NOAEL Studies Antioxidant

Butylated Hydroxytoluene NOAEL Studies

INCI: BHT

CAS: 128-37-0

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

COSMOS_DB 36 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB LOAEL 800 mg/kg bw/day mouse oral 7-13 Gestation day Developmental PAFA; ASP
COSMOS_DB NOAEL 300 mg/kg bw/day rat oral 175 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 500 mg/kg bw/day rat oral 730 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 200 mg/kg bw/day rat oral 560 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 50 mg/kg bw/day rat oral 730 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 6 mg/kg bw/day rat oral 365 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 750 mg/kg bw/day mouse oral 1036 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 150 mg/kg bw/day mouse oral 700 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 250 mg/kg bw/day rat oral 224 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 12.5 mg/kg bw/day rat oral 175 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 450 mg/kg bw/day mouse oral 756 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 600 mg/kg bw/day mouse oral 672 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 75 mg/kg bw/day mouse oral 305 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 160 mg/kg bw/day rat oral 730 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 790 mg/kg bw/day dog oral 365 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 4 mg/kg bw/day dog oral 365 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 660 mg/kg bw/day rat oral 161 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 100 mg/kg bw/day rat oral 49 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 620 mg/kg bw/day rat oral 49 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 465 mg/kg bw/day mouse oral 49 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 700 mg/kg bw/day rat oral 28 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 180 mg/kg bw/day mouse oral 10 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 225 mg/kg bw/day rat oral 10 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 280 mg/kg bw/day hamster oral 5 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 3.2 mg/kg bw/day rabbit oral 13 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 85 mg/kg bw/day guinea pig oral 14 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 408 mg/kg bw/day guinea pig oral 17 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 240 mg/kg bw/day mouse oral 7 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 608 mg/kg bw/day mouse oral NA Multigeneration Reproductive US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 698 mg/kg bw/day rat oral 28 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 25 mg/kg bw/day rat oral 90 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 918 mg/kg bw/day rat oral 7 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 330 mg/kg bw/day rat oral 224 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 34 mg/kg bw/day chinese hamster oral 14 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 58 mg/kg bw/day mouse oral 14 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 400 mg/kg bw/day mouse oral 1 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =25 mg/kg bw/day Rat oral: feed - reproduction toxicity EFSA ANS - 2012 - OutputID 490 - development - developmental - Scientific Opinion on the re-evaluation of butylated hydroxytoluene BHT (E 321) as a food additive - doi:10.2903/j.efsa.2012.2588
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =25 mg/kg bw/day Rat oral: feed - reproduction toxicity EFSA ANS - 2012 - OutputID 490 - development - developmental - Scientific Opinion on the re-evaluation of butylated hydroxytoluene BHT (E 321) as a food additive - doi:10.2903/j.efsa.2012.2588
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI =0.25 mg/kg bw/day Consumers - - ADI EFSA ANS - 2012 - OutputID 490 - Consumers - Scientific Opinion on the re-evaluation of butylated hydroxytoluene BHT (E 321) as a food additive - doi:10.2903/j.efsa.2012.2588
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI =0.25 mg/kg bw/day Consumers - - ADI EFSA ANS - 2012 - OutputID 490 - Consumers - Scientific Opinion on the re-evaluation of butylated hydroxytoluene BHT (E 321) as a food additive - doi:10.2903/j.efsa.2012.2588
IARC Monographs 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
IARC Monographs IARC carcinogenicity classification 3 IARC group - - 1987 IARC Monographs {"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"40, Sup 7"}
IARC Monographs IARC carcinogenicity classification 3 IARC group - - 1987 IARC Monographs {"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"40, Sup 7"}
IARC Monographs IARC carcinogenicity classification 3 IARC group - - 1987 IARC Monographs {"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"40, Sup 7"}
NTP_ICE_acute_oral 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_oral LD50 =890 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_2094; row=3749; data_type=In Vivo; mixture=Chemical; chemical_name=Butylated hydroxytoluene; preferred_name=Butylated hydroxytoluene; dtxsid=DTXSID2020216; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2020216; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID2020216; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 >6000 mg/kg bw Rat oral acute Rat Acute Oral Toxicity record_id=acute_oral_2096; row=3750; data_type=In Vivo; mixture=Chemical; chemical_name=Butylated hydroxytoluene; preferred_name=Butylated hydroxytoluene; dtxsid=DTXSID2020216; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2020216; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID2020216; source_file=acute_oral.xlsx
NTP_ICE_cancer 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_cancer IARC group 3 unitless - - - WOE; IARC Carcinogenicity sheet=Data; excel_row=2277; Record_ID=cancer_6431; Data_Type=WOE; Formulation_Name=Butylated hydroxytoluene; Mixture=Chemical; DTXSID=DTXSID2020216; Assay=IARC Carcinogenicity; Endpoint=IARC group; Response=3; Response_Unit=Unitless; URL=http://publications.iarc.fr/58; http://publications.iarc.fr/139; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2020216; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID2020216
NTP_ICE_cancer Top dose 6000 ppm Rat - - In Vivo; NTP Carcinogenicity sheet=Data; excel_row=2269; Record_ID=cancer_6432; Data_Type=In Vivo; Formulation_Name=Butylated hydroxytoluene; Mixture=Chemical; DTXSID=DTXSID2020216; Assay=NTP Carcinogenicity; Endpoint=Top dose; Response=6000; Response_Unit=ppm; Species=Rat; Strain=F344/N; Sex=Male; Reference=TR-150; URL=https://ntp.niehs.nih.gov/publications/reports/tr/100s/tr150/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2020216; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID2020216
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, Agonist sheet=Integrated_approaches; excel_row=5902; RecordID=ARPathway2016_761; DatasetName=ARPathway2016; DTXSID=DTXSID2020216; Assay=AR Pathway Model, Agonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID2020216; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID2020216
SCCS_vision_codex 120 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =450 mg/kg bw/day rat - Chronic reproductive toxicity {"citation":"Ref.: EFSA 2012","dose":"In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal.","effect":"n. In addition, BHT has been shown to increase the relative thyroid and adrenal weight in rats. In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal. EFSA concluded that none of the studies available could be used to derive a NOAEL. Ref.: EFSA 2012; ANSES 2016 SCCS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg b","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_001"}
SCCS_vision_codex NOAEL =25 mg/kg bw rat - Chronic reproductive toxicity {"dose":"3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.","effect":"CS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) wer","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_002"}
SCCS_vision_codex NOAEL =38 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: EFSA 2012","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"s on genotoxicity (Ma et al. 2017, Negritto et al. 2017), retrieved in the systematic literature searches performed by VKM, did not provide evidence of genotoxicity. Ref.: EFSA 2012; Ma 2017; Negritto 2017; VKM 2019 SCCS comment The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_005"}
SCCS_vision_codex NOAEL =247 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: Brooks 1976","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"y. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study. Ref.: Brooks 1976; Olsen 1986; EFSA 2012","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_006"}
SCCS_vision_codex NOAEL =25 mg/kg bw/day rat - - carcinogenicity {"dose":"The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.","effect":"mice, rats and chickens. BHT has been shown to increase the relative thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT","page":25,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_010"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 days NOAEL study {"dose":"Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al.","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 32 ANNEX 1: Table A-1. Summary of level 3-5 in vivo animal studies with emphasis on effects on liver (LE), thyroid (TE) and adrenals (AE) and indicated NOAEL’s (including studies with ≥2 doses only). Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al. 1989 Rat m oral highes t tolerat ed doses for 30 days 0.5% dietary BHT No detectable ↑ in 3H- thymidine labelling Time-limite","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_013"}
SCCS_vision_codex NOAEL =1636 - rat oral 144 wk NOAEL study {"dose":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m p...","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_014"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rat - 24 wk NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al.","effect":"al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al. 2008 rat 6 m per dose 28 days feedin g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_017"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses.","effect":"g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_018"}
SCCS_vision_codex NOAEL =7 - - - - NOAEL study {"dose":"BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_019"}
SCCS_vision_codex NOAEL =25 - - - - NOAEL study {"effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hydroalcoholic based fragrances | 0.8 | 4.67 | 0.00015 | 25 | 167 291","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_020"}
SCCS_vision_codex NOAEL =32 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_041"}
SCCS_vision_codex NOAEL =67 - rat - - NOAEL study {"dose":"Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","effect":"Unlabeled table on page 32: Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_042"}
SCCS_vision_codex NOAEL =33 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_045"}
SCCS_vision_codex NOAEL =500 - rat oral 14 wk NOAEL study {"dose":"1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_046"}
SCCS_vision_codex NOAEL =100 - rat oral 22 weeks NOAEL study {"effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 7M/5 0F F0 Oral F1 postn atal expos ure, | Main study Necrop sied at 22 weeks post weanin g | F0 0, 25, 100, 500 F1 0, 25, 100, 250 | at ≥500 F0 dams ↑ weight Abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 100 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_048"}
SCCS_vision_codex NOAEL =20 mg/kg/day rat - 8 wk NOAEL study {"dose":"Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","effect":"Unlabeled table on page 33: Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_050"}
SCCS_vision_codex NOAEL =50 - - - 4 wk NOAEL study {"dose":"Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","effect":"Unlabeled table on page 33: Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_053"}
SCCS_vision_codex NOAEL =34 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_054"}
SCCS_vision_codex NOAEL =225 - rat - 105 wk NOAEL study {"dose":"NCI 1979a | rat 20-50 m/f per dose;","effect":"Unlabeled table on page 34: NCI 1979a | rat 20-50 m/f per dose; Interi m sacrifi ces | 105 wk feedin g | 225, 450 | weight: no data tumors: not sign. | c-cell hyperplasia in males at ≥ 225 mg; no tumor induction | Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human health. | 225 (LOAEL, TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_056"}
SCCS_vision_codex NOAEL =515 - - - 107 wk NOAEL study {"dose":"NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m:","effect":"Unlabeled table on page 34: NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m: 0, 515, 1029 f: 0, 518, 1037 | weight: no data ↑ incidence of hepatocytomegaly and nonneoplastic lesions (peliosis, hepatocellular degeneration/necrosis, cytoplasmic vacuolation in males) | ‘no effects’ | ‘no effects’ | 515 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_057"}
SCCS_vision_codex NOAEL =30 - rat - 8 wk NOAEL study {"effect":"Unlabeled table on page 34: Fulton et al. 1980 | Rat 10 m | 8 wk feedin g | 0, 30, 151, 755, 1132 | Weight (abs↑ and rel↑) | 30 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_058"}
SCCS_vision_codex NOAEL =125 - rat - 104 wk NOAEL study {"dose":"1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","effect":"Unlabeled table on page 34: Hirose et al. 1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_059"}
SCCS_vision_codex NOAEL =250 - - - - NOAEL study {"effect":"Unlabeled table on page 34: no effect on enzyme act. T3/T4 | 250 (TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_061"}
SCCS_vision_codex NOAEL =15 - rat - 18 wk NOAEL study {"effect":"Unlabeled table on page 34: Furuka wa et al. 19844 | rat 10 m/gro up | 18 wk feedin g | 15, 50, 150, 300 | weight ↑ histopath (enlargement of hep. at ≥ 150 mg) | 15 (LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_062"}
SCCS_vision_codex NOAEL =1640 - - - 104 wk NOAEL study {"effect":"Unlabeled table on page 34: Inai et al. | mous e, 50 | 104 wk | m: 1640, | ↑ weight m proliferation (foci), | not affected or | no effects on | 1640 (LOAEL,","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_064"}
SCCS_vision_codex NOAEL =35 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_065"}
SCCS_vision_codex NOAEL =75 - rat - 76 wk NOAEL study {"effect":"Unlabeled table on page 35: William s et al. 1990 | rat males ; interi m sacrifi ces | 76 wk 110 wk feedin g | 7.5, 23, 75, 225, 450 900 (only 110 wk) | weight ↑ (at ≥ 450mg) no morphological changes | no effects (tumor induction) no effects (tumor induction) | no effects (tumors induction) no effects (tumor induction) | 75 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_066"}
SCCS_vision_codex NOAEL =200 - rat - 24 wk NOAEL study {"dose":"Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","effect":"Unlabeled table on page 35: Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_067"}
SCCS_vision_codex NOAEL =28 - rat - 28 days NOAEL study {"dose":"2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","effect":"Unlabeled table on page 35: Stieru m et al. 2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_068"}
SCCS_vision_codex NOAEL =450 mg/kg bw/day rat - Chronic reproductive toxicity {"citation":"Ref.: EFSA 2012","dose":"In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal.","effect":"n. In addition, BHT has been shown to increase the relative thyroid and adrenal weight in rats. In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal. EFSA concluded that none of the studies available could be used to derive a NOAEL. Ref.: EFSA 2012; ANSES 2016 SCCS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg b","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_001"}
SCCS_vision_codex NOAEL =25 mg/kg bw rat - Chronic reproductive toxicity {"dose":"3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.","effect":"CS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) wer","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_002"}
SCCS_vision_codex NOAEL =38 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: EFSA 2012","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"s on genotoxicity (Ma et al. 2017, Negritto et al. 2017), retrieved in the systematic literature searches performed by VKM, did not provide evidence of genotoxicity. Ref.: EFSA 2012; Ma 2017; Negritto 2017; VKM 2019 SCCS comment The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_005"}
SCCS_vision_codex NOAEL =247 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: Brooks 1976","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"y. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study. Ref.: Brooks 1976; Olsen 1986; EFSA 2012","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_006"}
SCCS_vision_codex NOAEL =25 mg/kg bw/day rat - - carcinogenicity {"dose":"The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.","effect":"mice, rats and chickens. BHT has been shown to increase the relative thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT","page":25,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_010"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 days NOAEL study {"dose":"Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al.","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 32 ANNEX 1: Table A-1. Summary of level 3-5 in vivo animal studies with emphasis on effects on liver (LE), thyroid (TE) and adrenals (AE) and indicated NOAEL’s (including studies with ≥2 doses only). Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al. 1989 Rat m oral highes t tolerat ed doses for 30 days 0.5% dietary BHT No detectable ↑ in 3H- thymidine labelling Time-limite","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_013"}
SCCS_vision_codex NOAEL =1636 - rat oral 144 wk NOAEL study {"dose":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m p...","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_014"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rat - 24 wk NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al.","effect":"al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al. 2008 rat 6 m per dose 28 days feedin g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_017"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses.","effect":"g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_018"}
SCCS_vision_codex NOAEL =7 - - - - NOAEL study {"dose":"BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_019"}
SCCS_vision_codex NOAEL =25 - - - - NOAEL study {"effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hydroalcoholic based fragrances | 0.8 | 4.67 | 0.00015 | 25 | 167 291","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_020"}
SCCS_vision_codex NOAEL =32 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_041"}
SCCS_vision_codex NOAEL =67 - rat - - NOAEL study {"dose":"Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","effect":"Unlabeled table on page 32: Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_042"}
SCCS_vision_codex NOAEL =33 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_045"}
SCCS_vision_codex NOAEL =500 - rat oral 14 wk NOAEL study {"dose":"1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_046"}
SCCS_vision_codex NOAEL =100 - rat oral 22 weeks NOAEL study {"effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 7M/5 0F F0 Oral F1 postn atal expos ure, | Main study Necrop sied at 22 weeks post weanin g | F0 0, 25, 100, 500 F1 0, 25, 100, 250 | at ≥500 F0 dams ↑ weight Abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 100 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_048"}
SCCS_vision_codex NOAEL =20 mg/kg/day rat - 8 wk NOAEL study {"dose":"Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","effect":"Unlabeled table on page 33: Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_050"}
SCCS_vision_codex NOAEL =50 - - - 4 wk NOAEL study {"dose":"Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","effect":"Unlabeled table on page 33: Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_053"}
SCCS_vision_codex NOAEL =34 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_054"}
SCCS_vision_codex NOAEL =225 - rat - 105 wk NOAEL study {"dose":"NCI 1979a | rat 20-50 m/f per dose;","effect":"Unlabeled table on page 34: NCI 1979a | rat 20-50 m/f per dose; Interi m sacrifi ces | 105 wk feedin g | 225, 450 | weight: no data tumors: not sign. | c-cell hyperplasia in males at ≥ 225 mg; no tumor induction | Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human health. | 225 (LOAEL, TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_056"}
SCCS_vision_codex NOAEL =515 - - - 107 wk NOAEL study {"dose":"NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m:","effect":"Unlabeled table on page 34: NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m: 0, 515, 1029 f: 0, 518, 1037 | weight: no data ↑ incidence of hepatocytomegaly and nonneoplastic lesions (peliosis, hepatocellular degeneration/necrosis, cytoplasmic vacuolation in males) | ‘no effects’ | ‘no effects’ | 515 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_057"}
SCCS_vision_codex NOAEL =30 - rat - 8 wk NOAEL study {"effect":"Unlabeled table on page 34: Fulton et al. 1980 | Rat 10 m | 8 wk feedin g | 0, 30, 151, 755, 1132 | Weight (abs↑ and rel↑) | 30 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_058"}
SCCS_vision_codex NOAEL =125 - rat - 104 wk NOAEL study {"dose":"1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","effect":"Unlabeled table on page 34: Hirose et al. 1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_059"}
SCCS_vision_codex NOAEL =250 - - - - NOAEL study {"effect":"Unlabeled table on page 34: no effect on enzyme act. T3/T4 | 250 (TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_061"}
SCCS_vision_codex NOAEL =15 - rat - 18 wk NOAEL study {"effect":"Unlabeled table on page 34: Furuka wa et al. 19844 | rat 10 m/gro up | 18 wk feedin g | 15, 50, 150, 300 | weight ↑ histopath (enlargement of hep. at ≥ 150 mg) | 15 (LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_062"}
SCCS_vision_codex NOAEL =1640 - - - 104 wk NOAEL study {"effect":"Unlabeled table on page 34: Inai et al. | mous e, 50 | 104 wk | m: 1640, | ↑ weight m proliferation (foci), | not affected or | no effects on | 1640 (LOAEL,","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_064"}
SCCS_vision_codex NOAEL =35 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_065"}
SCCS_vision_codex NOAEL =75 - rat - 76 wk NOAEL study {"effect":"Unlabeled table on page 35: William s et al. 1990 | rat males ; interi m sacrifi ces | 76 wk 110 wk feedin g | 7.5, 23, 75, 225, 450 900 (only 110 wk) | weight ↑ (at ≥ 450mg) no morphological changes | no effects (tumor induction) no effects (tumor induction) | no effects (tumors induction) no effects (tumor induction) | 75 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_066"}
SCCS_vision_codex NOAEL =200 - rat - 24 wk NOAEL study {"dose":"Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","effect":"Unlabeled table on page 35: Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_067"}
SCCS_vision_codex NOAEL =28 - rat - 28 days NOAEL study {"dose":"2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","effect":"Unlabeled table on page 35: Stieru m et al. 2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_068"}
SCCS_vision_codex NOAEL =450 mg/kg bw/day rat - Chronic reproductive toxicity {"citation":"Ref.: EFSA 2012","dose":"In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal.","effect":"n. In addition, BHT has been shown to increase the relative thyroid and adrenal weight in rats. In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal. EFSA concluded that none of the studies available could be used to derive a NOAEL. Ref.: EFSA 2012; ANSES 2016 SCCS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg b","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_001"}
SCCS_vision_codex NOAEL =25 mg/kg bw rat - Chronic reproductive toxicity {"dose":"3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.","effect":"CS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) wer","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_002"}
SCCS_vision_codex NOAEL =38 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: EFSA 2012","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"s on genotoxicity (Ma et al. 2017, Negritto et al. 2017), retrieved in the systematic literature searches performed by VKM, did not provide evidence of genotoxicity. Ref.: EFSA 2012; Ma 2017; Negritto 2017; VKM 2019 SCCS comment The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_005"}
SCCS_vision_codex NOAEL =247 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: Brooks 1976","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"y. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study. Ref.: Brooks 1976; Olsen 1986; EFSA 2012","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_006"}
SCCS_vision_codex NOAEL =25 mg/kg bw/day rat - - carcinogenicity {"dose":"The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.","effect":"mice, rats and chickens. BHT has been shown to increase the relative thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT","page":25,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_010"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 days NOAEL study {"dose":"Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al.","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 32 ANNEX 1: Table A-1. Summary of level 3-5 in vivo animal studies with emphasis on effects on liver (LE), thyroid (TE) and adrenals (AE) and indicated NOAEL’s (including studies with ≥2 doses only). Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al. 1989 Rat m oral highes t tolerat ed doses for 30 days 0.5% dietary BHT No detectable ↑ in 3H- thymidine labelling Time-limite","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_013"}
SCCS_vision_codex NOAEL =1636 - rat oral 144 wk NOAEL study {"dose":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m p...","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_014"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rat - 24 wk NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al.","effect":"al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al. 2008 rat 6 m per dose 28 days feedin g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_017"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses.","effect":"g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_018"}
SCCS_vision_codex NOAEL =7 - - - - NOAEL study {"dose":"BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_019"}
SCCS_vision_codex NOAEL =25 - - - - NOAEL study {"effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hydroalcoholic based fragrances | 0.8 | 4.67 | 0.00015 | 25 | 167 291","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_020"}
SCCS_vision_codex NOAEL =32 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_041"}
SCCS_vision_codex NOAEL =67 - rat - - NOAEL study {"dose":"Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","effect":"Unlabeled table on page 32: Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_042"}
SCCS_vision_codex NOAEL =33 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_045"}
SCCS_vision_codex NOAEL =500 - rat oral 14 wk NOAEL study {"dose":"1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_046"}
SCCS_vision_codex NOAEL =100 - rat oral 22 weeks NOAEL study {"effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 7M/5 0F F0 Oral F1 postn atal expos ure, | Main study Necrop sied at 22 weeks post weanin g | F0 0, 25, 100, 500 F1 0, 25, 100, 250 | at ≥500 F0 dams ↑ weight Abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 100 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_048"}
SCCS_vision_codex NOAEL =20 mg/kg/day rat - 8 wk NOAEL study {"dose":"Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","effect":"Unlabeled table on page 33: Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_050"}
SCCS_vision_codex NOAEL =50 - - - 4 wk NOAEL study {"dose":"Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","effect":"Unlabeled table on page 33: Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_053"}
SCCS_vision_codex NOAEL =34 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_054"}
SCCS_vision_codex NOAEL =225 - rat - 105 wk NOAEL study {"dose":"NCI 1979a | rat 20-50 m/f per dose;","effect":"Unlabeled table on page 34: NCI 1979a | rat 20-50 m/f per dose; Interi m sacrifi ces | 105 wk feedin g | 225, 450 | weight: no data tumors: not sign. | c-cell hyperplasia in males at ≥ 225 mg; no tumor induction | Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human health. | 225 (LOAEL, TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_056"}
SCCS_vision_codex NOAEL =515 - - - 107 wk NOAEL study {"dose":"NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m:","effect":"Unlabeled table on page 34: NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m: 0, 515, 1029 f: 0, 518, 1037 | weight: no data ↑ incidence of hepatocytomegaly and nonneoplastic lesions (peliosis, hepatocellular degeneration/necrosis, cytoplasmic vacuolation in males) | ‘no effects’ | ‘no effects’ | 515 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_057"}
SCCS_vision_codex NOAEL =30 - rat - 8 wk NOAEL study {"effect":"Unlabeled table on page 34: Fulton et al. 1980 | Rat 10 m | 8 wk feedin g | 0, 30, 151, 755, 1132 | Weight (abs↑ and rel↑) | 30 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_058"}
SCCS_vision_codex NOAEL =125 - rat - 104 wk NOAEL study {"dose":"1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","effect":"Unlabeled table on page 34: Hirose et al. 1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_059"}
SCCS_vision_codex NOAEL =250 - - - - NOAEL study {"effect":"Unlabeled table on page 34: no effect on enzyme act. T3/T4 | 250 (TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_061"}
SCCS_vision_codex NOAEL =15 - rat - 18 wk NOAEL study {"effect":"Unlabeled table on page 34: Furuka wa et al. 19844 | rat 10 m/gro up | 18 wk feedin g | 15, 50, 150, 300 | weight ↑ histopath (enlargement of hep. at ≥ 150 mg) | 15 (LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_062"}
SCCS_vision_codex NOAEL =1640 - - - 104 wk NOAEL study {"effect":"Unlabeled table on page 34: Inai et al. | mous e, 50 | 104 wk | m: 1640, | ↑ weight m proliferation (foci), | not affected or | no effects on | 1640 (LOAEL,","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_064"}
SCCS_vision_codex NOAEL =35 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_065"}
SCCS_vision_codex NOAEL =75 - rat - 76 wk NOAEL study {"effect":"Unlabeled table on page 35: William s et al. 1990 | rat males ; interi m sacrifi ces | 76 wk 110 wk feedin g | 7.5, 23, 75, 225, 450 900 (only 110 wk) | weight ↑ (at ≥ 450mg) no morphological changes | no effects (tumor induction) no effects (tumor induction) | no effects (tumors induction) no effects (tumor induction) | 75 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_066"}
SCCS_vision_codex NOAEL =200 - rat - 24 wk NOAEL study {"dose":"Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","effect":"Unlabeled table on page 35: Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_067"}
SCCS_vision_codex NOAEL =28 - rat - 28 days NOAEL study {"dose":"2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","effect":"Unlabeled table on page 35: Stieru m et al. 2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_068"}
SCCS_vision_codex NOAEL =450 mg/kg bw/day rat - Chronic reproductive toxicity {"citation":"Ref.: EFSA 2012","dose":"In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal.","effect":"n. In addition, BHT has been shown to increase the relative thyroid and adrenal weight in rats. In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal. EFSA concluded that none of the studies available could be used to derive a NOAEL. Ref.: EFSA 2012; ANSES 2016 SCCS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg b","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_001"}
SCCS_vision_codex NOAEL =25 mg/kg bw rat - Chronic reproductive toxicity {"dose":"3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.","effect":"CS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) wer","page":17,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_002"}
SCCS_vision_codex NOAEL =38 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: EFSA 2012","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"s on genotoxicity (Ma et al. 2017, Negritto et al. 2017), retrieved in the systematic literature searches performed by VKM, did not provide evidence of genotoxicity. Ref.: EFSA 2012; Ma 2017; Negritto 2017; VKM 2019 SCCS comment The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_005"}
SCCS_vision_codex NOAEL =247 mg/kg bw/day rat - - carcinogenicity {"citation":"Ref.: Brooks 1976","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","effect":"y. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study. Ref.: Brooks 1976; Olsen 1986; EFSA 2012","page":19,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_006"}
SCCS_vision_codex NOAEL =25 mg/kg bw/day rat - - carcinogenicity {"dose":"The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.","effect":"mice, rats and chickens. BHT has been shown to increase the relative thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT","page":25,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_010"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 days NOAEL study {"dose":"Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al.","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 32 ANNEX 1: Table A-1. Summary of level 3-5 in vivo animal studies with emphasis on effects on liver (LE), thyroid (TE) and adrenals (AE) and indicated NOAEL’s (including studies with ≥2 doses only). Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al. 1989 Rat m oral highes t tolerat ed doses for 30 days 0.5% dietary BHT No detectable ↑ in 3H- thymidine labelling Time-limite","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_013"}
SCCS_vision_codex NOAEL =1636 - rat oral 144 wk NOAEL study {"dose":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m p...","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_014"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rat - 24 wk NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al.","effect":"al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al. 2008 rat 6 m per dose 28 days feedin g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_017"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: Modified from EDC dossier 2019","dose":"3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses.","effect":"g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_018"}
SCCS_vision_codex NOAEL =7 - - - - NOAEL study {"dose":"BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_019"}
SCCS_vision_codex NOAEL =25 - - - - NOAEL study {"effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hydroalcoholic based fragrances | 0.8 | 4.67 | 0.00015 | 25 | 167 291","page":24,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_020"}
SCCS_vision_codex NOAEL =32 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_041"}
SCCS_vision_codex NOAEL =67 - rat - - NOAEL study {"dose":"Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","effect":"Unlabeled table on page 32: Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","page":32,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_042"}
SCCS_vision_codex NOAEL =33 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_045"}
SCCS_vision_codex NOAEL =500 - rat oral 14 wk NOAEL study {"dose":"1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_046"}
SCCS_vision_codex NOAEL =100 - rat oral 22 weeks NOAEL study {"effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 7M/5 0F F0 Oral F1 postn atal expos ure, | Main study Necrop sied at 22 weeks post weanin g | F0 0, 25, 100, 500 F1 0, 25, 100, 250 | at ≥500 F0 dams ↑ weight Abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 100 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_048"}
SCCS_vision_codex NOAEL =20 mg/kg/day rat - 8 wk NOAEL study {"dose":"Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","effect":"Unlabeled table on page 33: Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_050"}
SCCS_vision_codex NOAEL =50 - - - 4 wk NOAEL study {"dose":"Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","effect":"Unlabeled table on page 33: Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","page":33,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_053"}
SCCS_vision_codex NOAEL =34 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_054"}
SCCS_vision_codex NOAEL =225 - rat - 105 wk NOAEL study {"dose":"NCI 1979a | rat 20-50 m/f per dose;","effect":"Unlabeled table on page 34: NCI 1979a | rat 20-50 m/f per dose; Interi m sacrifi ces | 105 wk feedin g | 225, 450 | weight: no data tumors: not sign. | c-cell hyperplasia in males at ≥ 225 mg; no tumor induction | Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human health. | 225 (LOAEL, TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_056"}
SCCS_vision_codex NOAEL =515 - - - 107 wk NOAEL study {"dose":"NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m:","effect":"Unlabeled table on page 34: NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m: 0, 515, 1029 f: 0, 518, 1037 | weight: no data ↑ incidence of hepatocytomegaly and nonneoplastic lesions (peliosis, hepatocellular degeneration/necrosis, cytoplasmic vacuolation in males) | ‘no effects’ | ‘no effects’ | 515 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_057"}
SCCS_vision_codex NOAEL =30 - rat - 8 wk NOAEL study {"effect":"Unlabeled table on page 34: Fulton et al. 1980 | Rat 10 m | 8 wk feedin g | 0, 30, 151, 755, 1132 | Weight (abs↑ and rel↑) | 30 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_058"}
SCCS_vision_codex NOAEL =125 - rat - 104 wk NOAEL study {"dose":"1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","effect":"Unlabeled table on page 34: Hirose et al. 1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_059"}
SCCS_vision_codex NOAEL =250 - - - - NOAEL study {"effect":"Unlabeled table on page 34: no effect on enzyme act. T3/T4 | 250 (TE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_061"}
SCCS_vision_codex NOAEL =15 - rat - 18 wk NOAEL study {"effect":"Unlabeled table on page 34: Furuka wa et al. 19844 | rat 10 m/gro up | 18 wk feedin g | 15, 50, 150, 300 | weight ↑ histopath (enlargement of hep. at ≥ 150 mg) | 15 (LE)","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_062"}
SCCS_vision_codex NOAEL =1640 - - - 104 wk NOAEL study {"effect":"Unlabeled table on page 34: Inai et al. | mous e, 50 | 104 wk | m: 1640, | ↑ weight m proliferation (foci), | not affected or | no effects on | 1640 (LOAEL,","page":34,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_064"}
SCCS_vision_codex NOAEL =35 - - - - NOAEL study {"dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","effect":"Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_065"}
SCCS_vision_codex NOAEL =75 - rat - 76 wk NOAEL study {"effect":"Unlabeled table on page 35: William s et al. 1990 | rat males ; interi m sacrifi ces | 76 wk 110 wk feedin g | 7.5, 23, 75, 225, 450 900 (only 110 wk) | weight ↑ (at ≥ 450mg) no morphological changes | no effects (tumor induction) no effects (tumor induction) | no effects (tumors induction) no effects (tumor induction) | 75 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_066"}
SCCS_vision_codex NOAEL =200 - rat - 24 wk NOAEL study {"dose":"Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","effect":"Unlabeled table on page 35: Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_067"}
SCCS_vision_codex NOAEL =28 - rat - 28 days NOAEL study {"dose":"2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","effect":"Unlabeled table on page 35: Stieru m et al. 2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","page":35,"pdf":"sccs_o_257.pdf","row_type":"noael_study","study_id":"sccs_o_257_noael_068"}
ToxValDB_ECHA_IUCLID 53 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECHA_IUCLID LEL =538.05 mg/m3 Mouse inhalation - acute QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059759e4b063812d6fa6de; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/3/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15799127:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_1c30238f73d43f4a98d6c0a1d77b046a
ToxValDB_ECHA_IUCLID LEL =10700 mg/kg bw/day Guinea Pig oral - acute QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/3/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15804472:-:--; 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_8560478a155fa1656021f0a2b666fffa
ToxValDB_ECHA_IUCLID LEL >=940 mg/kg bw/day Cat oral - acute QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/3/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Oral_15813947_15813948: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_82bf96c31b6e00b8d1645b558d944b74
ToxValDB_ECHA_IUCLID LEL <=2100 mg/kg bw/day Cat oral - acute QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/3/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Oral_15813947_15813948: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_ab2d9b69d14394eeca3d18feb482c5ef
ToxValDB_ECHA_IUCLID LEL <=3200 mg/kg bw/day Rabbit oral - acute QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/3/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Oral_15814231_15814232:-:--; 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_31d6e17bf4b42a6d96095e7deec5c999
ToxValDB_ECHA_IUCLID LEL =200 mg/kg bw/day Mouse injection - acute QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61ccce4b096bca8773732; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/3/5?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15815633:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ac169636416b41379879986676b41e66
ToxValDB_ECHA_IUCLID LEL ~900 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30db; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15817032_15817033_15817034: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_4ec4bff2ee4d149b1bb082f65e40708b
ToxValDB_ECHA_IUCLID LEL =185 mg/kg bw/day Mouse oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c80fe4b0a7c65d2165fe; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15817340_15819075: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_57dd9810fa29a267880f6d2a3d71a748
ToxValDB_ECHA_IUCLID LEL =925 mg/kg bw/day Mouse oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c80fe4b0a7c65d2165fe; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15817341_15819073_15819074: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_8dffa2a399b222ca14440350d1a6bb49
ToxValDB_ECHA_IUCLID LEL =250 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30df; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15818421_15818745_15819262:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_c6bd4bc4b469efb7ee4af6c3daa3d980
ToxValDB_ECHA_IUCLID LEL >=23 mg/kg bw/day Mouse oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbf69; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15823212_15823213:F:-maternal; 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_f3bb95b8169bcffc8589edebe7fa64a7
ToxValDB_ECHA_IUCLID LEL <=608 mg/kg bw/day Mouse oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbf69; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15823212_15823213:F:-maternal; 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_2e8f36e341d14c87a3b4d9dccf6f65a1
ToxValDB_ECHA_IUCLID LEL =125 mg/kg bw/day Rat oral chronic; 104 weeks chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2cd1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15836171_15836172: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_8cc5b5ad30e23f32a84de95593eec04e
ToxValDB_ECHA_IUCLID LEL =500 mg/kg bw/day Rat oral chronic; 104 weeks chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2cd1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15836171_15836172: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_13732e713ffd1458ac315b3bc7cd1403
ToxValDB_ECHA_IUCLID LEL =100 mg/kg bw/day Rat oral chronic; 14 weeks chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2ce3; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15839242_15839243_15839244: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_0ba5cb63e1e2e154f72de49b0c9180c1
ToxValDB_ECHA_IUCLID LEL >=669 mg/kg bw/day Rat oral subchronic; 40 days subchronic QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d2217c8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15838212_15846931_15846932:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_89f82654065851e39533ddaa6b9abaf3
ToxValDB_ECHA_IUCLID LEL <=864 mg/kg bw/day Rat oral subchronic; 40 days subchronic QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d2217c8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15838212_15846931_15846932:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_29cb12c26eb646665c4b76dfb6245dc2
ToxValDB_ECHA_IUCLID LEL >=3480 mg/kg bw/day Mouse oral subchronic; 10 weeks subchronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2cef; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15847149_15847150: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_38737647da1e5c51c1ddbd541e7ce52f
ToxValDB_ECHA_IUCLID LEL <=4130 mg/kg bw/day Mouse oral subchronic; 10 weeks subchronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2cef; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15847149_15847150: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_73e0dfbbda4767f0ddb4f19c09429c6c
ToxValDB_ECHA_IUCLID LEL ~333 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa8be4b0a7c65d1b653c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15857319_15857783:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_a714264d32c1633a0bbf283312fbe4b2
ToxValDB_ECHA_IUCLID LEL =3000 ppm Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c8afe4b0a7c65d219b52; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15857764_15857840:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_571cf0f90f60b5f56bdb27299f9fcdc0
ToxValDB_ECHA_IUCLID LOAEL ~450 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30db; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15817032_15817033_15817034: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_ccb14b723c979f40c81be4dba74f71ae
ToxValDB_ECHA_IUCLID LOAEL ~3480 mg/kg bw/day Mouse oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c80fe4b0a7c65d216600; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15819076:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_8c3f461e1a9b4ff98c3d47bbb7b07331
ToxValDB_ECHA_IUCLID LOAEL =160 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30e7; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15819203_15819204_15819205:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_c2f287b3d730d69085595c5a21872abd
ToxValDB_ECHA_IUCLID LOAEL =225 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15819246_15819247_15819879_15819880_15819881_15819882:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ef3deb0ba0e5763df86c7bee9e8c7516
ToxValDB_ECHA_IUCLID LOAEL =250 mg/kg bw/day Rat oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac4ae4b0a7c65d1be4e9; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/34499/7/9/3?documentUUID=c664dab6-36ff-4cc4-8d00-5af27c01d424; YEAR=2018; ORIGINAL_YEAR=2018; TOXICOLOGICAL_EFFECT=fetus: fetal/pup body weight changes|fetus: changes in litter size and weights; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ECHA IUCLID:15820919:M/F:-fetal; 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_0b9d8c2541461882640346477335cc38
ToxValDB_ECHA_IUCLID LOAEL =500 mg/kg bw/day Rat oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbf79; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=fetus: fetal/pup body weight changes; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ECHA IUCLID:15821618:-:-fetal; 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_a61f90ee852f512237ce2e957ddbf2b0
ToxValDB_ECHA_IUCLID LOAEL =750 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac4ae4b0a7c65d1be4ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/34499/7/9/3?documentUUID=c664dab6-36ff-4cc4-8d00-5af27c01d424; YEAR=2018; ORIGINAL_YEAR=2018; TOXICOLOGICAL_EFFECT=maternal: early or late resorptions|maternal: total litter losses by resorption; TOXICOLOGICAL_EFFECT_CATEGORY=reproduction; STUDY_GROUP=ECHA IUCLID:15822516:F:-maternal; 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_c00b667e74b37110a0bf43df57930267
ToxValDB_ECHA_IUCLID LOAEL =167 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbf6f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822124_15822786_15822868_15823121:F:-maternal; 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_a5b40da71847064f9aecfa9f6e39862b
ToxValDB_ECHA_IUCLID LOAEL =1000 mg/kg bw/day Rat oral short-term; 7 days short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d2217b4; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=liver: body weight and weight gain|haematology|mortality|organ weights and organ / body weight ratios; TOXICOLOGICAL_EFFECT_CATEGORY=hematology|mortality/survival|organ weight; STUDY_GROUP=ECHA IUCLID:15831095:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0fa36b77f1bbc161bd5d51d12dc2a38d
ToxValDB_ECHA_IUCLID LOAEL =15 mg/kg bw/day Rat oral short-term; 1 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d2217c2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=hematological; TOXICOLOGICAL_EFFECT_CATEGORY=hematology; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15834865_15834866:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_48590910ad932865d8b2c26379c9953c
ToxValDB_ECHA_IUCLID LOAEL =326 mg/kg bw/day Rat oral short-term; 1 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d2217c2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=hematological; TOXICOLOGICAL_EFFECT_CATEGORY=hematology; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15834865_15834866:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_f399e980ea3322ed7becae5adb0fe155
ToxValDB_ECHA_IUCLID LOAEL =100 mg/kg bw/day Rat oral short-term; 3 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d221812; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15837763_15837764_15837765:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_096258fbb862dcaa9032c4195ed00b5c
ToxValDB_ECHA_IUCLID LOAEL =643 mg/kg bw/day Rat oral short-term; 3 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d221880; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=blood: haematology|mortality; TOXICOLOGICAL_EFFECT_CATEGORY=hematology|mortality/survival; STUDY_GROUP=ECHA IUCLID:15845166:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_6445ec1d097fa0aa9535ca852622e998
ToxValDB_ECHA_IUCLID LOEL =462.5 mg/kg bw/day Mouse oral chronic; 18 months chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2ced; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15841838: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_1c8635fc672547335c4ac0904fabaec8
ToxValDB_ECHA_IUCLID LOEL =500 mg/kg bw/day Rat oral acute; 1 days acute QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d221891; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15845816:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0a8e02a7064950c7de65b069216ca26d
ToxValDB_ECHA_IUCLID NOAEL =25 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30dd; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=liver: clinical biochemistry|histopathology: non-neoplastic|organ weights and organ / body weight ratios; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|nonneoplastic histopathology|organ weight; STUDY_GROUP=ECHA IUCLID:15817283: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_58cc9f0de4e1bce14c26039c6535f9eb
ToxValDB_ECHA_IUCLID NOAEL =10 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30e7; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15819203_15819204_15819205: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_b65091e0820e9c95e384f5621e546bc9
ToxValDB_ECHA_IUCLID NOAEL =75 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/8?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15819246_15819247_15819879_15819880_15819881_15819882:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_047848372848aa2c9165bfb0a5c4aa4f
ToxValDB_ECHA_IUCLID NOAEL =800 mg/kg bw/day Mouse oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbf65; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15820723_15821516:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_219dfd5f9e22b598198702a6ce53f9cf
ToxValDB_ECHA_IUCLID NOAEL =225 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbf61; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15821931_15822612:F:-maternal; 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_6693b6d1d597155a72303c566a299526
ToxValDB_ECHA_IUCLID NOAEL =180 mg/kg bw/day Mouse oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbf67; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822077_15822824:F:-maternal; 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_6c069c37238be5920deb8d6c0635e2ec
ToxValDB_ECHA_IUCLID NOAEL =500 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d1a6e4b0a7c65d22f7b1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822124_15822786_15822868_15823121:F:-maternal; 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_93fe5d3629e5dc5cda6754d833e7e5b4
ToxValDB_ECHA_IUCLID NOAEL =280 mg/kg bw/day Hamster oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d1a6e4b0a7c65d22f7cb; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822134_15822289:F:-maternal; 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_4aff9a1b1de7d4a81d60453f1df6f733
ToxValDB_ECHA_IUCLID NOAEL =50 mg/kg bw/day Monkey oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d1a6e4b0a7c65d22f7cf; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/3?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822398_15822799:F:-maternal; 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_114f2e063eb4e71d34999adea4d8b9a9
ToxValDB_ECHA_IUCLID NOAEL =23.4 mg/kg bw/day Rat oral chronic; 18 weeks chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2caf; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15830440:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0e4ef6b35aa1b5a6f3b1845a8e62e5c0
ToxValDB_ECHA_IUCLID NOAEL ~70 mg/kg bw/day Rat oral short-term; 1 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d2217df; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15837605:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_a7bd396475fa4fe6df4fbeeab96e43fa
ToxValDB_ECHA_IUCLID NOAEL =660 mg/kg bw/day Mouse oral short-term; 30 days short-term QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2ce5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15839620:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_1733d00ae3fda40e561ac43697e14b3d
ToxValDB_ECHA_IUCLID NOAEL >=61 mg/kg bw/day Pig oral subchronic; 42 days subchronic QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d221878; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15844980: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_1967e043e200445686e8b93db79be32b
ToxValDB_ECHA_IUCLID NOAEL =27.8 mg/kg bw/day Rat oral short-term; 4 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead28e4b0a7c65d1c2cf5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15846300:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_24bb0d5f15f0b640699f54d6f545cacd
ToxValDB_ECHA_IUCLID NOAEL =100 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa8be4b0a7c65d1b653e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15855410_15856228_15857465_15857899_15857912_15857930:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_be24d92faeb4548826d7e72b1fbe3dcc
ToxValDB_ECHA_IUCLID NOAEL =608 mg/kg bw/day Mouse oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa8be4b0a7c65d1b6538; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/9/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=F2: developmental neurotoxicity; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ECHA IUCLID:15860198:M/F:F2-; 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_c8d6baf77658fd234f254ee191658fbb
ToxValDB_ECHA_IUCLID NOEL =10 mg/kg bw/day Rat oral short-term; 3 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca5de4b0a7c65d221812; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/15975/7/6/2?documentUUID=81337846-206f-4eb9-8fb6-19030540d018; YEAR=1989; ORIGINAL_YEAR=1989; STUDY_GROUP=ECHA IUCLID:15837762: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_f39b7d691ff490703fac65b834ed8ecb
ToxValDB_ECOTOX 5 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECOTOX LOEL =1 % Rat oral subchronic; 56 days subchronic LONG_REF=Toxicol. Lett.55(3): 263-272 Shibata,M.A., E. Asakawa, A. Hagiwara, Y. Kurata, and S. Fukushima DNA Synthesis and Scanning Electron Microscopic Lesions in Renal Pelvic Epithelium of Rats Treated with Bladder Cancer Promoters 1991; TITLE=DNA Synthesis and Scanning Electron Microscopic Lesions in Renal Pelvic Epithelium of Rats Treated with Bladder Cancer Promoters; AUTHOR=Shibata,M.A., E. Asakawa, A. Hagiwara, Y. Kurata, and S. Fukushima; DOI=10.1016/0378-4274(91)90006-r; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=107545; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1991; ORIGINAL_YEAR=1991; TOXICOLOGICAL_EFFECT=Growth: Weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight; STUDY_GROUP=ECOTOX_dup_EPA ORD_15594699_15594700:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=2ca1b8b7e050a958d47ae76b15d17eb5
ToxValDB_ECOTOX LOEL =100 mg/kg bw/day Mouse oral acute; 1 days acute LONG_REF=Mutat. Res.519(1/2): 103-119 Sasaki,Y.F., S. Kawaguchi, A. Kamaya, M. Ohshita, K. Kabasawa, K. Iwama, K. Taniguchi, and S. Tsuda The Comet Assay with 8 Mouse Organs: Results with 39 Currently Used Food Additives 2002; TITLE=The Comet Assay with 8 Mouse Organs: Results with 39 Currently Used Food Additives; AUTHOR=Sasaki,Y.F., S. Kawaguchi, A. Kamaya, M. Ohshita, K. Kabasawa, K. Iwama, K. Taniguchi, and S. Tsuda; DOI=10.1016/s1383-5718(02)00128-6; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=75840; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=2002; ORIGINAL_YEAR=2002; TOXICOLOGICAL_EFFECT=Genetics: Damage; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15603124_15603125:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=2a06e71228789dc971eb8c4afd6d07bc
ToxValDB_ECOTOX NOEL =900 mg/kg bw/day Rat oral short-term; 1.625 days short-term LONG_REF=Mutat. Res.320(3): 189-205 Uno,Y., H. Takasawa, M. Miyagawa, Y. Inoue, T. Murata, and K. Yoshikawa An In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test Using Rat Hepatocytes as an Early Prediction Assay for Nongenotoxic Hepatocarcinogens Screening of 22 Known Positive and 25 Noncarcinogens 1994; TITLE=An In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test Using Rat Hepatocytes as an Early Prediction Assay for Nongenotoxic Hepatocarcinogens Screening of 22 Known Positive and 25 Noncarcinogens; AUTHOR=Uno,Y., H. Takasawa, M. Miyagawa, Y. Inoue, T. Murata, and K. Yoshikawa; DOI=10.1016/0165-1218(94)90046-9; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=75058; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1994; ORIGINAL_YEAR=1994; TOXICOLOGICAL_EFFECT=Cell(s): Viability; STUDY_GROUP=ECOTOX:15599293:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=9d4aa838b928802667ea70ef7074a504
ToxValDB_ECOTOX NOEL =1000 mg/kg bw/day Mouse oral short-term; 2 days short-term LONG_REF=Mutat. Res.343(2/3): 157-183 Miyagawa,M., H. Takasawa, A. Sugiyama, Y. Inoue, T. Murata, Y. Uno, and K. Yoshikawa The In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test with Hepatocytes Prepared from Male B6C3F1 Mice as an Early Prediction Assay for Putative Nongenotoxic (Ames-Negative) Mouse Hepatocarcinogens 1995; TITLE=The In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test with Hepatocytes Prepared from Male B6C3F1 Mice as an Early Prediction Assay for Putative Nongenotoxic (Ames-Negative) Mouse Hepatocarcinogens; AUTHOR=Miyagawa,M., H. Takasawa, A. Sugiyama, Y. Inoue, T. Murata, Y. Uno, and K. Yoshikawa; DOI=10.1016/0165-1218(95)90082-9; QUALITY=Control type: Carrier or solvent control; EXTERNAL_SOURCE_ID=75052; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=Cell(s): Viability; STUDY_GROUP=ECOTOX:15600045:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=8bdc4b118257ddb5ba1d4e8de3ab69e5
ToxValDB_ECOTOX NOEL =10 mg/kg bw/day Mouse oral acute; 1 days acute LONG_REF=Mutat. Res.519(1/2): 103-119 Sasaki,Y.F., S. Kawaguchi, A. Kamaya, M. Ohshita, K. Kabasawa, K. Iwama, K. Taniguchi, and S. Tsuda The Comet Assay with 8 Mouse Organs: Results with 39 Currently Used Food Additives 2002; TITLE=The Comet Assay with 8 Mouse Organs: Results with 39 Currently Used Food Additives; AUTHOR=Sasaki,Y.F., S. Kawaguchi, A. Kamaya, M. Ohshita, K. Kabasawa, K. Iwama, K. Taniguchi, and S. Tsuda; DOI=10.1016/s1383-5718(02)00128-6; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=75840; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=2002; ORIGINAL_YEAR=2002; TOXICOLOGICAL_EFFECT=Genetics: Damage; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15603124_15603125:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=c82c6e5b9f35fe860115fa0763315ca6
ToxValDB_EFSA 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_EFSA NOAEL =25 mg/kg bw/day Rat oral - developmental LONG_REF=EFSA ANS (2012). Scientific Opinion on the re-evaluation of butylated hydroxytoluene BHT (E 321) as a food additive. doi:10.2903/j.efsa.2012.2588.; TITLE=Scientific Opinion on the re-evaluation of butylated hydroxytoluene BHT (E 321) as a food additive; AUTHOR=EFSA ANS; DOI=doi:10.2903/j.efsa.2012.2588; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65201d30e4b0f0a60ddd1165; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://zenodo.org/record/5076033#.Y9fEoXbMI2z; YEAR=2012; ORIGINAL_YEAR=2012; TOXICOLOGICAL_EFFECT=development; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=EFSA:15614340: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_0144a6ce3f3b00a57f7c5a829ddb999c
ToxValDB_GESTIS_DNEL 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL systemic =1.76 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:15631031:-:--; 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_0828a1c059bd09eec7cf03170b731d05
ToxValDB_PPRTV_(CPHEA) 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_PPRTV_(CPHEA) RfD (provisional) =0.3 mg/kg bw/day Human oral - Toxicity Value LONG_REF=Olsen et al. 1986; AUTHOR=Olsen et al; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/640754bee4b08a6b3934b379; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/pprtv/basic-information-about-provisional-peer-reviewed-toxicity-values-pprtvs; SUBSOURCE_URL=https://cfpub.epa.gov/ncea/pprtv/chemicalLanding.cfm?pprtv_sub_id=1615; TOXICOLOGICAL_EFFECT=Decreased F1 adult weight at 138 weeks in male/female rats; STUDY_GROUP=PPRTV (CPHEA)_dup_PPRTV Summary_15653687_15653771:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_2bff1d6d1c25603e1efde4d3ea29f288
ToxValDB_PPRTV_(CPHEA) RfD (provisional) =1 mg/kg bw/day Human oral - Toxicity Value LONG_REF=Olsen et al. 1986; AUTHOR=Olsen et al; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/640754bee4b08a6b3934b379; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/pprtv/basic-information-about-provisional-peer-reviewed-toxicity-values-pprtvs; SUBSOURCE_URL=https://cfpub.epa.gov/ncea/pprtv/chemicalLanding.cfm?pprtv_sub_id=1615; TOXICOLOGICAL_EFFECT=Decreased F1 adult weight at 9 weeks in male/female rats; STUDY_GROUP=PPRTV (CPHEA)_dup_PPRTV Summary_15653687_15653771:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_2c2ba44f53b00fdbc281ceeab762debe
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 68 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 mg/kg bw - oral - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=(1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day.; EFFECT=___________________________________________________________________________ _________________________________________________________________________ 24 3.4 SAFETY EVALUATION (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY MoS calculations for separate product types and aggregated exposures are shown in Table 7. Based on effects on litter size and pup body weight gain during the lactation period, in the reproduction segment of the study Olsen et al. (1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day. This NOAEL also covers the observed increase in hepatocellular adenomas and carcinomas. Table 7. MoS calculations for the different product types and aggregated exposures Product category Conc. BHT (%) Eproduct 1 (mg/kg bw/d) SED (mg/kg bw/d) NOAEL (mg/kg bw/d) MoS Dermal Oral Hydroalcoholic based fragrances 0.8 4.67 0.00015 25 167 291 Shower gel 0.8 2.79 0.00009 25 280 018 Hand wash soap 0.8 3.33 0.00011 25 234 610 Shampoo 0.8 1.51 0.00005 25 517 384 H; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"(1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day.","duration":"","effect":"___________________________________________________________________________ _________________________________________________________________________ 24 3.4 SAFETY EVALUATION (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY MoS calculations for separate product types and aggregated exposures are shown in Table 7. Based on effects on litter size and pup body weight gain during the lactation period, in the reproduction segment of the study Olsen et al. (1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day. This NOAEL also covers the observed increase in hepatocellular adenomas and carcinomas. Table 7. MoS calculations for the different product types and aggregated exposures Product category Conc. BHT (%) Eproduct 1 (mg/kg bw/d) SED (mg/kg bw/d) NOAEL (mg/kg bw/d) MoS Dermal Oral Hydroalcoholic based fragrances 0.8 4.67 0.00015 25 167 291 Shower gel 0.8 2.79 0.00009 25 280 018 Hand wash soap 0.8 3.33 0.00011 25 234 610 Shampoo 0.8 1.51 0.00005 25 517 384 H","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":24,"route":"oral","species":"","study_id":"sccs_o_257_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 mg/kg bw - oral - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=(1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day.; EFFECT=____________ _________________________________________________________________________ 24 3.4 SAFETY EVALUATION (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY MoS calculations for separate product types and aggregated exposures are shown in Table 7. Based on effects on litter size and pup body weight gain during the lactation period, in the reproduction segment of the study Olsen et al. (1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day. This NOAEL also covers the observed increase in hepatocellular adenomas and carcinomas. Table 7. MoS calculations for the different product types and aggregated exposures Product category Conc. BHT (%) Eproduct 1 (mg/kg bw/d) SED (mg/kg bw/d) NOAEL (mg/kg bw/d) MoS Dermal Oral Hydroalcoholic based fragrances 0.8 4.67 0.00015 25 167 291 Shower gel 0.8 2.79 0.00009 25 280 018 Hand wash soap 0.8 3.33 0.00011 25 234 610 Shampoo 0.8 1.51 0.00005 25 517 384 Hair conditioner 0.8 0.67 0.00002 25 1 166 045 Body lotion 0.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"(1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day.","duration":"","effect":"____________ _________________________________________________________________________ 24 3.4 SAFETY EVALUATION (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY MoS calculations for separate product types and aggregated exposures are shown in Table 7. Based on effects on litter size and pup body weight gain during the lactation period, in the reproduction segment of the study Olsen et al. (1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day. This NOAEL also covers the observed increase in hepatocellular adenomas and carcinomas. Table 7. MoS calculations for the different product types and aggregated exposures Product category Conc. BHT (%) Eproduct 1 (mg/kg bw/d) SED (mg/kg bw/d) NOAEL (mg/kg bw/d) MoS Dermal Oral Hydroalcoholic based fragrances 0.8 4.67 0.00015 25 167 291 Shower gel 0.8 2.79 0.00009 25 280 018 Hand wash soap 0.8 3.33 0.00011 25 234 610 Shampoo 0.8 1.51 0.00005 25 517 384 Hair conditioner 0.8 0.67 0.00002 25 1 166 045 Body lotion 0.8","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":24,"route":"oral","species":"","study_id":"sccs_o_257_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 mg/kg bw - oral - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=(1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day.; EFFECT=ated exposures are shown in Table 7. Based on effects on litter size and pup body weight gain during the lactation period, in the reproduction segment of the study Olsen et al. (1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day. This NOAEL also covers the observed increase in hepatocellular adenomas and carcinomas. Table 7. MoS calculations for the different product types and aggregated exposures Product category Conc. BHT (%) Eproduct 1 (mg/kg bw/d) SED (mg/kg bw/d) NOAEL (mg/kg bw/d) MoS Dermal Oral Hydroalcoholic based fragrances 0.8 4.67 0.00015 25 167 291 Shower gel 0.8 2.79 0.00009 25 280 018 Hand wash soap 0.8 3.33 0.00011 25 234 610 Shampoo 0.8 1.51 0.00005 25 517 384 Hair conditioner 0.8 0.67 0.00002 25 1 166 045 Body lotion 0.8 123.2 0.00394 25 6 341 Face cream 0.8 24.14 0.00077 25 32 363 Hand cream 0.8 32.7 0.00105 25 23 891 Deodorant non-spray 0.8 22.08 0.00071 25 35 383 Hair styling 0.8 5.74 0.00018 25 136 106 Liquid foundation 0.8 7.9 0.00025 25 98 892 M; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"(1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day.","duration":"","effect":"ated exposures are shown in Table 7. Based on effects on litter size and pup body weight gain during the lactation period, in the reproduction segment of the study Olsen et al. (1986; described in the EFSA 2012), the NOAEL for non-neoplastic effects was 25 mg/kg bw per day. This NOAEL also covers the observed increase in hepatocellular adenomas and carcinomas. Table 7. MoS calculations for the different product types and aggregated exposures Product category Conc. BHT (%) Eproduct 1 (mg/kg bw/d) SED (mg/kg bw/d) NOAEL (mg/kg bw/d) MoS Dermal Oral Hydroalcoholic based fragrances 0.8 4.67 0.00015 25 167 291 Shower gel 0.8 2.79 0.00009 25 280 018 Hand wash soap 0.8 3.33 0.00011 25 234 610 Shampoo 0.8 1.51 0.00005 25 517 384 Hair conditioner 0.8 0.67 0.00002 25 1 166 045 Body lotion 0.8 123.2 0.00394 25 6 341 Face cream 0.8 24.14 0.00077 25 32 363 Hand cream 0.8 32.7 0.00105 25 23 891 Deodorant non-spray 0.8 22.08 0.00071 25 35 383 Hair styling 0.8 5.74 0.00018 25 136 106 Liquid foundation 0.8 7.9 0.00025 25 98 892 M","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":24,"route":"oral","species":"","study_id":"sccs_o_257_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.5 % rat oral 90 days - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=0.5; DOSE=Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al.; EFFECT=SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 32 ANNEX 1: Table A-1. Summary of level 3-5 in vivo animal studies with emphasis on effects on liver (LE), thyroid (TE) and adrenals (AE) and indicated NOAEL’s (including studies with ≥2 doses only). Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al. 1989 Rat m oral highes t tolerat ed doses for 30 days 0.5% dietary BHT No detectable ↑ in 3H- thymidine labelling Time-limite; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al.","duration":"90 days","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 32 ANNEX 1: Table A-1. Summary of level 3-5 in vivo animal studies with emphasis on effects on liver (LE), thyroid (TE) and adrenals (AE) and indicated NOAEL’s (including studies with ≥2 doses only). Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Level 3 Sønder gaard & Olsen, 19821 Rat oral 8, 26 or 90 days 0, 25, 250 ↑ uptake of 125I by the thyroid at all time period studied No effects on T3 and T4 levels ↑ thyroxine half-life after 13 days returning to normal after 75 days Briggs et al. 1989 Rat m oral highes t tolerat ed doses for 30 days 0.5% dietary BHT No detectable ↑ in 3H- thymidine labelling Time-limite","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"%","noael_value":"0.5","page":32,"route":"oral","species":"rat","study_id":"sccs_o_257_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1636 - rat oral 144 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e; DOSE=SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m p...; EFFECT=SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m p...","duration":"144 wk","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 33 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1994 11-19 most m per dose per group tion study, F1 up to 144 wk feedin g 100, 250 (in utero 500) centrilobular enlargement and eosinophilia noduli, foci at 250 mg (hyperactiv ity) (histopath) enzyme induction in all dose groups no effects (T4 induction) McFarla ne et al. 1997 Rat 2M/1 6F F0 oral F1 lactati on Dose rangin g study 14 wk 0, 500, 750, 1000 ↑ weight F0 dams at ≥500 500 (LOAEL) At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) 500 (maternal /fetal) McFarla ne e","page":33,"route":"oral","species":"rat","study_id":"sccs_o_257_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1636 - rat - 104 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 34 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Hiraga 19783 rat 5- 15 m/f per dose interi m sacrifi ces up to 104 wk feedin g 2.5, 10, 160 weight ↑ liver weight increased (at 160 mg) no tumor induction no clear tendency (weight, histopath) no clear tendency (weight, histopath) 10 (LE) NCI 1979a rat 20-50 m/f per dose; Interi m sacrifi ces 105 wk feedin g 225, 450 weight: no data tumors: not sign. c-cell hyperplasia in males at ≥ 225 mg; no tumor induction Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human he; DOSE=SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 34 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Hiraga 19783 rat 5-...; EFFECT=SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 34 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Hiraga 19783 rat 5- 15 m/f per dose interi m sacrifi ces up to 104 wk feedin g 2.5, 10, 160 weight ↑ liver weight increased (at 160 mg) no tumor induction no clear tendency (weight, histopath) no clear tendency (weight, histopath) 10 (LE) NCI 1979a rat 20-50 m/f per dose; Interi m sacrifi ces 105 wk feedin g 225, 450 weight: no data tumors: not sign. c-cell hyperplasia in males at ≥ 225 mg; no tumor induction Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human he; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 34 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Hiraga 19783 rat 5-...","duration":"104 wk","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 34 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Hiraga 19783 rat 5- 15 m/f per dose interi m sacrifi ces up to 104 wk feedin g 2.5, 10, 160 weight ↑ liver weight increased (at 160 mg) no tumor induction no clear tendency (weight, histopath) no clear tendency (weight, histopath) 10 (LE) NCI 1979a rat 20-50 m/f per dose; Interi m sacrifi ces 105 wk feedin g 225, 450 weight: no data tumors: not sign. c-cell hyperplasia in males at ≥ 225 mg; no tumor induction Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human he","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 34 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) Hiraga 19783 rat 5- 15 m/f per dose interi m sacrifi ces up to 104 wk feedin g 2.5, 10, 160 weight ↑ liver weight increased (at 160 mg) no tumor induction no clear tendency (weight, histopath) no clear tendency (weight, histopath) 10 (LE) NCI 1979a rat 20-50 m/f per dose; Interi m sacrifi ces 105 wk feedin g 225, 450 weight: no data tumors: not sign. c-cell hyperplasia in males at ≥ 225 mg; no tumor induction Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human he","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1636 - rat oral 16 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 35 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1988 m/f per dose; feedin g + 16 wk plain diet 3480 f: 1750, 4230 adenoma - only males no effects in females not examined amyloidosis LE) William s et al. 1990 rat males ; interi m sacrifi ces 76 wk 110 wk feedin g 7.5, 23, 75, 225, 450 900 (only 110 wk) weight ↑ (at ≥ 450mg) no morphological changes no effects (tumor induction) no effects (tumor induction) no effects (tumors induction) no effects (tumor induction) 75 (LE) Tanaka et al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 //; DOSE=SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 35 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1988 m/f per dose;...; EFFECT=SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 35 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1988 m/f per dose; feedin g + 16 wk plain diet 3480 f: 1750, 4230 adenoma - only males no effects in females not examined amyloidosis LE) William s et al. 1990 rat males ; interi m sacrifi ces 76 wk 110 wk feedin g 7.5, 23, 75, 225, 450 900 (only 110 wk) weight ↑ (at ≥ 450mg) no morphological changes no effects (tumor induction) no effects (tumor induction) no effects (tumors induction) no effects (tumor induction) 75 (LE) Tanaka et al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 //; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 35 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1988 m/f per dose;...","duration":"16 wk","effect":"SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 35 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1988 m/f per dose; feedin g + 16 wk plain diet 3480 f: 1750, 4230 adenoma - only males no effects in females not examined amyloidosis LE) William s et al. 1990 rat males ; interi m sacrifi ces 76 wk 110 wk feedin g 7.5, 23, 75, 225, 450 900 (only 110 wk) weight ↑ (at ≥ 450mg) no morphological changes no effects (tumor induction) no effects (tumor induction) no effects (tumors induction) no effects (tumor induction) 75 (LE) Tanaka et al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 //","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1636/21 Final version Opinion on Butylated hydroxytoluene (BHT) ___________________________________________________________________________________________ _________________________________________________________________________ 35 Refere nce Speci es Expos ure Doses (mg/k g bw) liver thyroid adrenals NOAEL (mg/kg bw/d) 1988 m/f per dose; feedin g + 16 wk plain diet 3480 f: 1750, 4230 adenoma - only males no effects in females not examined amyloidosis LE) William s et al. 1990 rat males ; interi m sacrifi ces 76 wk 110 wk feedin g 7.5, 23, 75, 225, 450 900 (only 110 wk) weight ↑ (at ≥ 450mg) no morphological changes no effects (tumor induction) no effects (tumor induction) no effects (tumors induction) no effects (tumor induction) 75 (LE) Tanaka et al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 //","page":35,"route":"oral","species":"rat","study_id":"sccs_o_257_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 10 mg/kg bw/day rat - 24 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=10; DOSE=1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al.; EFFECT=al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al. 2008 rat 6 m per dose 28 days feedin g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019; CITATION=Ref.: Modified from EDC dossier 2019; CITATION_NUMBERS=[2019]; REFERENCE=Ref.: Modified from EDC dossier 2019; DETAILS_JSON={"cas_number":"128-37-0","citation":"Ref.: Modified from EDC dossier 2019","dose":"1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al.","duration":"24 wk","effect":"al. 1993 Mous e 10 m/f per dose genera tion study 23, 68, 203, 608 // Safer & Al- Nugha mish 1999 rat, 10 m/ dose (2/ti me point) 6-24 wk feedin g 200, 400, 800 weight (abs↑) hypertrophy, degenerative figures no tumors 200 (LOAEL, LE) Stieru m et al. 2008 rat 6 m per dose 28 days feedin g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":35,"route":"","species":"rat","study_id":"sccs_o_257_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 15 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=15; DOSE=3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses.; EFFECT=g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019; CITATION=Ref.: Modified from EDC dossier 2019; CITATION_NUMBERS=[2019]; REFERENCE=Ref.: Modified from EDC dossier 2019; DETAILS_JSON={"cas_number":"128-37-0","citation":"Ref.: Modified from EDC dossier 2019","dose":"3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses.","duration":"","effect":"g 28, 88, 167, 321, 1159 weight, histopath effects at 1159 mg 28 (LE) enzyme induction 1According to the dossier, the study has severe technical limitations. 2According to the dossier, the study was poorly reported in Romanian. 3A NOAEL of 10 mg/kg bw/day was not applied by the SCCS due to the great difference between the two highest exposure doses. 4The report is in Japanese and the findings are poorly described in the EDC dossier. Since the SCCS have not been able to verify the results reported in the dossier, a NOAEL of 15 mg/kg bw/day will not be applied. Ref.: Modified from EDC dossier 2019","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"15","page":35,"route":"","species":"","study_id":"sccs_o_257_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 7 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS; DOSE=BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:Table 7. MoS calculations for the different product types and aggregated exposures: Product category | Conc. BHT (%) | Eproduct 1 (mg/kg bw/d) | SED (mg/kg bw/d) | NOAEL (mg/kg bw/d) | MoS","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Hydroalcoholic based fragrances | 0.8 | 4.67 | 0.00015 | 25 | 167 291; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hydroalcoholic based fragrances | 0.8 | 4.67 | 0.00015 | 25 | 167 291","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Shower gel | 0.8 | 2.79 | 0.00009 | 25 | 280 018; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Shower gel | 0.8 | 2.79 | 0.00009 | 25 | 280 018","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Hand wash soap | 0.8 | 3.33 | 0.00011 | 25 | 234 610; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hand wash soap | 0.8 | 3.33 | 0.00011 | 25 | 234 610","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Shampoo | 0.8 | 1.51 | 0.00005 | 25 | 517 384; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Shampoo | 0.8 | 1.51 | 0.00005 | 25 | 517 384","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Hair conditioner | 0.8 | 0.67 | 0.00002 | 25 | 1 166 045; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hair conditioner | 0.8 | 0.67 | 0.00002 | 25 | 1 166 045","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_024"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Body lotion | 0.8 | 123.2 | 0.00394 | 25 | 6 341; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Body lotion | 0.8 | 123.2 | 0.00394 | 25 | 6 341","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_025"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Face cream | 0.8 | 24.14 | 0.00077 | 25 | 32 363; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Face cream | 0.8 | 24.14 | 0.00077 | 25 | 32 363","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_026"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Hand cream | 0.8 | 32.7 | 0.00105 | 25 | 23 891; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hand cream | 0.8 | 32.7 | 0.00105 | 25 | 23 891","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_027"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Deodorant non-spray | 0.8 | 22.08 | 0.00071 | 25 | 35 383; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Deodorant non-spray | 0.8 | 22.08 | 0.00071 | 25 | 35 383","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_028"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Hair styling | 0.8 | 5.74 | 0.00018 | 25 | 136 106; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Hair styling | 0.8 | 5.74 | 0.00018 | 25 | 136 106","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_029"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Liquid foundation | 0.8 | 7.9 | 0.00025 | 25 | 98 892; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Liquid foundation | 0.8 | 7.9 | 0.00025 | 25 | 98 892","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_030"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Make-up remover | 0.8 | 8.33 | 0.00027 | 25 | 93 788; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Make-up remover | 0.8 | 8.33 | 0.00027 | 25 | 93 788","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_031"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Eye make-up | 0.8 | 0.33 | 0.00001 | 25 | 2 367 424; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Eye make-up | 0.8 | 0.33 | 0.00001 | 25 | 2 367 424","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_032"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Mascara | 0.8 | 0.42 | 0.00001 | 25 | 1 860 119; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Mascara | 0.8 | 0.42 | 0.00001 | 25 | 1 860 119","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_033"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Eyeliner | 0.8 | 0.08 | 0.000003 | 25 | 9 765 625; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Eyeliner | 0.8 | 0.08 | 0.000003 | 25 | 9 765 625","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_034"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Toothpaste | 0.1 | 2.16 | 0.00216 | 25 | 11 574; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Toothpaste | 0.1 | 2.16 | 0.00216 | 25 | 11 574","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_035"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Mouthwash | 0.001 | 32.54 | 0.00033 | 25 | 76 829; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Mouthwash | 0.001 | 32.54 | 0.00033 | 25 | 76 829","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_036"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Lipstick | 0.8 | 0.90 | 0.00720 | 25 | 3 472; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Lipstick | 0.8 | 0.90 | 0.00720 | 25 | 3 472","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_037"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - dermal - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Aggregated exposure: dermal | 237.89 | 0.00761 | 25 | 3 285; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Aggregated exposure: dermal | 237.89 | 0.00761 | 25 | 3 285","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"dermal","species":"","study_id":"sccs_o_257_noael_038"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - oral - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Aggregated exposure: oral | 35.60 | 0.00969 | 25 | 2 580; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Aggregated exposure: oral | 35.60 | 0.00969 | 25 | 2 580","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"oral","species":"","study_id":"sccs_o_257_noael_039"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; EFFECT=Table 7. MoS calculations for the different product types and aggregated exposures: Aggregated exposure: total | 273.49 | 0.00761 | 0.00969 | 25 | 1 445; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Table 7. MoS calculations for the different product types and aggregated exposures: Aggregated exposure: total | 273.49 | 0.00761 | 0.00969 | 25 | 1 445","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_257_noael_040"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 32 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); DOSE=Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); EFFECT=Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","duration":"","effect":"Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 32: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":32,"route":"","species":"","study_id":"sccs_o_257_noael_041"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 67 - rat - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=67 (LE); DOSE=Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE); EFFECT=Unlabeled table on page 32: Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","duration":"","effect":"Unlabeled table on page 32: Frawley et al., 1965 | rat 16 m/f per dose | genera tion study; final sacrific e at week 42 for F0 and F1 | 20, 67, 200 | weight ↑ serum cholesterol wk 28 ↑ histopath: no effects | no effects (weight and histopath) | no effects (weight and histopath) | 67 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"67 (LE)","page":32,"route":"","species":"rat","study_id":"sccs_o_257_noael_042"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - rat - 144 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25 (LE); DOSE=1986 | rat 40- 100 m/f per dose divide d in subgr oups | genera tion study;; EFFECT=Unlabeled table on page 32: Olsen et al. 1986 | rat 40- 100 m/f per dose divide d in subgr oups | genera tion study; F1 up to 144 wk feedin g | 25, 100, 250 (in utero 500) | adenoma and carcinoma, late (≥ wk 115) significant ↑at 250 mg | no effects (tumor induction) | no effects (tumor induction) | 25 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"1986 | rat 40- 100 m/f per dose divide d in subgr oups | genera tion study;","duration":"144 wk","effect":"Unlabeled table on page 32: Olsen et al. 1986 | rat 40- 100 m/f per dose divide d in subgr oups | genera tion study; F1 up to 144 wk feedin g | 25, 100, 250 (in utero 500) | adenoma and carcinoma, late (≥ wk 115) significant ↑at 250 mg | no effects (tumor induction) | no effects (tumor induction) | 25 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25 (LE)","page":32,"route":"","species":"rat","study_id":"sccs_o_257_noael_043"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - rat - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25 (TE); EFFECT=Unlabeled table on page 32: Price | rat | genera | 25, | weight (rel↑), | histopath | no effects | 25 (TE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 32: Price | rat | genera | 25, | weight (rel↑), | histopath | no effects | 25 (TE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25 (TE)","page":32,"route":"","species":"rat","study_id":"sccs_o_257_noael_044"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 33 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); DOSE=Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); EFFECT=Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","duration":"","effect":"Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 33: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":33,"route":"","species":"","study_id":"sccs_o_257_noael_045"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 500 - rat oral 14 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=500 (LOAEL); DOSE=1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL); EFFECT=Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","duration":"14 wk","effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 2M/1 6F F0 oral F1 lactati on | Dose rangin g study 14 wk | 0, 500, 750, 1000 | ↑ weight F0 dams at ≥500 | 500 (LOAEL)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"500 (LOAEL)","page":33,"route":"oral","species":"rat","study_id":"sccs_o_257_noael_046"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 500 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=500 (maternal /fetal); EFFECT=Unlabeled table on page 33: At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 500 (maternal /fetal); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 33: At ≥750: abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 500 (maternal /fetal)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"500 (maternal /fetal)","page":33,"route":"","species":"","study_id":"sccs_o_257_noael_047"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 100 - rat oral 22 weeks - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=100 (LE); EFFECT=Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 7M/5 0F F0 Oral F1 postn atal expos ure, | Main study Necrop sied at 22 weeks post weanin g | F0 0, 25, 100, 500 F1 0, 25, 100, 250 | at ≥500 F0 dams ↑ weight Abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 100 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"22 weeks","effect":"Unlabeled table on page 33: McFarla ne et al. 1997 | Rat 7M/5 0F F0 Oral F1 postn atal expos ure, | Main study Necrop sied at 22 weeks post weanin g | F0 0, 25, 100, 500 F1 0, 25, 100, 250 | at ≥500 F0 dams ↑ weight Abnormal hepatocytes (enlarged, vacuolized, proliferation of ER) | 100 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"100 (LE)","page":33,"route":"oral","species":"rat","study_id":"sccs_o_257_noael_048"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25 (LE); EFFECT=Unlabeled table on page 33: At ≥100 F1 pups ↑ weight abnormal hepatocytes | 25 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 33: At ≥100 F1 pups ↑ weight abnormal hepatocytes | 25 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25 (LE)","page":33,"route":"","species":"","study_id":"sccs_o_257_noael_049"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 20 mg/kg/day rat - 8 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=20; DOSE=Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //; EFFECT=Unlabeled table on page 33: Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","duration":"8 wk","effect":"Unlabeled table on page 33: Sporn & Schöbe sch 19612 | young rat 8/dos e | 8 wk? | 20, 200 | nitrogen content ‘greatly reduced’ at 20 mg/kg/day | non- significant increase in weight | //","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg/day","noael_value":"20","page":33,"route":"","species":"rat","study_id":"sccs_o_257_noael_050"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 100 - rat - 6 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=100 (LOAEL, AR); DOSE=Johnso n & Hewgill 1961 | rat weanl ing 3 m/f per dose ‘genet ic effect led to some variat ions in litters ’ | 6 wk | 100, 200, 300, 400, 500 | weight (rel↑) (at ≥ 200 mg) | weight (rel↑, only males), histopath: no changes | 100 (LOAEL, AR); EFFECT=Unlabeled table on page 33: Johnso n & Hewgill 1961 | rat weanl ing 3 m/f per dose ‘genet ic effect led to some variat ions in litters ’ | 6 wk | 100, 200, 300, 400, 500 | weight (rel↑) (at ≥ 200 mg) | weight (rel↑, only males), histopath: no changes | 100 (LOAEL, AR); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Johnso n & Hewgill 1961 | rat weanl ing 3 m/f per dose ‘genet ic effect led to some variat ions in litters ’ | 6 wk | 100, 200, 300, 400, 500 | weight (rel↑) (at ≥ 200 mg) | weight (rel↑, only males), histopath: no changes | 100 (LOAEL, AR)","duration":"6 wk","effect":"Unlabeled table on page 33: Johnso n & Hewgill 1961 | rat weanl ing 3 m/f per dose ‘genet ic effect led to some variat ions in litters ’ | 6 wk | 100, 200, 300, 400, 500 | weight (rel↑) (at ≥ 200 mg) | weight (rel↑, only males), histopath: no changes | 100 (LOAEL, AR)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"100 (LOAEL, AR)","page":33,"route":"","species":"rat","study_id":"sccs_o_257_noael_051"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 100 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=100 (LOAEL, LE); EFFECT=Unlabeled table on page 33: serum cholesterol ↑ (at all doses) | adrenal cholesterol ↑ (at ≥ 300 mg) | 100 (LOAEL, LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 33: serum cholesterol ↑ (at all doses) | adrenal cholesterol ↑ (at ≥ 300 mg) | 100 (LOAEL, LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"100 (LOAEL, LE)","page":33,"route":"","species":"","study_id":"sccs_o_257_noael_052"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 50 - - - 4 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=50 (LE); DOSE=Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE); EFFECT=Unlabeled table on page 33: Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","duration":"4 wk","effect":"Unlabeled table on page 33: Allan & Engblo m 1972 | monk ey, 2- 3 per dose | 4 wk gavag e | 50, 500 | histopath (slight decrease in smooth ER, lipid droplets at 500 mg) no stat. sign. tumors in males/females | “no effect on other organs” | “no effect on other organs” | 50 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"50 (LE)","page":33,"route":"","species":"","study_id":"sccs_o_257_noael_053"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 34 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); DOSE=Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); EFFECT=Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","duration":"","effect":"Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 34: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":34,"route":"","species":"","study_id":"sccs_o_257_noael_054"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 10 - rat - 104 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=10 (LE); DOSE=Hiraga 19783 | rat 5- 15 m/f per dose interi m sacrifi ces | up to 104 wk feedin g | 2.5, 10, 160 | weight ↑ liver weight increased (at 160 mg) no tumor induction | no clear tendency (weight, histopath) | no clear tendency (weight, histopath) | 10 (LE); EFFECT=Unlabeled table on page 34: Hiraga 19783 | rat 5- 15 m/f per dose interi m sacrifi ces | up to 104 wk feedin g | 2.5, 10, 160 | weight ↑ liver weight increased (at 160 mg) no tumor induction | no clear tendency (weight, histopath) | no clear tendency (weight, histopath) | 10 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Hiraga 19783 | rat 5- 15 m/f per dose interi m sacrifi ces | up to 104 wk feedin g | 2.5, 10, 160 | weight ↑ liver weight increased (at 160 mg) no tumor induction | no clear tendency (weight, histopath) | no clear tendency (weight, histopath) | 10 (LE)","duration":"104 wk","effect":"Unlabeled table on page 34: Hiraga 19783 | rat 5- 15 m/f per dose interi m sacrifi ces | up to 104 wk feedin g | 2.5, 10, 160 | weight ↑ liver weight increased (at 160 mg) no tumor induction | no clear tendency (weight, histopath) | no clear tendency (weight, histopath) | 10 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"10 (LE)","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_055"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 225 - rat - 105 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=225 (LOAEL, TE); DOSE=NCI 1979a | rat 20-50 m/f per dose;; EFFECT=Unlabeled table on page 34: NCI 1979a | rat 20-50 m/f per dose; Interi m sacrifi ces | 105 wk feedin g | 225, 450 | weight: no data tumors: not sign. | c-cell hyperplasia in males at ≥ 225 mg; no tumor induction | Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human health. | 225 (LOAEL, TE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"NCI 1979a | rat 20-50 m/f per dose;","duration":"105 wk","effect":"Unlabeled table on page 34: NCI 1979a | rat 20-50 m/f per dose; Interi m sacrifi ces | 105 wk feedin g | 225, 450 | weight: no data tumors: not sign. | c-cell hyperplasia in males at ≥ 225 mg; no tumor induction | Phaeochro mo-cytoma in males at ≥ 225 mg – not significant and not significant for human health. | 225 (LOAEL, TE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"225 (LOAEL, TE)","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_056"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 515 - - - 107 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=515 (LOAEL, LE); DOSE=NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m:; EFFECT=Unlabeled table on page 34: NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m: 0, 515, 1029 f: 0, 518, 1037 | weight: no data ↑ incidence of hepatocytomegaly and nonneoplastic lesions (peliosis, hepatocellular degeneration/necrosis, cytoplasmic vacuolation in males) | ‘no effects’ | ‘no effects’ | 515 (LOAEL, LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m:","duration":"107 wk","effect":"Unlabeled table on page 34: NCI 1979b | mous e, 50 m/f per dose; interi m sacrifi ces | 107 wk feedin g | m: 0, 515, 1029 f: 0, 518, 1037 | weight: no data ↑ incidence of hepatocytomegaly and nonneoplastic lesions (peliosis, hepatocellular degeneration/necrosis, cytoplasmic vacuolation in males) | ‘no effects’ | ‘no effects’ | 515 (LOAEL, LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"515 (LOAEL, LE)","page":34,"route":"","species":"","study_id":"sccs_o_257_noael_057"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 30 - rat - 8 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=30 (LOAEL, LE); EFFECT=Unlabeled table on page 34: Fulton et al. 1980 | Rat 10 m | 8 wk feedin g | 0, 30, 151, 755, 1132 | Weight (abs↑ and rel↑) | 30 (LOAEL, LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"8 wk","effect":"Unlabeled table on page 34: Fulton et al. 1980 | Rat 10 m | 8 wk feedin g | 0, 30, 151, 755, 1132 | Weight (abs↑ and rel↑) | 30 (LOAEL, LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"30 (LOAEL, LE)","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_058"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 125 - rat - 104 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=125 (LOAEL, LE); DOSE=1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE); EFFECT=Unlabeled table on page 34: Hirose et al. 1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","duration":"104 wk","effect":"Unlabeled table on page 34: Hirose et al. 1981 | rat 36-57 m/f per dose | 104 wk feedin g | 125, 500 | weight m (rel↑) no morphological changes | no effects (tumor induction) | no effects (tumor induction) | 125 (LOAEL, LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"125 (LOAEL, LE)","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_059"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - rat - 90 days - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25 (LE); DOSE=Sønder gaard & Olsen 19821 | rat 10-30 m per dose; | up to 90 days feedin g | 25, 250 | weight (rel↑) at 250 mg | weight (rel↑) | 25 (LE); EFFECT=Unlabeled table on page 34: Sønder gaard & Olsen 19821 | rat 10-30 m per dose; | up to 90 days feedin g | 25, 250 | weight (rel↑) at 250 mg | weight (rel↑) | 25 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Sønder gaard & Olsen 19821 | rat 10-30 m per dose; | up to 90 days feedin g | 25, 250 | weight (rel↑) at 250 mg | weight (rel↑) | 25 (LE)","duration":"90 days","effect":"Unlabeled table on page 34: Sønder gaard & Olsen 19821 | rat 10-30 m per dose; | up to 90 days feedin g | 25, 250 | weight (rel↑) at 250 mg | weight (rel↑) | 25 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25 (LE)","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_060"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 250 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=250 (TE); EFFECT=Unlabeled table on page 34: no effect on enzyme act. T3/T4 | 250 (TE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 34: no effect on enzyme act. T3/T4 | 250 (TE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"250 (TE)","page":34,"route":"","species":"","study_id":"sccs_o_257_noael_061"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 15 - rat - 18 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=15 (LE); EFFECT=Unlabeled table on page 34: Furuka wa et al. 19844 | rat 10 m/gro up | 18 wk feedin g | 15, 50, 150, 300 | weight ↑ histopath (enlargement of hep. at ≥ 150 mg) | 15 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"18 wk","effect":"Unlabeled table on page 34: Furuka wa et al. 19844 | rat 10 m/gro up | 18 wk feedin g | 15, 50, 150, 300 | weight ↑ histopath (enlargement of hep. at ≥ 150 mg) | 15 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"15 (LE)","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_062"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 25 - rat - 28 days - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25 (LE); DOSE=Powell et al., 1986 | rat 10 m per dose | 28 days gavag e | 25, 150, 500 | weight (rel↑), hepatomegaly, necrosis at 500 mg | 25 (LE); EFFECT=Unlabeled table on page 34: Powell et al., 1986 | rat 10 m per dose | 28 days gavag e | 25, 150, 500 | weight (rel↑), hepatomegaly, necrosis at 500 mg | 25 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Powell et al., 1986 | rat 10 m per dose | 28 days gavag e | 25, 150, 500 | weight (rel↑), hepatomegaly, necrosis at 500 mg | 25 (LE)","duration":"28 days","effect":"Unlabeled table on page 34: Powell et al., 1986 | rat 10 m per dose | 28 days gavag e | 25, 150, 500 | weight (rel↑), hepatomegaly, necrosis at 500 mg | 25 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"25 (LE)","page":34,"route":"","species":"rat","study_id":"sccs_o_257_noael_063"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1640 - - - 104 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=1640 (LOAEL,; EFFECT=Unlabeled table on page 34: Inai et al. | mous e, 50 | 104 wk | m: 1640, | ↑ weight m proliferation (foci), | not affected or | no effects on | 1640 (LOAEL,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"104 wk","effect":"Unlabeled table on page 34: Inai et al. | mous e, 50 | 104 wk | m: 1640, | ↑ weight m proliferation (foci), | not affected or | no effects on | 1640 (LOAEL,","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"1640 (LOAEL,","page":34,"route":"","species":"","study_id":"sccs_o_257_noael_064"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 35 - - - - - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=unclear:Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); DOSE=Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); EFFECT=Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","duration":"","effect":"Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 35: Refere nce | Speci es | Expos ure | Doses (mg/k g bw) | liver | thyroid | adrenals | NOAEL (mg/kg bw/d)","page":35,"route":"","species":"","study_id":"sccs_o_257_noael_065"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 75 - rat - 76 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=75 (LE); EFFECT=Unlabeled table on page 35: William s et al. 1990 | rat males ; interi m sacrifi ces | 76 wk 110 wk feedin g | 7.5, 23, 75, 225, 450 900 (only 110 wk) | weight ↑ (at ≥ 450mg) no morphological changes | no effects (tumor induction) no effects (tumor induction) | no effects (tumors induction) no effects (tumor induction) | 75 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"","duration":"76 wk","effect":"Unlabeled table on page 35: William s et al. 1990 | rat males ; interi m sacrifi ces | 76 wk 110 wk feedin g | 7.5, 23, 75, 225, 450 900 (only 110 wk) | weight ↑ (at ≥ 450mg) no morphological changes | no effects (tumor induction) no effects (tumor induction) | no effects (tumors induction) no effects (tumor induction) | 75 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"75 (LE)","page":35,"route":"","species":"rat","study_id":"sccs_o_257_noael_066"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 200 - rat - 24 wk - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=200 (LOAEL, LE); DOSE=Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE); EFFECT=Unlabeled table on page 35: Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","duration":"24 wk","effect":"Unlabeled table on page 35: Safer & Al- Nugha mish 1999 | rat, 10 m/ dose (2/ti me point) | 6-24 wk feedin g | 200, 400, 800 | weight (abs↑) hypertrophy, degenerative figures no tumors | 200 (LOAEL, LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"200 (LOAEL, LE)","page":35,"route":"","species":"rat","study_id":"sccs_o_257_noael_067"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 28 - rat - 28 days - SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=28 (LE); DOSE=2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE); EFFECT=Unlabeled table on page 35: Stieru m et al. 2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","duration":"28 days","effect":"Unlabeled table on page 35: Stieru m et al. 2008 | rat 6 m per dose | 28 days feedin g | 28, 88, 167, 321, 1159 | weight, histopath effects at 1159 mg | 28 (LE)","endpoint":"","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"","noael_value":"28 (LE)","page":35,"route":"","species":"rat","study_id":"sccs_o_257_noael_068"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 38 mg/kg bw/day rat - - carcinogenicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=38; DOSE=(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.; EFFECT=s on genotoxicity (Ma et al. 2017, Negritto et al. 2017), retrieved in the systematic literature searches performed by VKM, did not provide evidence of genotoxicity. Ref.: EFSA 2012; Ma 2017; Negritto 2017; VKM 2019 SCCS comment The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the; CITATION=Ref.: EFSA 2012; CITATION_NUMBERS=[2012]; REFERENCE=Ref.: EFSA 2012; DETAILS_JSON={"cas_number":"128-37-0","citation":"Ref.: EFSA 2012","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","duration":"","effect":"s on genotoxicity (Ma et al. 2017, Negritto et al. 2017), retrieved in the systematic literature searches performed by VKM, did not provide evidence of genotoxicity. Ref.: EFSA 2012; Ma 2017; Negritto 2017; VKM 2019 SCCS comment The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the","endpoint":"carcinogenicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"38","page":19,"route":"","species":"rat","study_id":"sccs_o_257_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 247 mg/kg bw/day rat - - carcinogenicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=247; DOSE=(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.; EFFECT=y. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study. Ref.: Brooks 1976; Olsen 1986; EFSA 2012; CITATION=Ref.: Brooks 1976; CITATION_NUMBERS=[1976]; REFERENCE=Ref.: Brooks 1976; DETAILS_JSON={"cas_number":"128-37-0","citation":"Ref.: Brooks 1976","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","duration":"","effect":"y. 3.3.7 Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. The NOAEL for non-neoplastic effects in the study of Olsen et al. (1986) was 25 mg/kg bw/day, based on the effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study. Ref.: Brooks 1976; Olsen 1986; EFSA 2012","endpoint":"carcinogenicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"247","page":19,"route":"","species":"rat","study_id":"sccs_o_257_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 25 mg/kg bw/day rat - - carcinogenicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.; EFFECT=mice, rats and chickens. BHT has been shown to increase the relative thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.","duration":"","effect":"mice, rats and chickens. BHT has been shown to increase the relative thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT","endpoint":"carcinogenicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":25,"route":"","species":"rat","study_id":"sccs_o_257_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 25 mg/kg bw/day rat - - carcinogenicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.; EFFECT=ve thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal mo; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al.","duration":"","effect":"ve thyroid and adrenal weight in rats. In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. None of the studies available can be used to derive a NOAEL. The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day derived from two 2-generation study in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal mo","endpoint":"carcinogenicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":25,"route":"","species":"rat","study_id":"sccs_o_257_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 38 mg/kg bw/day rat - - carcinogenicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=38; DOSE=(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.; EFFECT=tudy in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. Photo-induced toxicity /; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"(1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al.","duration":"","effect":"tudy in rats by Olsen et al. (1986), based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MOS calculations. Mutagenicity / genotoxicity The SCCS concurs with the conclusions of EFSA (2012) and VKM (2019) that BHT is not of concern with regard to genotoxicity. Carcinogenicity According to EFSA, BHT in high doses can exert tumour-promoting effects in some animal models. The data do not allow the establishment of a NOAEL for a carcinogen-promotional effect. BMD analyses of the data reported by Brooks et al. (1976) on the incidence of lung neoplasia in mice induced by BHT revealed a BMDL10 of 38 mg/kg bw/day, and of the data reported by Olsen et al. (1986) on the incidence of hepatocellular carcinomas in male rats induced by BHT a BMDL10 of 247 mg/kg bw/day. Photo-induced toxicity /","endpoint":"carcinogenicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"38","page":25,"route":"","species":"rat","study_id":"sccs_o_257_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 450 mg/kg bw/day rat - Chronic reproductive toxicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=450; DOSE=In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal.; EFFECT=n. In addition, BHT has been shown to increase the relative thyroid and adrenal weight in rats. In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal. EFSA concluded that none of the studies available could be used to derive a NOAEL. Ref.: EFSA 2012; ANSES 2016 SCCS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg b; CITATION=Ref.: EFSA 2012; CITATION_NUMBERS=[2012]; REFERENCE=Ref.: EFSA 2012; DETAILS_JSON={"cas_number":"128-37-0","citation":"Ref.: EFSA 2012","dose":"In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal.","duration":"Chronic","effect":"n. In addition, BHT has been shown to increase the relative thyroid and adrenal weight in rats. In rats, BHT given orally to male for 7 consecutive days at dose levels of 75 or 450 mg/kg bw/day induced hepatocellular proliferation, increased hepatocyte apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 in the liver during the treatment, and resulted in hepatocellular inhibition of mitosis following withdrawal. EFSA concluded that none of the studies available could be used to derive a NOAEL. Ref.: EFSA 2012; ANSES 2016 SCCS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg b","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"450","page":17,"route":"","species":"rat","study_id":"sccs_o_257_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 25 mg/kg bw rat - Chronic reproductive toxicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.; EFFECT=CS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) wer; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.","duration":"Chronic","effect":"CS comment In two old studies cited in ANSES (2016) (Johnson & Hewgill 1961; Gaunt et al. 1965), effects on adrenal weight without any histological changes were observed, whereas no effects on adrenal was observed in Price (1994). ANSES, therefore, considered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) wer","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":17,"route":"","species":"rat","study_id":"sccs_o_257_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 25 mg/kg bw rat - Chronic reproductive toxicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.; EFFECT=onsidered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) were fed BHT at intake doses of 0, 25, 108, or 276 mg/kg bw/day for male rats and of 0, 26, 106 and 287 mg/kg bw/day for female rats, respectively. The F0 rats were mated after 13 weeks of treatment. The F1 groups consisted of 100, 80, 80, and 100 F1 ra; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"128-37-0","citation":"","dose":"3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day.","duration":"Chronic","effect":"onsidered that the effects of BHT on the weight of adrenals in different strains of rats are of no relevant significance. 3.3.4.3 Chronic (> 12 months) toxicity and reproductive toxicity EFSA established an ADI for BHT of 0.25 mg/kg bw per day. The ADI was based on a NOAEL of 25 mg/kg bw per day derived from a 2-generation study in rats based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, using an uncertainty factor of 100. This NOAEL also covers the effects on hepatic enzyme induction (and consequent thyroid hyperactivity), as well as the increase in hepatocellular adenomas and carcinomas. In the 2-generation study by Olsen et al. (1986), groups of 60, 40, 40, or 60 Wistar rats of each sex (F0) were fed BHT at intake doses of 0, 25, 108, or 276 mg/kg bw/day for male rats and of 0, 26, 106 and 287 mg/kg bw/day for female rats, respectively. The F0 rats were mated after 13 weeks of treatment. The F1 groups consisted of 100, 80, 80, and 100 F1 ra","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":17,"route":"","species":"rat","study_id":"sccs_o_257_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 25 mg/kg bw/day rat - - reproductive toxicity SOURCE_SUBDIR=sccs_o_257; REPORT_TITLE=OPINION on Butylated Hydroxytoluene (BHT); OPINION_NUMBER=SCCS/1636/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 2 December 2021; VALUE_TEXT=25; DOSE=VKM 2019 SCCS comment The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day, derived from two 2-generation study in rats by Olsen et al.; EFFECT=___________________________________________________ _________________________________________________________________________ 19 the ADI established by EFSA needed to be revised. One original study (Pop et al., 2013) was qualified for a risk of bias, relevance of endpoint and weight of evidence evaluation. The results reported by Pop et al. (2013) did not indicate that the ADI established by EFSA needed to be revised. Ref.: Pop 2013; VKM 2019 SCCS comment The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day, derived from two 2-generation study in rats by Olsen et al. (1986) based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MoS calculations. 3.3.5 Reproductive toxicity See section 3.3.4. 3.3.6 Mutagenicity / genotoxicity According to EFSA, the majority of evidence indicates a lack of potential for BHT to induce point mutations or chromosomal aberrations, or to interact with or damage DNA. Pos; CITATION=Ref.: Pop 2013; CITATION_NUMBERS=[2013]; REFERENCE=Ref.: Pop 2013; DETAILS_JSON={"cas_number":"128-37-0","citation":"Ref.: Pop 2013","dose":"VKM 2019 SCCS comment The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day, derived from two 2-generation study in rats by Olsen et al.","duration":"","effect":"___________________________________________________ _________________________________________________________________________ 19 the ADI established by EFSA needed to be revised. One original study (Pop et al., 2013) was qualified for a risk of bias, relevance of endpoint and weight of evidence evaluation. The results reported by Pop et al. (2013) did not indicate that the ADI established by EFSA needed to be revised. Ref.: Pop 2013; VKM 2019 SCCS comment The SCCS concurs with the conclusion of EFSA (2012) and a NOAEL of 25 mg/kg bw/day, derived from two 2-generation study in rats by Olsen et al. (1986) based on effects on litter size, sex ratio and pup body weight gain during the lactation period in the reproduction segment of the study, will be used for MoS calculations. 3.3.5 Reproductive toxicity See section 3.3.4. 3.3.6 Mutagenicity / genotoxicity According to EFSA, the majority of evidence indicates a lack of potential for BHT to induce point mutations or chromosomal aberrations, or to interact with or damage DNA. Pos","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":19,"route":"","species":"rat","study_id":"sccs_o_257_noael_004"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier 1P9D0Z171K UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H24O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"1P9D0Z171K"}
openFDA substances FDA UNII substance identifier 1P9D0Z171K UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H24O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"1P9D0Z171K"}
openFDA substances FDA UNII substance identifier 1P9D0Z171K UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H24O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"1P9D0Z171K"}
openFDA substances FDA UNII substance identifier 1P9D0Z171K UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H24O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"1P9D0Z171K"}