAEL | =3.5 | mg/kg/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*) mg/kg bw/d Exposure: oral, gavage, once daily GLP statement: yes Date: 1987 – 1988 *) 4.5 mg/kg bw/d in weeks 1, 2","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_017"} |
| SCCS Opinion | NOAEL | =3.5 | mg/kg/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*) mg/kg bw/d Exposure: oral, gavage, once daily GLP statement: yes Date: 1987 – 1988 *) 4.5 mg/kg bw/d in weeks 1, 2","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_017"} |
| SCCS Opinion | NOAEL | =3.5 | mg/kg/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*) mg/kg bw/d Exposure: oral, gavage, once daily GLP statement: yes Date: 1987 – 1988 *) 4.5 mg/kg bw/d in weeks 1, 2","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_017"} |
| SCCS Opinion | NOAEL | =3.5 | mg/kg/d | rat | oral | - | reproductive toxicity | {"citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","effect":"and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*) mg/kg bw/d Exposure: oral, gavage, once daily GLP statement: yes Date: 1987 – 1988 *) 4.5 mg/kg bw/d in weeks 1, 2","page":51,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_017"} |
| SCCS Opinion | NOAEL | =5 | mg/kg/d | - | oral | chronic | repeated dose toxicity | {"citation":"Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT","dose":"tatistically significant at the highest dose.","effect":"tatistically significant at the highest dose. No treatment-related effects on sceletal muscle or sciatic nerve were observed in that study. Dermal administration of NaPT had no effect on tumour incidence. Thus, based on the results of this study, NaPT induced slight histopathologic changes at the treatment site but did not influence tumour formation. SCCS comment No information of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SC","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_011"} |
| SCCS Opinion | NOAEL | =5 | mg/kg bw/d | rat | dermal | 28-day | NOAEL study | {"dose":"l repeat-dose studies have been performed with ZPT.","effect":"l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two-year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Inhalation: Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects","page":44,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_014"} |
| SCCS Opinion | NOAEL | =5 | mg/kg/d | - | oral | chronic | repeated dose toxicity | {"citation":"Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT","dose":"tatistically significant at the highest dose.","effect":"tatistically significant at the highest dose. No treatment-related effects on sceletal muscle or sciatic nerve were observed in that study. Dermal administration of NaPT had no effect on tumour incidence. Thus, based on the results of this study, NaPT induced slight histopathologic changes at the treatment site but did not influence tumour formation. SCCS comment No information of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SC","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_011"} |
| SCCS Opinion | NOAEL | =5 | mg/kg bw/d | rat | dermal | 28-day | NOAEL study | {"dose":"l repeat-dose studies have been performed with ZPT.","effect":"l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two-year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Inhalation: Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects","page":44,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_014"} |
| SCCS Opinion | NOAEL | =5 | mg/kg/d | - | oral | chronic | repeated dose toxicity | {"citation":"Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT","dose":"tatistically significant at the highest dose.","effect":"tatistically significant at the highest dose. No treatment-related effects on sceletal muscle or sciatic nerve were observed in that study. Dermal administration of NaPT had no effect on tumour incidence. Thus, based on the results of this study, NaPT induced slight histopathologic changes at the treatment site but did not influence tumour formation. SCCS comment No information of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SC","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_011"} |
| SCCS Opinion | NOAEL | =5 | mg/kg bw/d | rat | dermal | 28-day | NOAEL study | {"dose":"l repeat-dose studies have been performed with ZPT.","effect":"l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two-year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Inhalation: Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects","page":44,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_014"} |
| SCCS Opinion | NOAEL | =5 | mg/kg/d | - | oral | chronic | repeated dose toxicity | {"citation":"Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT","dose":"tatistically significant at the highest dose.","effect":"tatistically significant at the highest dose. No treatment-related effects on sceletal muscle or sciatic nerve were observed in that study. Dermal administration of NaPT had no effect on tumour incidence. Thus, based on the results of this study, NaPT induced slight histopathologic changes at the treatment site but did not influence tumour formation. SCCS comment No information of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SC","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_011"} |
| SCCS Opinion | NOAEL | =5 | mg/kg bw/d | rat | dermal | 28-day | NOAEL study | {"dose":"l repeat-dose studies have been performed with ZPT.","effect":"l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two-year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Inhalation: Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects","page":44,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_014"} |
| SCCS Opinion | NOAEL | =7.5 | mg/kg/d | rat | dermal | 8-week | reproductive toxicity | {"citation":"Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies","dose":"with untreated females of untreated males were mated with treated females.","effect":"with untreated females of untreated males were mated with treated females. ZPT dosed rats from the 8-week treatment scheme did not differ significantly from controls in either growth or reproductive characteristics except a statistically significantly lower lactation index in females of the highest dose group. No toxic signs such as paralysis and no test-related histopathology was seen in the males. Further, neither reproduction nor neonatal viability was affected after topical administration of ZPT on GD 6—15. A NOAEL of 7.5 mg/kg/d can be derived from this dermal study. Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies. 3.4.8.2. Two generation reproduction toxicity Two two generation reproduction toxicity studies performed with sodium pyrithione, from which read-across to ZPT is considered appropriate (see section 3.3.5.3) have been provided. Guideline: not stated Species/strain/sex: Rat / Sprague-Dawley (OFA-SD","page":50,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_015"} |
| SCCS Opinion | NOAEL | =7.5 | mg/kg/d | rat | dermal | 8-week | reproductive toxicity | {"citation":"Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies","dose":"with untreated females of untreated males were mated with treated females.","effect":"with untreated females of untreated males were mated with treated females. ZPT dosed rats from the 8-week treatment scheme did not differ significantly from controls in either growth or reproductive characteristics except a statistically significantly lower lactation index in females of the highest dose group. No toxic signs such as paralysis and no test-related histopathology was seen in the males. Further, neither reproduction nor neonatal viability was affected after topical administration of ZPT on GD 6—15. A NOAEL of 7.5 mg/kg/d can be derived from this dermal study. Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies. 3.4.8.2. Two generation reproduction toxicity Two two generation reproduction toxicity studies performed with sodium pyrithione, from which read-across to ZPT is considered appropriate (see section 3.3.5.3) have been provided. Guideline: not stated Species/strain/sex: Rat / Sprague-Dawley (OFA-SD","page":50,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_015"} |
| SCCS Opinion | NOAEL | =7.5 | mg/kg/d | rat | dermal | 8-week | reproductive toxicity | {"citation":"Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies","dose":"with untreated females of untreated males were mated with treated females.","effect":"with untreated females of untreated males were mated with treated females. ZPT dosed rats from the 8-week treatment scheme did not differ significantly from controls in either growth or reproductive characteristics except a statistically significantly lower lactation index in females of the highest dose group. No toxic signs such as paralysis and no test-related histopathology was seen in the males. Further, neither reproduction nor neonatal viability was affected after topical administration of ZPT on GD 6—15. A NOAEL of 7.5 mg/kg/d can be derived from this dermal study. Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies. 3.4.8.2. Two generation reproduction toxicity Two two generation reproduction toxicity studies performed with sodium pyrithione, from which read-across to ZPT is considered appropriate (see section 3.3.5.3) have been provided. Guideline: not stated Species/strain/sex: Rat / Sprague-Dawley (OFA-SD","page":50,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_015"} |
| SCCS Opinion | NOAEL | =7.5 | mg/kg/d | rat | dermal | 8-week | reproductive toxicity | {"citation":"Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies","dose":"with untreated females of untreated males were mated with treated females.","effect":"with untreated females of untreated males were mated with treated females. ZPT dosed rats from the 8-week treatment scheme did not differ significantly from controls in either growth or reproductive characteristics except a statistically significantly lower lactation index in females of the highest dose group. No toxic signs such as paralysis and no test-related histopathology was seen in the males. Further, neither reproduction nor neonatal viability was affected after topical administration of ZPT on GD 6—15. A NOAEL of 7.5 mg/kg/d can be derived from this dermal study. Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies. 3.4.8.2. Two generation reproduction toxicity Two two generation reproduction toxicity studies performed with sodium pyrithione, from which read-across to ZPT is considered appropriate (see section 3.3.5.3) have been provided. Guideline: not stated Species/strain/sex: Rat / Sprague-Dawley (OFA-SD","page":50,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_015"} |
| SCCS Opinion | NOAEL | =11 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0","dose":"3 high dose males also had increased relative liver weights.","effect":"examination (apart from the female animal that died on day 10) no test-article related abnormalities were found. The relative organ weights of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism o","page":34,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_003"} |
| SCCS Opinion | NOAEL | =11 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0","dose":"3 high dose males also had increased relative liver weights.","effect":"examination (apart from the female animal that died on day 10) no test-article related abnormalities were found. The relative organ weights of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism o","page":34,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_003"} |
| SCCS Opinion | NOAEL | =11 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0","dose":"3 high dose males also had increased relative liver weights.","effect":"examination (apart from the female animal that died on day 10) no test-article related abnormalities were found. The relative organ weights of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism o","page":34,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_003"} |
| SCCS Opinion | NOAEL | =11 | mg/kg bw/d | rat | oral | 90-day | NOAEL study | {"citation":"Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0","dose":"3 high dose males also had increased relative liver weights.","effect":"examination (apart from the female animal that died on day 10) no test-article related abnormalities were found. The relative organ weights of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism o","page":34,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_003"} |
| SCCS Opinion | NOAEL | =14 | - | rat | oral | - | NOAEL study | {"dose":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_026"} |
| SCCS Opinion | NOAEL | =14 | - | rat | oral | - | NOAEL study | {"dose":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_026"} |
| SCCS Opinion | NOAEL | =14 | - | rat | oral | - | NOAEL study | {"dose":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_026"} |
| SCCS Opinion | NOAEL | =14 | - | rat | oral | - | NOAEL study | {"dose":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_026"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"ebrae, forelimb phalanges, metacarpals, hindlimb phalanges and metatarsals. There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up t","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_021"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"ebrae, forelimb phalanges, metacarpals, hindlimb phalanges and metatarsals. There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up t","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_021"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"ebrae, forelimb phalanges, metacarpals, hindlimb phalanges and metatarsals. There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up t","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_021"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"ebrae, forelimb phalanges, metacarpals, hindlimb phalanges and metatarsals. There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up t","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_021"} |
| SCCS Opinion | NOAEL | =25 | mg/kg bw/d | - | dermal | - | NOAEL study | {"citation":"Ref.: D1 In vitro studies Knox et al","dose":"p and on days 22-28 in the 50 mg/kg/d group.","effect":"p and on days 22-28 in the 50 mg/kg/d group. On day 14 grip strength was reduced in the 75 and 100 mg/kg/d group and on day 28 grip strength was reduced in the three highest dose groups. No consistent decreases or dose dependent changes were apparent in plasma, RBC or brain cholinesterase at any dose tested. Decreases in the electrophysiological values measured as the maximum amplitude were observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). A dermal NOAEL of 25 mg/kg bw/d can be derived from the study. Ref.: D1 In vitro studies Knox et al. (2004) performed in vitro studies using bag cell neurons of a marine snail (Aplysia) in order to investigate the mechanisms underlying the reversible neurotoxicity of pyrithiones by using sodium pyrithione. It could be demonstrated that NaPT caused intracellular Ca2+ elevation. Several hypotheses which could build the molecular basis for this calcium entry have been tested. It could be demonstrated that the elevation of intrace","page":76,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_027"} |
| SCCS Opinion | NOAEL | =25 | mg/kg bw/d | - | dermal | - | NOAEL study | {"citation":"Ref.: D1 In vitro studies Knox et al","dose":"p and on days 22-28 in the 50 mg/kg/d group.","effect":"p and on days 22-28 in the 50 mg/kg/d group. On day 14 grip strength was reduced in the 75 and 100 mg/kg/d group and on day 28 grip strength was reduced in the three highest dose groups. No consistent decreases or dose dependent changes were apparent in plasma, RBC or brain cholinesterase at any dose tested. Decreases in the electrophysiological values measured as the maximum amplitude were observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). A dermal NOAEL of 25 mg/kg bw/d can be derived from the study. Ref.: D1 In vitro studies Knox et al. (2004) performed in vitro studies using bag cell neurons of a marine snail (Aplysia) in order to investigate the mechanisms underlying the reversible neurotoxicity of pyrithiones by using sodium pyrithione. It could be demonstrated that NaPT caused intracellular Ca2+ elevation. Several hypotheses which could build the molecular basis for this calcium entry have been tested. It could be demonstrated that the elevation of intrace","page":76,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_027"} |
| SCCS Opinion | NOAEL | =25 | mg/kg bw/d | - | dermal | - | NOAEL study | {"citation":"Ref.: D1 In vitro studies Knox et al","dose":"p and on days 22-28 in the 50 mg/kg/d group.","effect":"p and on days 22-28 in the 50 mg/kg/d group. On day 14 grip strength was reduced in the 75 and 100 mg/kg/d group and on day 28 grip strength was reduced in the three highest dose groups. No consistent decreases or dose dependent changes were apparent in plasma, RBC or brain cholinesterase at any dose tested. Decreases in the electrophysiological values measured as the maximum amplitude were observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). A dermal NOAEL of 25 mg/kg bw/d can be derived from the study. Ref.: D1 In vitro studies Knox et al. (2004) performed in vitro studies using bag cell neurons of a marine snail (Aplysia) in order to investigate the mechanisms underlying the reversible neurotoxicity of pyrithiones by using sodium pyrithione. It could be demonstrated that NaPT caused intracellular Ca2+ elevation. Several hypotheses which could build the molecular basis for this calcium entry have been tested. It could be demonstrated that the elevation of intrace","page":76,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_027"} |
| SCCS Opinion | NOAEL | =25 | mg/kg bw/d | - | dermal | - | NOAEL study | {"citation":"Ref.: D1 In vitro studies Knox et al","dose":"p and on days 22-28 in the 50 mg/kg/d group.","effect":"p and on days 22-28 in the 50 mg/kg/d group. On day 14 grip strength was reduced in the 75 and 100 mg/kg/d group and on day 28 grip strength was reduced in the three highest dose groups. No consistent decreases or dose dependent changes were apparent in plasma, RBC or brain cholinesterase at any dose tested. Decreases in the electrophysiological values measured as the maximum amplitude were observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). A dermal NOAEL of 25 mg/kg bw/d can be derived from the study. Ref.: D1 In vitro studies Knox et al. (2004) performed in vitro studies using bag cell neurons of a marine snail (Aplysia) in order to investigate the mechanisms underlying the reversible neurotoxicity of pyrithiones by using sodium pyrithione. It could be demonstrated that NaPT caused intracellular Ca2+ elevation. Several hypotheses which could build the molecular basis for this calcium entry have been tested. It could be demonstrated that the elevation of intrace","page":76,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_027"} |
| SCCS Opinion | NOAEL | =30 | mg/kg bw /d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up to 15 and 100 mg ZPT/kg/d respectively (highest doses tested) and ingestion of","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_022"} |
| SCCS Opinion | NOAEL | =30 | mg/kg bw /d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up to 15 and 100 mg ZPT/kg/d respectively (highest doses tested) and ingestion of","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_022"} |
| SCCS Opinion | NOAEL | =30 | mg/kg bw /d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up to 15 and 100 mg ZPT/kg/d respectively (highest doses tested) and ingestion of","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_022"} |
| SCCS Opinion | NOAEL | =30 | mg/kg bw /d | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","effect":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up to 15 and 100 mg ZPT/kg/d respectively (highest doses tested) and ingestion of","page":57,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_022"} |
| SCCS Opinion | NOAEL | =50 | ppm | rat | - | Chronic | NOAEL study | {"citation":"Ref.: E14 ECHA's website (http://echa","dose":"A summary on repeat dose toxicity is given in section 3.4.5.2.","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 40 consumption, organ weights, and microscopic examination of selected tissues (brain, liver, kidneys, stomach, and skeletal muscle), authors considered the NOAEC for systemic toxicity as 1.5 mg/m3. Ref.: E14 ECHA's website (http://echa.europa.eu/) mentions a 90-d whole-body study performed in Sprague-Dawley. From this study, a NOAEL of 0.5 g/m³ air was derived. The study is not available for evaluation. A summary on repeat dose toxicity is given in section 3.4.5.2. 3.4.5.2. Chronic (> 12 months) toxicity Taken from SCCNFP/0671/03 A two year feeding study was conducted by Larson (1958). Young Wistar rats in groups of ten males and ten females were fed diets containing ZPT at levels of 0, 2, 5, 10, 25 and 50 ppm. These levels correspond to approximately 0, 0.1, 0.25, 0.5, 1.25 and 2.5 mg/kg/day for adult animals. At the start of the study","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_007"} |
| SCCS Opinion | NOAEL | =50 | ppm | rat | - | Chronic | NOAEL study | {"citation":"Ref.: E14 ECHA's website (http://echa","dose":"A summary on repeat dose toxicity is given in section 3.4.5.2.","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 40 consumption, organ weights, and microscopic examination of selected tissues (brain, liver, kidneys, stomach, and skeletal muscle), authors considered the NOAEC for systemic toxicity as 1.5 mg/m3. Ref.: E14 ECHA's website (http://echa.europa.eu/) mentions a 90-d whole-body study performed in Sprague-Dawley. From this study, a NOAEL of 0.5 g/m³ air was derived. The study is not available for evaluation. A summary on repeat dose toxicity is given in section 3.4.5.2. 3.4.5.2. Chronic (> 12 months) toxicity Taken from SCCNFP/0671/03 A two year feeding study was conducted by Larson (1958). Young Wistar rats in groups of ten males and ten females were fed diets containing ZPT at levels of 0, 2, 5, 10, 25 and 50 ppm. These levels correspond to approximately 0, 0.1, 0.25, 0.5, 1.25 and 2.5 mg/kg/day for adult animals. At the start of the study","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_007"} |
| SCCS Opinion | NOAEL | =50 | ppm | rat | - | Chronic | NOAEL study | {"citation":"Ref.: E14 ECHA's website (http://echa","dose":"A summary on repeat dose toxicity is given in section 3.4.5.2.","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 40 consumption, organ weights, and microscopic examination of selected tissues (brain, liver, kidneys, stomach, and skeletal muscle), authors considered the NOAEC for systemic toxicity as 1.5 mg/m3. Ref.: E14 ECHA's website (http://echa.europa.eu/) mentions a 90-d whole-body study performed in Sprague-Dawley. From this study, a NOAEL of 0.5 g/m³ air was derived. The study is not available for evaluation. A summary on repeat dose toxicity is given in section 3.4.5.2. 3.4.5.2. Chronic (> 12 months) toxicity Taken from SCCNFP/0671/03 A two year feeding study was conducted by Larson (1958). Young Wistar rats in groups of ten males and ten females were fed diets containing ZPT at levels of 0, 2, 5, 10, 25 and 50 ppm. These levels correspond to approximately 0, 0.1, 0.25, 0.5, 1.25 and 2.5 mg/kg/day for adult animals. At the start of the study","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_007"} |
| SCCS Opinion | NOAEL | =50 | ppm | rat | - | Chronic | NOAEL study | {"citation":"Ref.: E14 ECHA's website (http://echa","dose":"A summary on repeat dose toxicity is given in section 3.4.5.2.","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 40 consumption, organ weights, and microscopic examination of selected tissues (brain, liver, kidneys, stomach, and skeletal muscle), authors considered the NOAEC for systemic toxicity as 1.5 mg/m3. Ref.: E14 ECHA's website (http://echa.europa.eu/) mentions a 90-d whole-body study performed in Sprague-Dawley. From this study, a NOAEL of 0.5 g/m³ air was derived. The study is not available for evaluation. A summary on repeat dose toxicity is given in section 3.4.5.2. 3.4.5.2. Chronic (> 12 months) toxicity Taken from SCCNFP/0671/03 A two year feeding study was conducted by Larson (1958). Young Wistar rats in groups of ten males and ten females were fed diets containing ZPT at levels of 0, 2, 5, 10, 25 and 50 ppm. These levels correspond to approximately 0, 0.1, 0.25, 0.5, 1.25 and 2.5 mg/kg/day for adult animals. At the start of the study","page":40,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_007"} |
| SCCS Opinion | NOAEL | =88 | % | rat | oral | chronic | carcinogenicity | {"dose":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d...","effect":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment factors (AF) of 4 (interspecies differences in toxicokinetics) x 2.5 (interspecies differences in toxicodynamics or) x 3.16 (human variability in toxicokinetics) x 3.16 (human variability in toxicodynamics). Within REACH the interspecie","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_029"} |
| SCCS Opinion | NOAEL | =88 | % | rat | oral | chronic | carcinogenicity | {"dose":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d...","effect":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment factors (AF) of 4 (interspecies differences in toxicokinetics) x 2.5 (interspecies differences in toxicodynamics or) x 3.16 (human variability in toxicokinetics) x 3.16 (human variability in toxicodynamics). Within REACH the interspecie","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_029"} |
| SCCS Opinion | NOAEL | =88 | % | rat | oral | chronic | carcinogenicity | {"dose":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d...","effect":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment factors (AF) of 4 (interspecies differences in toxicokinetics) x 2.5 (interspecies differences in toxicodynamics or) x 3.16 (human variability in toxicokinetics) x 3.16 (human variability in toxicodynamics). Within REACH the interspecie","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_029"} |
| SCCS Opinion | NOAEL | =88 | % | rat | oral | chronic | carcinogenicity | {"dose":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d...","effect":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment factors (AF) of 4 (interspecies differences in toxicokinetics) x 2.5 (interspecies differences in toxicodynamics or) x 3.16 (human variability in toxicokinetics) x 3.16 (human variability in toxicodynamics). Within REACH the interspecie","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_029"} |
| SCCS Opinion | NOAEL | =100 | mg/kg bw/d | mouse | oral | 10 day | NOAEL study | {"citation":"Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice","dose":"In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females.","effect":"observed. In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females. Further, statistically significantly increased cholesterol levels were determind in high dose females. No toxicologically significant macroscopical or histopathological findings were observed. Based on a decreased body weight in top dose females and on haematological changes at the top dose, a NOAEL of 100 mg/kg bw/d is derived from this study. SCCS comments An average of 91 % of the initial concentrations of the active ingredient was found after a 10 day storage at room temperature. Some animals chewed or removed the tape. Data was collected in order to explain probably occurring unexplained toxicity. Oral exposure cannot fully be excluded from this study. Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice. This study is not available for evaluation. MAK (2012) describes two dermal","page":36,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_005"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/d | rat | oral | subchronic | repeated dose toxicity | {"citation":"Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats","dose":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level).","effect":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats. NOAELs of 50 and 25 mg/kg bw/d were obtained for male and female animals, respectively. A further subchronic toxicity study is mentioned on ECHA's website (http://echa.europa.eu/). The study is not available for evaluation. A NOAEL of 100 mg/kg/d was derived from that study. SCCS comment to studies with dermal administration of ZPT The fact that hindlimb weakness after dermal administration was not observed in some of the studies might be due to the dosing regimen and the vehicle used. In oral studies it could be demonstrated that in contrast to continuous administration, effects were less pronounced or not observable, when there were discontinuities in the dosing (e.g. 5 days per week). Further, when using water or DMSO as vehicle, toxic e","page":37,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_006"} |
| SCCS Opinion | NOAEL | =100 | % | rat | oral | chronic | carcinogenicity | {"dose":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (appl...","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment facto","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_028"} |
| SCCS Opinion | NOAEL | =100 | mg/kg bw/d | mouse | oral | 10 day | NOAEL study | {"citation":"Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice","dose":"In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females.","effect":"observed. In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females. Further, statistically significantly increased cholesterol levels were determind in high dose females. No toxicologically significant macroscopical or histopathological findings were observed. Based on a decreased body weight in top dose females and on haematological changes at the top dose, a NOAEL of 100 mg/kg bw/d is derived from this study. SCCS comments An average of 91 % of the initial concentrations of the active ingredient was found after a 10 day storage at room temperature. Some animals chewed or removed the tape. Data was collected in order to explain probably occurring unexplained toxicity. Oral exposure cannot fully be excluded from this study. Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice. This study is not available for evaluation. MAK (2012) describes two dermal","page":36,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_005"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/d | rat | oral | subchronic | repeated dose toxicity | {"citation":"Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats","dose":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level).","effect":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats. NOAELs of 50 and 25 mg/kg bw/d were obtained for male and female animals, respectively. A further subchronic toxicity study is mentioned on ECHA's website (http://echa.europa.eu/). The study is not available for evaluation. A NOAEL of 100 mg/kg/d was derived from that study. SCCS comment to studies with dermal administration of ZPT The fact that hindlimb weakness after dermal administration was not observed in some of the studies might be due to the dosing regimen and the vehicle used. In oral studies it could be demonstrated that in contrast to continuous administration, effects were less pronounced or not observable, when there were discontinuities in the dosing (e.g. 5 days per week). Further, when using water or DMSO as vehicle, toxic e","page":37,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_006"} |
| SCCS Opinion | NOAEL | =100 | % | rat | oral | chronic | carcinogenicity | {"dose":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (appl...","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment facto","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_028"} |
| SCCS Opinion | NOAEL | =100 | mg/kg bw/d | mouse | oral | 10 day | NOAEL study | {"citation":"Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice","dose":"In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females.","effect":"observed. In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females. Further, statistically significantly increased cholesterol levels were determind in high dose females. No toxicologically significant macroscopical or histopathological findings were observed. Based on a decreased body weight in top dose females and on haematological changes at the top dose, a NOAEL of 100 mg/kg bw/d is derived from this study. SCCS comments An average of 91 % of the initial concentrations of the active ingredient was found after a 10 day storage at room temperature. Some animals chewed or removed the tape. Data was collected in order to explain probably occurring unexplained toxicity. Oral exposure cannot fully be excluded from this study. Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice. This study is not available for evaluation. MAK (2012) describes two dermal","page":36,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_005"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/d | rat | oral | subchronic | repeated dose toxicity | {"citation":"Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats","dose":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level).","effect":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats. NOAELs of 50 and 25 mg/kg bw/d were obtained for male and female animals, respectively. A further subchronic toxicity study is mentioned on ECHA's website (http://echa.europa.eu/). The study is not available for evaluation. A NOAEL of 100 mg/kg/d was derived from that study. SCCS comment to studies with dermal administration of ZPT The fact that hindlimb weakness after dermal administration was not observed in some of the studies might be due to the dosing regimen and the vehicle used. In oral studies it could be demonstrated that in contrast to continuous administration, effects were less pronounced or not observable, when there were discontinuities in the dosing (e.g. 5 days per week). Further, when using water or DMSO as vehicle, toxic e","page":37,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_006"} |
| SCCS Opinion | NOAEL | =100 | % | rat | oral | chronic | carcinogenicity | {"dose":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (appl...","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment facto","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_028"} |
| SCCS Opinion | NOAEL | =100 | mg/kg bw/d | mouse | oral | 10 day | NOAEL study | {"citation":"Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice","dose":"In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females.","effect":"observed. In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females. Further, statistically significantly increased cholesterol levels were determind in high dose females. No toxicologically significant macroscopical or histopathological findings were observed. Based on a decreased body weight in top dose females and on haematological changes at the top dose, a NOAEL of 100 mg/kg bw/d is derived from this study. SCCS comments An average of 91 % of the initial concentrations of the active ingredient was found after a 10 day storage at room temperature. Some animals chewed or removed the tape. Data was collected in order to explain probably occurring unexplained toxicity. Oral exposure cannot fully be excluded from this study. Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice. This study is not available for evaluation. MAK (2012) describes two dermal","page":36,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_005"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/d | rat | oral | subchronic | repeated dose toxicity | {"citation":"Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats","dose":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level).","effect":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats. NOAELs of 50 and 25 mg/kg bw/d were obtained for male and female animals, respectively. A further subchronic toxicity study is mentioned on ECHA's website (http://echa.europa.eu/). The study is not available for evaluation. A NOAEL of 100 mg/kg/d was derived from that study. SCCS comment to studies with dermal administration of ZPT The fact that hindlimb weakness after dermal administration was not observed in some of the studies might be due to the dosing regimen and the vehicle used. In oral studies it could be demonstrated that in contrast to continuous administration, effects were less pronounced or not observable, when there were discontinuities in the dosing (e.g. 5 days per week). Further, when using water or DMSO as vehicle, toxic e","page":37,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_006"} |
| SCCS Opinion | NOAEL | =100 | % | rat | oral | chronic | carcinogenicity | {"dose":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (appl...","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment facto","page":80,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_028"} |
| SCCS Opinion | NOAEL | =500 | - | - | oral | chronic | carcinogenicity | {"dose":"be considered adequate to assess repeat-dose effects of ZPT.","effect":"be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_013"} |
| SCCS Opinion | NOAEL | =500 | - | - | oral | chronic | carcinogenicity | {"dose":"be considered adequate to assess repeat-dose effects of ZPT.","effect":"be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_013"} |
| SCCS Opinion | NOAEL | =500 | - | - | oral | chronic | carcinogenicity | {"dose":"be considered adequate to assess repeat-dose effects of ZPT.","effect":"be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_013"} |
| SCCS Opinion | NOAEL | =500 | - | - | oral | chronic | carcinogenicity | {"dose":"be considered adequate to assess repeat-dose effects of ZPT.","effect":"be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","page":43,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_013"} |
| SCCS Opinion | NOAEL | =1995 | - | rat | oral | - | NOAEL study | {"dose":"We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":". Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_024"} |
| SCCS Opinion | NOAEL | =1995 | - | rat | oral | - | NOAEL study | {"dose":"We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":". Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_024"} |
| SCCS Opinion | NOAEL | =1995 | - | rat | oral | - | NOAEL study | {"dose":"We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":". Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_024"} |
| SCCS Opinion | NOAEL | =1995 | - | rat | oral | - | NOAEL study | {"dose":"We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","effect":". Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo","page":73,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_024"} |
| SCCS Opinion | NOAEL | =2000 | mg/kg | - | oral | sub-chronic | repeated dose toxicity | {"dose":"Several oral repeat-dose studies of different durations have been performed with ZPT.","effect":"2000 mg/kg. Acute inhalation studies have been performed with ZPT. According to one of the studies, classification as Acute Tox 3; H331 (toxic if inhaled) according to CLP as suggested by the registrant(s) under REACH (ECHA website (http://echa.europa.eu/) is justified. Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and a chronic oral studies performed with sodium pyrithione can be considered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T","page":81,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_032"} |
| SCCS Opinion | NOAEL | =2000 | mg/kg | - | oral | sub-chronic | repeated dose toxicity | {"dose":"Several oral repeat-dose studies of different durations have been performed with ZPT.","effect":"2000 mg/kg. Acute inhalation studies have been performed with ZPT. According to one of the studies, classification as Acute Tox 3; H331 (toxic if inhaled) according to CLP as suggested by the registrant(s) under REACH (ECHA website (http://echa.europa.eu/) is justified. Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and a chronic oral studies performed with sodium pyrithione can be considered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T","page":81,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_032"} |
| SCCS Opinion | NOAEL | =2000 | mg/kg | - | oral | sub-chronic | repeated dose toxicity | {"dose":"Several oral repeat-dose studies of different durations have been performed with ZPT.","effect":"2000 mg/kg. Acute inhalation studies have been performed with ZPT. According to one of the studies, classification as Acute Tox 3; H331 (toxic if inhaled) according to CLP as suggested by the registrant(s) under REACH (ECHA website (http://echa.europa.eu/) is justified. Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and a chronic oral studies performed with sodium pyrithione can be considered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T","page":81,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_032"} |
| SCCS Opinion | NOAEL | =2000 | mg/kg | - | oral | sub-chronic | repeated dose toxicity | {"dose":"Several oral repeat-dose studies of different durations have been performed with ZPT.","effect":"2000 mg/kg. Acute inhalation studies have been performed with ZPT. According to one of the studies, classification as Acute Tox 3; H331 (toxic if inhaled) according to CLP as suggested by the registrant(s) under REACH (ECHA website (http://echa.europa.eu/) is justified. Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and a chronic oral studies performed with sodium pyrithione can be considered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T","page":81,"pdf":"sccs_o_133.pdf","row_type":"noael_study","study_id":"sccs_o_133_noael_032"} |
EPA ToxRefDB v3 7 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| EPA ToxRefDB v3 | LEL | =1.5 | mg/kg bw/day | rabbit (new zealand white; New Zealand White) | oral | 6 GD to 18 GD | DEV | study_id=1753; toxval_study_source_id=studyid1753_Adult Pregnancy_F0_F_reproductive; toxval_effect_list=reproductive performance-postimplantation loss-postimplantation loss|reproductive performance-pregnancy-pregnancy|reproductive performance-aborted-aborted|reproductive performance-resorptions-resorptions; dose_level=2; study_year=1993; study_citation=Schardein, J. (1993) Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc. Unpublished Study Prepared By International Research And Development Corp. 161 P.; dsstox_substance_id=DTXSID7026314; admin_method=Gavage/Intubation; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| EPA ToxRefDB v3 | LEL | =3 | mg/kg bw/day | rabbit (new zealand white; New Zealand White) | oral | 6 GD to 18 GD | DEV | study_id=1753; toxval_study_source_id=studyid1753_Fetal_Fetal_MF_developmental; toxval_effect_list=developmental malformation-general-[other]; dose_level=3; study_year=1993; study_citation=Schardein, J. (1993) Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc. Unpublished Study Prepared By International Research And Development Corp. 161 P.; dsstox_substance_id=DTXSID7026314; admin_method=Gavage/Intubation; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| EPA ToxRefDB v3 | LEL | =15 | mg/kg bw/day | rat (sprague dawley; Sprague Dawley (CD)) | oral | 6 GD to 15 GD | DEV | study_id=1754; toxval_study_source_id=studyid1754_Adult Pregnancy_Fetal_MF_reproductive; toxval_effect_list=offspring survival early-live fetuses-live fetuses; dose_level=3; study_year=1993; study_citation=James L Schardein. 1993. Developmental Toxicity Study in Rats with Zinc Omadine (pyrithione) Study #: 397-055: International Research and Development Corporation, Mattawan, MI: May 27, 1993; dsstox_substance_id=DTXSID7026314; admin_method=Gavage/Intubation; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| EPA ToxRefDB v3 | LEL | =1000 | mg/kg bw/day | rat (sprague dawley; Sprague Dawley (CD)) | dermal | 0 week to 13 week | SUB | study_id=6066; toxval_study_source_id=studyid6066_Adult_F0_F_systemic; toxval_effect_list=in life observation-food consumption-food consumption|in life observation-food consumption-food efficiency|in life observation-body weight-body weight|in life observation-clinical signs-skin discoloration; dose_level=3; study_year=1993; study_citation=Ulrich, CE. 1993. 90-day subchronic dermal toxicity study on zinc omadine in rats. International Research and Development Corp., Mattawan, MI. Study no. 397-057. MRID 42827902.; dsstox_substance_id=DTXSID7026314; admin_method=Topical; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| EPA ToxRefDB v3 | NEL | =0.5 | mg/kg bw/day | rabbit (new zealand white; New Zealand White) | oral | 6 GD to 18 GD | DEV | study_id=1753; toxval_study_source_id=studyid1753_Adult Pregnancy_F0_F_reproductive; toxval_effect_list=reproductive performance-pregnancy-pregnancy|reproductive performance-postimplantation loss-postimplantation loss|reproductive performance-resorptions-resorptions|reproductive performance-aborted-aborted; dose_level=1; study_year=1993; study_citation=Schardein, J. (1993) Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc. Unpublished Study Prepared By International Research And Development Corp. 161 P.; dsstox_substance_id=DTXSID7026314; admin_method=Gavage/Intubation; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| EPA ToxRefDB v3 | NEL | =0.75 | mg/kg bw/day | rat (sprague dawley; Sprague Dawley (CD)) | oral | 6 GD to 15 GD | DEV | study_id=1754; toxval_study_source_id=studyid1754_Adult Pregnancy_F0_F_reproductive; toxval_effect_list=reproductive performance-resorptions-resorptions|reproductive performance-postimplantation loss-postimplantation loss; dose_level=1; study_year=1993; study_citation=James L Schardein. 1993. Developmental Toxicity Study in Rats with Zinc Omadine (pyrithione) Study #: 397-055: International Research and Development Corporation, Mattawan, MI: May 27, 1993; dsstox_substance_id=DTXSID7026314; admin_method=Gavage/Intubation; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
| EPA ToxRefDB v3 | NEL | =100 | mg/kg bw/day | rat (sprague dawley; Sprague Dawley (CD)) | dermal | 0 week to 13 week | SUB | study_id=6066; toxval_study_source_id=studyid6066_Adult_F0_F_systemic; toxval_effect_list=in life observation-clinical signs-skin discoloration|in life observation-food consumption-food consumption|in life observation-food consumption-food efficiency|in life observation-body weight-body weight; dose_level=2; study_year=1993; study_citation=Ulrich, CE. 1993. 90-day subchronic dermal toxicity study on zinc omadine in rats. International Research and Development Corp., Mattawan, MI. Study no. 397-057. MRID 42827902.; dsstox_substance_id=DTXSID7026314; admin_method=Topical; cas_source=toxval_ToxRefDB.xlsx:DTXSID; blob_url=https://clowder.edap-cluster.com/files/688cbadae4b02565bc3f8c07/blob; blob_sha256=69dd2da06ffc6a98a1bed684c347d8b2f31e6d35d607d4f2f83ebb6845a708d5 |
ECHA 24 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ECHA | LOAEL | =1 | mg/kg bw/day | Rat | oral | subchronic; 90 days | subchronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead3fe4b0a7c65d1c349a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15843458_15850950: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_7f554975f3a4d904c22fecb8d8734119 |
| ECHA | LOAEL | =1.4 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa8be4b0a7c65d1b6652; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/9/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID:15855934: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_839c881c1ffbf08fa8f20acd195015eb |
| ECHA | LOAEL | =1.5 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa8be4b0a7c65d1b6658; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/9/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID:15860702: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_1ff63d31d6e61eec7976a2e6ac30ff6f |
| ECHA | LOAEL | =1.95 | mg/kg bw/day | Rat | oral | - | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9e4e4b0a7c65d1b3412; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/8?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15816136_15820336: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_03dd225cec1f27157b8138c12a176f9b |
| ECHA | LOAEL | =2.5 | mg/m3 | Rat | inhalation | - | repeat dose other | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c85ae4b0a7c65d21815f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/10/1?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825563_15825564: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_855a896e517a40ab2618588b1087b8a4 |
| ECHA | LOAEL | =2.8 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa8be4b0a7c65d1b6652; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/9/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID:15855043:M: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_124cb9bbed69f4f7a796643e9664cb24 |
| ECHA | LOAEL | =3 | mg/kg bw/day | Rat | oral | - | developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabdde4b0a7c65d1bc2d1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/9/3?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID:15824216:-:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_1026735f36b9a1ad9e10fc64c1feb251 |
| ECHA | LOAEL | =3.5 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa8be4b0a7c65d1b6658; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/9/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID:15855465: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_1706906e892fa6773567e576be7b00d4 |
| ECHA | LOAEL | =6 | mg/m3 | Rat | inhalation | short-term; 21 days | short-term | QUALITY=1 (reliable without restriction); 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/14333/7/6/3?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Inhalation_15829194_15829195: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_d5266ae168817f11b4f63f579de03dfc |
| ECHA | LOAEL | >8 | mg/kg bw/day | Monkey | oral | chronic; 93 days | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca6be4b0a7c65d221d31; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15837800_15837801: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_909deb79cf5f60cde9bf133453f0d8a1 |
| ECHA | LOAEL | =22 | mg/kg bw/day | Monkey | oral | short-term; 28 days | short-term | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca76e4b0a7c65d221e13; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15848008_15849123: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_fdc1be50cc8473ef4cd427edfd6da405 |
| ECHA | LOAEL | =75 | mg/kg bw/day | Rat | oral | - | repeat dose other | GUIDELINE=OECD Guideline 424 (Neurotoxicity Study in Rodents); QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa3ee4b0a7c65d1b4ee8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/10/1?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825627_15826080: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_5cf58c538fd9b713c72bbe5725a9d734 |
| ECHA | LOAEL | =1000 | mg/kg bw/day | Rat | dermal | - | repeat dose other | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c85ae4b0a7c65d218163; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/10/1?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825681_15825682: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_417c9a70ce18075e4b314a19d17148fe |
| ECHA | NOAEL | =0.39 | mg/kg bw/day | Rat | oral | chronic; 94 days | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead3fe4b0a7c65d1c3498; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15839644_15850690: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_8835ffb8b8468b0001d47532c8ba2a7f |
| ECHA | NOAEL | =0.5 | mg/m3 | Rat | inhalation | - | repeat dose other | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c85ae4b0a7c65d21815f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/10/1?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825563_15825564: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_bf9a839d1cabc9dbf91a367f08536009 |
| ECHA | NOAEL | =0.78 | mg/kg bw/day | Rat | oral | - | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9e4e4b0a7c65d1b3412; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/8?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15816136_15820336: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_9b059da8be7d088a7f85b1b837a52c06 |
| ECHA | NOAEL | =2 | mg/m3 | Rat | inhalation | short-term; 21 days | short-term | QUALITY=1 (reliable without restriction); 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/14333/7/6/3?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Inhalation_15829194_15829195: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_8ea9428859756016f515a3580738bdc5 |
| ECHA | NOAEL | =11 | mg/kg bw/day | Monkey | oral | short-term; 28 days | short-term | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca76e4b0a7c65d221e13; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15848008_15849123: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_6d230709bdaf56d40f43a8cf3ab54080 |
| ECHA | NOAEL | =25 | mg/kg bw/day | Rat | oral | - | repeat dose other | GUIDELINE=OECD Guideline 424 (Neurotoxicity Study in Rodents); QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa3ee4b0a7c65d1b4ee8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/10/1?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825627_15826080: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_6ba2045eb1ddfc0548c5dbf18d9d6a50 |
| ECHA | NOAEL | =100 | mg/kg bw/day | Rat | dermal | - | repeat dose other | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c85ae4b0a7c65d218163; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/10/1?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825681_15825682: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_8dbf7d312d93e119469747305a7336c0 |
| ECHA | NOEL | =0.2 | mg/kg bw/day | Rat | oral | subchronic; 90 days | subchronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead3fe4b0a7c65d1c349a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/2?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15843458_15850950: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_08a3543ea2b41013afec22c4c7305a5b |
| ECHA | NOEL | =5 | mg/kg bw/day | Mouse | dermal | chronic; 80 weeks | chronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61e3be4b096bca8778e1f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/4?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Dermal_15826448_15826449: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_6e3a695a35c340a9c26cc28f349d60b5 |
| ECHA | NOEL | =11 | mg/kg bw/day | Monkey | oral | - | repeat dose other | GUIDELINE=other:; QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c85ae4b0a7c65d218167; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/10/1?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID:15825955: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_0b1a3d4c28e519d6221c0abe3ce4d146 |
| ECHA | NOEL | =15 | mg/kg bw/day | Mouse | dermal | chronic; 80 weeks | chronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61e3be4b096bca8778e1f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14333/7/6/4?documentUUID=ba3559d3-0936-47ff-8796-f4017e5bc7a0; YEAR=1994; ORIGINAL_YEAR=1994; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Dermal_15826448_15826449: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_30469a82dfc7ce36a5e0c2b56b6b84e2 |
ToxValDB ECOTOX 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB ECOTOX | NOEL | =20 | % w/v | Mouse | dermal | short-term; 5 days | short-term | LONG_REF=Food Chem. Toxicol.29(1): 57-64 Lansdown,A.B.G. Interspecies Variations in Response to Topical Application of Selected Zinc Compounds 1991; TITLE=Interspecies Variations in Response to Topical Application of Selected Zinc Compounds; AUTHOR=Lansdown,A.B.G.; DOI=10.1016/0278-6915(91)90063-d; QUALITY=Control type: Carrier or solvent control; EXTERNAL_SOURCE_ID=85721; 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=1991; ORIGINAL_YEAR=1991; TOXICOLOGICAL_EFFECT=Genetics: Mitotic index (# mitoses/total cells); TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX:15600663:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=07041e6ba83b15c2339b252e34b7229d |
ToxValDB ToxRefDB 5 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB ToxRefDB | LEL | =1.5 | mg/kg bw/day | Rabbit | oral | short-term (developmental); 13 days | reproduction developmental | LONG_REF=Schardein, J. (1993) Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc. Unpublished Study Prepared By International Research And Development Corp. 161 P.; TITLE=Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc; AUTHOR=Schardein, J; EXTERNAL_SOURCE_ID=1753; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=reproductive: reproductive performance-postimplantation loss-postimplantation loss|reproductive: reproductive performance-pregnancy-pregnancy|reproductive: reproductive performance-aborted-aborted|reproductive: reproductive performance-resorptions-resorptions; TOXICOLOGICAL_EFFECT_CATEGORY=reproduction; STUDY_GROUP=ToxRefDB_dup_-_15689545_15689546_15689547_15689548:F:F0adult-pregnancy; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_fb86eee79f926467a60584d87a9ace0e |
| ToxValDB ToxRefDB | LEL | =3 | mg/kg bw/day | Rabbit | oral | short-term (developmental); 13 days | developmental | LONG_REF=Schardein, J. (1993) Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc. Unpublished Study Prepared By International Research And Development Corp. 161 P.; TITLE=Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc; AUTHOR=Schardein, J; EXTERNAL_SOURCE_ID=1753; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=developmental: developmental malformation-general-[other]; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ToxRefDB_dup_-_15689557_15689558:M/F:fetusfetal; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_5b45dbced821041e46a8a0afc2735447 |
| ToxValDB ToxRefDB | LEL | =15 | mg/kg bw/day | Rat | oral | short-term (developmental); 10 days | developmental | LONG_REF=James L Schardein. 1993. Developmental Toxicity Study in Rats with Zinc Omadine (pyrithione) Study #: 397-055: International Research and Development Corporation, Mattawan, MI: May 27, 1993; TITLE=Developmental Toxicity Study in Rats with Zinc Omadine (pyrithione); AUTHOR=James L Schardein; EXTERNAL_SOURCE_ID=1754; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=reproductive: offspring survival early-live fetuses-live fetuses; TOXICOLOGICAL_EFFECT_CATEGORY=reproduction; STUDY_GROUP=ToxRefDB_dup_-_15689561_15689562:M/F:fetusadult-pregnancy; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_66dd4fc5493a5945da30f1aa7d6e445f |
| ToxValDB ToxRefDB | NEL | =0.5 | mg/kg bw/day | Rabbit | oral | short-term (developmental); 13 days | reproduction developmental | LONG_REF=Schardein, J. (1993) Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc. Unpublished Study Prepared By International Research And Development Corp. 161 P.; TITLE=Developmental Toxicity Study In New Zealand White Rabbits With Zinc Omadine: Lab Project Number: 397-056: Irdc; AUTHOR=Schardein, J; EXTERNAL_SOURCE_ID=1753; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=reproductive: reproductive performance-resorptions-resorptions|reproductive: reproductive performance-aborted-aborted|reproductive: reproductive performance-pregnancy-pregnancy|reproductive: reproductive performance-postimplantation loss-postimplantation loss; TOXICOLOGICAL_EFFECT_CATEGORY=reproduction; STUDY_GROUP=ToxRefDB_dup_-_15689545_15689546_15689547_15689548:F:F0adult-pregnancy; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_06373a2d2350a91e545bc28d45e5e4ea |
| ToxValDB ToxRefDB | NEL | =0.75 | mg/kg bw/day | Rat | oral | short-term (developmental); 10 days | reproduction developmental | LONG_REF=James L Schardein. 1993. Developmental Toxicity Study in Rats with Zinc Omadine (pyrithione) Study #: 397-055: International Research and Development Corporation, Mattawan, MI: May 27, 1993; TITLE=Developmental Toxicity Study in Rats with Zinc Omadine (pyrithione); AUTHOR=James L Schardein; EXTERNAL_SOURCE_ID=1754; EXTERNAL_SOURCE_ID_DESC=ToxRefDB Study ID; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66bca4a3e4b0a7c65d2a792a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://github.com/USEPA/CompTox-ToxRefDB; YEAR=1993; ORIGINAL_YEAR=1993; TOXICOLOGICAL_EFFECT=reproductive: reproductive performance-resorptions-resorptions|reproductive: reproductive performance-postimplantation loss-postimplantation loss; TOXICOLOGICAL_EFFECT_CATEGORY=reproduction; STUDY_GROUP=ToxRefDB_dup_-_15689559_15689560:F:F0adult-pregnancy; QC_CATEGORY=Data source QC'd by data provider prior to ToxRefDB import; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d39f1e543d19f4369b61fb72a5d44896 |
Regulatory source 38 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| Regulatory source | - | 0.5 | mg/kg/day | rat | oral | 14 days | - | SOURCE_SUBDIR=out225_en; REPORT_TITLE=OPINION CONCERNING ZINC PYRITHIONE COLIPA n° P81; OPINION_NUMBER=SCCNFP/0671/03; COMMITTEE=SCCNFP; REPORT_DATE=17 December 2002; VALUE_TEXT=0.5; DOSE=lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).; EFFECT=lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater the animals usually died without developing a paralysis. The dose/time response with respect to paralysis is not yet completely understood, since it is complicated by several variables that are discussed below. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 µg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two year study period. Hind-limb Paralysis Several studies have been conducted to determine the dose range that produces paralysis, the reversibility of this effect, and the ultrastructural cellular changes involved. The results of these studies have been fully considered as part of the safety evaluation of ZPT. In many of the studies reported, ZPT was added to the diet of th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","duration":"14 days","effect":"lysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater the animals usually died without developing a paralysis. The dose/time response with respect to paralysis is not yet completely understood, since it is complicated by several variables that are discussed below. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 µg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two year study period. Hind-limb Paralysis Several studies have been conducted to determine the dose range that produces paralysis, the reversibility of this effect, and the ultrastructural cellular changes involved. The results of these studies have been fully considered as part of the safety evaluation of ZPT. In many of the studies reported, ZPT was added to the diet of th","endpoint":"","ingredient":"s indicated","loael_value":"","noael_unit":"mg/kg/day","noael_value":"0.5","page":8,"route":"oral","species":"rat","study_id":"out225_en_noael_001"} |
| Regulatory source | - | 0.6 | mg/kg/d | rat | oral | chronic | - | SOURCE_SUBDIR=out225_en; REPORT_TITLE=OPINION CONCERNING ZINC PYRITHIONE COLIPA n° P81; OPINION_NUMBER=SCCNFP/0671/03; COMMITTEE=SCCNFP; REPORT_DATE=17 December 2002; VALUE_TEXT=0.6; DOSE=Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten.; EFFECT=produced mild or no neurologic deficit or electrophysiologic changes prior to death. Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten. The work by Chrisman and Ross (1978) is especially important in that it confirmed the no-effect level [10 ppm (0.6mg/kg/d) of ZPT in diet] determined by Larson (1958) in the chronic feeding study summarised below. In addition to confirming the NOEL, the work also serves to point out the sensitivity of the rat to the neurologic effects of ZPT (see also Sahenk and Mendell (1980)).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten.","duration":"chronic","effect":"produced mild or no neurologic deficit or electrophysiologic changes prior to death. Milligram/kilogram equivalents have not been provided for dietary concentration of ZPT above 50 ppm because of excessive body weight loss and extreme variability in the amount of chow eaten. The work by Chrisman and Ross (1978) is especially important in that it confirmed the no-effect level [10 ppm (0.6mg/kg/d) of ZPT in diet] determined by Larson (1958) in the chronic feeding study summarised below. In addition to confirming the NOEL, the work also serves to point out the sensitivity of the rat to the neurologic effects of ZPT (see also Sahenk and Mendell (1980)).","endpoint":"","ingredient":"s indicated","loael_value":"","noael_unit":"mg/kg/d","noael_value":"0.6","page":11,"route":"oral","species":"rat","study_id":"out225_en_noael_002"} |
| Regulatory source | carcinogenicity | 100 | mg/kg/d | human | oral | chronic | carcinogenicity | SOURCE_SUBDIR=out225_en; REPORT_TITLE=OPINION CONCERNING ZINC PYRITHIONE COLIPA n° P81; OPINION_NUMBER=SCCNFP/0671/03; COMMITTEE=SCCNFP; REPORT_DATE=17 December 2002; VALUE_TEXT=100; DOSE=No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.; EFFECT=or after practical application to humans. Thus the scientific evaluation of the submission, the results of these investigations on ZPT have been separated as to (i) ingredient based data, (ii) product based data and, where applicable, to the mode of application. As to probable neurotoxicological properties of ZPT the results of investigations in several species can be summarized as follows: In chronic toxicity experiments it was shown that an oral application of 500 µg/kg/d applied over (~ 18 m) can be regarded as NOAEL. No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","duration":"chronic","effect":"or after practical application to humans. Thus the scientific evaluation of the submission, the results of these investigations on ZPT have been separated as to (i) ingredient based data, (ii) product based data and, where applicable, to the mode of application. As to probable neurotoxicological properties of ZPT the results of investigations in several species can be summarized as follows: In chronic toxicity experiments it was shown that an oral application of 500 µg/kg/d applied over (~ 18 m) can be regarded as NOAEL. No evidence of a carcinogenic response was seen when ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological","endpoint":"carcinogenicity","ingredient":"s indicated","loael_value":"","noael_unit":"mg/kg/d","noael_value":"100","page":31,"route":"oral","species":"human","study_id":"out225_en_noael_003"} |
| Regulatory source | reproductive toxicity | 400 | mg/kg/day | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=out225_en; REPORT_TITLE=OPINION CONCERNING ZINC PYRITHIONE COLIPA n° P81; OPINION_NUMBER=SCCNFP/0671/03; COMMITTEE=SCCNFP; REPORT_DATE=17 December 2002; VALUE_TEXT=400; DOSE=n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.; EFFECT=n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological studies 2.5 mg/kg/day applied orally to rats was the NOAEL maternally, no reproductive effects were observed in rabbits and rats when ZPT was topically administered up to 400 mg/kg/day. Toxicokinetic investigations revealed : * percutaneous absorption of ZPT varies from approximately 0.03 to 3.4% * the distribution of radioactivity in tissues after oral administration of labelled ZPT showed that the radioactivity rapidly disappeared from the blood, and the primary route of excretion was via the urine. The residual radioactivity was low (4.5% of dose), ZPT was distributed; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies.","duration":"","effect":"n ZPT was applied topically up to 100 mg/kg/d or given orally up to 5 mg/kg/d in lifetime studies. The presence of ZPT did not impact upon the low irritation potential of the cosmetic formulations tested. The same observation was valid for a shampoo formulation investigated in a mucous membranes test. The appropriate experiments showed that ZPT alone as well as part of cosmetic formulations had a low potential to induce contact hypersensitivity. In teratological studies 2.5 mg/kg/day applied orally to rats was the NOAEL maternally, no reproductive effects were observed in rabbits and rats when ZPT was topically administered up to 400 mg/kg/day. Toxicokinetic investigations revealed : * percutaneous absorption of ZPT varies from approximately 0.03 to 3.4% * the distribution of radioactivity in tissues after oral administration of labelled ZPT showed that the radioactivity rapidly disappeared from the blood, and the primary route of excretion was via the urine. The residual radioactivity was low (4.5% of dose), ZPT was distributed","endpoint":"reproductive toxicity","ingredient":"s indicated","loael_value":"","noael_unit":"mg/kg/day","noael_value":"400","page":31,"route":"oral","species":"rat","study_id":"out225_en_noael_004"} |
| Regulatory source | - | 0.5 | mg/kg/day | rat | oral | 14 days | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=0.5; DOSE=No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).; EFFECT=uration) Oral studies Summary taken from SCCNFP/0671/03 Concerning ZPT: No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater, the animals usually died without developing paralysis. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 μg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two-year study period. Concerning shampoo formulations containing ZPT: Orally administered ZPT in a shampoo formulation produces a reversible paralysis in rats and rabbits within one to two weeks at levels of 10 mg/kg/day. A dose level of 10 mg/kg/day of ZPT in shampoo was used in a monkey gavage study which lasted 16 weeks. No adverse effects were observed. Because of the e; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day).","duration":"14 days","effect":"uration) Oral studies Summary taken from SCCNFP/0671/03 Concerning ZPT: No significant effects have been noted other than the hind-limb weakness or paralysis which occurred in rats and rabbits within 8 to 14 days when ZPT was administered in the diet at levels from 165 ppm to 330 ppm (8-16 mg/kg/day). Doses greater than 330 ppm required longer periods of administration before paralysis occurred. At levels of 1000 ppm or greater, the animals usually died without developing paralysis. With respect to paralysis, a NOEL of 0.5 mg/kg/day (500 μg/kg/d) has been determined in two year feeding studies in rats. At this dose no toxic effects were observed over the two-year study period. Concerning shampoo formulations containing ZPT: Orally administered ZPT in a shampoo formulation produces a reversible paralysis in rats and rabbits within one to two weeks at levels of 10 mg/kg/day. A dose level of 10 mg/kg/day of ZPT in shampoo was used in a monkey gavage study which lasted 16 weeks. No adverse effects were observed. Because of the e","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/day","noael_value":"0.5","page":32,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_001"} |
| Regulatory source | - | 0.5 | mg/kg/d | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=0.5; DOSE=3 high dose males also had increased relative liver weights.; EFFECT=s of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule after uptake and that A; CITATION=Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0; CITATION_NUMBERS=[10,2003]; REFERENCE=Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0","dose":"3 high dose males also had increased relative liver weights.","duration":"90-day","effect":"s of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule after uptake and that A","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"0.5","page":34,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_004"} |
| Regulatory source | - | 0.5 | mg/kg/d | - | oral | chronic | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=0.5; DOSE=From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived.; EFFECT=ppm diet. Ratios of organ weights to body weights did not differ significantly among the surviving groups at termination. Histopathologic examinations did not reveal any lesions that appeared to be attributable to the administration of ZPT. These observations included careful attention to retina, optic nerve, cerebral cortex, and other parts of the central and peripheral nervous systems. There were no significant differences in the rate of frequency of neoplasms between any of the groups. From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived. Further data Two oral chronic studies performed with ZPT are mentioned at ECHA's website (http://echa.europa.eu/), one is apparently the study by Larson (1958) already evaluated for SCCNFP 0671/03. According to the Batch number given, the second study must have been performed with NaPT although not specifically stated on ECHA's website. Data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule af; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived.","duration":"chronic","effect":"ppm diet. Ratios of organ weights to body weights did not differ significantly among the surviving groups at termination. Histopathologic examinations did not reveal any lesions that appeared to be attributable to the administration of ZPT. These observations included careful attention to retina, optic nerve, cerebral cortex, and other parts of the central and peripheral nervous systems. There were no significant differences in the rate of frequency of neoplasms between any of the groups. From this study, an oral NOAEL of 0.5 mg/kg/d (500 µg/kg/d) was derived. Further data Two oral chronic studies performed with ZPT are mentioned at ECHA's website (http://echa.europa.eu/), one is apparently the study by Larson (1958) already evaluated for SCCNFP 0671/03. According to the Batch number given, the second study must have been performed with NaPT although not specifically stated on ECHA's website. Data on metabolism of ZPT (see section “toxicokinetics” and see also SCCNFP/0671/03) demonstrate that Zn is cleaved from the molecule af","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"0.5","page":40,"route":"oral","species":"","study_id":"sccs_o_133_noael_008"} |
| Regulatory source | - | 2 | mg/kg/d | - | oral | 28 days | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=2.0; DOSE=Electrocardiograms of the high dose group were essentially normal.; LOAEL_VALUE=2.0 mg/kg/d; EFFECT=mistry and urinalysis. Electrocardiograms of the high dose group were essentially normal. No abnormal findings were noted following gross and histopathological examination. Relative kidney weights in the intermediate and high dose were reduced compared to control, which was attributed to high kidney weights in the control animals. Relative uterus weight was reduced in a dose-related manner at 2.0 and 8.0 mg/kg/d and was associated with apparent immaturity of the uteri. From this study, a LOAEL of 2.0 mg/kg/d and a NOAEL of 0.5 mg/kg/d can be derived. Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B.7 Species/strain/sex: Monkey / Cynomolgus / both sexes Group size: 4 per sex /dose at 5.5 and 11.0 mg/kg/d, 6 per sex /dose at 22.0 mg/kg/d Controls: 6 male, 6 female Test substance: Zinc Omadine ® powder Batch: 9204084481 Purity: 96.3 % Vehicle: Dose levels: 0, 5.5, 11.0, 22.0 mg/kg/d Exposure: oral, gelatine capsules, once daily for 28 days GLP statement: yes Date: 1992 Stability statement: it was confirmed by the spon; CITATION=Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B; CITATION_NUMBERS=[9]; REFERENCE=Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B","dose":"Electrocardiograms of the high dose group were essentially normal.","duration":"28 days","effect":"mistry and urinalysis. Electrocardiograms of the high dose group were essentially normal. No abnormal findings were noted following gross and histopathological examination. Relative kidney weights in the intermediate and high dose were reduced compared to control, which was attributed to high kidney weights in the control animals. Relative uterus weight was reduced in a dose-related manner at 2.0 and 8.0 mg/kg/d and was associated with apparent immaturity of the uteri. From this study, a LOAEL of 2.0 mg/kg/d and a NOAEL of 0.5 mg/kg/d can be derived. Ref.: E9 Guideline: MITI Guideline (Japan), similar to EC B.7 Species/strain/sex: Monkey / Cynomolgus / both sexes Group size: 4 per sex /dose at 5.5 and 11.0 mg/kg/d, 6 per sex /dose at 22.0 mg/kg/d Controls: 6 male, 6 female Test substance: Zinc Omadine ® powder Batch: 9204084481 Purity: 96.3 % Vehicle: Dose levels: 0, 5.5, 11.0, 22.0 mg/kg/d Exposure: oral, gelatine capsules, once daily for 28 days GLP statement: yes Date: 1992 Stability statement: it was confirmed by the spon","endpoint":"","ingredient":"Bis[(2","loael_value":"2.0 mg/kg/d","noael_unit":"mg/kg/d","noael_value":"2.0","page":33,"route":"oral","species":"","study_id":"sccs_o_133_noael_002"} |
| Regulatory source | - | 5 | mg/kg bw/d | rat | dermal | 28-day | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=5; DOSE=l repeat-dose studies have been performed with ZPT.; EFFECT=l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two-year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Inhalation: Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"l repeat-dose studies have been performed with ZPT.","duration":"28-day","effect":"l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two-year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Inhalation: Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"5","page":44,"route":"dermal","species":"rat","study_id":"sccs_o_133_noael_014"} |
| Regulatory source | - | 5 | mg/kg bw/d | rat | dermal | 28-day | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=5; DOSE=l repeat-dose studies have been performed with ZPT.; EFFECT=l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects. In a 90-day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"l repeat-dose studies have been performed with ZPT.","duration":"28-day","effect":"l repeat-dose studies have been performed with ZPT. Interpretation of the findings is partly hampered by the fact that grooming was not always prevented and that intermittent exposure regimens (causing recovery) have been applied. From a 28-day dermal neurotoxicity study in which grooming was prevented, NOAELs of 25 and 50 mg/kg bw/d were derived in female and male animals, respectively based on reduced electrophysiological parameters and muscle tone. In a two year dermal chronic study performed with NaPT, a local NOEL of 5 mg/kg bw/d was derived. Three inhalation studies of different durations have been performed, two of them are available for evaluation. In a 21-day nose only study performed in Sprague-Dawley rats, a LOAEC of 2 mg/m3 is derived based on histopathological data in tissues of the respiratory tract and non-respiratory tissues. In a 28-day nose only study performed in Sprague- Dawley rats, no NOAEC could be derived for local effects in the lung and an NOAEC of 1.5 mg/m3 was derived for systemic effects. In a 90-day","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"5","page":82,"route":"dermal","species":"rat","study_id":"sccs_o_133_noael_034"} |
| Regulatory source | - | 11 | mg/kg bw/d | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=11; DOSE=3 high dose males also had increased relative liver weights.; EFFECT=examination (apart from the female animal that died on day 10) no test-article related abnormalities were found. The relative organ weights of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism o; CITATION=Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0; CITATION_NUMBERS=[10,2003]; REFERENCE=Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0","dose":"3 high dose males also had increased relative liver weights.","duration":"90-day","effect":"examination (apart from the female animal that died on day 10) no test-article related abnormalities were found. The relative organ weights of the adrenal glands and the liver of the high-dosed females were increased. 3 high dose males also had increased relative liver weights. No significant organ weight changes were observed at the lower doses. On histopathologic examination, no abnormalities were observed in the surviving animals. Based on decreased lymphocyte counts in male animals observed at 11 mg/kg bw/d an NOAEL of 5.5 mg/kg/d is derived from this study. Ref.: E10 In addition to repeat dose studies performed with ZPT, HSE (2003) derives a NOEL of 0.5 mg/kg/d based on hind limb muscle atrophy from an oral 90-day study in Sprague-Dawley rats performed with sodium pyrithione, which is described in HSE (2003), therein cited as Unpublished, 1988. This study is not available for evaluation by the SCCS. A read across from sodium pyrithione to ZPT is considered appropriate based on the following reasoning: data on metabolism o","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"11","page":34,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_003"} |
| Regulatory source | - | 14 | - | rat | oral | - | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=unclear:one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific; DOSE=one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).; EFFECT=one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","duration":"","effect":"one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"","noael_value":"unclear:one (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the rat oral dose”). The SCCS notes, that the manuscript concerning dermal PBPK modelling of ZPT submitted to the SCCS has not yet been published in a peer-reviewed scientific","page":73,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_026"} |
| Regulatory source | - | 25 | mg/kg bw/d | - | dermal | - | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=25; DOSE=p and on days 22-28 in the 50 mg/kg/d group.; EFFECT=p and on days 22-28 in the 50 mg/kg/d group. On day 14 grip strength was reduced in the 75 and 100 mg/kg/d group and on day 28 grip strength was reduced in the three highest dose groups. No consistent decreases or dose dependent changes were apparent in plasma, RBC or brain cholinesterase at any dose tested. Decreases in the electrophysiological values measured as the maximum amplitude were observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). A dermal NOAEL of 25 mg/kg bw/d can be derived from the study. Ref.: D1 In vitro studies Knox et al. (2004) performed in vitro studies using bag cell neurons of a marine snail (Aplysia) in order to investigate the mechanisms underlying the reversible neurotoxicity of pyrithiones by using sodium pyrithione. It could be demonstrated that NaPT caused intracellular Ca2+ elevation. Several hypotheses which could build the molecular basis for this calcium entry have been tested. It could be demonstrated that the elevation of intrace; CITATION=Ref.: D1 In vitro studies Knox et al; CITATION_NUMBERS=[1]; REFERENCE=Ref.: D1 In vitro studies Knox et al; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: D1 In vitro studies Knox et al","dose":"p and on days 22-28 in the 50 mg/kg/d group.","duration":"","effect":"p and on days 22-28 in the 50 mg/kg/d group. On day 14 grip strength was reduced in the 75 and 100 mg/kg/d group and on day 28 grip strength was reduced in the three highest dose groups. No consistent decreases or dose dependent changes were apparent in plasma, RBC or brain cholinesterase at any dose tested. Decreases in the electrophysiological values measured as the maximum amplitude were observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). A dermal NOAEL of 25 mg/kg bw/d can be derived from the study. Ref.: D1 In vitro studies Knox et al. (2004) performed in vitro studies using bag cell neurons of a marine snail (Aplysia) in order to investigate the mechanisms underlying the reversible neurotoxicity of pyrithiones by using sodium pyrithione. It could be demonstrated that NaPT caused intracellular Ca2+ elevation. Several hypotheses which could build the molecular basis for this calcium entry have been tested. It could be demonstrated that the elevation of intrace","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"25","page":76,"route":"dermal","species":"","study_id":"sccs_o_133_noael_027"} |
| Regulatory source | - | 50 | ppm | rat | - | Chronic | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=50; DOSE=A summary on repeat dose toxicity is given in section 3.4.5.2.; EFFECT=SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 40 consumption, organ weights, and microscopic examination of selected tissues (brain, liver, kidneys, stomach, and skeletal muscle), authors considered the NOAEC for systemic toxicity as 1.5 mg/m3. Ref.: E14 ECHA's website (http://echa.europa.eu/) mentions a 90-d whole-body study performed in Sprague-Dawley. From this study, a NOAEL of 0.5 g/m³ air was derived. The study is not available for evaluation. A summary on repeat dose toxicity is given in section 3.4.5.2. 3.4.5.2. Chronic (> 12 months) toxicity Taken from SCCNFP/0671/03 A two year feeding study was conducted by Larson (1958). Young Wistar rats in groups of ten males and ten females were fed diets containing ZPT at levels of 0, 2, 5, 10, 25 and 50 ppm. These levels correspond to approximately 0, 0.1, 0.25, 0.5, 1.25 and 2.5 mg/kg/day for adult animals. At the start of the study; CITATION=Ref.: E14 ECHA's website (http://echa; CITATION_NUMBERS=[14]; REFERENCE=Ref.: E14 ECHA's website (http://echa; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E14 ECHA's website (http://echa","dose":"A summary on repeat dose toxicity is given in section 3.4.5.2.","duration":"Chronic","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 40 consumption, organ weights, and microscopic examination of selected tissues (brain, liver, kidneys, stomach, and skeletal muscle), authors considered the NOAEC for systemic toxicity as 1.5 mg/m3. Ref.: E14 ECHA's website (http://echa.europa.eu/) mentions a 90-d whole-body study performed in Sprague-Dawley. From this study, a NOAEL of 0.5 g/m³ air was derived. The study is not available for evaluation. A summary on repeat dose toxicity is given in section 3.4.5.2. 3.4.5.2. Chronic (> 12 months) toxicity Taken from SCCNFP/0671/03 A two year feeding study was conducted by Larson (1958). Young Wistar rats in groups of ten males and ten females were fed diets containing ZPT at levels of 0, 2, 5, 10, 25 and 50 ppm. These levels correspond to approximately 0, 0.1, 0.25, 0.5, 1.25 and 2.5 mg/kg/day for adult animals. At the start of the study","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"ppm","noael_value":"50","page":40,"route":"","species":"rat","study_id":"sccs_o_133_noael_007"} |
| Regulatory source | - | 100 | mg/kg bw/d | mouse | oral | 10 day | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=100; DOSE=In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females.; EFFECT=observed. In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females. Further, statistically significantly increased cholesterol levels were determind in high dose females. No toxicologically significant macroscopical or histopathological findings were observed. Based on a decreased body weight in top dose females and on haematological changes at the top dose, a NOAEL of 100 mg/kg bw/d is derived from this study. SCCS comments An average of 91 % of the initial concentrations of the active ingredient was found after a 10 day storage at room temperature. Some animals chewed or removed the tape. Data was collected in order to explain probably occurring unexplained toxicity. Oral exposure cannot fully be excluded from this study. Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice. This study is not available for evaluation. MAK (2012) describes two dermal; CITATION=Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice; CITATION_NUMBERS=[26]; REFERENCE=Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice","dose":"In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females.","duration":"10 day","effect":"observed. In animals receiving 1000 mg/kg/d, statistically significantly increased leucocyte counts were found in males, statistically significantly depressed erythrocyte counts and haematocrit levels were found in females. Further, statistically significantly increased cholesterol levels were determind in high dose females. No toxicologically significant macroscopical or histopathological findings were observed. Based on a decreased body weight in top dose females and on haematological changes at the top dose, a NOAEL of 100 mg/kg bw/d is derived from this study. SCCS comments An average of 91 % of the initial concentrations of the active ingredient was found after a 10 day storage at room temperature. Some animals chewed or removed the tape. Data was collected in order to explain probably occurring unexplained toxicity. Oral exposure cannot fully be excluded from this study. Ref.: E26 ECHA mentions a further dermal toxicity study performed in mice. This study is not available for evaluation. MAK (2012) describes two dermal","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"100","page":36,"route":"oral","species":"mouse","study_id":"sccs_o_133_noael_005"} |
| Regulatory source | - | 500 | - | rat | - | - | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=unclear:the model to humans in terms of e.g. partition coefficients, organ masses and volumes) and whether and to which extent species differences (e.g. with respect to enterohepatic circulation, with respect to metabolic parameters) have been considered when scaling the rat models to humans. Further, no description has been provided how the rat model had been verified by human clinical study results. Therefore, it cannot be reproduced, whether the human external dose of ZPT equivalents, that would correspond to the rat NOAEL of 500 µg/kg/d (2260 and 2170 µg/kg/d), are sound and reliable values to base MoS calculation on. Thus, solely from the information available from the SOT 2008 poster (Ref. A25) and the statements in the submission (see citations (1) and (2) above) the human model cannot be used for deriving quantitative threshold values, as there is no transparent information on the human model and its validation. This is in line with the REACH guidance on information requirements and chemical safety assessment, Chapter R-8, wher; DOSE=Therefore, it cannot be reproduced, whether the human external dose of ZPT equivalents, that would correspond to the rat NOAEL of 500 µg/kg/d (2260 and 2170 µg/kg/d), are sound and reliable values to base MoS calculation on.; EFFECT=SCCS-rejected applicant NOAEL: the model to humans in terms of e.g. partition coefficients, organ masses and volumes) and whether and to which extent species differences (e.g. with respect to enterohepatic circulation, with respect to metabolic parameters) have been considered when scaling the rat models to humans. Further, no description has been provided how the rat model had been verified by human clinical study results. Therefore, it cannot be reproduced, whether the human external dose of ZPT equivalents, that would correspond to the rat NOAEL of 500 µg/kg/d (2260 and 2170 µg/kg/d), are sound and reliable values to base MoS calculation on. Thus, solely from the information available from the SOT 2008 poster (Ref. A25) and the statements in the submission (see citations (1) and (2) above) the human model cannot be used for deriving quantitative threshold values, as there is no transparent information on the human model and its validation. This is in line with the REACH guidance on information requirements and chemical safety assessment, Chapter R-8, wher; CITATION=(Ref. A25); CITATION_NUMBERS=[25]; REFERENCE=(Ref. A25); DETAILS_JSON={"cas_number":"13463-41-7","citation":"(Ref. A25)","dose":"Therefore, it cannot be reproduced, whether the human external dose of ZPT equivalents, that would correspond to the rat NOAEL of 500 µg/kg/d (2260 and 2170 µg/kg/d), are sound and reliable values to base MoS calculation on.","duration":"","effect":"SCCS-rejected applicant NOAEL: the model to humans in terms of e.g. partition coefficients, organ masses and volumes) and whether and to which extent species differences (e.g. with respect to enterohepatic circulation, with respect to metabolic parameters) have been considered when scaling the rat models to humans. Further, no description has been provided how the rat model had been verified by human clinical study results. Therefore, it cannot be reproduced, whether the human external dose of ZPT equivalents, that would correspond to the rat NOAEL of 500 µg/kg/d (2260 and 2170 µg/kg/d), are sound and reliable values to base MoS calculation on. Thus, solely from the information available from the SOT 2008 poster (Ref. A25) and the statements in the submission (see citations (1) and (2) above) the human model cannot be used for deriving quantitative threshold values, as there is no transparent information on the human model and its validation. This is in line with the REACH guidance on information requirements and chemical safety assessment, Chapter R-8, wher","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"","noael_value":"unclear:the model to humans in terms of e.g. partition coefficients, organ masses and volumes) and whether and to which extent species differences (e.g. with respect to enterohepatic circulation, with respect to metabolic parameters) have been considered when scaling the rat models to humans. Further, no description has been provided how the rat model had been verified by human clinical study results. Therefore, it cannot be reproduced, whether the human external dose of ZPT equivalents, that would correspond to the rat NOAEL of 500 µg/kg/d (2260 and 2170 µg/kg/d), are sound and reliable values to base MoS calculation on. Thus, solely from the information available from the SOT 2008 poster (Ref. A25) and the statements in the submission (see citations (1) and (2) above) the human model cannot be used for deriving quantitative threshold values, as there is no transparent information on the human model and its validation. This is in line with the REACH guidance on information requirements and chemical safety assessment, Chapter R-8, wher","page":69,"route":"","species":"rat","study_id":"sccs_o_133_noael_023"} |
| Regulatory source | - | 500 | - | rat | oral | - | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=unclear:the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the; DOSE=We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).; EFFECT=the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","duration":"","effect":"the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"","noael_value":"unclear:the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK model to predict the “Human Applied Dermal Dose” that would yield the same systemic exposure as the rat oral NOAEL. The resulting ratios of human/rat dose represent the dose equivalence ratio for oral dosing of the rat and dermal dosing of humans. The human dose/rat dose ratio is 0.93 for PT and 2.07 for 14C-PT. Therefore, the PBPK models predict systemic dose equivalence when the human applied dermal dose is approximately equal to or 2-fold higher than the","page":73,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_025"} |
| Regulatory source | - | 1995 | - | rat | oral | - | - | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=unclear:. Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo; DOSE=We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).; EFFECT=. Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose).","duration":"","effect":". Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo","endpoint":"","ingredient":"Bis[(2","loael_value":"","noael_unit":"","noael_value":"unclear:. Further, the overall confidence in the human dermal model is low as it has not been demonstrated that it reproduces a variety of data from at least more than one experiment and it exhibits further weaknesses when reflecting arguments concerning the credibility of PBPK models which are given in Kohn, 1995. In this respect, the argumentation given by the applicant in response to SCCS/1512/13 cannot be accepted (“The most important and relevant aspect of the model is shown in the table below. We took the oral rat NOAEL, 500 µg/kg/day, and used the rat PBPK model to predict the corresponding area-under-curve (AUC) of pyrithione (PT) or 14C-PT (PTC, i.e., parent and metabolites) concentration plasma (i.e., internal dose). The predicted plasma AUC (0-∞) values corresponding to the 500 µg/kg/day dose group in the rat are 68.6 hr. ∙ µg/L for PT and 3416 hr. ∙ µg/L for plasma PTC. These values represent the systemic exposure to PT or PTC at the dose corresponding to the NOAEL from the 2 yr oral toxicity study. We then used the PBPK mo","page":73,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_024"} |
| Regulatory source | carcinogenicity | 0.5 | mg/kg bw/d | rat | - | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=0.5; DOSE=Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose.; EFFECT=were no toxicologically relevant treatment-related findings. Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose. The effects were also observed to a lesser degree at 1.5 mg/kg bw/d. The incidence of neoplastic findings was not influenced by substance treatment. Under the conditions of this study, NaPT was not carcinogenic to rats. Based on the non- neoplastic findings observed, a NOAEL of 0.5 mg/kg bw/d can be derived from this study. Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0.5 and 1.3 mg/kg (satellite) 20 per sex for the chronic study at the highest dose (satellite) Controls: 56 males and females for the carcinogenic study (main group) 12 males and females for the chronic study (satellite) Test substance: Natrium Pyrion 40% LSG Batch: 99072150 Purity:; CITATION=Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0; CITATION_NUMBERS=[11,453,56,12]; REFERENCE=Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0","dose":"Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose.","duration":"chronic","effect":"were no toxicologically relevant treatment-related findings. Non-neoplastic findings observed at the high dose were degeneration of muscle fibres, degeneration of spinal cord and sciatic nerve fibres and peripheral retinal atrophy at the high dose. The effects were also observed to a lesser degree at 1.5 mg/kg bw/d. The incidence of neoplastic findings was not influenced by substance treatment. Under the conditions of this study, NaPT was not carcinogenic to rats. Based on the non- neoplastic findings observed, a NOAEL of 0.5 mg/kg bw/d can be derived from this study. Ref.: E11 Guideline: OECD TG 453 Species/strain/sex: Rat / Sprague-Dawley Group size: 56 per sex /dose for the carcinogenic study (main group) 12 per sex for the chronic study at 0.5 and 1.3 mg/kg (satellite) 20 per sex for the chronic study at the highest dose (satellite) Controls: 56 males and females for the carcinogenic study (main group) 12 males and females for the chronic study (satellite) Test substance: Natrium Pyrion 40% LSG Batch: 99072150 Purity:","endpoint":"carcinogenicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.5","page":41,"route":"","species":"rat","study_id":"sccs_o_133_noael_009"} |
| Regulatory source | carcinogenicity | 0.5 | mg/kg/d | - | - | Chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=0.5; DOSE=Signs of toxicity (e.g. impaired limbs, motility impairment, ataxia, reduced body weights) were observed in animals at the mid and high dose.; EFFECT=were fixed and examined histopathologically. Results: Chronic study: Signs of toxicity (e.g. impaired limbs, motility impairment, ataxia, reduced body weights) were observed in animals at the mid and high dose. At microscopic examination, treatment- related changes were seen in the skeletal muscle of male and female animals in the high and mid dose groups at the end of the study. Dose-dependent changes in sciatic nerve were also observed in high-dose animals. From the results of the chronic part of the study, a NOAEL of 0.5 mg/kg/d was established. Carcinogenic study: Signs of toxicity such as ataxia, decrease muscle tone and emaciation were observed in animals of both sexes. Lower body weight was noted in low and high dose males and in mid- and high dose females. Low dose males were sacrificed on week 97 due to high mortality compared to controls, mortality in mid- and high dose females was higher compared to controls. However, there were no indications of significant different incidences of predominant pathology between con; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"Signs of toxicity (e.g. impaired limbs, motility impairment, ataxia, reduced body weights) were observed in animals at the mid and high dose.","duration":"Chronic","effect":"were fixed and examined histopathologically. Results: Chronic study: Signs of toxicity (e.g. impaired limbs, motility impairment, ataxia, reduced body weights) were observed in animals at the mid and high dose. At microscopic examination, treatment- related changes were seen in the skeletal muscle of male and female animals in the high and mid dose groups at the end of the study. Dose-dependent changes in sciatic nerve were also observed in high-dose animals. From the results of the chronic part of the study, a NOAEL of 0.5 mg/kg/d was established. Carcinogenic study: Signs of toxicity such as ataxia, decrease muscle tone and emaciation were observed in animals of both sexes. Lower body weight was noted in low and high dose males and in mid- and high dose females. Low dose males were sacrificed on week 97 due to high mortality compared to controls, mortality in mid- and high dose females was higher compared to controls. However, there were no indications of significant different incidences of predominant pathology between con","endpoint":"carcinogenicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"0.5","page":42,"route":"","species":"","study_id":"sccs_o_133_noael_010"} |
| Regulatory source | carcinogenicity | 88 | % | rat | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=88; DOSE=ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d...; EFFECT=ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment factors (AF) of 4 (interspecies differences in toxicokinetics) x 2.5 (interspecies differences in toxicodynamics or) x 3.16 (human variability in toxicokinetics) x 3.16 (human variability in toxicodynamics). Within REACH the interspecie; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d...","duration":"chronic","effect":"ithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment factors (AF) of 4 (interspecies differences in toxicokinetics) x 2.5 (interspecies differences in toxicodynamics or) x 3.16 (human variability in toxicokinetics) x 3.16 (human variability in toxicodynamics). Within REACH the interspecie","endpoint":"carcinogenicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"%","noael_value":"88","page":80,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_029"} |
| Regulatory source | carcinogenicity | 100 | % | rat | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=100; DOSE=SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (appl...; EFFECT=SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment facto; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (appl...","duration":"chronic","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 80 Systemic exposure dose (4.66 µg/kg/d+ 1 SD) = 5.25 µg/kg/d Lowest observed adverse effect level (mg/kg) = 500 µg/kg/d (oral chronic/carcinogenicity study, rat) Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d Margin of Safety (100 %bioavailability) NOAEL / SED = 31.8 Margin of Safety (88 %bioavailability) NOAEL / SED = 28.0 A reduced MoS is suggested for the safety evaluation of ZPT. Different frameworks (e.g. WHO/IPCS) further split up the MoS of 100 into sub-factors which could be replaced by data-derived subfactors, if such data is available: the MoS of 100 is composed of assessment facto","endpoint":"carcinogenicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"%","noael_value":"100","page":80,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_028"} |
| Regulatory source | carcinogenicity | 100 | % | rat | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=100; DOSE=SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 81 (oral chronic/carcinogenicity study, rat)167 Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/k...; EFFECT=SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 81 (oral chronic/carcinogenicity study, rat)167 Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d A = 1.51 mg/kg bw/d (shampoo) + 0.6 mg/kg bw/d (conditioner) = 2.11 mg/kg/d. C (%) (concentration of substance in finished cosmetic product) (%) = 2 Dap (%) = 1 Assuming 1 % dermal absorption in humans is supported by a human clinical study using 2 % ZPT shampoo formulations in combination with 0.1 % or 0.25 % ZPT containing leave-on formulations. In this study up to 0.22 % of the appli; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 81 (oral chronic/carcinogenicity study, rat)167 Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/k...","duration":"chronic","effect":"SCCS/1512/13 Revision of the opinion on zinc pyrithione (Colipa P81) ___________________________________________________________________________________________ 81 (oral chronic/carcinogenicity study, rat)167 Adjusted to NOAEL (application of adjustment factor of 3) = 167 µg/kg/d 100 % bioavailability = 167 µg/kg/d 88% bioavailability = 147 µg/kg/d A = 1.51 mg/kg bw/d (shampoo) + 0.6 mg/kg bw/d (conditioner) = 2.11 mg/kg/d. C (%) (concentration of substance in finished cosmetic product) (%) = 2 Dap (%) = 1 Assuming 1 % dermal absorption in humans is supported by a human clinical study using 2 % ZPT shampoo formulations in combination with 0.1 % or 0.25 % ZPT containing leave-on formulations. In this study up to 0.22 % of the appli","endpoint":"carcinogenicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"%","noael_value":"100","page":81,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_031"} |
| Regulatory source | carcinogenicity | 500 | - | - | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=unclear:be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.; DOSE=be considered adequate to assess repeat-dose effects of ZPT.; EFFECT=be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"be considered adequate to assess repeat-dose effects of ZPT.","duration":"chronic","effect":"be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","endpoint":"carcinogenicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"","noael_value":"unclear:be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","page":43,"route":"oral","species":"","study_id":"sccs_o_133_noael_013"} |
| Regulatory source | carcinogenicity | 500 | - | - | oral | chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=unclear:sidered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.; DOSE=sidered adequate to assess repeat-dose effects of ZPT.; EFFECT=sidered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"sidered adequate to assess repeat-dose effects of ZPT.","duration":"chronic","effect":"sidered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","endpoint":"carcinogenicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"","noael_value":"unclear:sidered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. Two oral chronic studies performed with NaPT have been provided by the applicant. In a combined chronic toxicity/carcinogenicity study the dose of 500 µg/kg bw/d is considered as LOAEL by the SCCS.","page":81,"route":"oral","species":"","study_id":"sccs_o_133_noael_033"} |
| Regulatory source | developmental toxicity | 0.5 | mg/kg bw/d | rat | dermal | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=0.5; DOSE=f 12 % were observed in controls and low dose animals, which increased with increasing dose.; EFFECT=f 12 % were observed in controls and low dose animals, which increased with increasing dose. The number of dams with viable fetuses was decreased at the highest dose. The incidence of fetuses with abnormalities was increased at the highest dose. The cases of fetal abnormalities were different in type and there was no dose-relationship. A very high incidence of post-implantation losses was observed at the highest dose, which is considered treatment-related, but might be seen as a consequence of maternal toxicity. A NOAEL of 0.5 mg/kg bw/d for maternal and developmental toxicity can be derived from this study. Ref.: E24 Guideline: OPPTS 870.3700 Species/strain/sex: Rat / Crl:CD® (SD)IGS BR VAF/Plus®/ female Group size: 24 at 10, 15 and 30 mg/kg bw/d; 25 at 60.0 mg/kg bw/d Controls: 23 animals, vehicle Test substance: Zinc Pyridinethione (ZPT) – an off-white to tan powder Batch: 0108244691 Purity: 95 – 99 % Vehicle: reverse osmosis membrane deinonized water Dose levels: 10.0, 15.0, 30.0 and 60.0 mg/kg/d Exposure: dermal, ingestio; CITATION=Ref.: E24 Guideline: OPPTS 870; CITATION_NUMBERS=[24,870]; REFERENCE=Ref.: E24 Guideline: OPPTS 870; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E24 Guideline: OPPTS 870","dose":"f 12 % were observed in controls and low dose animals, which increased with increasing dose.","duration":"developmental","effect":"f 12 % were observed in controls and low dose animals, which increased with increasing dose. The number of dams with viable fetuses was decreased at the highest dose. The incidence of fetuses with abnormalities was increased at the highest dose. The cases of fetal abnormalities were different in type and there was no dose-relationship. A very high incidence of post-implantation losses was observed at the highest dose, which is considered treatment-related, but might be seen as a consequence of maternal toxicity. A NOAEL of 0.5 mg/kg bw/d for maternal and developmental toxicity can be derived from this study. Ref.: E24 Guideline: OPPTS 870.3700 Species/strain/sex: Rat / Crl:CD® (SD)IGS BR VAF/Plus®/ female Group size: 24 at 10, 15 and 30 mg/kg bw/d; 25 at 60.0 mg/kg bw/d Controls: 23 animals, vehicle Test substance: Zinc Pyridinethione (ZPT) – an off-white to tan powder Batch: 0108244691 Purity: 95 – 99 % Vehicle: reverse osmosis membrane deinonized water Dose levels: 10.0, 15.0, 30.0 and 60.0 mg/kg/d Exposure: dermal, ingestio","endpoint":"developmental toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.5","page":56,"route":"dermal","species":"rat","study_id":"sccs_o_133_noael_020"} |
| Regulatory source | developmental toxicity | 0.75 | mg/kg/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=0.75; DOSE=Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose.; EFFECT=Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose. At 3.0 mg/kg bw/d, a slight increase in the incidence of fetal malformations and a less pronounced increase in mean postimplantation loss compared to controls were observed. However, as fetal effects occur at dosages where maternal toxicity is observed, the test article is not considered as a developmental toxicant. A NOAEL of 0.75 mg/kg/d is derived from the study for maternal and developmental toxicity. Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test substance: Zinc Omadine ®, 48 % aqueous solution Batch: 33-22902781 Purity: 52.2 % Vehicle: deionised water Dose levels: 0.5, 2.0, 4.0, 8.0 and 12.0 mg/kg bw/d Exposure: oral, gavage, once daily on GD 6 - 18 GLP statement: yes Date: 1993 Dose lev; CITATION=Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test; CITATION_NUMBERS=[23,83,3,414,20]; REFERENCE=Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test","dose":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose.","duration":"developmental","effect":"Colipa P81) ___________________________________________________________________________________________ 56 postimplantation loss) and mean fetal weight were also adversely affected at the high dose. At 3.0 mg/kg bw/d, a slight increase in the incidence of fetal malformations and a less pronounced increase in mean postimplantation loss compared to controls were observed. However, as fetal effects occur at dosages where maternal toxicity is observed, the test article is not considered as a developmental toxicant. A NOAEL of 0.75 mg/kg/d is derived from the study for maternal and developmental toxicity. Ref.: E23 Guideline: US-EPA 83-3 (Comparable to OECD TG 414) Species/strain/sex: New Zealand White Rabbits Group size: 20 females/dose Controls: 20 female animals receiving vehicle Test substance: Zinc Omadine ®, 48 % aqueous solution Batch: 33-22902781 Purity: 52.2 % Vehicle: deionised water Dose levels: 0.5, 2.0, 4.0, 8.0 and 12.0 mg/kg bw/d Exposure: oral, gavage, once daily on GD 6 - 18 GLP statement: yes Date: 1993 Dose lev","endpoint":"developmental toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"0.75","page":56,"route":"oral","species":"rabbit","study_id":"sccs_o_133_noael_019"} |
| Regulatory source | irritation | 2 | % | human | - | - | irritation | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=2.0; DOSE=With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism:; EFFECT=ing grounds: With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism: (1) it results from the concomitant use of rinse-off shampoo in combination with leave-on tonic, (2) it is a value, to which 1 standard deviation has been added in order to cope for more extended periods of application and (3) it results from the upper boundary of internal exposure determined in the human clinical study. With respect to the TD part: (1) the previously derived NOAEL of 500 µg/kg bw/d has been converted to a LOAEL based on the occurrence of some effects which could not be retraced further due to unavailability of data. (2) ZPT has been used as an anti-dandruff active in shampoo formulations at levels of 1.0 and 2.0% since the 1940’s. During this time there has been little evidence of any serious adverse effects from this usage, and those few effects that have been recorded are limited to eye and skin irritation as can be expected for surfactant-based formulations. Therefore a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism:","duration":"","effect":"ing grounds: With respect to the TK part: the value of the systemic exposure dose of 5.25 µg/kg bw/d comprises three layers of conservatism: (1) it results from the concomitant use of rinse-off shampoo in combination with leave-on tonic, (2) it is a value, to which 1 standard deviation has been added in order to cope for more extended periods of application and (3) it results from the upper boundary of internal exposure determined in the human clinical study. With respect to the TD part: (1) the previously derived NOAEL of 500 µg/kg bw/d has been converted to a LOAEL based on the occurrence of some effects which could not be retraced further due to unavailability of data. (2) ZPT has been used as an anti-dandruff active in shampoo formulations at levels of 1.0 and 2.0% since the 1940’s. During this time there has been little evidence of any serious adverse effects from this usage, and those few effects that have been recorded are limited to eye and skin irritation as can be expected for surfactant-based formulations. Therefore a","endpoint":"irritation","ingredient":"Bis[(2","loael_value":"","noael_unit":"%","noael_value":"2.0","page":80,"route":"","species":"human","study_id":"sccs_o_133_noael_030"} |
| Regulatory source | repeated dose toxicity | 5 | mg/kg/d | - | oral | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=5; DOSE=tatistically significant at the highest dose.; EFFECT=tatistically significant at the highest dose. No treatment-related effects on sceletal muscle or sciatic nerve were observed in that study. Dermal administration of NaPT had no effect on tumour incidence. Thus, based on the results of this study, NaPT induced slight histopathologic changes at the treatment site but did not influence tumour formation. SCCS comment No information of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SC; CITATION=Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT; CITATION_NUMBERS=[12]; REFERENCE=Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT","dose":"tatistically significant at the highest dose.","duration":"chronic","effect":"tatistically significant at the highest dose. No treatment-related effects on sceletal muscle or sciatic nerve were observed in that study. Dermal administration of NaPT had no effect on tumour incidence. Thus, based on the results of this study, NaPT induced slight histopathologic changes at the treatment site but did not influence tumour formation. SCCS comment No information of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SC","endpoint":"repeated dose toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"5","page":43,"route":"oral","species":"","study_id":"sccs_o_133_noael_011"} |
| Regulatory source | repeated dose toxicity | 5 | mg/kg/d | - | oral | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=5; DOSE=For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study.; EFFECT=rmation of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T; CITATION=Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT; CITATION_NUMBERS=[12]; REFERENCE=Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT","dose":"For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study.","duration":"chronic","effect":"rmation of effects/findings in skeletal muscles and/or sciatic nerves can be obtained from that study. For local effects at the treatment site, a NOEL of 5 mg/kg/d can be obtained from that study. Ref.: E12 Summary on repeat dose toxicity and chronic toxicity Oral: Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and two chronic oral studies performed with sodium pyrithione (NaPT) can be considered adequate to assess repeat-dose effects of ZPT. A NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T","endpoint":"repeated dose toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"5","page":43,"route":"oral","species":"","study_id":"sccs_o_133_noael_012"} |
| Regulatory source | repeated dose toxicity | 100 | mg/kg/d | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=100; DOSE=re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level).; EFFECT=re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats. NOAELs of 50 and 25 mg/kg bw/d were obtained for male and female animals, respectively. A further subchronic toxicity study is mentioned on ECHA's website (http://echa.europa.eu/). The study is not available for evaluation. A NOAEL of 100 mg/kg/d was derived from that study. SCCS comment to studies with dermal administration of ZPT The fact that hindlimb weakness after dermal administration was not observed in some of the studies might be due to the dosing regimen and the vehicle used. In oral studies it could be demonstrated that in contrast to continuous administration, effects were less pronounced or not observable, when there were discontinuities in the dosing (e.g. 5 days per week). Further, when using water or DMSO as vehicle, toxic e; CITATION=Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats; CITATION_NUMBERS=[1,2003,2012]; REFERENCE=Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats","dose":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level).","duration":"subchronic","effect":"re observed in the 50 and 75 mg/kg/d group (electrophysiological measurements not taken at the 100 mg/kg/d dose level). Ref.: D1 Arch Chemicals 2003 (Link given in MAK (2012)) SCCS comment This study demonstrated that hindlimb effects occur after short-term repeated dermal exposure of rats. NOAELs of 50 and 25 mg/kg bw/d were obtained for male and female animals, respectively. A further subchronic toxicity study is mentioned on ECHA's website (http://echa.europa.eu/). The study is not available for evaluation. A NOAEL of 100 mg/kg/d was derived from that study. SCCS comment to studies with dermal administration of ZPT The fact that hindlimb weakness after dermal administration was not observed in some of the studies might be due to the dosing regimen and the vehicle used. In oral studies it could be demonstrated that in contrast to continuous administration, effects were less pronounced or not observable, when there were discontinuities in the dosing (e.g. 5 days per week). Further, when using water or DMSO as vehicle, toxic e","endpoint":"repeated dose toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"100","page":37,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_006"} |
| Regulatory source | repeated dose toxicity | 2000 | mg/kg | - | oral | sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=2000; DOSE=Several oral repeat-dose studies of different durations have been performed with ZPT.; EFFECT=2000 mg/kg. Acute inhalation studies have been performed with ZPT. According to one of the studies, classification as Acute Tox 3; H331 (toxic if inhaled) according to CLP as suggested by the registrant(s) under REACH (ECHA website (http://echa.europa.eu/) is justified. Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and a chronic oral studies performed with sodium pyrithione can be considered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"13463-41-7","citation":"","dose":"Several oral repeat-dose studies of different durations have been performed with ZPT.","duration":"sub-chronic","effect":"2000 mg/kg. Acute inhalation studies have been performed with ZPT. According to one of the studies, classification as Acute Tox 3; H331 (toxic if inhaled) according to CLP as suggested by the registrant(s) under REACH (ECHA website (http://echa.europa.eu/) is justified. Several oral repeat-dose studies of different durations have been performed with ZPT. In addition, one sub-chronic and a chronic oral studies performed with sodium pyrithione can be considered adequate to assess repeat-dose effects of ZPT. An oral NOAEL of 500 µg/kg/d obtained from a chronic oral study (Larson, 1958) performed with ZPT based on paralysis/hind-limb weakness has been derived in SCCNFP 0671/03. The SCCS is aware that HSE (2003) considered the Larson 1958 study as inadequate due to insufficiently large group sizes to ensure statistical power. However, a 90-day oral study performed with sodium pyrithione (not available to the SCCS) which was considered adequate by HSE, also lead to a NOAEL of 500 µg/kg/d, supporting the outcome of the Larsson study. T","endpoint":"repeated dose toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg","noael_value":"2000","page":81,"route":"oral","species":"","study_id":"sccs_o_133_noael_032"} |
| Regulatory source | reproductive toxicity | 1.5 | mg/kg/d | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=1.5; DOSE=However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.; EFFECT=the top dose. There were no effects on the success or duration of gestation, number of live births, viability, lactation and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*; CITATION=Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes; CITATION_NUMBERS=[22,83,4,416,25]; REFERENCE=Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","duration":"","effect":"the top dose. There were no effects on the success or duration of gestation, number of live births, viability, lactation and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*","endpoint":"reproductive toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"1.5","page":51,"route":"","species":"rat","study_id":"sccs_o_133_noael_016"} |
| Regulatory source | reproductive toxicity | 1.5 | mg/kg bw/d | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=1.5; DOSE=At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females.; EFFECT=parental animals and offspring from two generations: in parental animals, a reduction in body weight gain, atrophy of hind limb muscles, hindlimb paralysis, impaired movement and adverse effects on F0 generation fertility and mating performance were observed. In the offspring, there was evidence of a slight retardation of development during lactation. At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females. From the results of this study, a parental NOAEL of 1.5 mg/kg bw/d can be derived. For the offspring, NOAELs of 1.5 and 0.5 mg/kg bw/d can be derived for male and female animals, respectively. Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa.europa.eu/). This study is not available for evaluation: - a 2-generation study performed according to EPA OPPTS 870.3800 in male and female Sprague-Dawley rats receiving 0, 0.7, 1.4, and 2.8 mg/kg/d aqueous substance by gavage. For parental animals, NOAELs of 1.4 and 0.7 mg/kg/d were; CITATION=Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa; CITATION_NUMBERS=[21,2]; REFERENCE=Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa","dose":"At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females.","duration":"","effect":"parental animals and offspring from two generations: in parental animals, a reduction in body weight gain, atrophy of hind limb muscles, hindlimb paralysis, impaired movement and adverse effects on F0 generation fertility and mating performance were observed. In the offspring, there was evidence of a slight retardation of development during lactation. At 1.5 mg/kg bw/d toxic changes in the parental animals were limited to atrophy of the hindlimb muscles in a few females. From the results of this study, a parental NOAEL of 1.5 mg/kg bw/d can be derived. For the offspring, NOAELs of 1.5 and 0.5 mg/kg bw/d can be derived for male and female animals, respectively. Ref.: E21 A further two-2-generation study is mentioned on ECHA's website (http://echa.europa.eu/). This study is not available for evaluation: - a 2-generation study performed according to EPA OPPTS 870.3800 in male and female Sprague-Dawley rats receiving 0, 0.7, 1.4, and 2.8 mg/kg/d aqueous substance by gavage. For parental animals, NOAELs of 1.4 and 0.7 mg/kg/d were","endpoint":"reproductive toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1.5","page":52,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_018"} |
| Regulatory source | reproductive toxicity | 3.5 | mg/kg/d | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=3.5; DOSE=However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.; EFFECT=and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*) mg/kg bw/d Exposure: oral, gavage, once daily GLP statement: yes Date: 1987 – 1988 *) 4.5 mg/kg bw/d in weeks 1, 2; CITATION=Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes; CITATION_NUMBERS=[22,83,4,416,25]; REFERENCE=Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Tes","dose":"However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15.","duration":"","effect":"and the cumulative survival score in the F2 generation. In F2 pups no effects on pup weight were observed. No abnormalities were found following necropsy. No effects on development of ear opening, righting reflex or eye opening were observed. However, in the top dose a reduced incidence of startle response (by 10 %), an indicator of delayed development, was observed on day 15. From this study, a NOAEL of 1.5 mg/kg/d was established for parental toxicity based on hind limb impairment and skeletal muscle atrophy. An NOAEL of 3.5 mg/kg/d was derived for fertility effects. Ref.: E22 Guideline: US EPA 83-4 (Complies with OECD 416) Species/strain/sex: Rat / Crl:CD® (SD) BR Group size: 25 per sex / dose Controls: 25 per sex, 0 mg test substance in vehicle Test substance: Sodium Omadine / Sodium Pyrithione Batch: 8508-P-166H Purity: 41.2 % [w/w] aqueous solution Vehicle: distilled water Dose levels: 0.5, 1.5 and 3.5*) mg/kg bw/d Exposure: oral, gavage, once daily GLP statement: yes Date: 1987 – 1988 *) 4.5 mg/kg bw/d in weeks 1, 2","endpoint":"reproductive toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"3.5","page":51,"route":"oral","species":"rat","study_id":"sccs_o_133_noael_017"} |
| Regulatory source | reproductive toxicity | 7.5 | mg/kg/d | rat | dermal | 8-week | reproductive toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=7.5; DOSE=with untreated females of untreated males were mated with treated females.; EFFECT=with untreated females of untreated males were mated with treated females. ZPT dosed rats from the 8-week treatment scheme did not differ significantly from controls in either growth or reproductive characteristics except a statistically significantly lower lactation index in females of the highest dose group. No toxic signs such as paralysis and no test-related histopathology was seen in the males. Further, neither reproduction nor neonatal viability was affected after topical administration of ZPT on GD 6—15. A NOAEL of 7.5 mg/kg/d can be derived from this dermal study. Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies. 3.4.8.2. Two generation reproduction toxicity Two two generation reproduction toxicity studies performed with sodium pyrithione, from which read-across to ZPT is considered appropriate (see section 3.3.5.3) have been provided. Guideline: not stated Species/strain/sex: Rat / Sprague-Dawley (OFA-SD; CITATION=Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies; CITATION_NUMBERS=[43,671,3]; REFERENCE=Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies","dose":"with untreated females of untreated males were mated with treated females.","duration":"8-week","effect":"with untreated females of untreated males were mated with treated females. ZPT dosed rats from the 8-week treatment scheme did not differ significantly from controls in either growth or reproductive characteristics except a statistically significantly lower lactation index in females of the highest dose group. No toxic signs such as paralysis and no test-related histopathology was seen in the males. Further, neither reproduction nor neonatal viability was affected after topical administration of ZPT on GD 6—15. A NOAEL of 7.5 mg/kg/d can be derived from this dermal study. Reference: B43 SCCS comment This study was already available for SCCNFP 0671/03, but therein it was discussed together with the developmental/teratogenic studies. 3.4.8.2. Two generation reproduction toxicity Two two generation reproduction toxicity studies performed with sodium pyrithione, from which read-across to ZPT is considered appropriate (see section 3.3.5.3) have been provided. Guideline: not stated Species/strain/sex: Rat / Sprague-Dawley (OFA-SD","endpoint":"reproductive toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg/d","noael_value":"7.5","page":50,"route":"dermal","species":"rat","study_id":"sccs_o_133_noael_015"} |
| Regulatory source | reproductive toxicity | 15 | mg/kg bw/d | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=15; DOSE=There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...; EFFECT=ebrae, forelimb phalanges, metacarpals, hindlimb phalanges and metatarsals. There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up t; CITATION=Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2; CITATION_NUMBERS=[1,671,3,2]; REFERENCE=Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","duration":"developmental","effect":"ebrae, forelimb phalanges, metacarpals, hindlimb phalanges and metatarsals. There was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up t","endpoint":"reproductive toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"15","page":57,"route":"","species":"rat","study_id":"sccs_o_133_noael_021"} |
| Regulatory source | reproductive toxicity | 30 | mg/kg bw /d | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_133; REPORT_TITLE=OPINION ON Zinc pyrithione COLIPA n° P81 - Text from previous opinion (SCCNFP/0671/03) has not been edited -; OPINION_NUMBER=SCCS/1512/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 june 2014; VALUE_TEXT=30; DOSE=here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...; EFFECT=here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up to 15 and 100 mg ZPT/kg/d respectively (highest doses tested) and ingestion of; CITATION=Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2; CITATION_NUMBERS=[1,671,3,2]; REFERENCE=Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2; DETAILS_JSON={"cas_number":"13463-41-7","citation":"Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2","dose":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched...","duration":"developmental","effect":"here was an increased number of rats with limited use of hindlimbs in the 30 mg/kg/d group and an (significantly) increased number of rats with erythema grade 1, flaking grade 1, limited or no use of hindlimbs, low muscle tone, shuffling gait, dehydration, ungroomed coat, low carriage, chromodacryorrhea, emaciation, chromorhinorrhea and hunched posture in the 60 mg/kg/d dose group. Based on the results of this study, a maternal (systemic) NOAEL of 15 mg/kg bw/d based on limited use of hindlimbs and a developmental NOAEL of 30 mg/kg bw /d were derived. ZPT was not considered as a selective developmental toxicant. Ref.: E1 Conclusion on Reproductive toxicity In SCCNFP 0671/03 the following conclusions were drawn with respect to Reproductive toxicity of ZPT: - 2.5 mg/kg/d administered orally to rats is a no effect level for teratological effects - no reproductive effects have been observed when ZPT was applied topically to rats and rabbits at levels up to 15 and 100 mg ZPT/kg/d respectively (highest doses tested) and ingestion of","endpoint":"reproductive toxicity","ingredient":"Bis[(2","loael_value":"","noael_unit":"mg/kg bw /d","noael_value":"30","page":57,"route":"","species":"rat","study_id":"sccs_o_133_noael_022"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | R953O2RHZ5 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"2C5H4NOS.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R953O2RHZ5"} |
| openFDA substances | FDA UNII substance identifier | R953O2RHZ5 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"2C5H4NOS.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R953O2RHZ5"} |
| openFDA substances | FDA UNII substance identifier | R953O2RHZ5 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"2C5H4NOS.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R953O2RHZ5"} |
| openFDA substances | FDA UNII substance identifier | R953O2RHZ5 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"2C5H4NOS.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R953O2RHZ5"} |