NOAEL Studies Cosmetic Ingredient

Methyl Pyrrolidone NOAEL Studies

INCI: METHYL PYRROLIDONE (N-METHYL-2-PYRROLIDONE, NMP)

CAS: 872-50-4

Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.

California Proposition 65 8 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
California Proposition 65 California Proposition 65 MADL ABinhalation=3200; oral=17000 (dermal) ug/day - - 2001-06-15 Maximum allowable dose level {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"row_type":"madl","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 MADL ABinhalation=3200; oral=17000 (dermal) ug/day - - 2001-06-15 Maximum allowable dose level {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"row_type":"madl","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 MADL ABinhalation=3200; oral=17000 (dermal) ug/day - - 2001-06-15 Maximum allowable dose level {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"row_type":"madl","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 MADL ABinhalation=3200; oral=17000 (dermal) ug/day - - 2001-06-15 Maximum allowable dose level {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"row_type":"madl","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 listing ABdevelopmental listing type - - 2001-06-15 California Proposition 65 listing {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 listing ABdevelopmental listing type - - 2001-06-15 California Proposition 65 listing {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 listing ABdevelopmental listing type - - 2001-06-15 California Proposition 65 listing {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 listing ABdevelopmental listing type - - 2001-06-15 California Proposition 65 listing {"cancer_reproductive":"developmental","listed_date":"2001-06-15","listing_mechanism":"AB","madl":"inhalation=3200; oral=17000 (dermal)","nsrl":null,"source_table":"prop65_listings"}
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =90 mg/kg bw/day Mouse - - chronic/long term toxicity EFSA AFC - 2005 - OutputID 337 - organ weights - hepatotoxicity - Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to a 7th list of substances for food contact materials - doi:10.2903/j.efsa.2005.201a
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =90 mg/kg bw/day Mouse - - chronic/long term toxicity EFSA AFC - 2005 - OutputID 337 - organ weights - hepatotoxicity - Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to a 7th list of substances for food contact materials - doi:10.2903/j.efsa.2005.201a
INCHEM_WHO_cicads_cicads_cicad35 24 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =74 mg/kg bw - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=f74d585b1a1ba645; raw_unit=mg/kg body weight; context=The LOAEL for repeated doses was 74 mg/kg body weight administered on days 7–11 of gestation.
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =107.142857142857 mg/kg bw/day Rat inhalation 7 days Reproductive toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=af5f9ccc4f355304; raw_unit=mg/kg body weight per day; unit_normalization=converted from weekly dose; context=LOAEL = 750 mg/kg body weight per day Becci et al., 1982 In a reproduction study, male rats (12 per dose level) were exposed whole body to 0 or 618 mg NMP/m 3 (vapour; <50% relative humidity) for 6 h/day, 7 days/week, for 90 days.
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =360 mg/m3 Rat dermal - Developmental toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=1fd4b20a8b9c89de; raw_unit=mg/m 3; context=LOAEL = 360 mg/m 3 Lee et al., 1987 Rat; range-finding developmental toxicity study; dermal; days 6–15 0 mg/kg body weight per day 500 mg/kg body weight per day 1100 mg/kg body weight per day 2500 mg/kg body weight per day – – – – None None Massive resorption; decreased body we
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =478 mg/m3 - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=a6a7362aa417fa70; raw_unit=mg/m 3; context=LOAEL = 478 mg/m 3 Maternal toxicity:
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =622 mg/m3 - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=239455562d79ef01; raw_unit=mg/m 3; context=LOAEL = 622 mg/m 3 Maternal toxicity:
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =680 mg/m3 - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=3679c8c889529adc; raw_unit=mg/m 3; context=LOAEL = 680 mg/m 3 Maternal toxicity:
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =750 mg/kg bw/day - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=fc6f35250e400718; raw_unit=mg/kg body weight per day; context=LOAEL = 750 mg/kg body weight per day Maternal toxicity:
INCHEM_WHO_cicads_cicads_cicad35 LOAEL =1100 mg/kg bw/day Rat dermal - Developmental toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=82a74a15dffd29bb; raw_unit=mg/kg body weight per day; context=LOAEL = 1100 mg/kg body weight per day Becci et al., 1982 Rat; developmental toxicity study; dermal; days 6–15 0 mg/kg body weight per day 75 mg/kg body weight per day 237 mg/kg body weight per day 750 mg/kg body weight per day None None None Increased resorption, delayed ossification None None No
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =100 mg/m3 - inhalation - Developmental toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=f96fdb53ff2f6e99; raw_unit=mg/m 3; context=In an inhalation study (whole-body exposure), the NOAEL for maternal effects was 100 mg/m 3 , and the NOAEL for developmental effects was 360 mg/m 3 .
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =169 mg/kg bw - oral - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=d483fcb37c02cf1c; raw_unit=mg/kg body weight; context=The NOAEL for this study was 3000 mg NMP/kg diet (equivalent to mean doses of 169 mg/kg body weight in males and 217 mg/kg body weight in females) (E.I. du Pont de Nemours and Company, 1995b).
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =206 mg/m3 - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=5b89b590f88633e8; raw_unit=mg/m 3; context=NOAEL = 206 mg/m 3 ;
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =217 mg/kg bw - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=0deb8de7ab7b6553; raw_unit=mg/kg; context=La NOAEL était respectivement égale à 169 et à 217 mg/kg p.c. pour les mâles et les femelles.
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =237 mg/kg bw - - - Developmental toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=9f8a48316195d9f1; raw_unit=mg/kg body weight; context=The NOAEL for both developmental effects and maternal toxicity (decreased body weight gain) was 237 mg/kg body weight.
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =237 mg/kg bw/day - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=3c01bcd93ca2808d; raw_unit=mg/kg body weight per day; context=NOAEL = 237 mg/kg body weight per day;
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =250 mg/kg bw/day Dog oral - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=c63be3991524adc4; raw_unit=mg/kg body weight per day; context=The NOAEL for dietary exposure in dogs in this study is 250 mg/kg body weight per day.
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =360 mg/m3 - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=d893ccf8652b40eb; raw_unit=mg/m 3; context=NOAEL = 360 mg/m 3 Maternal toxicity:
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =429 mg/kg bw - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=52265a33dae29736; raw_unit=mg/kg; context=La dose sans effet indésirable observable (NOAEL) était de 429 mg/kg p.c. pour les mâles et de 1548 mg/kg p.c. pour les femelles.
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =500 mg/m3 - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=769b92d12ab204e7; raw_unit=mg/m 3; context=The NOAEL was 500 mg/m 3 .
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =514 mg/kg bw - - - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=d91ef8610b6d1095; raw_unit=mg/kg body weight; context=The NOAEL in this study was 514 mg/kg body weight.
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =618 mg/m3 Rat inhalation two-generation Developmental toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=d480b40d8adc6292; raw_unit=mg/m 3; context=NOAEL = 618 mg/m 3 Fries et al., 1992 Rat; two-generation study; inhalation (whole body) 0 mg/m 3 478 mg/m 3 None Fetal body weight decrease (mean 7%) None None Developmental toxicity:
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =622 mg/m3 Rat inhalation 3 days Developmental toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=e6674c884d58e804; raw_unit=mg/m 3; context=NOAEL = 622 mg/m 3 Hass et al., 1994 Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m 3 100 mg/m 3 360 mg/m 3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity:
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =680 mg/m3 Rat inhalation - Developmental toxicity document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=4107de33fce45ca1; raw_unit=mg/m 3; context=NOAEL = 680 mg/m 3 Hass et al., 1995 Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m 3 622 mg/m 3 None Decreased body weight; neurobehavioural effects None None Developmental toxicity:
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =2500 mg/kg diet Mouse oral - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=0d4d90e3352ca90a; raw_unit=mg/kg diet; context=Based on this study, the NOAEL was found to be 2500 mg/kg diet (720 mg/kg body weight) in male mice and 7500 mg/kg diet (2970 mg/kg body weight) in female mice.
INCHEM_WHO_cicads_cicads_cicad35 NOAEL =6000 mg/kg diet Rat oral - Toxicology study document_id=cicads_cicads_cicad35; title=N-METHYL-2-PYRROLIDONE (CICAD 35, 2001); path=mirror/documents/cicads/cicads/cicad35.htm; row_hash=390b52ec72beee7b; raw_unit=mg/kg diet; context=Based on this study, the NOAEL was found to be 6000 mg/kg diet (429 mg/kg body weight) in male rats and 18 000 mg/kg diet (1548 mg/kg body weight) in female rats.
NTP_ICE_acute_oral 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_oral LD50 =3914 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_11105; row=9994; data_type=In Vivo; mixture=Chemical; chemical_name=N-Methyl-2-pyrrolidone; preferred_name=N-Methyl-2-pyrrolidone; dtxsid=DTXSID6020856; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6020856; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID6020856; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =4320 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_11107; row=9993; data_type=In Vivo; mixture=Chemical; chemical_name=N-Methyl-2-pyrrolidone; preferred_name=N-Methyl-2-pyrrolidone; dtxsid=DTXSID6020856; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6020856; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID6020856; source_file=acute_oral.xlsx
NTP_ICE_adme_parameters 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_adme_parameters Clint 0.2081 uL/min/10^6 cells Human - - Measured; httk, Human Hepatic Intrinsic Clearance sheet=Data; excel_row=2343; Record_ID=adme_parameters_1109; Data_Type=Measured; DTXSID=DTXSID6020856; Assay=httk, Human Hepatic Intrinsic Clearance; Endpoint=Clint; Response=0.2081; Response_Unit=ul/min/10^6 cells; Species=Human; Reference=httk2.3.1, Linakis 2020; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6020856; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID6020856
NTP_ICE_adme_parameters Clint 0.3239 uL/min/10^6 cells Rat - - Measured; httk, Rat Hepatic Intrinsic Clearance sheet=Data; excel_row=2344; Record_ID=adme_parameters_1109; Data_Type=Measured; DTXSID=DTXSID6020856; Assay=httk, Rat Hepatic Intrinsic Clearance; Endpoint=Clint; Response=0.3239; Response_Unit=ul/min/10^6 cells; Species=Rat; Reference=httk2.3.1, Linakis 2020; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6020856; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID6020856
NTP_ICE_adme_parameters Fu 0.7131 fraction Rat - - Measured; httk, Rat Plasma Fraction Unbound sheet=Data; excel_row=2341; Record_ID=adme_parameters_1109; Data_Type=Measured; DTXSID=DTXSID6020856; Assay=httk, Rat Plasma Fraction Unbound; Endpoint=Fu; Response=0.7131; Response_Unit=Unitless Fraction; Species=Rat; Reference=httk2.3.1, Linakis 2020; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6020856; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID6020856
NTP_ICE_adme_parameters Fu 0.888 fraction Human - - Measured; httk, Human Plasma Fraction Unbound sheet=Data; excel_row=2342; Record_ID=adme_parameters_1109; Data_Type=Measured; DTXSID=DTXSID6020856; Assay=httk, Human Plasma Fraction Unbound; Endpoint=Fu; Response=0.888; Response_Unit=Unitless Fraction; Species=Human; Reference=httk2.3.1, Wambaugh 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6020856; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID6020856
NTP_ICE_endocrine 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_endocrine Model Score 0 unitless - - - ARPathway2016; AR Pathway Model, Antagonist sheet=Integrated_approaches; excel_row=12268; RecordID=ARPathway2016_1660; DatasetName=ARPathway2016; DTXSID=DTXSID6020856; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6020856; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID6020856
SCCS_vision_codex 168 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =1 - rabbit - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: Rabbit, | 200 mg/ | m3 | No | ne | None | maternal toxicity: 1 | 993b.","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_093"}
SCCS_vision_codex NOAEL =1 - rabbit - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: Rabbit, | 200 mg/ | m3 | No | ne | None | maternal toxicity: 1 | 993b.","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_093"}
SCCS_vision_codex NOAEL =1 - rabbit - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: Rabbit, | 200 mg/ | m3 | No | ne | None | maternal toxicity: 1 | 993b.","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_093"}
SCCS_vision_codex NOAEL =1 - rabbit - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: Rabbit, | 200 mg/ | m3 | No | ne | None | maternal toxicity: 1 | 993b.","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_093"}
SCCS_vision_codex NOAEL =2 - rat oral developmental reproductive toxicity {"dose":", occurred in the absence of significant maternal toxicity in rats treated by gavage.","effect":", occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_048"}
SCCS_vision_codex NOAEL =2 - rat oral developmental reproductive toxicity {"dose":", occurred in the absence of significant maternal toxicity in rats treated by gavage.","effect":", occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_048"}
SCCS_vision_codex NOAEL =2 - rat oral developmental reproductive toxicity {"dose":", occurred in the absence of significant maternal toxicity in rats treated by gavage.","effect":", occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_048"}
SCCS_vision_codex NOAEL =2 - rat oral developmental reproductive toxicity {"dose":", occurred in the absence of significant maternal toxicity in rats treated by gavage.","effect":", occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_048"}
SCCS_vision_codex NOAEL =4 - rat inhalation Developmental developmental toxicity {"effect":"ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_042"}
SCCS_vision_codex NOAEL =4 - rat inhalation Developmental developmental toxicity {"effect":"ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_042"}
SCCS_vision_codex NOAEL =4 - rat inhalation Developmental developmental toxicity {"effect":"ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_042"}
SCCS_vision_codex NOAEL =4 - rat inhalation Developmental developmental toxicity {"effect":"ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_042"}
SCCS_vision_codex NOAEL =6 - rat inhalation developmental developmental toxicity {"effect":"t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_045"}
SCCS_vision_codex NOAEL =6 - rat inhalation developmental developmental toxicity {"effect":"t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_045"}
SCCS_vision_codex NOAEL =6 - rat inhalation developmental developmental toxicity {"effect":"t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_045"}
SCCS_vision_codex NOAEL =6 - rat inhalation developmental developmental toxicity {"effect":"t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_045"}
SCCS_vision_codex NOAEL =11 % rat inhalation developmental reproductive toxicity {"dose":"NOAEL = 55 mg/kg bw/day Developmental toxicity:","effect":"ted. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developm","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_038"}
SCCS_vision_codex NOAEL =11 % rat inhalation developmental reproductive toxicity {"dose":"NOAEL = 55 mg/kg bw/day Developmental toxicity:","effect":"ted. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developm","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_038"}
SCCS_vision_codex NOAEL =11 % rat inhalation developmental reproductive toxicity {"dose":"NOAEL = 55 mg/kg bw/day Developmental toxicity:","effect":"ted. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developm","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_038"}
SCCS_vision_codex NOAEL =11 % rat inhalation developmental reproductive toxicity {"dose":"NOAEL = 55 mg/kg bw/day Developmental toxicity:","effect":"ted. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developm","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_038"}
SCCS_vision_codex NOAEL =14.8 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 66 3","dose":"EL = 48 mg/kg bw/day, see Table 2).","effect":"EL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information o","page":34,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_057"}
SCCS_vision_codex NOAEL =14.8 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 66 3","dose":"EL = 48 mg/kg bw/day, see Table 2).","effect":"EL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information o","page":34,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_057"}
SCCS_vision_codex NOAEL =14.8 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 66 3","dose":"EL = 48 mg/kg bw/day, see Table 2).","effect":"EL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information o","page":34,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_057"}
SCCS_vision_codex NOAEL =14.8 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 66 3","dose":"EL = 48 mg/kg bw/day, see Table 2).","effect":"EL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information o","page":34,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_057"}
SCCS_vision_codex NOAEL =28 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_065"}
SCCS_vision_codex NOAEL =28 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_065"}
SCCS_vision_codex NOAEL =28 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_065"}
SCCS_vision_codex NOAEL =28 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_065"}
SCCS_vision_codex NOAEL =29 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_075"}
SCCS_vision_codex NOAEL =29 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_075"}
SCCS_vision_codex NOAEL =29 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_075"}
SCCS_vision_codex NOAEL =29 - - - - NOAEL study {"dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","effect":"Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_075"}
SCCS_vision_codex NOAEL =40 % rabbit dermal developmental developmental toxicity {"dose":"NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","effect":"Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_068"}
SCCS_vision_codex NOAEL =40 % rabbit dermal developmental developmental toxicity {"dose":"NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","effect":"Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_068"}
SCCS_vision_codex NOAEL =40 % rabbit dermal developmental developmental toxicity {"dose":"NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","effect":"Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_068"}
SCCS_vision_codex NOAEL =40 % rabbit dermal developmental developmental toxicity {"dose":"NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","effect":"Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_068"}
SCCS_vision_codex NOAEL =45 - rat inhalation developmental developmental toxicity {"effect":"45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_044"}
SCCS_vision_codex NOAEL =45 - rat inhalation developmental developmental toxicity {"effect":"45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_044"}
SCCS_vision_codex NOAEL =45 - rat inhalation developmental developmental toxicity {"effect":"45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_044"}
SCCS_vision_codex NOAEL =45 - rat inhalation developmental developmental toxicity {"effect":"45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_044"}
SCCS_vision_codex NOAEL =48 mg/kg bw/day rabbit inhalation - NOAEL study {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations). SCCS consider this value uncertain. The experiment was performed prior to 1991, it is not up to modern standards and the description of the experiment is unsatisfactory. 3.3.9 Toxicokinetics Fig. 1: Proposed metabolism of NMP (Taken from ref. 59) A metabolic pathway has been suggested for humans: NMP is first hydroxylated to 5- hydroxy-N-methyl-2-pyrrol","page":31,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_053"}
SCCS_vision_codex NOAEL =48 mg/kg bw/day rabbit inhalation - NOAEL study {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations). SCCS consider this value uncertain. The experiment was performed prior to 1991, it is not up to modern standards and the description of the experiment is unsatisfactory. 3.3.9 Toxicokinetics Fig. 1: Proposed metabolism of NMP (Taken from ref. 59) A metabolic pathway has been suggested for humans: NMP is first hydroxylated to 5- hydroxy-N-methyl-2-pyrrol","page":31,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_053"}
SCCS_vision_codex NOAEL =48 mg/kg bw/day rabbit inhalation - NOAEL study {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations). SCCS consider this value uncertain. The experiment was performed prior to 1991, it is not up to modern standards and the description of the experiment is unsatisfactory. 3.3.9 Toxicokinetics Fig. 1: Proposed metabolism of NMP (Taken from ref. 59) A metabolic pathway has been suggested for humans: NMP is first hydroxylated to 5- hydroxy-N-methyl-2-pyrrol","page":31,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_053"}
SCCS_vision_codex NOAEL =48 mg/kg bw/day rabbit inhalation - NOAEL study {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations). SCCS consider this value uncertain. The experiment was performed prior to 1991, it is not up to modern standards and the description of the experiment is unsatisfactory. 3.3.9 Toxicokinetics Fig. 1: Proposed metabolism of NMP (Taken from ref. 59) A metabolic pathway has been suggested for humans: NMP is first hydroxylated to 5- hydroxy-N-methyl-2-pyrrol","page":31,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_053"}
SCCS_vision_codex NOAEL =55 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:","effect":"kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in f","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_021"}
SCCS_vision_codex NOAEL =55 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:","effect":"kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in f","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_021"}
SCCS_vision_codex NOAEL =55 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:","effect":"kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in f","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_021"}
SCCS_vision_codex NOAEL =55 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:","effect":"kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in f","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_021"}
SCCS_vision_codex NOAEL =61 - - - developmental reproductive toxicity {"effect":"Table 2: NOAELs for developmental toxicity: fertility or the un | born ch | ild (Pr | ev | iously, Repr | otox. Cat | .2; R | 61: May cause h | arm to the","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_098"}
SCCS_vision_codex NOAEL =61 - - - developmental reproductive toxicity {"effect":"Table 2: NOAELs for developmental toxicity: fertility or the un | born ch | ild (Pr | ev | iously, Repr | otox. Cat | .2; R | 61: May cause h | arm to the","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_098"}
SCCS_vision_codex NOAEL =61 - - - developmental reproductive toxicity {"effect":"Table 2: NOAELs for developmental toxicity: fertility or the un | born ch | ild (Pr | ev | iously, Repr | otox. Cat | .2; R | 61: May cause h | arm to the","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_098"}
SCCS_vision_codex NOAEL =61 - - - developmental reproductive toxicity {"effect":"Table 2: NOAELs for developmental toxicity: fertility or the un | born ch | ild (Pr | ev | iously, Repr | otox. Cat | .2; R | 61: May cause h | arm to the","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_098"}
SCCS_vision_codex NOAEL =74 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","effect":"Table 2: NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_096"}
SCCS_vision_codex NOAEL =74 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","effect":"Table 2: NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_096"}
SCCS_vision_codex NOAEL =74 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","effect":"Table 2: NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_096"}
SCCS_vision_codex NOAEL =74 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","effect":"Table 2: NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_096"}
SCCS_vision_codex NOAEL =125 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"350 mg/kg bw/day Developmental toxicity:","effect":"ertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_032"}
SCCS_vision_codex NOAEL =125 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"350 mg/kg bw/day Developmental toxicity:","effect":"ertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_032"}
SCCS_vision_codex NOAEL =125 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"350 mg/kg bw/day Developmental toxicity:","effect":"ertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_032"}
SCCS_vision_codex NOAEL =125 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"350 mg/kg bw/day Developmental toxicity:","effect":"ertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49)","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_032"}
SCCS_vision_codex NOAEL =160 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny. Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_014"}
SCCS_vision_codex NOAEL =160 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny. Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_014"}
SCCS_vision_codex NOAEL =160 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny. Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_014"}
SCCS_vision_codex NOAEL =160 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny. Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_014"}
SCCS_vision_codex NOAEL =169 mg/kg bw/day mouse oral 90 days NOAEL study {"citation":"Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days","dose":"Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg).","effect":"e effect. Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg). Relative and absolute kidney weights were increased at 18000 mg/kg in both sexes, but no pathological changes were found. Changes in the relative weight of lungs, brain (males and females), and testes (13% increase) occurred at 18000 mg/kg. They were not associated with morphological changes. The NOAEL was 169 mg/kg bw/day in males and 217 mg/kg bw/day in females (3000 mg/kg for both sexes) based on body weight effects and changes in three neurobehavioral parameters (males only) at higher doses. Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days. The mean daily NMP dose was 0, 277, 619, and 1931 mg/kg bw/day. The purity of NMP was 99.9%. Experimental evaluations included clinical signs, food consumption, body weight, haematology and clinical chemistry,","page":15,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_004"}
SCCS_vision_codex NOAEL =169 mg/kg bw/day mouse oral 90 days NOAEL study {"citation":"Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days","dose":"Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg).","effect":"e effect. Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg). Relative and absolute kidney weights were increased at 18000 mg/kg in both sexes, but no pathological changes were found. Changes in the relative weight of lungs, brain (males and females), and testes (13% increase) occurred at 18000 mg/kg. They were not associated with morphological changes. The NOAEL was 169 mg/kg bw/day in males and 217 mg/kg bw/day in females (3000 mg/kg for both sexes) based on body weight effects and changes in three neurobehavioral parameters (males only) at higher doses. Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days. The mean daily NMP dose was 0, 277, 619, and 1931 mg/kg bw/day. The purity of NMP was 99.9%. Experimental evaluations included clinical signs, food consumption, body weight, haematology and clinical chemistry,","page":15,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_004"}
SCCS_vision_codex NOAEL =169 mg/kg bw/day mouse oral 90 days NOAEL study {"citation":"Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days","dose":"Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg).","effect":"e effect. Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg). Relative and absolute kidney weights were increased at 18000 mg/kg in both sexes, but no pathological changes were found. Changes in the relative weight of lungs, brain (males and females), and testes (13% increase) occurred at 18000 mg/kg. They were not associated with morphological changes. The NOAEL was 169 mg/kg bw/day in males and 217 mg/kg bw/day in females (3000 mg/kg for both sexes) based on body weight effects and changes in three neurobehavioral parameters (males only) at higher doses. Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days. The mean daily NMP dose was 0, 277, 619, and 1931 mg/kg bw/day. The purity of NMP was 99.9%. Experimental evaluations included clinical signs, food consumption, body weight, haematology and clinical chemistry,","page":15,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_004"}
SCCS_vision_codex NOAEL =169 mg/kg bw/day mouse oral 90 days NOAEL study {"citation":"Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days","dose":"Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg).","effect":"e effect. Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg). Relative and absolute kidney weights were increased at 18000 mg/kg in both sexes, but no pathological changes were found. Changes in the relative weight of lungs, brain (males and females), and testes (13% increase) occurred at 18000 mg/kg. They were not associated with morphological changes. The NOAEL was 169 mg/kg bw/day in males and 217 mg/kg bw/day in females (3000 mg/kg for both sexes) based on body weight effects and changes in three neurobehavioral parameters (males only) at higher doses. Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days. The mean daily NMP dose was 0, 277, 619, and 1931 mg/kg bw/day. The purity of NMP was 99.9%. Experimental evaluations included clinical signs, food consumption, body weight, haematology and clinical chemistry,","page":15,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_004"}
SCCS_vision_codex NOAEL =175 mg/kg bw/day rat inhalation Developmental reproductive toxicity {"dose":"NOAEL = 250 mg/kg bw/day Developmental toxicity:","effect":"xicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_037"}
SCCS_vision_codex NOAEL =175 mg/kg bw/day rat inhalation Developmental reproductive toxicity {"dose":"NOAEL = 250 mg/kg bw/day Developmental toxicity:","effect":"xicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_037"}
SCCS_vision_codex NOAEL =175 mg/kg bw/day rat inhalation Developmental reproductive toxicity {"dose":"NOAEL = 250 mg/kg bw/day Developmental toxicity:","effect":"xicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_037"}
SCCS_vision_codex NOAEL =175 mg/kg bw/day rat inhalation Developmental reproductive toxicity {"dose":"NOAEL = 250 mg/kg bw/day Developmental toxicity:","effect":"xicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_037"}
SCCS_vision_codex NOAEL =207 mg/kg bw/day mouse oral chronic NOAEL study {"citation":"Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years","dose":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum.","effect":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum. In addition, polytarteris in the cecum, mesenteric lymph node and in the testis were observed. The toxicological significance of these findings was not clear. NMP was not oncogenic in males and females up to doses of 15 000 mg/kg. The primary NMP-related effect was an increase in chronic progressive nephropathy in males. The NOAEL was 207 mg/kg bw/day in males and 283 mg/kg bw/day in females (5000 mg/kg in both sexes). Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years. The mean daily NMP dose was 0, 89, 173, and 1089 mg/kg bw/day for males and 115, 221, and 1399 mg/kg bw/day in females. The purity of NMP was 99.8%. Evaluations: Body weight, food consumption, clinical signs, haematology at 12, and 18 months (high dose), and microscopic evaluation of a standard set of tissues and","page":19,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_012"}
SCCS_vision_codex NOAEL =207 mg/kg bw/day mouse oral chronic NOAEL study {"citation":"Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years","dose":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum.","effect":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum. In addition, polytarteris in the cecum, mesenteric lymph node and in the testis were observed. The toxicological significance of these findings was not clear. NMP was not oncogenic in males and females up to doses of 15 000 mg/kg. The primary NMP-related effect was an increase in chronic progressive nephropathy in males. The NOAEL was 207 mg/kg bw/day in males and 283 mg/kg bw/day in females (5000 mg/kg in both sexes). Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years. The mean daily NMP dose was 0, 89, 173, and 1089 mg/kg bw/day for males and 115, 221, and 1399 mg/kg bw/day in females. The purity of NMP was 99.8%. Evaluations: Body weight, food consumption, clinical signs, haematology at 12, and 18 months (high dose), and microscopic evaluation of a standard set of tissues and","page":19,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_012"}
SCCS_vision_codex NOAEL =207 mg/kg bw/day mouse oral chronic NOAEL study {"citation":"Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years","dose":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum.","effect":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum. In addition, polytarteris in the cecum, mesenteric lymph node and in the testis were observed. The toxicological significance of these findings was not clear. NMP was not oncogenic in males and females up to doses of 15 000 mg/kg. The primary NMP-related effect was an increase in chronic progressive nephropathy in males. The NOAEL was 207 mg/kg bw/day in males and 283 mg/kg bw/day in females (5000 mg/kg in both sexes). Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years. The mean daily NMP dose was 0, 89, 173, and 1089 mg/kg bw/day for males and 115, 221, and 1399 mg/kg bw/day in females. The purity of NMP was 99.8%. Evaluations: Body weight, food consumption, clinical signs, haematology at 12, and 18 months (high dose), and microscopic evaluation of a standard set of tissues and","page":19,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_012"}
SCCS_vision_codex NOAEL =207 mg/kg bw/day mouse oral chronic NOAEL study {"citation":"Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years","dose":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum.","effect":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum. In addition, polytarteris in the cecum, mesenteric lymph node and in the testis were observed. The toxicological significance of these findings was not clear. NMP was not oncogenic in males and females up to doses of 15 000 mg/kg. The primary NMP-related effect was an increase in chronic progressive nephropathy in males. The NOAEL was 207 mg/kg bw/day in males and 283 mg/kg bw/day in females (5000 mg/kg in both sexes). Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years. The mean daily NMP dose was 0, 89, 173, and 1089 mg/kg bw/day for males and 115, 221, and 1399 mg/kg bw/day in females. The purity of NMP was 99.8%. Evaluations: Body weight, food consumption, clinical signs, haematology at 12, and 18 months (high dose), and microscopic evaluation of a standard set of tissues and","page":19,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_012"}
SCCS_vision_codex NOAEL =237 mg/kg bw/day rabbit dermal developmental developmental toxicity {"citation":"Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study","dose":"No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.","effect":"ncidence of resorptions, decreases in the number of viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,","page":23,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_016"}
SCCS_vision_codex NOAEL =237 mg/kg bw/day rabbit dermal developmental developmental toxicity {"citation":"Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study","dose":"No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.","effect":"ncidence of resorptions, decreases in the number of viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,","page":23,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_016"}
SCCS_vision_codex NOAEL =237 mg/kg bw/day rabbit dermal developmental developmental toxicity {"citation":"Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study","dose":"No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.","effect":"ncidence of resorptions, decreases in the number of viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,","page":23,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_016"}
SCCS_vision_codex NOAEL =237 mg/kg bw/day rabbit dermal developmental developmental toxicity {"citation":"Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study","dose":"No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.","effect":"ncidence of resorptions, decreases in the number of viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,","page":23,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_016"}
SCCS_vision_codex NOAEL =247 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_089"}
SCCS_vision_codex NOAEL =247 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_089"}
SCCS_vision_codex NOAEL =247 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_089"}
SCCS_vision_codex NOAEL =247 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_089"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat oral 5 days NOAEL study {"citation":"Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 we","dose":"At exposure termination, no significant differences between high-dose and control groups were reported.","effect":"telet count and megakaryocytes within a normal range were observed. At exposure termination, no significant differences between high-dose and control groups were reported. However, the authors mentioned several findings considered incidental or of doubtful significance: trend towards a decrease in body weight gains with increasing doses (body weights showed no significant differences), slight increase in platelet count with increased megakaryocytes and decrease in male serum cholesterol with increasing doses. The NOAEL for dietary exposure in dogs in this study is 250 mg/kg bw/day. Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 weeks. These groups were sacrificed and examined at the end of exposure. An additional two satellite groups (10 rats per sex per dose level) were identically exposed to 0 or 3000 mg/m³ and sacrificed after 13 weeks of exposure and a 4-week post-exposure period to obt","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_006"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat oral 5 days NOAEL study {"citation":"Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 we","dose":"At exposure termination, no significant differences between high-dose and control groups were reported.","effect":"telet count and megakaryocytes within a normal range were observed. At exposure termination, no significant differences between high-dose and control groups were reported. However, the authors mentioned several findings considered incidental or of doubtful significance: trend towards a decrease in body weight gains with increasing doses (body weights showed no significant differences), slight increase in platelet count with increased megakaryocytes and decrease in male serum cholesterol with increasing doses. The NOAEL for dietary exposure in dogs in this study is 250 mg/kg bw/day. Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 weeks. These groups were sacrificed and examined at the end of exposure. An additional two satellite groups (10 rats per sex per dose level) were identically exposed to 0 or 3000 mg/m³ and sacrificed after 13 weeks of exposure and a 4-week post-exposure period to obt","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_006"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat oral 5 days NOAEL study {"citation":"Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 we","dose":"At exposure termination, no significant differences between high-dose and control groups were reported.","effect":"telet count and megakaryocytes within a normal range were observed. At exposure termination, no significant differences between high-dose and control groups were reported. However, the authors mentioned several findings considered incidental or of doubtful significance: trend towards a decrease in body weight gains with increasing doses (body weights showed no significant differences), slight increase in platelet count with increased megakaryocytes and decrease in male serum cholesterol with increasing doses. The NOAEL for dietary exposure in dogs in this study is 250 mg/kg bw/day. Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 weeks. These groups were sacrificed and examined at the end of exposure. An additional two satellite groups (10 rats per sex per dose level) were identically exposed to 0 or 3000 mg/m³ and sacrificed after 13 weeks of exposure and a 4-week post-exposure period to obt","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_006"}
SCCS_vision_codex NOAEL =250 mg/kg bw/day rat oral 5 days NOAEL study {"citation":"Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 we","dose":"At exposure termination, no significant differences between high-dose and control groups were reported.","effect":"telet count and megakaryocytes within a normal range were observed. At exposure termination, no significant differences between high-dose and control groups were reported. However, the authors mentioned several findings considered incidental or of doubtful significance: trend towards a decrease in body weight gains with increasing doses (body weights showed no significant differences), slight increase in platelet count with increased megakaryocytes and decrease in male serum cholesterol with increasing doses. The NOAEL for dietary exposure in dogs in this study is 250 mg/kg bw/day. Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 weeks. These groups were sacrificed and examined at the end of exposure. An additional two satellite groups (10 rats per sex per dose level) were identically exposed to 0 or 3000 mg/m³ and sacrificed after 13 weeks of exposure and a 4-week post-exposure period to obt","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_006"}
SCCS_vision_codex NOAEL =277 mg/kg bw/day dog oral 90 days NOAEL study {"citation":"Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99","dose":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident.","effect":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident. Centrilobular hepatocellular hypertrophy was observed at 7500 mg/kg (1/10, 0/10, 2/10, and 9/10 in males at 0, 1000, 2500, and 7500 mg/kg, respectively; and 1/10, 0/10, 3/10, and 10/10 in females at 0, 1000, 2500, and 7500 mg/kg, respectively). These findings were regarded as an adaptation process, but were clearly attributed to NMP exposure. No other histopathological changes were detected. The NOAEL was set at 277 mg/kg bw/day (1000 mg/kg) based on the liver responses at higher doses. (Transient changes in biochemical parameters were also observed at > 1000 mg/kg). Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99.9%) at doses of 0, 25, 79, or 250 mg/kg bw/day in the diet for 90 days showed no statistically significant adverse effects. A dose-dependent decrease in body weight gain and an increase in platelet count and megakaryocytes within a normal range were observed. At expo","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_005"}
SCCS_vision_codex NOAEL =277 mg/kg bw/day dog oral 90 days NOAEL study {"citation":"Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99","dose":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident.","effect":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident. Centrilobular hepatocellular hypertrophy was observed at 7500 mg/kg (1/10, 0/10, 2/10, and 9/10 in males at 0, 1000, 2500, and 7500 mg/kg, respectively; and 1/10, 0/10, 3/10, and 10/10 in females at 0, 1000, 2500, and 7500 mg/kg, respectively). These findings were regarded as an adaptation process, but were clearly attributed to NMP exposure. No other histopathological changes were detected. The NOAEL was set at 277 mg/kg bw/day (1000 mg/kg) based on the liver responses at higher doses. (Transient changes in biochemical parameters were also observed at > 1000 mg/kg). Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99.9%) at doses of 0, 25, 79, or 250 mg/kg bw/day in the diet for 90 days showed no statistically significant adverse effects. A dose-dependent decrease in body weight gain and an increase in platelet count and megakaryocytes within a normal range were observed. At expo","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_005"}
SCCS_vision_codex NOAEL =277 mg/kg bw/day dog oral 90 days NOAEL study {"citation":"Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99","dose":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident.","effect":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident. Centrilobular hepatocellular hypertrophy was observed at 7500 mg/kg (1/10, 0/10, 2/10, and 9/10 in males at 0, 1000, 2500, and 7500 mg/kg, respectively; and 1/10, 0/10, 3/10, and 10/10 in females at 0, 1000, 2500, and 7500 mg/kg, respectively). These findings were regarded as an adaptation process, but were clearly attributed to NMP exposure. No other histopathological changes were detected. The NOAEL was set at 277 mg/kg bw/day (1000 mg/kg) based on the liver responses at higher doses. (Transient changes in biochemical parameters were also observed at > 1000 mg/kg). Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99.9%) at doses of 0, 25, 79, or 250 mg/kg bw/day in the diet for 90 days showed no statistically significant adverse effects. A dose-dependent decrease in body weight gain and an increase in platelet count and megakaryocytes within a normal range were observed. At expo","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_005"}
SCCS_vision_codex NOAEL =277 mg/kg bw/day dog oral 90 days NOAEL study {"citation":"Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99","dose":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident.","effect":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident. Centrilobular hepatocellular hypertrophy was observed at 7500 mg/kg (1/10, 0/10, 2/10, and 9/10 in males at 0, 1000, 2500, and 7500 mg/kg, respectively; and 1/10, 0/10, 3/10, and 10/10 in females at 0, 1000, 2500, and 7500 mg/kg, respectively). These findings were regarded as an adaptation process, but were clearly attributed to NMP exposure. No other histopathological changes were detected. The NOAEL was set at 277 mg/kg bw/day (1000 mg/kg) based on the liver responses at higher doses. (Transient changes in biochemical parameters were also observed at > 1000 mg/kg). Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99.9%) at doses of 0, 25, 79, or 250 mg/kg bw/day in the diet for 90 days showed no statistically significant adverse effects. A dose-dependent decrease in body weight gain and an increase in platelet count and megakaryocytes within a normal range were observed. At expo","page":16,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_005"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day rat inhalation developmental developmental toxicity {"citation":"Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of","dose":"The NOAEL was set at 300 mg/kg bw/day.","effect":"ere were no signs of maternal toxicity (death, food consumption, body weight, uterus weight), nor local effects at the application site. There was a significant increase in the incidence of foetuses with skeletal alterations, due to the occurrence of accessory 13th ribs. At 1000 mg/m³, their foetal and litter incidences were 15% and 60%, respectively (historical value 8.4 and 40 %, respectively). There was no effect on foetal body weight, or on the incidence of external, soft tissue and skeletal malformations. The NOAEL was set at 300 mg/kg bw/day. Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of gestation. The exposure consisted of a mixture of aerosol/vapour of unknown particle size distribution. No effects of the NMP exposure on the outcome of pregnancy, embryonal growth rate, or development in vital organs and skeletons of the foetuses were found. Nor were there abnormal clinical signs o","page":24,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_018"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day rat inhalation developmental developmental toxicity {"citation":"Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of","dose":"The NOAEL was set at 300 mg/kg bw/day.","effect":"ere were no signs of maternal toxicity (death, food consumption, body weight, uterus weight), nor local effects at the application site. There was a significant increase in the incidence of foetuses with skeletal alterations, due to the occurrence of accessory 13th ribs. At 1000 mg/m³, their foetal and litter incidences were 15% and 60%, respectively (historical value 8.4 and 40 %, respectively). There was no effect on foetal body weight, or on the incidence of external, soft tissue and skeletal malformations. The NOAEL was set at 300 mg/kg bw/day. Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of gestation. The exposure consisted of a mixture of aerosol/vapour of unknown particle size distribution. No effects of the NMP exposure on the outcome of pregnancy, embryonal growth rate, or development in vital organs and skeletons of the foetuses were found. Nor were there abnormal clinical signs o","page":24,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_018"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day rat inhalation developmental developmental toxicity {"citation":"Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of","dose":"The NOAEL was set at 300 mg/kg bw/day.","effect":"ere were no signs of maternal toxicity (death, food consumption, body weight, uterus weight), nor local effects at the application site. There was a significant increase in the incidence of foetuses with skeletal alterations, due to the occurrence of accessory 13th ribs. At 1000 mg/m³, their foetal and litter incidences were 15% and 60%, respectively (historical value 8.4 and 40 %, respectively). There was no effect on foetal body weight, or on the incidence of external, soft tissue and skeletal malformations. The NOAEL was set at 300 mg/kg bw/day. Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of gestation. The exposure consisted of a mixture of aerosol/vapour of unknown particle size distribution. No effects of the NMP exposure on the outcome of pregnancy, embryonal growth rate, or development in vital organs and skeletons of the foetuses were found. Nor were there abnormal clinical signs o","page":24,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_018"}
SCCS_vision_codex NOAEL =300 mg/kg bw/day rat inhalation developmental developmental toxicity {"citation":"Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of","dose":"The NOAEL was set at 300 mg/kg bw/day.","effect":"ere were no signs of maternal toxicity (death, food consumption, body weight, uterus weight), nor local effects at the application site. There was a significant increase in the incidence of foetuses with skeletal alterations, due to the occurrence of accessory 13th ribs. At 1000 mg/m³, their foetal and litter incidences were 15% and 60%, respectively (historical value 8.4 and 40 %, respectively). There was no effect on foetal body weight, or on the incidence of external, soft tissue and skeletal malformations. The NOAEL was set at 300 mg/kg bw/day. Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of gestation. The exposure consisted of a mixture of aerosol/vapour of unknown particle size distribution. No effects of the NMP exposure on the outcome of pregnancy, embryonal growth rate, or development in vital organs and skeletons of the foetuses were found. Nor were there abnormal clinical signs o","page":24,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_018"}
SCCS_vision_codex NOAEL =332 mg/kg bw/day rat - developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorpti...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_033"}
SCCS_vision_codex NOAEL =332 mg/kg bw/day rat - developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorpti...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_033"}
SCCS_vision_codex NOAEL =332 mg/kg bw/day rat - developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorpti...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_033"}
SCCS_vision_codex NOAEL =332 mg/kg bw/day rat - developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorpti...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_033"}
SCCS_vision_codex NOAEL =350 mg/kg bw/day rat oral developmental reproductive toxicity {"dose":"NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","effect":"mortality, body weights, feed consumption, clinical observations, reproductive performance or fertility. No effects on histological male and female in the P1. At 350mg/kg bw/day, in the F2 generation: - Decreases in the number of pups surviving lactation, and in pup body weights. No changes in microscopic evaluations of reproductive tissues as well in sperm assessments (P1-F1). Post weaning developmental landmarks (day of preputial separation and vaginal opening) determined in F1 generation were not affected. NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","page":21,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_013"}
SCCS_vision_codex NOAEL =350 mg/kg bw/day rat oral developmental reproductive toxicity {"dose":"NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","effect":"mortality, body weights, feed consumption, clinical observations, reproductive performance or fertility. No effects on histological male and female in the P1. At 350mg/kg bw/day, in the F2 generation: - Decreases in the number of pups surviving lactation, and in pup body weights. No changes in microscopic evaluations of reproductive tissues as well in sperm assessments (P1-F1). Post weaning developmental landmarks (day of preputial separation and vaginal opening) determined in F1 generation were not affected. NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","page":21,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_013"}
SCCS_vision_codex NOAEL =350 mg/kg bw/day rat oral developmental reproductive toxicity {"dose":"NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","effect":"mortality, body weights, feed consumption, clinical observations, reproductive performance or fertility. No effects on histological male and female in the P1. At 350mg/kg bw/day, in the F2 generation: - Decreases in the number of pups surviving lactation, and in pup body weights. No changes in microscopic evaluations of reproductive tissues as well in sperm assessments (P1-F1). Post weaning developmental landmarks (day of preputial separation and vaginal opening) determined in F1 generation were not affected. NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","page":21,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_013"}
SCCS_vision_codex NOAEL =350 mg/kg bw/day rat oral developmental reproductive toxicity {"dose":"NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","effect":"mortality, body weights, feed consumption, clinical observations, reproductive performance or fertility. No effects on histological male and female in the P1. At 350mg/kg bw/day, in the F2 generation: - Decreases in the number of pups surviving lactation, and in pup body weights. No changes in microscopic evaluations of reproductive tissues as well in sperm assessments (P1-F1). Post weaning developmental landmarks (day of preputial separation and vaginal opening) determined in F1 generation were not affected. NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","page":21,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_013"}
SCCS_vision_codex NOAEL =360 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_088"}
SCCS_vision_codex NOAEL =360 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_088"}
SCCS_vision_codex NOAEL =360 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_088"}
SCCS_vision_codex NOAEL =360 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_088"}
SCCS_vision_codex NOAEL =400 mg/kg bw rabbit - Developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"d 42 g, respectively at 400 mg/kg bw).","effect":"d 42 g, respectively at 400 mg/kg bw). However, there was no statistical difference in weight gain during the overall gestation period (GD 0-21) and after correction for gravid uterine weight. No changes in food consumption were found. - Developmental toxicity: At 400 mg/kg bw/day: Reduced foetal body weight (10-11 %) and an increased incidence of stunted foetuses (foetuses: 1/340, 1/393, 2/395, and 12/397; litters: 1/21, 1/25, 2/24, and 6/25; at 0, 40, 125 and 400 mg/kg bw, respectively). No teratogenic effects. NOAEL for maternal and developmental toxicity: 125 mg/kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of missh","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_020"}
SCCS_vision_codex NOAEL =400 mg/kg bw rabbit - Developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"d 42 g, respectively at 400 mg/kg bw).","effect":"d 42 g, respectively at 400 mg/kg bw). However, there was no statistical difference in weight gain during the overall gestation period (GD 0-21) and after correction for gravid uterine weight. No changes in food consumption were found. - Developmental toxicity: At 400 mg/kg bw/day: Reduced foetal body weight (10-11 %) and an increased incidence of stunted foetuses (foetuses: 1/340, 1/393, 2/395, and 12/397; litters: 1/21, 1/25, 2/24, and 6/25; at 0, 40, 125 and 400 mg/kg bw, respectively). No teratogenic effects. NOAEL for maternal and developmental toxicity: 125 mg/kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of missh","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_020"}
SCCS_vision_codex NOAEL =400 mg/kg bw rabbit - Developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"d 42 g, respectively at 400 mg/kg bw).","effect":"d 42 g, respectively at 400 mg/kg bw). However, there was no statistical difference in weight gain during the overall gestation period (GD 0-21) and after correction for gravid uterine weight. No changes in food consumption were found. - Developmental toxicity: At 400 mg/kg bw/day: Reduced foetal body weight (10-11 %) and an increased incidence of stunted foetuses (foetuses: 1/340, 1/393, 2/395, and 12/397; litters: 1/21, 1/25, 2/24, and 6/25; at 0, 40, 125 and 400 mg/kg bw, respectively). No teratogenic effects. NOAEL for maternal and developmental toxicity: 125 mg/kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of missh","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_020"}
SCCS_vision_codex NOAEL =400 mg/kg bw rabbit - Developmental developmental toxicity {"citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"d 42 g, respectively at 400 mg/kg bw).","effect":"d 42 g, respectively at 400 mg/kg bw). However, there was no statistical difference in weight gain during the overall gestation period (GD 0-21) and after correction for gravid uterine weight. No changes in food consumption were found. - Developmental toxicity: At 400 mg/kg bw/day: Reduced foetal body weight (10-11 %) and an increased incidence of stunted foetuses (foetuses: 1/340, 1/393, 2/395, and 12/397; litters: 1/21, 1/25, 2/24, and 6/25; at 0, 40, 125 and 400 mg/kg bw, respectively). No teratogenic effects. NOAEL for maternal and developmental toxicity: 125 mg/kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of missh","page":26,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_020"}
SCCS_vision_codex NOAEL =429 mg/kg bw/day mouse oral 28 days NOAEL study {"citation":"Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively). The weight of testes was also altered (not detailed). The authors concluded that, rather than specific organ toxicity, a general systemic response seemed to occur. The NOAEL was 429 mg/kg bw/day (6000 ppm) for males and (1548 mg/kg bw/day (18000 ppm) for females. Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days. The mean daily NMP dose was 0, 130, 720, 2130, and 2670 mg/kg bw/day in males and 0, 180, 920, 2970, and 4060 mg/kg bw/day in females. The purity of NMP was 99.9%. Experimental evaluations included food consumption, body weight, haematology, clinical chemistry, and gross","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_002"}
SCCS_vision_codex NOAEL =429 mg/kg bw/day mouse oral 28 days NOAEL study {"citation":"Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively). The weight of testes was also altered (not detailed). The authors concluded that, rather than specific organ toxicity, a general systemic response seemed to occur. The NOAEL was 429 mg/kg bw/day (6000 ppm) for males and (1548 mg/kg bw/day (18000 ppm) for females. Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days. The mean daily NMP dose was 0, 130, 720, 2130, and 2670 mg/kg bw/day in males and 0, 180, 920, 2970, and 4060 mg/kg bw/day in females. The purity of NMP was 99.9%. Experimental evaluations included food consumption, body weight, haematology, clinical chemistry, and gross","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_002"}
SCCS_vision_codex NOAEL =429 mg/kg bw/day mouse oral 28 days NOAEL study {"citation":"Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively). The weight of testes was also altered (not detailed). The authors concluded that, rather than specific organ toxicity, a general systemic response seemed to occur. The NOAEL was 429 mg/kg bw/day (6000 ppm) for males and (1548 mg/kg bw/day (18000 ppm) for females. Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days. The mean daily NMP dose was 0, 130, 720, 2130, and 2670 mg/kg bw/day in males and 0, 180, 920, 2970, and 4060 mg/kg bw/day in females. The purity of NMP was 99.9%. Experimental evaluations included food consumption, body weight, haematology, clinical chemistry, and gross","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_002"}
SCCS_vision_codex NOAEL =429 mg/kg bw/day mouse oral 28 days NOAEL study {"citation":"Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively).","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively). The weight of testes was also altered (not detailed). The authors concluded that, rather than specific organ toxicity, a general systemic response seemed to occur. The NOAEL was 429 mg/kg bw/day (6000 ppm) for males and (1548 mg/kg bw/day (18000 ppm) for females. Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days. The mean daily NMP dose was 0, 130, 720, 2130, and 2670 mg/kg bw/day in males and 0, 180, 920, 2970, and 4060 mg/kg bw/day in females. The purity of NMP was 99.9%. Experimental evaluations included food consumption, body weight, haematology, clinical chemistry, and gross","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_002"}
SCCS_vision_codex NOAEL =494 - rat inhalation developmental developmental toxicity {"citation":"Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol","dose":"54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol;","effect":"ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight","page":25,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_019"}
SCCS_vision_codex NOAEL =494 - rat inhalation developmental developmental toxicity {"citation":"Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol","dose":"54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol;","effect":"ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight","page":25,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_019"}
SCCS_vision_codex NOAEL =494 - rat inhalation developmental developmental toxicity {"citation":"Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol","dose":"54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol;","effect":"ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight","page":25,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_019"}
SCCS_vision_codex NOAEL =494 - rat inhalation developmental developmental toxicity {"citation":"Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol","dose":"54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol;","effect":"ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight","page":25,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_019"}
SCCS_vision_codex NOAEL =500 mg/kg bw/day - - developmental reproductive toxicity {"dose":"Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day.","effect":"inuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter size, reduced postnatal survival and pup weight. Significant reductions in the male fertility index and the female fecundity index of the F1 generation were also reported, without a clear NOAEL. Clear adverse effects were found at 500 mg/kg bw/day (Fertility index of males mated twice: 93-83, 72-69, 72-60, and 47-35 in the control, low-, mid- and high-dose groups, respectively. Fecundity index of females mated twice: 96-93, 82-74, 75-64, 61-50 in the control, low-, mid-, and high-dose groups, respectively). There was also an increased incidence of F1 females with decreased corpora lutea at the high-dose. Histological changes were noted at the high dose. There was a reduced incidence of females with pigm","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_015"}
SCCS_vision_codex NOAEL =500 - - - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_094"}
SCCS_vision_codex NOAEL =500 mg/kg bw/day - - developmental reproductive toxicity {"dose":"Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day.","effect":"inuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter size, reduced postnatal survival and pup weight. Significant reductions in the male fertility index and the female fecundity index of the F1 generation were also reported, without a clear NOAEL. Clear adverse effects were found at 500 mg/kg bw/day (Fertility index of males mated twice: 93-83, 72-69, 72-60, and 47-35 in the control, low-, mid- and high-dose groups, respectively. Fecundity index of females mated twice: 96-93, 82-74, 75-64, 61-50 in the control, low-, mid-, and high-dose groups, respectively). There was also an increased incidence of F1 females with decreased corpora lutea at the high-dose. Histological changes were noted at the high dose. There was a reduced incidence of females with pigm","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_015"}
SCCS_vision_codex NOAEL =500 - - - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_094"}
SCCS_vision_codex NOAEL =500 mg/kg bw/day - - developmental reproductive toxicity {"dose":"Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day.","effect":"inuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter size, reduced postnatal survival and pup weight. Significant reductions in the male fertility index and the female fecundity index of the F1 generation were also reported, without a clear NOAEL. Clear adverse effects were found at 500 mg/kg bw/day (Fertility index of males mated twice: 93-83, 72-69, 72-60, and 47-35 in the control, low-, mid- and high-dose groups, respectively. Fecundity index of females mated twice: 96-93, 82-74, 75-64, 61-50 in the control, low-, mid-, and high-dose groups, respectively). There was also an increased incidence of F1 females with decreased corpora lutea at the high-dose. Histological changes were noted at the high dose. There was a reduced incidence of females with pigm","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_015"}
SCCS_vision_codex NOAEL =500 - - - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_094"}
SCCS_vision_codex NOAEL =500 mg/kg bw/day - - developmental reproductive toxicity {"dose":"Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day.","effect":"inuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter size, reduced postnatal survival and pup weight. Significant reductions in the male fertility index and the female fecundity index of the F1 generation were also reported, without a clear NOAEL. Clear adverse effects were found at 500 mg/kg bw/day (Fertility index of males mated twice: 93-83, 72-69, 72-60, and 47-35 in the control, low-, mid- and high-dose groups, respectively. Fecundity index of females mated twice: 96-93, 82-74, 75-64, 61-50 in the control, low-, mid-, and high-dose groups, respectively). There was also an increased incidence of F1 females with decreased corpora lutea at the high-dose. Histological changes were noted at the high dose. There was a reduced incidence of females with pigm","page":22,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_015"}
SCCS_vision_codex NOAEL =500 - - - developmental developmental toxicity {"effect":"Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48)","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_094"}
SCCS_vision_codex NOAEL =600 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"NOAEL = 237 mg/kg bw/day;","effect":"ased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study,","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_029"}
SCCS_vision_codex NOAEL =600 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"NOAEL = 237 mg/kg bw/day;","effect":"ased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study,","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_029"}
SCCS_vision_codex NOAEL =600 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"NOAEL = 237 mg/kg bw/day;","effect":"ased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study,","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_029"}
SCCS_vision_codex NOAEL =600 mg/kg bw/day rat oral Developmental reproductive toxicity {"dose":"NOAEL = 237 mg/kg bw/day;","effect":"ased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study,","page":28,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_029"}
SCCS_vision_codex NOAEL =618 - rat inhalation 7 days reproductive toxicity {"effect":"Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_085"}
SCCS_vision_codex NOAEL =618 - rat inhalation 7 days reproductive toxicity {"effect":"Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_085"}
SCCS_vision_codex NOAEL =618 - rat inhalation 7 days reproductive toxicity {"effect":"Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_085"}
SCCS_vision_codex NOAEL =618 - rat inhalation 7 days reproductive toxicity {"effect":"Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_085"}
SCCS_vision_codex NOAEL =622 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_087"}
SCCS_vision_codex NOAEL =622 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_087"}
SCCS_vision_codex NOAEL =622 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_087"}
SCCS_vision_codex NOAEL =622 - rat inhalation developmental developmental toxicity {"effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_087"}
SCCS_vision_codex NOAEL =630 mg/kg bw/day mouse inhalation developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3 500 mg/m3 1000 mg/m3 None None None Slight foetal toxicity None None None Small decrease in gravid uterine weight Developmental and maternal toxicity: NOAEL = 500 mg/m3 BASF, 1991, 1993b. (47, 48) Intraperitoneal injection Mouse, developmental toxicity; days 11-15 0 630 1570 None Increased resorption rate and malformation - Developmental toxicity: LOAEL = 630 mg/kg bw/day EPA, 1988 (51) Mou","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_047"}
SCCS_vision_codex NOAEL =630 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","effect":"Table 2: NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_095"}
SCCS_vision_codex NOAEL =630 mg/kg bw/day mouse inhalation developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3 500 mg/m3 1000 mg/m3 None None None Slight foetal toxicity None None None Small decrease in gravid uterine weight Developmental and maternal toxicity: NOAEL = 500 mg/m3 BASF, 1991, 1993b. (47, 48) Intraperitoneal injection Mouse, developmental toxicity; days 11-15 0 630 1570 None Increased resorption rate and malformation - Developmental toxicity: LOAEL = 630 mg/kg bw/day EPA, 1988 (51) Mou","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_047"}
SCCS_vision_codex NOAEL =630 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","effect":"Table 2: NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_095"}
SCCS_vision_codex NOAEL =630 mg/kg bw/day mouse inhalation developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3 500 mg/m3 1000 mg/m3 None None None Slight foetal toxicity None None None Small decrease in gravid uterine weight Developmental and maternal toxicity: NOAEL = 500 mg/m3 BASF, 1991, 1993b. (47, 48) Intraperitoneal injection Mouse, developmental toxicity; days 11-15 0 630 1570 None Increased resorption rate and malformation - Developmental toxicity: LOAEL = 630 mg/kg bw/day EPA, 1988 (51) Mou","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_047"}
SCCS_vision_codex NOAEL =630 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","effect":"Table 2: NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_095"}
SCCS_vision_codex NOAEL =630 mg/kg bw/day mouse inhalation developmental developmental toxicity {"dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3...","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3 500 mg/m3 1000 mg/m3 None None None Slight foetal toxicity None None None Small decrease in gravid uterine weight Developmental and maternal toxicity: NOAEL = 500 mg/m3 BASF, 1991, 1993b. (47, 48) Intraperitoneal injection Mouse, developmental toxicity; days 11-15 0 630 1570 None Increased resorption rate and malformation - Developmental toxicity: LOAEL = 630 mg/kg bw/day EPA, 1988 (51) Mou","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_047"}
SCCS_vision_codex NOAEL =630 mg/kg - - developmental developmental toxicity {"dose":"NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","effect":"Table 2: NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","page":30,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_095"}
SCCS_vision_codex NOAEL =680 - rat inhalation developmental developmental toxicity {"effect":"NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_043"}
SCCS_vision_codex NOAEL =680 - rat inhalation developmental developmental toxicity {"effect":"NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_043"}
SCCS_vision_codex NOAEL =680 - rat inhalation developmental developmental toxicity {"effect":"NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_043"}
SCCS_vision_codex NOAEL =680 - rat inhalation developmental developmental toxicity {"effect":"NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_043"}
SCCS_vision_codex NOAEL =750 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day. In summary, NOAEL for maternal and developmental toxicity was 250 and 125 mg/kg bw/day, respectively. Thus, oral administration of NMP produced developmental toxicity below maternally toxic levels. The authors state that the study was conducted according to the current OECD and EU guidelines. Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats. Pregnant rats (groups of 18-24 rats) were given 5-hydroxy-N-methyl-2- pyrrolidone (5-HNMP; 0, 250, 500, 750, or 1000 mg/kg bw/day),","page":27,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_023"}
SCCS_vision_codex NOAEL =750 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day. In summary, NOAEL for maternal and developmental toxicity was 250 and 125 mg/kg bw/day, respectively. Thus, oral administration of NMP produced developmental toxicity below maternally toxic levels. The authors state that the study was conducted according to the current OECD and EU guidelines. Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats. Pregnant rats (groups of 18-24 rats) were given 5-hydroxy-N-methyl-2- pyrrolidone (5-HNMP; 0, 250, 500, 750, or 1000 mg/kg bw/day),","page":27,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_023"}
SCCS_vision_codex NOAEL =750 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day. In summary, NOAEL for maternal and developmental toxicity was 250 and 125 mg/kg bw/day, respectively. Thus, oral administration of NMP produced developmental toxicity below maternally toxic levels. The authors state that the study was conducted according to the current OECD and EU guidelines. Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats. Pregnant rats (groups of 18-24 rats) were given 5-hydroxy-N-methyl-2- pyrrolidone (5-HNMP; 0, 250, 500, 750, or 1000 mg/kg bw/day),","page":27,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_023"}
SCCS_vision_codex NOAEL =750 mg/kg bw/day rat oral developmental developmental toxicity {"citation":"Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day.","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day. In summary, NOAEL for maternal and developmental toxicity was 250 and 125 mg/kg bw/day, respectively. Thus, oral administration of NMP produced developmental toxicity below maternally toxic levels. The authors state that the study was conducted according to the current OECD and EU guidelines. Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats. Pregnant rats (groups of 18-24 rats) were given 5-hydroxy-N-methyl-2- pyrrolidone (5-HNMP; 0, 250, 500, 750, or 1000 mg/kg bw/day),","page":27,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_023"}
SCCS_vision_codex NOAEL =1995 - rat inhalation 7 days reproductive toxicity {"effect":"olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_041"}
SCCS_vision_codex NOAEL =1995 - rat inhalation 7 days reproductive toxicity {"effect":"olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_041"}
SCCS_vision_codex NOAEL =1995 - rat inhalation 7 days reproductive toxicity {"effect":"olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_041"}
SCCS_vision_codex NOAEL =1995 - rat inhalation 7 days reproductive toxicity {"effect":"olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL","page":29,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_041"}
SCCS_vision_codex NOAEL =2060 mg/kg bw/day rat oral 28 days NOAEL study {"citation":"Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD","dose":"In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day.","effect":"ion showed adverse effects on seminiferous tubule epithelium and formation of multinucleate giant cells and clumping of sloughed-off cells. In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day. At 2060 mg/kg bw/day, symptoms of general toxicity, such as tremor, restlessness, ruffled fur, and defensive reactions, were registered. The NOAEL was 514 mg NMP/kg bw. Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD.BR) (five per sex) were given 0, 2000, 6000, 18 000, or 30 000 mg NMP/kg diet for 28 days. The mean daily NMP doses were 0, 149, 429, 1234, and 2019 mg/kg bw/day in males and 0, 161, 493, 1548, and 2268 mg/kg bw/day in females. The purity of NMP was 99.9%. No mortality occurred. Lower body weights and body weight gains were noted at ≥ 1234 mg/kg bw/day in males and at 2268 mg/kg bw/day in females. In males, the body weight gains over","page":13,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_001"}
SCCS_vision_codex NOAEL =2060 mg/kg bw/day rat oral 28 days NOAEL study {"citation":"Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD","dose":"In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day.","effect":"ion showed adverse effects on seminiferous tubule epithelium and formation of multinucleate giant cells and clumping of sloughed-off cells. In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day. At 2060 mg/kg bw/day, symptoms of general toxicity, such as tremor, restlessness, ruffled fur, and defensive reactions, were registered. The NOAEL was 514 mg NMP/kg bw. Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD.BR) (five per sex) were given 0, 2000, 6000, 18 000, or 30 000 mg NMP/kg diet for 28 days. The mean daily NMP doses were 0, 149, 429, 1234, and 2019 mg/kg bw/day in males and 0, 161, 493, 1548, and 2268 mg/kg bw/day in females. The purity of NMP was 99.9%. No mortality occurred. Lower body weights and body weight gains were noted at ≥ 1234 mg/kg bw/day in males and at 2268 mg/kg bw/day in females. In males, the body weight gains over","page":13,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_001"}
SCCS_vision_codex NOAEL =2060 mg/kg bw/day rat oral 28 days NOAEL study {"citation":"Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD","dose":"In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day.","effect":"ion showed adverse effects on seminiferous tubule epithelium and formation of multinucleate giant cells and clumping of sloughed-off cells. In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day. At 2060 mg/kg bw/day, symptoms of general toxicity, such as tremor, restlessness, ruffled fur, and defensive reactions, were registered. The NOAEL was 514 mg NMP/kg bw. Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD.BR) (five per sex) were given 0, 2000, 6000, 18 000, or 30 000 mg NMP/kg diet for 28 days. The mean daily NMP doses were 0, 149, 429, 1234, and 2019 mg/kg bw/day in males and 0, 161, 493, 1548, and 2268 mg/kg bw/day in females. The purity of NMP was 99.9%. No mortality occurred. Lower body weights and body weight gains were noted at ≥ 1234 mg/kg bw/day in males and at 2268 mg/kg bw/day in females. In males, the body weight gains over","page":13,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_001"}
SCCS_vision_codex NOAEL =2060 mg/kg bw/day rat oral 28 days NOAEL study {"citation":"Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD","dose":"In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day.","effect":"ion showed adverse effects on seminiferous tubule epithelium and formation of multinucleate giant cells and clumping of sloughed-off cells. In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day. At 2060 mg/kg bw/day, symptoms of general toxicity, such as tremor, restlessness, ruffled fur, and defensive reactions, were registered. The NOAEL was 514 mg NMP/kg bw. Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD.BR) (five per sex) were given 0, 2000, 6000, 18 000, or 30 000 mg NMP/kg diet for 28 days. The mean daily NMP doses were 0, 149, 429, 1234, and 2019 mg/kg bw/day in males and 0, 161, 493, 1548, and 2268 mg/kg bw/day in females. The purity of NMP was 99.9%. No mortality occurred. Lower body weights and body weight gains were noted at ≥ 1234 mg/kg bw/day in males and at 2268 mg/kg bw/day in females. In males, the body weight gains over","page":13,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_001"}
SCCS_vision_codex NOAEL =7500 mg/kg rat inhalation 5 days NOAEL study {"citation":"Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below","dose":"Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters.","effect":"ealed pathological changes, consistent with the renal effects observed in the surviving animals. There was no effect on body weight or food consumption, or changes in haematological parameters at any doses, in either males or females. Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters. Cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10 000 mg/kg and in 2 males at 7500 mg/kg. The NOAEL was 720 mg/kg bw/day (2500 mg/kg) in males and 2970 mg/kg bw/day (7500 mg/kg) in females, based on the kidney histopathology. Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below 10 µm in diameter) 6 hr/day, 5 days/week for 4 weeks. The purity of NMP was 100%. Experimental evaluations included body weight, haematology, clinical chemistry, and gross and microscopic examination of","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_003"}
SCCS_vision_codex NOAEL =7500 mg/kg rat inhalation 5 days NOAEL study {"citation":"Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below","dose":"Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters.","effect":"ealed pathological changes, consistent with the renal effects observed in the surviving animals. There was no effect on body weight or food consumption, or changes in haematological parameters at any doses, in either males or females. Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters. Cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10 000 mg/kg and in 2 males at 7500 mg/kg. The NOAEL was 720 mg/kg bw/day (2500 mg/kg) in males and 2970 mg/kg bw/day (7500 mg/kg) in females, based on the kidney histopathology. Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below 10 µm in diameter) 6 hr/day, 5 days/week for 4 weeks. The purity of NMP was 100%. Experimental evaluations included body weight, haematology, clinical chemistry, and gross and microscopic examination of","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_003"}
SCCS_vision_codex NOAEL =7500 mg/kg rat inhalation 5 days NOAEL study {"citation":"Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below","dose":"Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters.","effect":"ealed pathological changes, consistent with the renal effects observed in the surviving animals. There was no effect on body weight or food consumption, or changes in haematological parameters at any doses, in either males or females. Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters. Cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10 000 mg/kg and in 2 males at 7500 mg/kg. The NOAEL was 720 mg/kg bw/day (2500 mg/kg) in males and 2970 mg/kg bw/day (7500 mg/kg) in females, based on the kidney histopathology. Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below 10 µm in diameter) 6 hr/day, 5 days/week for 4 weeks. The purity of NMP was 100%. Experimental evaluations included body weight, haematology, clinical chemistry, and gross and microscopic examination of","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_003"}
SCCS_vision_codex NOAEL =7500 mg/kg rat inhalation 5 days NOAEL study {"citation":"Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below","dose":"Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters.","effect":"ealed pathological changes, consistent with the renal effects observed in the surviving animals. There was no effect on body weight or food consumption, or changes in haematological parameters at any doses, in either males or females. Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters. Cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10 000 mg/kg and in 2 males at 7500 mg/kg. The NOAEL was 720 mg/kg bw/day (2500 mg/kg) in males and 2970 mg/kg bw/day (7500 mg/kg) in females, based on the kidney histopathology. Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below 10 µm in diameter) 6 hr/day, 5 days/week for 4 weeks. The purity of NMP was 100%. Experimental evaluations included body weight, haematology, clinical chemistry, and gross and microscopic examination of","page":14,"pdf":"sccs_o_050.pdf","row_type":"noael_study","study_id":"sccs_o_050_noael_003"}
ToxValDB_EFSA 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_EFSA NOAEL =90 mg/kg bw/day Mouse oral - chronic LONG_REF=EFSA AFC (2005). Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to a 7th list of substances for food contact materials. doi:10.2903/j.efsa.2005.201a.; TITLE=Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to a 7th list of substances for food contact materials; AUTHOR=EFSA AFC; DOI=doi:10.2903/j.efsa.2005.201a; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65201d30e4b0f0a60ddd1165; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://zenodo.org/record/5076033#.Y9fEoXbMI2z; YEAR=2005; ORIGINAL_YEAR=2005; TOXICOLOGICAL_EFFECT=organ weight; TOXICOLOGICAL_EFFECT_CATEGORY=organ weight; STUDY_GROUP=EFSA:15614275: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_185ed050727649abbba78ce4e70a4576
ToxValDB_EPA_TSCA_8e 6 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_EPA_TSCA_8e LEL =243.272 mg/m3 Rat inhalation short-term (developmental); 15 days reproduction developmental STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=2002-2-8EHQ-02-15084A_8ehq_0202_15084a.pdf; TOXICOLOGICAL_EFFECT=P0: decreased body weight gain; STUDY_GROUP=EPA TSCA 8e_dup_-_15957286_15957287:F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_6f0d1af6b1db066d1097fc1fe77e0097
ToxValDB_EPA_TSCA_8e LEL =250 mg/kg bw/day Rat oral short-term (developmental); 15 days reproduction developmental STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=tscats/88020000070_872504_383824CAFF240A098525702F005F4B59.pdf; TOXICOLOGICAL_EFFECT=F1: decreased fetal weight, malformations; STUDY_GROUP=EPA TSCA 8e:15957285:M/F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_e3f72eb1be5971f7fc9d9b206063b53e
ToxValDB_EPA_TSCA_8e LEL =486.545 mg/m3 Rat inhalation short-term (developmental); 15 days reproduction developmental STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=2002-2-8EHQ-02-15084A_8ehq_0202_15084a.pdf; TOXICOLOGICAL_EFFECT=P0: decreased food consumption; STUDY_GROUP=EPA TSCA 8e_dup_-_15957286_15957287:F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_f7e2a7ab69195afdd43c65d2f922cd06
ToxValDB_EPA_TSCA_8e LEL =500 mg/kg bw/day Rat oral short-term (developmental); 15 days reproduction developmental STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=tscats/88020000070_872504_383824CAFF240A098525702F005F4B59.pdf; TOXICOLOGICAL_EFFECT=P0: decreased body weight and food consumption; STUDY_GROUP=EPA TSCA 8e_dup_-_15957283_15957284:F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_2d16f0c725b8dff0d035c861e47cab5b
ToxValDB_EPA_TSCA_8e LEL =750 mg/kg bw/day Rat oral short-term (developmental); 15 days reproduction developmental STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=tscats/88020000070_872504_383824CAFF240A098525702F005F4B59.pdf; TOXICOLOGICAL_EFFECT=P0: post-implantation loss; STUDY_GROUP=EPA TSCA 8e_dup_-_15957283_15957284:F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_f7d7c802854561a7a6c1664c53e1c24a
ToxValDB_EPA_TSCA_8e LEL =1332 mg/kg bw/day Mouse oral chronic; 18 months chronic STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c96d15e4b02565fc7d3269; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://chemview.epa.gov; SUBSOURCE_URL=https://chemview.epa.gov/chemview/proxy?filename=tscats/89990000047_872504_928F3BD8B6CAC6E48525695A0048B941.pdf; TOXICOLOGICAL_EFFECT=increased tumor incidences; STUDY_GROUP=EPA TSCA 8e:15957282:M/F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_bf1dc2c16da69cf5d1137f5c1a4be153
ToxValDB_EU_SCOEL 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_EU_SCOEL LOAEL =400 mg/m3 Rat inhalation chronic; 2 years chronic LONG_REF=Lee, K.P., Chromey, N.C., Culik, R., Barnes, J.R., Schneider, P.W. (1987). Toxicity of N-methyl-2pyrrolidone (NMP): teratogenic, subchronic and two-year inhalation studies. Fund.Appl.Toxicol., 9,222-235.; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c985b9e4b02565fc7d35ab; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu; SUBSOURCE_URL=https://echa.europa.eu/documents/10162/35144386/091_1-methyl-2-pyrrolidone_oel_en.pdf; YEAR=2007; ORIGINAL_YEAR=2007; TOXICOLOGICAL_EFFECT=minimal inflammation of the lung and slight systemic toxicity was reported in male rats; STUDY_GROUP=EU SCOEL:15952254:M:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_6d46e7207543c45853152b42afb7338f
ToxValDB_GESTIS_DNEL 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL local =40 mg/m3 Human inhalation - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15633497_15633498:-:--; 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_df7d8ffbd92d0c252d7754a1f850246e
ToxValDB_GESTIS_DNEL DNEL systemic =14.4 mg/m3 Human inhalation - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15633497_15633498:-:--; 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_69c84e1d3f9d97b7d88fd4772d1bba48
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 98 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 28 - - - - - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference; DOSE=Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference; EFFECT=Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","duration":"","effect":"Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 28: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":28,"route":"","species":"","study_id":"sccs_o_050_noael_065"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 29 - - - - - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference; DOSE=Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference; EFFECT=Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","duration":"","effect":"Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 29: Species; type of study | Exposure (mg/kg bw/d) | Toxicity | NOAEL/LOAEL (mg/kg bw/day) | Reference","page":29,"route":"","species":"","study_id":"sccs_o_050_noael_075"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 40 % rabbit dermal - - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=40; DOSE=40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44); EFFECT=Unlabeled table on page 28: Rabbit; maternal toxicity; dermal; 40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44)","duration":"","effect":"Unlabeled table on page 28: Rabbit; maternal toxicity; dermal; 40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44)","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"40","page":28,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_069"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 48 mg/kg bw/day rabbit inhalation - - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=48; DOSE=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations).; EFFECT=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations). SCCS consider this value uncertain. The experiment was performed prior to 1991, it is not up to modern standards and the description of the experiment is unsatisfactory. 3.3.9 Toxicokinetics Fig. 1: Proposed metabolism of NMP (Taken from ref. 59) A metabolic pathway has been suggested for humans: NMP is first hydroxylated to 5- hydroxy-N-methyl-2-pyrrol; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations).","duration":"","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 31 The NOAEL of 48 mg/kg bw/day from the inhalation study of rabbits was used for setting specific concentration limit for NMP (see section 3.3.12 Special investigations). SCCS consider this value uncertain. The experiment was performed prior to 1991, it is not up to modern standards and the description of the experiment is unsatisfactory. 3.3.9 Toxicokinetics Fig. 1: Proposed metabolism of NMP (Taken from ref. 59) A metabolic pathway has been suggested for humans: NMP is first hydroxylated to 5- hydroxy-N-methyl-2-pyrrol","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"48","page":31,"route":"inhalation","species":"rabbit","study_id":"sccs_o_050_noael_053"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 169 mg/kg bw/day mouse oral 90 days - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=169; DOSE=Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg).; EFFECT=e effect. Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg). Relative and absolute kidney weights were increased at 18000 mg/kg in both sexes, but no pathological changes were found. Changes in the relative weight of lungs, brain (males and females), and testes (13% increase) occurred at 18000 mg/kg. They were not associated with morphological changes. The NOAEL was 169 mg/kg bw/day in males and 217 mg/kg bw/day in females (3000 mg/kg for both sexes) based on body weight effects and changes in three neurobehavioral parameters (males only) at higher doses. Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days. The mean daily NMP dose was 0, 277, 619, and 1931 mg/kg bw/day. The purity of NMP was 99.9%. Experimental evaluations included clinical signs, food consumption, body weight, haematology and clinical chemistry,; CITATION=Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days; CITATION_NUMBERS=[25,6,3,1,20,1000,2500,7500,90]; REFERENCE=Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days","dose":"Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg).","duration":"90 days","effect":"e effect. Females had increased absolute and relative liver weights that were associated with an increased incidence of centrilobular hepatocellular hypertrophy (0/10 at 0, 3000 and 7500 mg/kg, and 6/10 at 18000 mg/kg). Relative and absolute kidney weights were increased at 18000 mg/kg in both sexes, but no pathological changes were found. Changes in the relative weight of lungs, brain (males and females), and testes (13% increase) occurred at 18000 mg/kg. They were not associated with morphological changes. The NOAEL was 169 mg/kg bw/day in males and 217 mg/kg bw/day in females (3000 mg/kg for both sexes) based on body weight effects and changes in three neurobehavioral parameters (males only) at higher doses. Ref.: 25 Mice Mice (B6C3F1) (20 per sex) were administered 0, 1000, 2500, or 7500 mg NMP/kg diet for 90 days. The mean daily NMP dose was 0, 277, 619, and 1931 mg/kg bw/day. The purity of NMP was 99.9%. Experimental evaluations included clinical signs, food consumption, body weight, haematology and clinical chemistry,","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"169","page":15,"route":"oral","species":"mouse","study_id":"sccs_o_050_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 169 mg/kg bw/day rat dermal 4-week - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=169; DOSE=A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration.; EFFECT=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 17 registered in the 3000 mg/m³ group sacrificed at the end of exposure were also registered in the satellite group at the end of the 4-week post-exposure observation period. The NOAEL was 500 mg NMP/m³ for both male and female rats. Ref.: 27 Comment No dermal exposure data were found. A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration. Although the urine discolouration was compound-related, it was not associated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and cha; CITATION=Ref.: 27 Comment No dermal exposure data were found; CITATION_NUMBERS=[27]; REFERENCE=Ref.: 27 Comment No dermal exposure data were found; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 27 Comment No dermal exposure data were found","dose":"A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration.","duration":"4-week","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 17 registered in the 3000 mg/m³ group sacrificed at the end of exposure were also registered in the satellite group at the end of the 4-week post-exposure observation period. The NOAEL was 500 mg NMP/m³ for both male and female rats. Ref.: 27 Comment No dermal exposure data were found. A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration. Although the urine discolouration was compound-related, it was not associated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and cha","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"169","page":17,"route":"dermal","species":"rat","study_id":"sccs_o_050_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 207 mg/kg bw/day mouse oral chronic - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=207; DOSE=ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum.; EFFECT=ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum. In addition, polytarteris in the cecum, mesenteric lymph node and in the testis were observed. The toxicological significance of these findings was not clear. NMP was not oncogenic in males and females up to doses of 15 000 mg/kg. The primary NMP-related effect was an increase in chronic progressive nephropathy in males. The NOAEL was 207 mg/kg bw/day in males and 283 mg/kg bw/day in females (5000 mg/kg in both sexes). Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years. The mean daily NMP dose was 0, 89, 173, and 1089 mg/kg bw/day for males and 115, 221, and 1399 mg/kg bw/day in females. The purity of NMP was 99.8%. Evaluations: Body weight, food consumption, clinical signs, haematology at 12, and 18 months (high dose), and microscopic evaluation of a standard set of tissues and; CITATION=Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years; CITATION_NUMBERS=[38,6,3,1,50,600,1200,7200,2]; REFERENCE=Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years","dose":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum.","duration":"chronic","effect":"ospermia/germ cell debris in the epididymides (11/62, 14/62, 12/62, and 35/62 at 0 1600, 5000 and 15 000 mg/kg, respectively), and fibrous osteodystrophy in the femur/knee joint and sternum. In addition, polytarteris in the cecum, mesenteric lymph node and in the testis were observed. The toxicological significance of these findings was not clear. NMP was not oncogenic in males and females up to doses of 15 000 mg/kg. The primary NMP-related effect was an increase in chronic progressive nephropathy in males. The NOAEL was 207 mg/kg bw/day in males and 283 mg/kg bw/day in females (5000 mg/kg in both sexes). Ref.: 38 Mice Mice (B6C3F1) (50 /sex/dose) were administered 0, 600, 1200, or 7200 mg NMP/kg diet for 2 years. The mean daily NMP dose was 0, 89, 173, and 1089 mg/kg bw/day for males and 115, 221, and 1399 mg/kg bw/day in females. The purity of NMP was 99.8%. Evaluations: Body weight, food consumption, clinical signs, haematology at 12, and 18 months (high dose), and microscopic evaluation of a standard set of tissues and","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"207","page":19,"route":"oral","species":"mouse","study_id":"sccs_o_050_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 250 mg/kg bw/day rat oral 5 days - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=250; DOSE=At exposure termination, no significant differences between high-dose and control groups were reported.; EFFECT=telet count and megakaryocytes within a normal range were observed. At exposure termination, no significant differences between high-dose and control groups were reported. However, the authors mentioned several findings considered incidental or of doubtful significance: trend towards a decrease in body weight gains with increasing doses (body weights showed no significant differences), slight increase in platelet count with increased megakaryocytes and decrease in male serum cholesterol with increasing doses. The NOAEL for dietary exposure in dogs in this study is 250 mg/kg bw/day. Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 weeks. These groups were sacrificed and examined at the end of exposure. An additional two satellite groups (10 rats per sex per dose level) were identically exposed to 0 or 3000 mg/m³ and sacrificed after 13 weeks of exposure and a 4-week post-exposure period to obt; CITATION=Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 we; CITATION_NUMBERS=[26,10,500,1000,3000,6,5,13]; REFERENCE=Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 we; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 we","dose":"At exposure termination, no significant differences between high-dose and control groups were reported.","duration":"5 days","effect":"telet count and megakaryocytes within a normal range were observed. At exposure termination, no significant differences between high-dose and control groups were reported. However, the authors mentioned several findings considered incidental or of doubtful significance: trend towards a decrease in body weight gains with increasing doses (body weights showed no significant differences), slight increase in platelet count with increased megakaryocytes and decrease in male serum cholesterol with increasing doses. The NOAEL for dietary exposure in dogs in this study is 250 mg/kg bw/day. Ref.: 26 Inhalation Rats In a medium-term exposure study, rats (10 per sex per dose level) were exposed (head only) to 0, 500, 1000, or 3000 mg NMP/m³ for 6 h/day, 5 days/week, for 13 weeks. These groups were sacrificed and examined at the end of exposure. An additional two satellite groups (10 rats per sex per dose level) were identically exposed to 0 or 3000 mg/m³ and sacrificed after 13 weeks of exposure and a 4-week post-exposure period to obt","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":16,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 277 mg/kg bw/day dog oral 90 days - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=277; DOSE=liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident.; EFFECT=liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident. Centrilobular hepatocellular hypertrophy was observed at 7500 mg/kg (1/10, 0/10, 2/10, and 9/10 in males at 0, 1000, 2500, and 7500 mg/kg, respectively; and 1/10, 0/10, 3/10, and 10/10 in females at 0, 1000, 2500, and 7500 mg/kg, respectively). These findings were regarded as an adaptation process, but were clearly attributed to NMP exposure. No other histopathological changes were detected. The NOAEL was set at 277 mg/kg bw/day (1000 mg/kg) based on the liver responses at higher doses. (Transient changes in biochemical parameters were also observed at > 1000 mg/kg). Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99.9%) at doses of 0, 25, 79, or 250 mg/kg bw/day in the diet for 90 days showed no statistically significant adverse effects. A dose-dependent decrease in body weight gain and an increase in platelet count and megakaryocytes within a normal range were observed. At expo; CITATION=Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99; CITATION_NUMBERS=[25,99]; REFERENCE=Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99","dose":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident.","duration":"90 days","effect":"liver weight was also slightly higher at all doses in females, although a dose-response relationship was not evident. Centrilobular hepatocellular hypertrophy was observed at 7500 mg/kg (1/10, 0/10, 2/10, and 9/10 in males at 0, 1000, 2500, and 7500 mg/kg, respectively; and 1/10, 0/10, 3/10, and 10/10 in females at 0, 1000, 2500, and 7500 mg/kg, respectively). These findings were regarded as an adaptation process, but were clearly attributed to NMP exposure. No other histopathological changes were detected. The NOAEL was set at 277 mg/kg bw/day (1000 mg/kg) based on the liver responses at higher doses. (Transient changes in biochemical parameters were also observed at > 1000 mg/kg). Ref.: 25 Dogs Dogs (Beagle) (six per sex) that were administered NMP (purity: 99.9%) at doses of 0, 25, 79, or 250 mg/kg bw/day in the diet for 90 days showed no statistically significant adverse effects. A dose-dependent decrease in body weight gain and an increase in platelet count and megakaryocytes within a normal range were observed. At expo","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"277","page":16,"route":"oral","species":"dog","study_id":"sccs_o_050_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 429 mg/kg bw/day mouse oral 28 days - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=429; DOSE=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively).; EFFECT=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively). The weight of testes was also altered (not detailed). The authors concluded that, rather than specific organ toxicity, a general systemic response seemed to occur. The NOAEL was 429 mg/kg bw/day (6000 ppm) for males and (1548 mg/kg bw/day (18000 ppm) for females. Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days. The mean daily NMP dose was 0, 130, 720, 2130, and 2670 mg/kg bw/day in males and 0, 180, 920, 2970, and 4060 mg/kg bw/day in females. The purity of NMP was 99.9%. Experimental evaluations included food consumption, body weight, haematology, clinical chemistry, and gross; CITATION=Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days; CITATION_NUMBERS=[23,6,3,1,500,2500,7500,10,28]; REFERENCE=Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively).","duration":"28 days","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 14 Males showed degeneration and/or atrophy of the testicular seminiferous tubules (0/5, 0/5, 0/5, 1/5, and 5/5, at 0, 149, 429, 1234, and 2019 mg/kg bw/day, respectively). The weight of testes was also altered (not detailed). The authors concluded that, rather than specific organ toxicity, a general systemic response seemed to occur. The NOAEL was 429 mg/kg bw/day (6000 ppm) for males and (1548 mg/kg bw/day (18000 ppm) for females. Ref.: 23 Mice In a repeated-dose toxicity study, mice (B6C3F1/CrlBR) (five per sex) were given 0, 500, 2500, 7500, or 10 000 mg NMP/kg diet for 28 days. The mean daily NMP dose was 0, 130, 720, 2130, and 2670 mg/kg bw/day in males and 0, 180, 920, 2970, and 4060 mg/kg bw/day in females. The purity of NMP was 99.9%. Experimental evaluations included food consumption, body weight, haematology, clinical chemistry, and gross","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"429","page":14,"route":"oral","species":"mouse","study_id":"sccs_o_050_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =600 mg/kg bw/day rabbit dermal - - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 600; DOSE=40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44); EFFECT=Unlabeled table on page 28: Rabbit; maternal toxicity; dermal; 40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44)","duration":"","effect":"Unlabeled table on page 28: Rabbit; maternal toxicity; dermal; 40% aqueous solution | 0 400 600 800 | None None None Increased clotting time | Maternal toxicity NOAEL = 600 mg/kg bw/day | BASF, 1993 a (44)","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 600","page":28,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_074"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 2060 mg/kg bw/day rat oral 28 days - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=2060; DOSE=In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day.; EFFECT=ion showed adverse effects on seminiferous tubule epithelium and formation of multinucleate giant cells and clumping of sloughed-off cells. In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day. At 2060 mg/kg bw/day, symptoms of general toxicity, such as tremor, restlessness, ruffled fur, and defensive reactions, were registered. The NOAEL was 514 mg NMP/kg bw. Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD.BR) (five per sex) were given 0, 2000, 6000, 18 000, or 30 000 mg NMP/kg diet for 28 days. The mean daily NMP doses were 0, 149, 429, 1234, and 2019 mg/kg bw/day in males and 0, 161, 493, 1548, and 2268 mg/kg bw/day in females. The purity of NMP was 99.9%. No mortality occurred. Lower body weights and body weight gains were noted at ≥ 1234 mg/kg bw/day in males and at 2268 mg/kg bw/day in females. In males, the body weight gains over; CITATION=Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD; CITATION_NUMBERS=[22]; REFERENCE=Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD","dose":"In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day.","duration":"28 days","effect":"ion showed adverse effects on seminiferous tubule epithelium and formation of multinucleate giant cells and clumping of sloughed-off cells. In both sexes, a dose-dependent increase in relative liver and kidney weights and a decrease in body weight gain were observed at 1028 and 2060 mg/kg bw/day, and lymphocyte count decreased following exposure to 1028 and 2060 mg/kg bw/day. At 2060 mg/kg bw/day, symptoms of general toxicity, such as tremor, restlessness, ruffled fur, and defensive reactions, were registered. The NOAEL was 514 mg NMP/kg bw. Ref.: 22 In a repeated-dose toxicity study, rats (Orl:CD.BR) (five per sex) were given 0, 2000, 6000, 18 000, or 30 000 mg NMP/kg diet for 28 days. The mean daily NMP doses were 0, 149, 429, 1234, and 2019 mg/kg bw/day in males and 0, 161, 493, 1548, and 2268 mg/kg bw/day in females. The purity of NMP was 99.9%. No mortality occurred. Lower body weights and body weight gains were noted at ≥ 1234 mg/kg bw/day in males and at 2268 mg/kg bw/day in females. In males, the body weight gains over","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2060","page":13,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 7500 mg/kg rat inhalation 5 days - SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=7500; DOSE=Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters.; EFFECT=ealed pathological changes, consistent with the renal effects observed in the surviving animals. There was no effect on body weight or food consumption, or changes in haematological parameters at any doses, in either males or females. Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters. Cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10 000 mg/kg and in 2 males at 7500 mg/kg. The NOAEL was 720 mg/kg bw/day (2500 mg/kg) in males and 2970 mg/kg bw/day (7500 mg/kg) in females, based on the kidney histopathology. Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below 10 µm in diameter) 6 hr/day, 5 days/week for 4 weeks. The purity of NMP was 100%. Experimental evaluations included body weight, haematology, clinical chemistry, and gross and microscopic examination of; CITATION=Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below; CITATION_NUMBERS=[23,15,100,500,1000,95]; REFERENCE=Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below","dose":"Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters.","duration":"5 days","effect":"ealed pathological changes, consistent with the renal effects observed in the surviving animals. There was no effect on body weight or food consumption, or changes in haematological parameters at any doses, in either males or females. Except from a lower serum ALP in females at 4060 mg/kg bw/day, there were no changes in the clinical chemistry parameters. Cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10 000 mg/kg and in 2 males at 7500 mg/kg. The NOAEL was 720 mg/kg bw/day (2500 mg/kg) in males and 2970 mg/kg bw/day (7500 mg/kg) in females, based on the kidney histopathology. Ref.: 23 Inhalation Rats Rats (Crl:CD) (15/sex/dose) were exposed to 100, 500, and 1000 mg/m³ NMP (aerosol- vapour mixture) with an additional control (air) (> 95 % of the droplets below 10 µm in diameter) 6 hr/day, 5 days/week for 4 weeks. The purity of NMP was 100%. Experimental evaluations included body weight, haematology, clinical chemistry, and gross and microscopic examination of","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg","noael_value":"7500","page":14,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 169 mg/kg bw/day rat dermal 4-week carcinogenicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=169; DOSE=A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration.; EFFECT=registered in the satellite group at the end of the 4-week post-exposure observation period. The NOAEL was 500 mg NMP/m³ for both male and female rats. Ref.: 27 Comment No dermal exposure data were found. A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration. Although the urine discolouration was compound-related, it was not associated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg N; CITATION=Ref.: 27 Comment No dermal exposure data were found; CITATION_NUMBERS=[27]; REFERENCE=Ref.: 27 Comment No dermal exposure data were found; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 27 Comment No dermal exposure data were found","dose":"A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration.","duration":"4-week","effect":"registered in the satellite group at the end of the 4-week post-exposure observation period. The NOAEL was 500 mg NMP/m³ for both male and female rats. Ref.: 27 Comment No dermal exposure data were found. A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration. Although the urine discolouration was compound-related, it was not associated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg N","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"169","page":17,"route":"dermal","species":"rat","study_id":"sccs_o_050_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 250 mg/kg bw/day rat inhalation 90-day carcinogenicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=250; DOSE=A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters.; EFFECT=ated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg NMP/m³ for both male and female rats. 3.3.5.3 Chronic (> 12 months) toxicity See section 3.3.7 Carcinogenicity 3.3.6 Mutagenicity / Genotoxicity In vitro NMP has been tested in bacterial mutagenicity assays in the dose range of 0.01–1000 µmol/plate (0.99 µg/plate to 99 mg/plate) with and without metabolic activation by Aroclor- induced rat liver S9. In the direct plate incorporation in Salm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters.","duration":"90-day","effect":"ated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg NMP/m³ for both male and female rats. 3.3.5.3 Chronic (> 12 months) toxicity See section 3.3.7 Carcinogenicity 3.3.6 Mutagenicity / Genotoxicity In vitro NMP has been tested in bacterial mutagenicity assays in the dose range of 0.01–1000 µmol/plate (0.99 µg/plate to 99 mg/plate) with and without metabolic activation by Aroclor- induced rat liver S9. In the direct plate incorporation in Salm","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":17,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 250 mg/kg bw/day rat inhalation 90-day carcinogenicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=250; DOSE=A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters.; EFFECT=egnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg NMP/m³ for both male and female rats. 3.3.5.3 Chronic (> 12 months) toxicity See section 3.3.7 Carcinogenicity 3.3.6 Mutagenicity / Genotoxicity In vitro NMP has been tested in bacterial mutagenicity assays in the dose range of 0.01–1000 µmol/plate (0.99 µg/plate to 99 mg/plate) with and without metabolic activation by Aroclor- induced rat liver S9. In the direct plate incorporation in Salmonella typhimurium strains TA97, TA98, TA100, TA102, and TA104 at highest dose, signs of cytotoxicity (decreas; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters.","duration":"90-day","effect":"egnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg NMP/m³ for both male and female rats. 3.3.5.3 Chronic (> 12 months) toxicity See section 3.3.7 Carcinogenicity 3.3.6 Mutagenicity / Genotoxicity In vitro NMP has been tested in bacterial mutagenicity assays in the dose range of 0.01–1000 µmol/plate (0.99 µg/plate to 99 mg/plate) with and without metabolic activation by Aroclor- induced rat liver S9. In the direct plate incorporation in Salmonella typhimurium strains TA97, TA98, TA100, TA102, and TA104 at highest dose, signs of cytotoxicity (decreas","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":17,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 277 mg/kg bw/day rat dermal 90-day carcinogenicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=277; DOSE=A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration.; EFFECT=ts. Ref.: 27 Comment No dermal exposure data were found. A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration. Although the urine discolouration was compound-related, it was not associated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg NMP/m³ for both male and female rats. 3.3.5.3 Chronic (> 12 months) toxicity See section 3.3.7 Carcinogenicity 3.3.6 Mutagenicity / Genotoxicity I; CITATION=Ref.: 27 Comment No dermal exposure data were found; CITATION_NUMBERS=[27]; REFERENCE=Ref.: 27 Comment No dermal exposure data were found; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 27 Comment No dermal exposure data were found","dose":"A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration.","duration":"90-day","effect":"ts. Ref.: 27 Comment No dermal exposure data were found. A dose-dependant yellow coloration of urine was generally reported in rodents, whatever the route of administration. Although the urine discolouration was compound-related, it was not associated to changes in kidneys. It was probably due to the presence of a metabolite of NMP and reflected body impregnation. A NOAEL of 169 mg/kg bw/day in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 89 mg/kg bw/day in male mice in a 2-year study based on increased liver weighs and 173 mg/kg bw/day based on liver tumours (see Section 3.3.7. Carcinogenicity) A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. After inhalation, the NOAEL was 500 mg NMP/m³ for both male and female rats. 3.3.5.3 Chronic (> 12 months) toxicity See section 3.3.7 Carcinogenicity 3.3.6 Mutagenicity / Genotoxicity I","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"277","page":17,"route":"dermal","species":"rat","study_id":"sccs_o_050_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 1 - rabbit - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=maternal toxicity: 1; EFFECT=Table 2: NOAELs for developmental toxicity: Rabbit, | 200 mg/ | m3 | No | ne | None | maternal toxicity: 1 | 993b.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: Rabbit, | 200 mg/ | m3 | No | ne | None | maternal toxicity: 1 | 993b.","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"maternal toxicity: 1","page":30,"route":"","species":"rabbit","study_id":"sccs_o_050_noael_093"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 1 - - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=ory 1b; H360: M; EFFECT=Table 2: NOAELs for developmental toxicity: NMP has been cla | ssified | due to | i | ts reprotoxic | effect as | categ | ory 1b; H360: M | ay damage; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: NMP has been cla | ssified | due to | i | ts reprotoxic | effect as | categ | ory 1b; H360: M | ay damage","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"ory 1b; H360: M","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_097"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 2 - - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Table 2: NOAELs for developmental toxicity: Species; type of | Exposu | re | Toxi | city | NOAEL/LOAEL | Reference; EFFECT=Table 2: NOAELs for developmental toxicity: Species; type of | Exposu | re | Toxi | city | NOAEL/LOAEL | Reference; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: Species; type of | Exposu | re | Toxi | city | NOAEL/LOAEL | Reference","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Table 2: NOAELs for developmental toxicity: Species; type of | Exposu | re | Toxi | city | NOAEL/LOAEL | Reference","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_090"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 2 - - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48); EFFECT=Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48)","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_091"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 2 - - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Table 2: NOAELs for developmental toxicity: reprotoxic effect i | n relati | on to | N | MP. As a co | nsequenc | e the | NOAEL should b | e based on; EFFECT=Table 2: NOAELs for developmental toxicity: reprotoxic effect i | n relati | on to | N | MP. As a co | nsequenc | e the | NOAEL should b | e based on; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: reprotoxic effect i | n relati | on to | N | MP. As a co | nsequenc | e the | NOAEL should b | e based on","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Table 2: NOAELs for developmental toxicity: reprotoxic effect i | n relati | on to | N | MP. As a co | nsequenc | e the | NOAEL should b | e based on","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_092"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 4 - rat inhalation Developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce; EFFECT=ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"Developmental","effect":"ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:ion (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduce","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_042"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 6 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); EFFECT=t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:t; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_045"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 6 - rat inhalation 3 days developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:(whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); EFFECT=(whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"3 days","effect":"(whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:(whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_046"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =14.8 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 14.8; DOSE=EL = 48 mg/kg bw/day, see Table 2).; EFFECT=EL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information o; CITATION=Ref.: 66 3; CITATION_NUMBERS=[66,3]; REFERENCE=Ref.: 66 3; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 66 3","dose":"EL = 48 mg/kg bw/day, see Table 2).","duration":"developmental","effect":"EL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information o","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 14.8","page":34,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_057"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 29 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day | 0 mg/m3 680 mg/m3 | None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification | None None | Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 | Hass et al., 1995 (45); EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day | 0 mg/m3 680 mg/m3 | None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification | None None | Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 | Hass et al., 1995 (45); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day | 0 mg/m3 680 mg/m3 | None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification | None None | Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 | Hass et al., 1995 (45)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day | 0 mg/m3 680 mg/m3 | None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification | None None | Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 | Hass et al., 1995 (45)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_080"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 29 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46); EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_081"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 29 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24); EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_082"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 29 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54); EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_083"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 40 % rabbit dermal developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=40; DOSE=NOAEL = 300 mg/kg bw/day | BASF, 1993a (44); EFFECT=Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","duration":"developmental","effect":"Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"40","page":28,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_068"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 45 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); EFFECT=45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_044"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 55 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=55; DOSE=49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:; EFFECT=kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in f; CITATION=Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio; CITATION_NUMBERS=[49,55,175,540,15,20,6,18]; REFERENCE=Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:","duration":"developmental","effect":"kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in f","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"55","page":26,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 55 mg/kg bw/day rat oral Developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=55; DOSE=toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:; EFFECT=toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in foetal weight (37%), malformations considered a; CITATION=Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation; CITATION_NUMBERS=[50,332,997,6,15]; REFERENCE=Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation","dose":"toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity:","duration":"Developmental","effect":"toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of misshapen skull bones and of 27 presacral vertebrae. NOAEL for maternal toxicity: 55 mg/kg bw/day. NOAEL for developmental toxicity: 175 mg/kg bw/day. Ref.: 50 Daily doses of 0, 332 or 997 mg NMP/kg bw/day were administered to Sprague-Dawley rats by gavage on days 6–15 of gestation. At 997 mg/kg bw/day: Marked reductions in maternal body weight and placental weight were observed. There was a large number of resorptions (24/29 dams showed complete resorption) and only 15 live and 1 dead foetus were present at term. Observations in the live foetuses included reduction in foetal weight (37%), malformations considered a","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"55","page":26,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =55 mg/kg bw/day rabbit - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 55; DOSE=NOAEL = 55 mg/kg bw/day Developmental toxicity:; EFFECT=Unlabeled table on page 29: Rabbit; developmental study, days 6-18. | 0 55 175 540 | None None None Increased resorptions, malformations | None None Decreased weight gain Decreased weight gain | Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day | GAF, 1992 (50); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 55 mg/kg bw/day Developmental toxicity:","duration":"developmental","effect":"Unlabeled table on page 29: Rabbit; developmental study, days 6-18. | 0 55 175 540 | None None None Increased resorptions, malformations | None None Decreased weight gain Decreased weight gain | Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day | GAF, 1992 (50)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 55","page":29,"route":"","species":"rabbit","study_id":"sccs_o_050_noael_077"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =74 mg/kg - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 74; DOSE=NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52); EFFECT=Table 2: NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: developmental | we | ight and | dose = 74 mg/kg ( | 52)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg","noael_value":"= 74","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_096"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =125 mg/kg bw/day rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 125; DOSE=d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity:; LOAEL_VALUE=332 mg/kg bw/day; EFFECT=d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-g; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity:","duration":"developmental","effect":"d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-g","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"332 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 125","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_035"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 125 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=125; DOSE=NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after o...; EFFECT=rotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) and will be used in calculation of MOS. This NOAEL was reported for developmental toxicity in two independant studies (49, 53). It is noted that teratogenic effects were not observed after inhalation exposure.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after o...","duration":"developmental","effect":"rotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) and will be used in calculation of MOS. This NOAEL was reported for developmental toxicity in two independant studies (49, 53). It is noted that teratogenic effects were not observed after inhalation exposure.","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"125","page":30,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_052"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =125 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 125; DOSE=66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg...; EFFECT=bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information on the stability of NMP in cosmetic products is available. Acute toxicity N; CITATION=Ref.: 66 3; CITATION_NUMBERS=[66,3]; REFERENCE=Ref.: 66 3; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 66 3","dose":"66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg...","duration":"developmental","effect":"bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NOAEL, for developmental effect, rat, oral exposure = 125 mg/kg bw/day MOS NOAEL / SED = 8.4 The MOS is too low to be accepted. 3.3.14 Discussion The safety has only been evaluated for dermal exposure. The final concentration of NMP in cosmetic products is not known. It is noted that NMP may enhance the dermal absorption of other cosmetic ingredients. Physico-chemical properties NMP is colourless liquid with mild amine odour. It is completely miscible with water. It is only slowly oxidized by air. No information on the stability of NMP in cosmetic products is available. Acute toxicity N","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 125","page":34,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_058"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 125 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=125; DOSE=t, occurred in the absence of significant maternal toxicity in rats treated by gavage.; EFFECT=t, occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) is considered the most relevant observation and will be used in the calculation of MOS. Toxicokinetics and metabolism NMP is readily absorbed by all three routes of exposure (inhalation, oral, and skin administration). Once absorbed, NMP is widely distributed throughout the body, metabolized, and primarily eliminated in the urine (the majority within 24 hours after treatment), with negligible t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"t, occurred in the absence of significant maternal toxicity in rats treated by gavage.","duration":"developmental","effect":"t, occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) is considered the most relevant observation and will be used in the calculation of MOS. Toxicokinetics and metabolism NMP is readily absorbed by all three routes of exposure (inhalation, oral, and skin administration). Once absorbed, NMP is widely distributed throughout the body, metabolized, and primarily eliminated in the urine (the majority within 24 hours after treatment), with negligible t","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"125","page":36,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_063"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 125 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=125; DOSE=in rats treated by gavage.; EFFECT=in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) is considered the most relevant observation and will be used in the calculation of MOS. Toxicokinetics and metabolism NMP is readily absorbed by all three routes of exposure (inhalation, oral, and skin administration). Once absorbed, NMP is widely distributed throughout the body, metabolized, and primarily eliminated in the urine (the majority within 24 hours after treatment), with negligible tissue residues remaining after 4-5 days post-dose. NMP was s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"in rats treated by gavage.","duration":"developmental","effect":"in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) is considered the most relevant observation and will be used in the calculation of MOS. Toxicokinetics and metabolism NMP is readily absorbed by all three routes of exposure (inhalation, oral, and skin administration). Once absorbed, NMP is widely distributed throughout the body, metabolized, and primarily eliminated in the urine (the majority within 24 hours after treatment), with negligible tissue residues remaining after 4-5 days post-dose. NMP was s","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"125","page":36,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_064"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =125 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 125; DOSE=NOAEL = 125 mg/kg bw/day | EXXON, 1992 (49); EFFECT=Unlabeled table on page 28: Rat; developmental study, days 6-15, gavage 5 ml/kg | 0 40 125 400 | None None None Reduced foetal weight and stunted foetuses | None None None Bodyweight gain depressed | Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day | EXXON, 1992 (49); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 125 mg/kg bw/day | EXXON, 1992 (49)","duration":"developmental","effect":"Unlabeled table on page 28: Rat; developmental study, days 6-15, gavage 5 ml/kg | 0 40 125 400 | None None None Reduced foetal weight and stunted foetuses | None None None Bodyweight gain depressed | Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day | EXXON, 1992 (49)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 125","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_072"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 160 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=160; DOSE=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny.; EFFECT=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny. Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter; CITATION=Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations; CITATION_NUMBERS=[39,30,50,160,500,10]; REFERENCE=Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny.","duration":"developmental","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 22 NOAEL for developmental toxicity was 160 mg/kg bw/day for F1 and F2 progeny. Ref.: 39 Rats (30/sex/group) received 0, 50, 160, and 500 mg/kg bw/day by oral diet 10 days prior to mating and continuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"160","page":22,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 237 mg/kg bw/day rabbit dermal developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=237; DOSE=No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.; EFFECT=ncidence of resorptions, decreases in the number of viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,; CITATION=Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study; CITATION_NUMBERS=[43]; REFERENCE=Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study","dose":"No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.","duration":"developmental","effect":"ncidence of resorptions, decreases in the number of viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"237","page":23,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 237 mg/kg bw/day rabbit dermal developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=237; DOSE=No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.; EFFECT=viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,; CITATION=Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study; CITATION_NUMBERS=[43]; REFERENCE=Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study","dose":"No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day.","duration":"developmental","effect":"viable foetuses and in the foetal body weight (20 %). Delayed ossification of several bones (i.e. skull, hyoid, sternebrae, vertebrae) and increase in the incidence of extra ribs. Skeletal malformations including fused/split ribs (8 foetuses from 5 litters), and fusion of the exoccipital and atlas bones (4 foetuses from 4 litters). No increase in the incidence of soft tissue variations or malformations. - No treatment-related effects at 75 and 237 mg/kg bw/day. NOAEL for developmental toxicity: 237 mg/kg bw/day. NOAEL for maternal toxicity: 237 mg/kg bw/day. The lower maternal weight may be due, at least partly, to the increased resorption rate and the lower foetal body weight. Ref.: 43 Rabbits The maternal toxicity in rabbits after dermal application was studied in a range-finding study. Pregnant rabbits (15 per dose level) were exposed daily to dermal doses of 0, 400,","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"237","page":23,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =237 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 237; DOSE=ls Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity:; EFFECT=ls Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"ls Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity:","duration":"developmental","effect":"ls Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 237","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_026"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =237 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 237; DOSE=mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity:; EFFECT=mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None N; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity:","duration":"developmental","effect":"mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None N","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 237","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_027"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =237 mg/kg bw/day rat dermal developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 237; DOSE=NOAEL = 237 mg/kg bw/day;; EFFECT=Unlabeled table on page 28: Rat; developmental toxicity study; dermal; days 6–15 | 0 75 237 750 | None None None Increased resorption, delayed ossification | None None None Decreased body weight gain | Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day | Becci et al., 1982 (43); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 237 mg/kg bw/day;","duration":"developmental","effect":"Unlabeled table on page 28: Rat; developmental toxicity study; dermal; days 6–15 | 0 75 237 750 | None None None Increased resorption, delayed ossification | None None None Decreased body weight gain | Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day | Becci et al., 1982 (43)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 237","page":28,"route":"dermal","species":"rat","study_id":"sccs_o_050_noael_067"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =247 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3; EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day | 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 | None None None Reduced foetal weight | None None Reduced weight gain Reduced weight gain | Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 | Saillenfait et al., 2003 (54)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_089"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =250 mg/kg bw/day rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 250; DOSE=xicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity:; LOAEL_VALUE=332 mg/kg bw/day; EFFECT=xicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 m; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"xicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity:","duration":"developmental","effect":"xicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 m","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"332 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 250","page":29,"route":"","species":"rat","study_id":"sccs_o_050_noael_034"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =250 mg/kg bw/day rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 250; DOSE=NOAEL = 250 mg/kg bw/day Developmental toxicity:; EFFECT=Unlabeled table on page 29: Rat, developmental study, days 6-20 | 0 125 250 500 750 | None None Decreased foetal weight Malformation Malformation | None None None Reduced weight gain Reduced weight gain | Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day | Saillenfait et al., 2002 (53); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 250 mg/kg bw/day Developmental toxicity:","duration":"developmental","effect":"Unlabeled table on page 29: Rat, developmental study, days 6-20 | 0 125 250 500 750 | None None Decreased foetal weight Malformation Malformation | None None None Reduced weight gain Reduced weight gain | Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day | Saillenfait et al., 2002 (53)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 250","page":29,"route":"","species":"rat","study_id":"sccs_o_050_noael_076"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 300 mg/kg bw/day rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=300; DOSE=The NOAEL was set at 300 mg/kg bw/day.; EFFECT=ere were no signs of maternal toxicity (death, food consumption, body weight, uterus weight), nor local effects at the application site. There was a significant increase in the incidence of foetuses with skeletal alterations, due to the occurrence of accessory 13th ribs. At 1000 mg/m³, their foetal and litter incidences were 15% and 60%, respectively (historical value 8.4 and 40 %, respectively). There was no effect on foetal body weight, or on the incidence of external, soft tissue and skeletal malformations. The NOAEL was set at 300 mg/kg bw/day. Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of gestation. The exposure consisted of a mixture of aerosol/vapour of unknown particle size distribution. No effects of the NMP exposure on the outcome of pregnancy, embryonal growth rate, or development in vital organs and skeletons of the foetuses were found. Nor were there abnormal clinical signs o; CITATION=Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of; CITATION_NUMBERS=[44,25,100,360,6,15]; REFERENCE=Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of","dose":"The NOAEL was set at 300 mg/kg bw/day.","duration":"developmental","effect":"ere were no signs of maternal toxicity (death, food consumption, body weight, uterus weight), nor local effects at the application site. There was a significant increase in the incidence of foetuses with skeletal alterations, due to the occurrence of accessory 13th ribs. At 1000 mg/m³, their foetal and litter incidences were 15% and 60%, respectively (historical value 8.4 and 40 %, respectively). There was no effect on foetal body weight, or on the incidence of external, soft tissue and skeletal malformations. The NOAEL was set at 300 mg/kg bw/day. Ref.: 44 Inhalation Rats In a developmental toxicity study, pregnant rats (25 per dose level) were exposed whole body to 0, 100, or 360 mg NMP/m³ (100% pure) for 6 h/day on days 6–15 of gestation. The exposure consisted of a mixture of aerosol/vapour of unknown particle size distribution. No effects of the NMP exposure on the outcome of pregnancy, embryonal growth rate, or development in vital organs and skeletons of the foetuses were found. Nor were there abnormal clinical signs o","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":24,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =300 mg/kg bw/day rabbit dermal developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 300; DOSE=NOAEL = 300 mg/kg bw/day | BASF, 1993a (44); EFFECT=Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","duration":"developmental","effect":"Unlabeled table on page 28: Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution | 0 100 300 1000 | None None None Increased number of foetuses with skeletal alterations | None None None None | Developmental toxicity: NOAEL = 300 mg/kg bw/day | BASF, 1993a (44)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 300","page":28,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_073"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =332 mg/kg bw/day rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 332; DOSE=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorpti...; LOAEL_VALUE=332 mg/kg bw/day; EFFECT=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorpti...","duration":"developmental","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 29 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rat, developmental study, days 6-15, 0 332 997 None Foetal weight reduced Increased resorptions None Placental weight reduced Maternal weight reduced Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day EPA, 1988 (51) Rat, developmental study, days 6-20 0 125 250 500 750 None None Decreased foetal weight Malformation Malformation None None None Reduced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"332 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 332","page":29,"route":"","species":"rat","study_id":"sccs_o_050_noael_033"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =332 mg/kg bw/day rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 332; DOSE=LOAEL = 332 mg/kg bw/day | EPA, 1988 (51); LOAEL_VALUE=332 mg/kg bw/day; EFFECT=Unlabeled table on page 29: Rat, developmental study, days 6-15, | 0 332 997 | None Foetal weight reduced Increased resorptions | None Placental weight reduced Maternal weight reduced | Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day | EPA, 1988 (51); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"LOAEL = 332 mg/kg bw/day | EPA, 1988 (51)","duration":"developmental","effect":"Unlabeled table on page 29: Rat, developmental study, days 6-15, | 0 332 997 | None Foetal weight reduced Increased resorptions | None Placental weight reduced Maternal weight reduced | Maternal and foetal toxicity: LOAEL = 332 mg/kg bw/day | EPA, 1988 (51)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"332 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 332","page":29,"route":"","species":"rat","study_id":"sccs_o_050_noael_084"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =360 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3; EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day | 0 mg/m3 100 mg/m3 360 mg/m3 | None None None | None None Lethargy and irregular respiration during the first 3 days of exposure | Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 | Lee et al., 1987 (24)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_088"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 400 mg/kg bw rabbit - Developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=400; DOSE=d 42 g, respectively at 400 mg/kg bw).; EFFECT=d 42 g, respectively at 400 mg/kg bw). However, there was no statistical difference in weight gain during the overall gestation period (GD 0-21) and after correction for gravid uterine weight. No changes in food consumption were found. - Developmental toxicity: At 400 mg/kg bw/day: Reduced foetal body weight (10-11 %) and an increased incidence of stunted foetuses (foetuses: 1/340, 1/393, 2/395, and 12/397; litters: 1/21, 1/25, 2/24, and 6/25; at 0, 40, 125 and 400 mg/kg bw, respectively). No teratogenic effects. NOAEL for maternal and developmental toxicity: 125 mg/kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of missh; CITATION=Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio; CITATION_NUMBERS=[49,55,175,540,15,20,6,18]; REFERENCE=Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestatio","dose":"d 42 g, respectively at 400 mg/kg bw).","duration":"Developmental","effect":"d 42 g, respectively at 400 mg/kg bw). However, there was no statistical difference in weight gain during the overall gestation period (GD 0-21) and after correction for gravid uterine weight. No changes in food consumption were found. - Developmental toxicity: At 400 mg/kg bw/day: Reduced foetal body weight (10-11 %) and an increased incidence of stunted foetuses (foetuses: 1/340, 1/393, 2/395, and 12/397; litters: 1/21, 1/25, 2/24, and 6/25; at 0, 40, 125 and 400 mg/kg bw, respectively). No teratogenic effects. NOAEL for maternal and developmental toxicity: 125 mg/kg bw/day. Ref.: 49 In another developmental toxicity study, orally doses of 55, 175, or 540 mg NMP/kg bw/day were administered to pregnant rabbits (15 - 20 per dose level) on days 6–18 of gestation. - Maternal toxicity: Decreased food intake and weight gain during dosing at 175 and 540 mg/kg bw/day. - Developmental toxicity: At 540 mg/kg bw/day: Increased incidences of resorptions. Cardiovascular malformations and malformed skull bones. Increased incidence of missh","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"400","page":26,"route":"","species":"rabbit","study_id":"sccs_o_050_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 494 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight; DOSE=54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol;; EFFECT=ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight; CITATION=Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; CITATION_NUMBERS=[54,300,1000,2000]; REFERENCE=Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol","dose":"54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol;","duration":"developmental","effect":"ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:ration. There were no adverse effects on embryo/foetal viability or evidence of teratogenicity at any concentration tested. Foetal toxicity indicated by reduced foetal weight was observed at 494 mg/m³. The authors concluded that inhalation exposure of pregnant rats to NMP (vapours) during the entire post-implantation phase of gestation is neither teratogenic nor embryo-lethal. Evidence of developmental toxicity was limited to intrauterine growth retardation that occurred in the presence of maternal toxicity. The NOAEL for maternal and developmental toxicity was 124 and 247 mg/m³, respectively. Ref.: 54 Rabbits In a pre-test of developmental toxicity, five pregnant rabbits per dose level were exposed to 0, 300, 1000, or 2000 mg NMP/m³ (vapour/aerosol; MMAD 3.8–4.0 µm) for 6 h/day on days 7–19 post-insemination. Maternal toxicity was expressed as prolonged clotting time, decreased plasma protein content, and increased liver weight at both 1000 and 2000 mg/m³. Small but dose-related decrease was observed in gravid uterine weight","page":25,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =500 mg/kg bw/day rat dermal developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 500; DOSE=NOAEL = 500 mg/kg bw/day | Becci et al., 1982 (43); EFFECT=Unlabeled table on page 28: Rat; range-finding developmental toxicity study; dermal; days 6–15 | 0 500 1100 2500 | None None Massive resorption; decreased bw gain Lethal | Maternal toxicity: NOAEL = 500 mg/kg bw/day | Becci et al., 1982 (43); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 500 mg/kg bw/day | Becci et al., 1982 (43)","duration":"developmental","effect":"Unlabeled table on page 28: Rat; range-finding developmental toxicity study; dermal; days 6–15 | 0 500 1100 2500 | None None Massive resorption; decreased bw gain Lethal | Maternal toxicity: NOAEL = 500 mg/kg bw/day | Becci et al., 1982 (43)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 500","page":28,"route":"dermal","species":"rat","study_id":"sccs_o_050_noael_066"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =500 - - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=NOAEL = 500 mg/m3 (; EFFECT=Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: developmental | 500 mg/ | m3 | No | ne | None | NOAEL = 500 mg/m3 ( | 47, 48)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"NOAEL = 500 mg/m3 (","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_094"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =622 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3; EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day | 0 mg/m3 622 mg/m3 | None Decreased body weight; neuro- behavioural effects | None None | Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 | Hass et al., 1994 (46)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_087"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =630 mg/kg bw/day mouse inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 630; DOSE=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3...; LOAEL_VALUE=630 mg/kg bw/day; EFFECT=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3 500 mg/m3 1000 mg/m3 None None None Slight foetal toxicity None None None Small decrease in gravid uterine weight Developmental and maternal toxicity: NOAEL = 500 mg/m3 BASF, 1991, 1993b. (47, 48) Intraperitoneal injection Mouse, developmental toxicity; days 11-15 0 630 1570 None Increased resorption rate and malformation - Developmental toxicity: LOAEL = 630 mg/kg bw/day EPA, 1988 (51) Mou; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3...","duration":"developmental","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 30 Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Rabbit, developmental toxicity; inhalation (whole body); days 7-19, 6h/day 0 mg/m3 200 mg/m3 500 mg/m3 1000 mg/m3 None None None Slight foetal toxicity None None None Small decrease in gravid uterine weight Developmental and maternal toxicity: NOAEL = 500 mg/m3 BASF, 1991, 1993b. (47, 48) Intraperitoneal injection Mouse, developmental toxicity; days 11-15 0 630 1570 None Increased resorption rate and malformation - Developmental toxicity: LOAEL = 630 mg/kg bw/day EPA, 1988 (51) Mou","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"630 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 630","page":30,"route":"inhalation","species":"mouse","study_id":"sccs_o_050_noael_047"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =630 mg/kg - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 630; DOSE=NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg; LOAEL_VALUE=630 mg/kg; EFFECT=Table 2: NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: developmental | 1570 | re | sorption rate | LOAEL = 630 mg/kg","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"630 mg/kg","noael_unit":"mg/kg","noael_value":"= 630","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_095"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =680 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); EFFECT=NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL = 360 mg/m3 Maternal toxicity: NOAEL = 100 mg/m3 Lee et al., 1987 (24) Rat; developmental toxicity; inhalation (whole body); days 6-20, 6 h/day 0 mg/m3 124 mg/m3 247 mg/m3 494 mg/m3 None None None Reduced foetal weight None None Reduced weight gain Reduced weight gain Developmental toxicity: NOAEL = 247 mg/m3 Maternal toxicity: NOAEL = 124 mg/m3 Saillenfait et al., 2003 (54)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_043"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity =680 - rat inhalation developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3; EFFECT=Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day | 0 mg/m3 680 mg/m3 | None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification | None None | Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 | Hass et al., 1995 (45); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 29: Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day | 0 mg/m3 680 mg/m3 | None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification | None None | Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 | Hass et al., 1995 (45)","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_086"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 750 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=750; DOSE=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day.; EFFECT=SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day. In summary, NOAEL for maternal and developmental toxicity was 250 and 125 mg/kg bw/day, respectively. Thus, oral administration of NMP produced developmental toxicity below maternally toxic levels. The authors state that the study was conducted according to the current OECD and EU guidelines. Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats. Pregnant rats (groups of 18-24 rats) were given 5-hydroxy-N-methyl-2- pyrrolidone (5-HNMP; 0, 250, 500, 750, or 1000 mg/kg bw/day),; CITATION=Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats; CITATION_NUMBERS=[53]; REFERENCE=Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats","dose":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day.","duration":"developmental","effect":"SCCS/1413/11 Opinion on N-Methyl-2-pyrrolidine (NMP) ___________________________________________________________________________________________ 27 ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg bw/day. In summary, NOAEL for maternal and developmental toxicity was 250 and 125 mg/kg bw/day, respectively. Thus, oral administration of NMP produced developmental toxicity below maternally toxic levels. The authors state that the study was conducted according to the current OECD and EU guidelines. Ref.: 53 The developmental toxicity of the three main metabolites of NMP was studied in Sprague- Dawley rats. Pregnant rats (groups of 18-24 rats) were given 5-hydroxy-N-methyl-2- pyrrolidone (5-HNMP; 0, 250, 500, 750, or 1000 mg/kg bw/day),","endpoint":"developmental toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"750","page":27,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 169 mg/kg bw/day rat oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=169; DOSE=Repeated dose toxicity No dermal repeated dose toxicity data were found.; EFFECT=– 68% of NMP was absorbed. Also in this case, the absorption was higher for neat NMP than for diluted NMP. In the absence of adequate experimental data with concentrations of NMP relevant for this assessment, SCCS will use the default value of 100% dermal absorption in the calculation of the MOS. 100% dermal absorption was also used in ECHA's recent proposal for Identification of NMP as a Substance of Very High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results avail; CITATION=(Ref. 65); CITATION_NUMBERS=[65]; REFERENCE=(Ref. 65); DETAILS_JSON={"cas_number":"872-50-4","citation":"(Ref. 65)","dose":"Repeated dose toxicity No dermal repeated dose toxicity data were found.","duration":"90-day","effect":"– 68% of NMP was absorbed. Also in this case, the absorption was higher for neat NMP than for diluted NMP. In the absence of adequate experimental data with concentrations of NMP relevant for this assessment, SCCS will use the default value of 100% dermal absorption in the calculation of the MOS. 100% dermal absorption was also used in ECHA's recent proposal for Identification of NMP as a Substance of Very High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results avail","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"169","page":35,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_059"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 250 mg/kg bw/day rat oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=250; DOSE=Repeated dose toxicity No dermal repeated dose toxicity data were found.; EFFECT=ption was also used in ECHA's recent proposal for Identification of NMP as a Substance of Very High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results available indicate that NMP can cause aneuploidy in a fungal test in vitro. However, NMP does not express a genotoxic effect in a standard bacterial assay and in two well-conducted in vivo assays (bone marrow chromosome aberration assay and micronucleus assay). NMP is not considered to have in vivo genotoxic potential.; CITATION=(Ref. 65); CITATION_NUMBERS=[65]; REFERENCE=(Ref. 65); DETAILS_JSON={"cas_number":"872-50-4","citation":"(Ref. 65)","dose":"Repeated dose toxicity No dermal repeated dose toxicity data were found.","duration":"90-day","effect":"ption was also used in ECHA's recent proposal for Identification of NMP as a Substance of Very High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results available indicate that NMP can cause aneuploidy in a fungal test in vitro. However, NMP does not express a genotoxic effect in a standard bacterial assay and in two well-conducted in vivo assays (bone marrow chromosome aberration assay and micronucleus assay). NMP is not considered to have in vivo genotoxic potential.","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":35,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_061"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 250 mg/kg bw/day rat oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=250; DOSE=Repeated dose toxicity No dermal repeated dose toxicity data were found.; EFFECT=ery High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results available indicate that NMP can cause aneuploidy in a fungal test in vitro. However, NMP does not express a genotoxic effect in a standard bacterial assay and in two well-conducted in vivo assays (bone marrow chromosome aberration assay and micronucleus assay). NMP is not considered to have in vivo genotoxic potential. Carcinogenicity The potential carcinogenicity of NMP has been investigated in two long-ter; CITATION=(Ref. 65); CITATION_NUMBERS=[65]; REFERENCE=(Ref. 65); DETAILS_JSON={"cas_number":"872-50-4","citation":"(Ref. 65)","dose":"Repeated dose toxicity No dermal repeated dose toxicity data were found.","duration":"90-day","effect":"ery High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results available indicate that NMP can cause aneuploidy in a fungal test in vitro. However, NMP does not express a genotoxic effect in a standard bacterial assay and in two well-conducted in vivo assays (bone marrow chromosome aberration assay and micronucleus assay). NMP is not considered to have in vivo genotoxic potential. Carcinogenicity The potential carcinogenicity of NMP has been investigated in two long-ter","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":35,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_062"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 277 mg/kg bw/day rat oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=277; DOSE=Repeated dose toxicity No dermal repeated dose toxicity data were found.; EFFECT=f NMP relevant for this assessment, SCCS will use the default value of 100% dermal absorption in the calculation of the MOS. 100% dermal absorption was also used in ECHA's recent proposal for Identification of NMP as a Substance of Very High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results available indicate that NMP can cause aneuploidy in a fungal test in vitro. However, NMP does not express a genotoxic effect in a standard bacterial assay and in two well-conducted; CITATION=(Ref. 65); CITATION_NUMBERS=[65]; REFERENCE=(Ref. 65); DETAILS_JSON={"cas_number":"872-50-4","citation":"(Ref. 65)","dose":"Repeated dose toxicity No dermal repeated dose toxicity data were found.","duration":"90-day","effect":"f NMP relevant for this assessment, SCCS will use the default value of 100% dermal absorption in the calculation of the MOS. 100% dermal absorption was also used in ECHA's recent proposal for Identification of NMP as a Substance of Very High Concern (SVHC) (Ref. 65). Repeated dose toxicity No dermal repeated dose toxicity data were found. A NOAEL of 169 mg/kg bw/day based oral administration in male rats was found in a 90-day study based on body weight effects and changes in three neurobehavioral parameters. The NOAEL was 277 mg/kg bw/day in mice based on the liver responses in a 90-day study and 173 mg/kg bw/day based on liver tumours in male mice. A NOAEL of 250 mg/kg bw/day (highest dose tested) was found in a 90-day study with dogs. The NOAEL was 500 mg NMP/m³ for both male and female rats after inhalation. Mutagenicity/Genotoxicity The results available indicate that NMP can cause aneuploidy in a fungal test in vitro. However, NMP does not express a genotoxic effect in a standard bacterial assay and in two well-conducted","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"277","page":35,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_060"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 2 - rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:, occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50); DOSE=, occurred in the absence of significant maternal toxicity in rats treated by gavage.; EFFECT=, occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":", occurred in the absence of significant maternal toxicity in rats treated by gavage.","duration":"developmental","effect":", occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:, occurred in the absence of significant maternal toxicity in rats treated by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50)","page":30,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_048"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 2 - rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:d by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48; DOSE=In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity.; EFFECT=d by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity.","duration":"developmental","effect":"d by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:d by gavage. In one experiment, a foetus showing the characteristic malformations elicited by NMP was also observed at a dose level with no maternal toxicity. It is considered unlikely that the embryolethality and the foetal malformations could have been secondary to the general toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48","page":30,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_049"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 11 % rat inhalation developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=11; DOSE=NOAEL = 55 mg/kg bw/day Developmental toxicity:; EFFECT=ted. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 55 mg/kg bw/day Developmental toxicity:","duration":"developmental","effect":"ted. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developm","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"11","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_038"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 11 % rat inhalation Developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=11; DOSE=NOAEL = 55 mg/kg bw/day Developmental toxicity:; EFFECT=tal study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Mate; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 55 mg/kg bw/day Developmental toxicity:","duration":"Developmental","effect":"tal study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Mate","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"11","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_039"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 11 % rat inhalation 7 days reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=11; DOSE=NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity:; EFFECT=toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effect; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity:","duration":"7 days","effect":"toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effect","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"11","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_040"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 11 % rat inhalation 7 days reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=11; EFFECT=Unlabeled table on page 29: Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week | 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 | None None None Pup body weight decrease (4–11%) | None None None Decrease in response to sound | Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; | Solomon et al., 1995 (41); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"7 days","effect":"Unlabeled table on page 29: Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week | 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 | None None None Pup body weight decrease (4–11%) | None None None Decrease in response to sound | Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; | Solomon et al., 1995 (41)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"11","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_078"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 29 - rat inhalation 7 days reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42); EFFECT=Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"7 days","effect":"Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42)","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_079"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =48 mg/kg bw/day rabbit dermal developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 48; DOSE=SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2).; EFFECT=___________ 34 A method named “the German method” has been used for a few substances toxic for reproduction, including NMP. The method is not validated. An EU expert group (linked to ECHA) is currently working to develop “Guidance for setting specific concentration limits for substances classified for reproductive toxicity according to the CLP regulation (EC/1272/2008)”. This will probably be finalised in 2011. The specific concentration limit according to the German method is calculated from the formula: SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%); CITATION=Ref.: 66 3; CITATION_NUMBERS=[66,3]; REFERENCE=Ref.: 66 3; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 66 3","dose":"SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2).","duration":"developmental","effect":"___________ 34 A method named “the German method” has been used for a few substances toxic for reproduction, including NMP. The method is not validated. An EU expert group (linked to ECHA) is currently working to develop “Guidance for setting specific concentration limits for substances classified for reproductive toxicity according to the CLP regulation (EC/1272/2008)”. This will probably be finalised in 2011. The specific concentration limit according to the German method is calculated from the formula: SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 48","page":34,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_054"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =48 mg/kg bw/day rabbit dermal developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 48; DOSE=SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2).; EFFECT=d” has been used for a few substances toxic for reproduction, including NMP. The method is not validated. An EU expert group (linked to ECHA) is currently working to develop “Guidance for setting specific concentration limits for substances classified for reproductive toxicity according to the CLP regulation (EC/1272/2008)”. This will probably be finalised in 2011. The specific concentration limit according to the German method is calculated from the formula: SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of hum; CITATION=Ref.: 66 3; CITATION_NUMBERS=[66,3]; REFERENCE=Ref.: 66 3; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 66 3","dose":"SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2).","duration":"developmental","effect":"d” has been used for a few substances toxic for reproduction, including NMP. The method is not validated. An EU expert group (linked to ECHA) is currently working to develop “Guidance for setting specific concentration limits for substances classified for reproductive toxicity according to the CLP regulation (EC/1272/2008)”. This will probably be finalised in 2011. The specific concentration limit according to the German method is calculated from the formula: SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of hum","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 48","page":34,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_055"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =48 mg/kg bw/day rabbit dermal developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 48; DOSE=SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2).; EFFECT=NMP. The method is not validated. An EU expert group (linked to ECHA) is currently working to develop “Guidance for setting specific concentration limits for substances classified for reproductive toxicity according to the CLP regulation (EC/1272/2008)”. This will probably be finalised in 2011. The specific concentration limit according to the German method is calculated from the formula: SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NO; CITATION=Ref.: 66 3; CITATION_NUMBERS=[66,3]; REFERENCE=Ref.: 66 3; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 66 3","dose":"SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2).","duration":"developmental","effect":"NMP. The method is not validated. An EU expert group (linked to ECHA) is currently working to develop “Guidance for setting specific concentration limits for substances classified for reproductive toxicity according to the CLP regulation (EC/1272/2008)”. This will probably be finalised in 2011. The specific concentration limit according to the German method is calculated from the formula: SCL = NOAEL x 100/1000 In the case of NMP the lowest NOAEL was found for developmental toxicity in rabbits after inhalation (NOAEL = 48 mg/kg bw/day, see Table 2). SCL = 48 mg/kg bw/day x 100/1000 mg/kg bw/day = 4.8% ~ 5%. Ref.: 66 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY N-Methyl-2-pyrrolidone (NMP) The safety calculation is only considering dermal exposure Exposure 17.8 g/day, 5% NMP (17.8 x 0.05x1000) = 890 mg/day Maximum absorption through the skin (100%) 890 x 1 = 890 mg/day Typical body weight of human = 60 kg Systemic exposure dose (SED) 890/60 = 14.8 mg/kg bw/day NO","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 48","page":34,"route":"dermal","species":"rabbit","study_id":"sccs_o_050_noael_056"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =55 mg/kg bw/day rat inhalation Developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 55; DOSE=NOAEL = 250 mg/kg bw/day Developmental toxicity:; EFFECT=uced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 250 mg/kg bw/day Developmental toxicity:","duration":"Developmental","effect":"uced weight gain Reduced weight gain Maternal toxicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 55","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_036"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 61 - - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=61: May cause h; EFFECT=Table 2: NOAELs for developmental toxicity: fertility or the un | born ch | ild (Pr | ev | iously, Repr | otox. Cat | .2; R | 61: May cause h | arm to the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"developmental","effect":"Table 2: NOAELs for developmental toxicity: fertility or the un | born ch | ild (Pr | ev | iously, Repr | otox. Cat | .2; R | 61: May cause h | arm to the","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"61: May cause h","page":30,"route":"","species":"","study_id":"sccs_o_050_noael_098"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =125 mg/kg bw/day rat oral Developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 125; DOSE=350 mg/kg bw/day Developmental toxicity:; EFFECT=ertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"350 mg/kg bw/day Developmental toxicity:","duration":"Developmental","effect":"ertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 125","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_032"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 125 mg/kg bw/day rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=125; DOSE=NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after o...; EFFECT=toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) and will be used in calculation of MOS. This NOAEL was reported for developmental toxicity in two independant studies (49, 53). It is noted that teratogenic eff; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after o...","duration":"developmental","effect":"toxicity of NMP. The developmental effects were specific and severe and are considered the most important reprotoxic effect in relation to NMP. As a consequence the NOAEL should be based on developmental toxicity. Table 2 list the lowest NOAEL from the different experiments. NMP has been classified due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) and will be used in calculation of MOS. This NOAEL was reported for developmental toxicity in two independant studies (49, 53). It is noted that teratogenic eff","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"125","page":30,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_050"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 125 mg/kg bw/day rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=125; DOSE=NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after o...; EFFECT=ed due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) and will be used in calculation of MOS. This NOAEL was reported for developmental toxicity in two independant studies (49, 53). It is noted that teratogenic effects were not observed after inhalation exposure.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after o...","duration":"developmental","effect":"ed due to its reprotoxic effect as category 1b; H360: May damage fertility or the unborn child (Previously, Reprotox. Cat.2; R 61: May cause harm to the unborn child). Table 2: NOAELs for developmental toxicity Exposure NOAEL (mg/kg bw/day) Reference Dermal rat rabbit 237 300 Becci et al., 1982 (43) BASF, 1993a (44) Oral rat rabbit 125 175 Sailenfait et al., 2002 (53) GAF, 1992 (50) Inhalation rat 60 (247 mg/m3 6h) Sailenfait et al., 2003 (54) rabbit 48 (500 mg/m3 6h) BASF, 1991, 1993b (47, 48) The lowest NOAEL after oral administration of NMP in rats (125 mg/kg bw/day) and will be used in calculation of MOS. This NOAEL was reported for developmental toxicity in two independant studies (49, 53). It is noted that teratogenic effects were not observed after inhalation exposure.","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"125","page":30,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_051"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 160 mg/kg bw/day rat oral Developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=160; DOSE=40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility:; EFFECT=toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility:","duration":"Developmental","effect":"toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Maternal and developmental toxicity: NOAEL = 125 mg/kg bw/day EXXON, 1992 (49)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"160","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_031"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 160 mg/kg bw/day rat - 10 days reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=160; DOSE=160 mg/kg bw/day | OEHHA, 1999 (40); EFFECT=Unlabeled table on page 28: Rat; two generation. Staring 10 days prior to mating. | 0 50 160 500 | None None None Decreased number of pups | None None None Reduced body weight | NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day | OEHHA, 1999 (40); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"160 mg/kg bw/day | OEHHA, 1999 (40)","duration":"10 days","effect":"Unlabeled table on page 28: Rat; two generation. Staring 10 days prior to mating. | 0 50 160 500 | None None None Decreased number of pups | None None None Reduced body weight | NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day | OEHHA, 1999 (40)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"160","page":28,"route":"","species":"rat","study_id":"sccs_o_050_noael_071"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =175 mg/kg bw/day rat inhalation Developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 175; DOSE=NOAEL = 250 mg/kg bw/day Developmental toxicity:; EFFECT=xicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 250 mg/kg bw/day Developmental toxicity:","duration":"Developmental","effect":"xicity: NOAEL = 250 mg/kg bw/day Developmental toxicity: NOAEL = 125 mg/kg bw/day Saillenfait et al., 2002 (53) Mouse, developmental study, days 11-15 0 1055 2637 None Increased resorption, malformations - Both developmental and maternal toxicity are insufficiently reported. EPA, 1988 (51) Rabbit; developmental study, days 6-18. 0 55 175 540 None None None Increased resorptions, malformations None None Decreased weight gain Decreased weight gain Maternal toxicity: NOAEL = 55 mg/kg bw/day Developmental toxicity: NOAEL = 175 mg/kg bw/day GAF, 1992 (50) Inhalation Rat; two-generation; inhalation (whole body), 6 h/day, 7 days/week 0 mg/m3 41 mg/m3 206 mg/m3 478 mg/m3 None None None Pup body weight decrease (4–11%) None None None Decrease in response to sound Reproductive toxicity: NOAEL = 206 mg/m3; Maternal toxicity: NOAEL = 206 mg/m3; Solomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 175","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_037"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =300 mg/kg bw/day rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 300; DOSE=NOAEL = 237 mg/kg bw/day;; EFFECT=ay Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreas; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 237 mg/kg bw/day;","duration":"developmental","effect":"ay Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreas","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 300","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_028"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 350 mg/kg bw/day rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=350; DOSE=NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.; EFFECT=mortality, body weights, feed consumption, clinical observations, reproductive performance or fertility. No effects on histological male and female in the P1. At 350mg/kg bw/day, in the F2 generation: - Decreases in the number of pups surviving lactation, and in pup body weights. No changes in microscopic evaluations of reproductive tissues as well in sperm assessments (P1-F1). Post weaning developmental landmarks (day of preputial separation and vaginal opening) determined in F1 generation were not affected. NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","duration":"developmental","effect":"mortality, body weights, feed consumption, clinical observations, reproductive performance or fertility. No effects on histological male and female in the P1. At 350mg/kg bw/day, in the F2 generation: - Decreases in the number of pups surviving lactation, and in pup body weights. No changes in microscopic evaluations of reproductive tissues as well in sperm assessments (P1-F1). Post weaning developmental landmarks (day of preputial separation and vaginal opening) determined in F1 generation were not affected. NOAEL for reproductive performance and fertility was 350 mg/kg bw/day for the F0 and F1 parental rats.","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"350","page":21,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 350 mg/kg bw/day rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=350; DOSE=NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal;; EFFECT=t; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Matern; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal;","duration":"developmental","effect":"t; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study, days 6-15, gavage 5 ml/kg 0 40 125 400 None None None Reduced foetal weight and stunted foetuses None None None Bodyweight gain depressed Matern","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"350","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_030"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 350 mg/kg bw/day rat - Developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=350; DOSE=350 mg/kg bw/day Developmental toxicity:; EFFECT=Unlabeled table on page 28: Rat; two-generation | 0 50 160 500-350 | None None None Decreased number of pups | None None None None | NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day | BASF, 1999 (39); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"350 mg/kg bw/day Developmental toxicity:","duration":"Developmental","effect":"Unlabeled table on page 28: Rat; two-generation | 0 50 160 500-350 | None None None Decreased number of pups | None None None None | NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day | BASF, 1999 (39)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"350","page":28,"route":"","species":"rat","study_id":"sccs_o_050_noael_070"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 500 mg/kg bw/day - - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=500; DOSE=Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day.; EFFECT=inuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter size, reduced postnatal survival and pup weight. Significant reductions in the male fertility index and the female fecundity index of the F1 generation were also reported, without a clear NOAEL. Clear adverse effects were found at 500 mg/kg bw/day (Fertility index of males mated twice: 93-83, 72-69, 72-60, and 47-35 in the control, low-, mid- and high-dose groups, respectively. Fecundity index of females mated twice: 96-93, 82-74, 75-64, 61-50 in the control, low-, mid-, and high-dose groups, respectively). There was also an increased incidence of F1 females with decreased corpora lutea at the high-dose. Histological changes were noted at the high dose. There was a reduced incidence of females with pigm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day.","duration":"developmental","effect":"inuing throughout mating, gestation and lactation for both generations. Maternal toxicity was reported as reduced food intake, body weight, and/or body weight gain in the F0 and F1 generations at 500 mg/kg bw/day. There was evidence of developmental toxicity in both generations at 500 mg/kg bw/day, as evidenced by reduced litter size, reduced postnatal survival and pup weight. Significant reductions in the male fertility index and the female fecundity index of the F1 generation were also reported, without a clear NOAEL. Clear adverse effects were found at 500 mg/kg bw/day (Fertility index of males mated twice: 93-83, 72-69, 72-60, and 47-35 in the control, low-, mid- and high-dose groups, respectively. Fecundity index of females mated twice: 96-93, 82-74, 75-64, 61-50 in the control, low-, mid-, and high-dose groups, respectively). There was also an increased incidence of F1 females with decreased corpora lutea at the high-dose. Histological changes were noted at the high dose. There was a reduced incidence of females with pigm","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"500","page":22,"route":"","species":"","study_id":"sccs_o_050_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =500 mg/kg bw/day rat dermal developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 500; DOSE=The LOAEL for repeated doses was 74 mg/kg bw administered on days 7–11 of gestation.; LOAEL_VALUE=74 mg/kg bw; EFFECT=fusions and curvature of neck and chest vertebrae, and fusion of sternebrae and ribs were observed. The LOAEL for repeated doses was 74 mg/kg bw administered on days 7–11 of gestation. No information on maternal toxicity is given in this study; thus, evaluation of the results is difficult Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1. Table 1: Summary of reproductive toxicity of NMP in animals Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et; CITATION=Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1; CITATION_NUMBERS=[52,1]; REFERENCE=Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1","dose":"The LOAEL for repeated doses was 74 mg/kg bw administered on days 7–11 of gestation.","duration":"developmental","effect":"fusions and curvature of neck and chest vertebrae, and fusion of sternebrae and ribs were observed. The LOAEL for repeated doses was 74 mg/kg bw administered on days 7–11 of gestation. No information on maternal toxicity is given in this study; thus, evaluation of the results is difficult Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1. Table 1: Summary of reproductive toxicity of NMP in animals Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"74 mg/kg bw","noael_unit":"mg/kg bw/day","noael_value":"= 500","page":28,"route":"dermal","species":"rat","study_id":"sccs_o_050_noael_024"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =500 mg/kg bw/day rat dermal developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 500; DOSE=Summary of reproductive toxicity of NMP in animals Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity:; EFFECT=ernal toxicity is given in this study; thus, evaluation of the results is difficult Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1. Table 1: Summary of reproductive toxicity of NMP in animals Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Develop; CITATION=Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1; CITATION_NUMBERS=[52,1]; REFERENCE=Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1; DETAILS_JSON={"cas_number":"872-50-4","citation":"Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1","dose":"Summary of reproductive toxicity of NMP in animals Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity:","duration":"developmental","effect":"ernal toxicity is given in this study; thus, evaluation of the results is difficult Ref.: 52 The results from the reproductive studies of NMP in animals are summarized in Table 1. Table 1: Summary of reproductive toxicity of NMP in animals Toxicity Species; type of study Exposure (mg/kg bw/d) Foetal Maternal NOAEL/LOAEL (mg/kg bw/day) Reference Dermal Rat; range-finding developmental toxicity study; dermal; days 6–15 0 500 1100 2500 None None Massive resorption; decreased bw gain Lethal Maternal toxicity: NOAEL = 500 mg/kg bw/day Becci et al., 1982 (43) Rat; developmental toxicity study; dermal; days 6–15 0 75 237 750 None None None Increased resorption, delayed ossification None None None Decreased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Develop","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 500","page":28,"route":"dermal","species":"rat","study_id":"sccs_o_050_noael_025"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =600 mg/kg bw/day rat oral Developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT== 600; DOSE=NOAEL = 237 mg/kg bw/day;; EFFECT=ased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"NOAEL = 237 mg/kg bw/day;","duration":"Developmental","effect":"ased body weight gain Developmental toxicity: NOAEL = 237 mg/kg bw/day; Maternal toxicity: NOAEL = 237 mg/kg bw/day Becci et al., 1982 (43) Rabbit; developmental toxicity study; dermal; days 7-19; 40% aqueous solution 0 100 300 1000 None None None Increased number of foetuses with skeletal alterations None None None None Developmental toxicity: NOAEL = 300 mg/kg bw/day BASF, 1993a (44) Rabbit; maternal toxicity; dermal; 40% aqueous solution 0 400 600 800 None None None Increased clotting time Maternal toxicity NOAEL = 600 mg/kg bw/day BASF, 1993 a (44) Oral Rat; two-generation 0 50 160 500-350 None None None Decreased number of pups None None None None NOAEL reproductive performance and fertility: 350 mg/kg bw/day Developmental toxicity: 160 mg/kg bw/day BASF, 1999 (39) Rat; two generation. Staring 10 days prior to mating. 0 50 160 500 None None None Decreased number of pups None None None Reduced body weight NOAEL reproductive performance and developmental toxicity: 160 mg/kg bw/day OEHHA, 1999 (40) Rat; developmental study,","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 600","page":28,"route":"oral","species":"rat","study_id":"sccs_o_050_noael_029"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity =618 - rat inhalation 7 days reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=Reproductive toxicity: NOAEL = 618 mg/m3; EFFECT=Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"7 days","effect":"Unlabeled table on page 29: Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days | 0 mg/m3 618 mg/m3 | None None | None None | Reproductive toxicity: NOAEL = 618 mg/m3 | Fries et al., 1992 (42)","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"Reproductive toxicity: NOAEL = 618 mg/m3","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_085"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 1995 - rat inhalation 7 days reproductive toxicity SOURCE_SUBDIR=sccs_o_050; REPORT_TITLE=OPINION ON N-Methyl-2-pyrrolidone (NMP); OPINION_NUMBER=SCCS/1413/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 14 December 2010; VALUE_TEXT=unclear:olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL; EFFECT=olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"872-50-4","citation":"","dose":"","duration":"7 days","effect":"olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:olomon et al., 1995 (41) Rat; testes and semen toxicity study; inhalation (whole body); 6 h/day, 7 days/week; <90 days 0 mg/m3 618 mg/m3 None None None None Reproductive toxicity: NOAEL = 618 mg/m3 Fries et al., 1992 (42) Rat; developmental toxicity; inhalation (whole body); days 4–20, 6 h/day 0 mg/m3 680 mg/m3 None Increased pre- implantation loss but no effect on number of implantations per dam or number of live foetuses; delayed ossification None None Developmental toxicity: LOAEL = 680 mg/m3 Maternal toxicity: NOAEL = 680 mg/m3 Hass et al., 1995 (45) Rat; developmental toxicity; inhalation (whole body); days 7–20, 6 h/day 0 mg/m3 622 mg/m3 None Decreased body weight; neuro- behavioural effects None None Developmental toxicity: LOAEL = 622 mg/m3 Maternal toxicity: NOAEL = 622 mg/m3 Hass et al., 1994 (46) Rat; developmental toxicity; inhalation (whole body); days 6–15, 6 h/day 0 mg/m3 100 mg/m3 360 mg/m3 None None None None None Lethargy and irregular respiration during the first 3 days of exposure Developmental toxicity: NOAEL","page":29,"route":"inhalation","species":"rat","study_id":"sccs_o_050_noael_041"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier JR9CE63FPM UNII - - - chemical {"approval_status":null,"molecular_formula":"C5H9NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"JR9CE63FPM"}
openFDA substances FDA UNII substance identifier JR9CE63FPM UNII - - - chemical {"approval_status":null,"molecular_formula":"C5H9NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"JR9CE63FPM"}
openFDA substances FDA UNII substance identifier JR9CE63FPM UNII - - - chemical {"approval_status":null,"molecular_formula":"C5H9NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"JR9CE63FPM"}
openFDA substances FDA UNII substance identifier JR9CE63FPM UNII - - - chemical {"approval_status":null,"molecular_formula":"C5H9NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"JR9CE63FPM"}