NOAEL Studies Cosmetic Ingredient

BHA (Butylated Hydroxyanisole) NOAEL Studies

INCI: BUTYLATED HYDROXYANISOLE

CAS: 25013-16-5

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

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CIR_vision_codex 12 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
CIR_vision_codex NOAEL =100 mg/kg bw/d rat oral - oral toxicity {"citation":"125); 300); 210)","dose":"In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased...","effect":"contact and food packaging materials, including: as a pressure-sensitive adhesive (21CFR175.125), as an antioxidant in resinous and polymeric coatings (21CFR175.300), as a defoaming agent (21CFR176.210), and as a component of polyethylene film (21CFR179.45). In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased mortality and behavioral effects in rat pups at higher dose levels, and using an uncertainty factor of 100, the EFSA Panel on Food Additives and Nutrient Sources added to Food revised the acceptable daily intake (ADI) of BHA from 0.5 mg/kg bw/d to 1 mg/kg bw/d.11 TOXICOKINETIC STUDIES Dermal Absorption In Vitro The dermal absorption of BHA was measured in an in vitro preparation of human skin.12 After a 16-h continuous application of 0.07% BHA, approximately 30% of the applie...","page":6,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_001"}
CIR_vision_codex NOAEL =420 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk.","effect":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_002"}
CIR_vision_codex NOAEL =220 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"posed to 100 or 500 mg/kg BHA for 13 wk.","effect":"posed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_003"}
CIR_vision_codex NOAEL =100 mg/kg bw/d rat oral - oral toxicity {"citation":"125); 300); 210)","dose":"In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased...","effect":"contact and food packaging materials, including: as a pressure-sensitive adhesive (21CFR175.125), as an antioxidant in resinous and polymeric coatings (21CFR175.300), as a defoaming agent (21CFR176.210), and as a component of polyethylene film (21CFR179.45). In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased mortality and behavioral effects in rat pups at higher dose levels, and using an uncertainty factor of 100, the EFSA Panel on Food Additives and Nutrient Sources added to Food revised the acceptable daily intake (ADI) of BHA from 0.5 mg/kg bw/d to 1 mg/kg bw/d.11 TOXICOKINETIC STUDIES Dermal Absorption In Vitro The dermal absorption of BHA was measured in an in vitro preparation of human skin.12 After a 16-h continuous application of 0.07% BHA, approximately 30% of the applie...","page":6,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_001"}
CIR_vision_codex NOAEL =420 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk.","effect":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_002"}
CIR_vision_codex NOAEL =220 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"posed to 100 or 500 mg/kg BHA for 13 wk.","effect":"posed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_003"}
CIR_vision_codex NOAEL =100 mg/kg bw/d rat oral - oral toxicity {"citation":"125); 300); 210)","dose":"In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased...","effect":"contact and food packaging materials, including: as a pressure-sensitive adhesive (21CFR175.125), as an antioxidant in resinous and polymeric coatings (21CFR175.300), as a defoaming agent (21CFR176.210), and as a component of polyethylene film (21CFR179.45). In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased mortality and behavioral effects in rat pups at higher dose levels, and using an uncertainty factor of 100, the EFSA Panel on Food Additives and Nutrient Sources added to Food revised the acceptable daily intake (ADI) of BHA from 0.5 mg/kg bw/d to 1 mg/kg bw/d.11 TOXICOKINETIC STUDIES Dermal Absorption In Vitro The dermal absorption of BHA was measured in an in vitro preparation of human skin.12 After a 16-h continuous application of 0.07% BHA, approximately 30% of the applie...","page":6,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_001"}
CIR_vision_codex NOAEL =420 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk.","effect":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_002"}
CIR_vision_codex NOAEL =220 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"posed to 100 or 500 mg/kg BHA for 13 wk.","effect":"posed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_003"}
CIR_vision_codex NOAEL =100 mg/kg bw/d rat oral - oral toxicity {"citation":"125); 300); 210)","dose":"In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased...","effect":"contact and food packaging materials, including: as a pressure-sensitive adhesive (21CFR175.125), as an antioxidant in resinous and polymeric coatings (21CFR175.300), as a defoaming agent (21CFR176.210), and as a component of polyethylene film (21CFR179.45). In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased mortality and behavioral effects in rat pups at higher dose levels, and using an uncertainty factor of 100, the EFSA Panel on Food Additives and Nutrient Sources added to Food revised the acceptable daily intake (ADI) of BHA from 0.5 mg/kg bw/d to 1 mg/kg bw/d.11 TOXICOKINETIC STUDIES Dermal Absorption In Vitro The dermal absorption of BHA was measured in an in vitro preparation of human skin.12 After a 16-h continuous application of 0.07% BHA, approximately 30% of the applie...","page":6,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_001"}
CIR_vision_codex NOAEL =420 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk.","effect":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_002"}
CIR_vision_codex NOAEL =220 mg/kg/d rat oral 13 wk reproductive toxicity {"citation":"100; 500; 13","dose":"posed to 100 or 500 mg/kg BHA for 13 wk.","effect":"posed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","page":10,"pdf":"TR890.pdf","row_type":"noael_study","study_id":"TR890_noael_003"}
COSMOS_DB 30 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB NOAEL 2000 mg/kg bw/day rat oral 90 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1000 mg/kg bw/day rat oral 32 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1200 mg/kg bw/day hamster oral 140 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 250 mg/kg bw/day dog oral 180 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 125 mg/kg bw/day rat oral 728 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 500 mg/kg bw/day rat oral 728 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 750 mg/kg bw/day mouse oral 728 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 325 mg/kg bw/day dog oral 180 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 400 mg/kg bw/day swine oral 110 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 60 mg/kg bw/day dog oral 180 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 50 mg/kg bw/day swine oral 110 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 2400 mg/kg bw/day hamster oral 28 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 100 mg/kg bw/day dog oral 365 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 200 mg/kg bw/day rabbit oral 13 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 225 mg/kg bw/day mouse oral 10 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 120 mg/kg bw/day hamster oral 5 day Developmental US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 662 mg/kg bw/day house shrew oral 560 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 237 mg/kg bw/day dog oral 180 day Subchronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 600 mg/kg bw/day rat oral 770 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 840 mg/kg bw/day syrian hamster oral 225 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1125 mg/kg bw/day mouse oral 10 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 375 mg/kg bw/day rat oral 14 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 150 mg/kg bw/day mouse oral 14 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1180 mg/kg bw/day rat oral 14 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 300 mg/kg bw/day mouse oral 1 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 974 mg/kg bw/day rat oral 728 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1375 mg/kg bw/day rat oral 728 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 956 mg/kg bw/day rat oral 728 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1041 mg/kg bw/day rat oral 728 day Carcinogenicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 1500 mg/kg bw/day mouse oral 21 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
California Proposition 65 6 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
California Proposition 65 California Proposition 65 NSRL AB4000 ug/day - - 1990-01-01 No significant risk level {"cancer_reproductive":"cancer","listed_date":"1990-01-01","listing_mechanism":"AB","madl":null,"nsrl":"4000","row_type":"nsrl","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 NSRL AB4000 ug/day - - 1990-01-01 No significant risk level {"cancer_reproductive":"cancer","listed_date":"1990-01-01","listing_mechanism":"AB","madl":null,"nsrl":"4000","row_type":"nsrl","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 NSRL AB4000 ug/day - - 1990-01-01 No significant risk level {"cancer_reproductive":"cancer","listed_date":"1990-01-01","listing_mechanism":"AB","madl":null,"nsrl":"4000","row_type":"nsrl","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 listing ABcancer listing type - - 1990-01-01 California Proposition 65 listing {"cancer_reproductive":"cancer","listed_date":"1990-01-01","listing_mechanism":"AB","madl":null,"nsrl":"4000","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 listing ABcancer listing type - - 1990-01-01 California Proposition 65 listing {"cancer_reproductive":"cancer","listed_date":"1990-01-01","listing_mechanism":"AB","madl":null,"nsrl":"4000","source_table":"prop65_listings"}
California Proposition 65 California Proposition 65 listing ABcancer listing type - - 1990-01-01 California Proposition 65 listing {"cancer_reproductive":"cancer","listed_date":"1990-01-01","listing_mechanism":"AB","madl":null,"nsrl":"4000","source_table":"prop65_listings"}
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =100 mg/kg bw/day Rat oral: unspecified - reproduction toxicity EFSA ANS - 2011 - OutputID 488 - development - developmental - Scientific Opinion on the re-evaluation of butylated hydroxyanisole BHA (E 320) as a food additive - doi:10.2903/j.efsa.2011.2392
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =100 mg/kg bw/day Rat oral: unspecified - reproduction toxicity EFSA ANS - 2011 - OutputID 488 - development - developmental - Scientific Opinion on the re-evaluation of butylated hydroxyanisole BHA (E 320) as a food additive - doi:10.2903/j.efsa.2011.2392
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI =1 mg/kg bw/day Consumers - - ADI EFSA ANS - 2011 - OutputID 488 - Consumers - Scientific Opinion on the re-evaluation of butylated hydroxyanisole BHA (E 320) as a food additive - doi:10.2903/j.efsa.2011.2392
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI =1 mg/kg bw/day Consumers - - ADI EFSA ANS - 2011 - OutputID 488 - Consumers - Scientific Opinion on the re-evaluation of butylated hydroxyanisole BHA (E 320) as a food additive - doi:10.2903/j.efsa.2011.2392
IARC Monographs 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
IARC Monographs IARC carcinogenicity classification 2B 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 2B 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 2B IARC group - - 1987 IARC Monographs {"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"40, Sup 7"}
NTP_ICE_cancer 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_cancer IARC group 2 unitless - - - WOE; IARC Carcinogenicity sheet=Data; excel_row=7430; Record_ID=cancer_837; Data_Type=WOE; Formulation_Name=Butylated hydroxyanisole; Mixture=Chemical; DTXSID=DTXSID7020215; Assay=IARC Carcinogenicity; Endpoint=IARC group; Response=2B; Response_Unit=Unitless; URL=http://publications.iarc.fr/58; http://publications.iarc.fr/139; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7020215; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7020215
NTP_ICE_endocrine 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_endocrine NOEL 500 mg/kg bw/day Rat Oral Treatment_Duration=10 days; Age_at_First_Dose=PND 51; Age_Ovariectomized_or_Castrated=PND 42; Time_Elapsed_Between_Surgery_and_Treatment=8 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=18 to 36 hours; Number_of_Doses_Tested=8 In Vivo; Hershberger-Agonist sheet=Data_invivo; excel_row=1836; Record_ID=endocrine_invivo_788; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID7020215; Assay=Hershberger-Agonist; Endpoint=NOEL; Response=500; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Sprague-Dawley; Strain=Sprague-Dawley; Sex=Male (castrated); Route=Oral; Reference_Hormone=Testosterone propionate; Reference_Hormone_Dose=0.4; Reference_Hormone_Dose_Units=mg/kg/day; Reference_Hormone_Route=Subcutaneous; Additional_Information=Browne et al. 2018 unique record identifier 156; Reference=Kang et al. 2005; 16023279; 10.1016/j.tox.2005.05.027|Browne et al. 2018; 30205136; 10.1016/j.reprotox.2018.08.016; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7020215; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID7020215
SCCS_vision_codex 28 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =50 mg/kg bw/d rat oral 4 weeks repeated dose toxicity {"citation":"Ref.: Miyakawa et al","dose":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx.","effect":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx. 1000 mg/kg body weight) in DMSO three times a week for 4 weeks. Repeated dermal dosing did not result in lethality or lung toxicity. Ref.: Miyakawa et al. 1986 SCCS conclusion on repeated dose toxicity After oral administration, the forestomach and liver were identified as target organs in oral repeat-dose studies in various animal species over different durations (see Annex I). The totality of these studies points to an NOAEL of 50 mg/kg bw/d based on liver effects. Systemic effects were not observed after repeated dermal application of BHA. Therefore, the SCCS will use 50 mg/kg bw/d as a point of departure (PoD) for MoS calculation. 3.4.5 Reproductive toxicity 3.4.5.1 Fertility and reproduction toxicity Fertility and toxicity to reproduction was investigated in a study similar to OECD TG 415. Groups of 12 male and 12 female Sprague-Dawley rats each received 0, 10, 100 or 500 mg BHA/kg bw/d (purity 99.9%) by gavage, dissolved in co","page":22,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_001"}
SCCS_vision_codex NOAEL =400 mg/kg bw/day rabbit oral 7 to day reproductive toxicity {"citation":"Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt p","dose":"There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters).","effect":"tokes and Scudder, 1974, quoted from EFSA, 2011 Doses of 0, 50, 200 or 400 mg BHA/kg bw/day were given orally by gavage to groups of pregnant New Zealand white rabbits from day 7 to day 18 of pregnancy. There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study. Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt pigs The pigs were maintained on the diet for three weeks and then artificially inseminated. Resulting numbers of pregnant animals were: 9 in the 0 mg/kg bw/day dose group, 11 in the 50 mg/kg bw/day dose group, 13 in the 200 mg/kg bw/day dose group and 1","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - developmental reproductive toxicity {"citation":"Ref.: Hansen et al","dose":"increased relative to the control at all dose levels tested.","effect":"increased relative to the control at all dose levels tested. There was no effect of BHA on the reproductive and developmental parameters. Anses noted that the histological picture of the thyroid indicated a reduced activity which was not confirmed by other parameters. In this study, it was not clear when the dosing period started (on the day of insemination or at the start of pregnancy). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study and that the NOAEL for maternal toxicity is 200 mg/kg bw/day. Ref.: Hansen et al., 1982, quoted from EFSA, 2011 and Anses, 2024 Anses (2024) mentions a further, poorly reported study (Clegg, 1965) administering BHA at 750 mg/kg bw/d BHA on GD 1-20 (n=32 females), BHA at 750 mg/kg bw/d for 70 days before pairing, continuing through pregnancy (n= 47 females) and a single administration of BHA on GD 9, 11 or 13 (n=111 females) to Albino rats. BHA also administered at 500 mg/kg bw/d Porton SPF rats for 7 weeks before pairing continuin","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_004"}
SCCS_vision_codex NOAEL =0.082 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"bw/d is used as a PoD for risk assessment. As explained in section 3.2.1 (Dermal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_006"}
SCCS_vision_codex NOAEL =0.079 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"rmal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_008"}
SCCS_vision_codex NOAEL =0.0029 mg/kg bw/d - - - NOAEL study {"dose":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_011"}
SCCS_vision_codex NOAEL =55 mg/kg bw/d rat oral 104 wk NOAEL study {"dose":"0.5, 50, 250 mg/kg bw/d), diet NOAEL:","effect":"pronounced hyperplasia: 1/14; hyperkeratosis: 1/14 close to esophagus: moderate hyperplasia: 1/14; hyperkeratosis 5/14 Species, Strain, number of animals per group Exposure Findings Reference Rat, Norway Hooded; Each 20 ♂, ♀ 8 mo 0; 0,001; 0,1; 0,5% BHA (ca. 0.5, 50, 250 mg/kg bw/d), diet NOAEL: 50 mg/kg bw/d 250 mg/kg bw/d: increased liver weight (investigated tissues: liver, kidney, spleen, testes) Brown et al., 1959 Rat, F344 50 ♂ 104 wk 0; 0,125; 0,25; 0,5; 1; 2% BHA (55, 110, 230, 428, 1323 mg/kg bw/d), diet NOAEL: 55 mg/kg bw/d from 110 mg/kg bw/d: decreased bw gain; forestomach hyperplasia at 230 and 428 mg/kg bw/d: hyperplasia of liver (not dose- dependent) Ito et al., 1986a Rat, F344 up to 31 ♂ 104 wk 0; 0,4% BHA (0 and ca. 200 mg/kg bw/d), diet At 200 mg/kg bw/d: Rel. liver and kidney weight increased Hirose et al., 1997 Rat, F344 27 ♂ 110 wk 0 and 12000mg BHA/kg diet (ca. 600 mg/kg bw/d) At 600 mg/kg bw/d: liver weight affected, liver effects, forestomach hyperplasia Williams et al., 1990b Rat, F344 50 ♂ 2 years 0, 1%","page":60,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_018"}
SCCS_vision_codex NOAEL =50 mg/kg bw/d rat oral 4 weeks repeated dose toxicity {"citation":"Ref.: Miyakawa et al","dose":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx.","effect":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx. 1000 mg/kg body weight) in DMSO three times a week for 4 weeks. Repeated dermal dosing did not result in lethality or lung toxicity. Ref.: Miyakawa et al. 1986 SCCS conclusion on repeated dose toxicity After oral administration, the forestomach and liver were identified as target organs in oral repeat-dose studies in various animal species over different durations (see Annex I). The totality of these studies points to an NOAEL of 50 mg/kg bw/d based on liver effects. Systemic effects were not observed after repeated dermal application of BHA. Therefore, the SCCS will use 50 mg/kg bw/d as a point of departure (PoD) for MoS calculation. 3.4.5 Reproductive toxicity 3.4.5.1 Fertility and reproduction toxicity Fertility and toxicity to reproduction was investigated in a study similar to OECD TG 415. Groups of 12 male and 12 female Sprague-Dawley rats each received 0, 10, 100 or 500 mg BHA/kg bw/d (purity 99.9%) by gavage, dissolved in co","page":22,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_001"}
SCCS_vision_codex NOAEL =400 mg/kg bw/day rabbit oral 7 to day reproductive toxicity {"citation":"Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt p","dose":"There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters).","effect":"tokes and Scudder, 1974, quoted from EFSA, 2011 Doses of 0, 50, 200 or 400 mg BHA/kg bw/day were given orally by gavage to groups of pregnant New Zealand white rabbits from day 7 to day 18 of pregnancy. There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study. Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt pigs The pigs were maintained on the diet for three weeks and then artificially inseminated. Resulting numbers of pregnant animals were: 9 in the 0 mg/kg bw/day dose group, 11 in the 50 mg/kg bw/day dose group, 13 in the 200 mg/kg bw/day dose group and 1","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - developmental reproductive toxicity {"citation":"Ref.: Hansen et al","dose":"increased relative to the control at all dose levels tested.","effect":"increased relative to the control at all dose levels tested. There was no effect of BHA on the reproductive and developmental parameters. Anses noted that the histological picture of the thyroid indicated a reduced activity which was not confirmed by other parameters. In this study, it was not clear when the dosing period started (on the day of insemination or at the start of pregnancy). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study and that the NOAEL for maternal toxicity is 200 mg/kg bw/day. Ref.: Hansen et al., 1982, quoted from EFSA, 2011 and Anses, 2024 Anses (2024) mentions a further, poorly reported study (Clegg, 1965) administering BHA at 750 mg/kg bw/d BHA on GD 1-20 (n=32 females), BHA at 750 mg/kg bw/d for 70 days before pairing, continuing through pregnancy (n= 47 females) and a single administration of BHA on GD 9, 11 or 13 (n=111 females) to Albino rats. BHA also administered at 500 mg/kg bw/d Porton SPF rats for 7 weeks before pairing continuin","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_004"}
SCCS_vision_codex NOAEL =0.082 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"bw/d is used as a PoD for risk assessment. As explained in section 3.2.1 (Dermal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_006"}
SCCS_vision_codex NOAEL =0.079 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"rmal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_008"}
SCCS_vision_codex NOAEL =0.0029 mg/kg bw/d - - - NOAEL study {"dose":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_011"}
SCCS_vision_codex NOAEL =50 mg/kg bw/d rat oral 4 weeks repeated dose toxicity {"citation":"Ref.: Miyakawa et al","dose":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx.","effect":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx. 1000 mg/kg body weight) in DMSO three times a week for 4 weeks. Repeated dermal dosing did not result in lethality or lung toxicity. Ref.: Miyakawa et al. 1986 SCCS conclusion on repeated dose toxicity After oral administration, the forestomach and liver were identified as target organs in oral repeat-dose studies in various animal species over different durations (see Annex I). The totality of these studies points to an NOAEL of 50 mg/kg bw/d based on liver effects. Systemic effects were not observed after repeated dermal application of BHA. Therefore, the SCCS will use 50 mg/kg bw/d as a point of departure (PoD) for MoS calculation. 3.4.5 Reproductive toxicity 3.4.5.1 Fertility and reproduction toxicity Fertility and toxicity to reproduction was investigated in a study similar to OECD TG 415. Groups of 12 male and 12 female Sprague-Dawley rats each received 0, 10, 100 or 500 mg BHA/kg bw/d (purity 99.9%) by gavage, dissolved in co","page":22,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_001"}
SCCS_vision_codex NOAEL =400 mg/kg bw/day rabbit oral 7 to day reproductive toxicity {"citation":"Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt p","dose":"There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters).","effect":"tokes and Scudder, 1974, quoted from EFSA, 2011 Doses of 0, 50, 200 or 400 mg BHA/kg bw/day were given orally by gavage to groups of pregnant New Zealand white rabbits from day 7 to day 18 of pregnancy. There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study. Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt pigs The pigs were maintained on the diet for three weeks and then artificially inseminated. Resulting numbers of pregnant animals were: 9 in the 0 mg/kg bw/day dose group, 11 in the 50 mg/kg bw/day dose group, 13 in the 200 mg/kg bw/day dose group and 1","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - developmental reproductive toxicity {"citation":"Ref.: Hansen et al","dose":"increased relative to the control at all dose levels tested.","effect":"increased relative to the control at all dose levels tested. There was no effect of BHA on the reproductive and developmental parameters. Anses noted that the histological picture of the thyroid indicated a reduced activity which was not confirmed by other parameters. In this study, it was not clear when the dosing period started (on the day of insemination or at the start of pregnancy). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study and that the NOAEL for maternal toxicity is 200 mg/kg bw/day. Ref.: Hansen et al., 1982, quoted from EFSA, 2011 and Anses, 2024 Anses (2024) mentions a further, poorly reported study (Clegg, 1965) administering BHA at 750 mg/kg bw/d BHA on GD 1-20 (n=32 females), BHA at 750 mg/kg bw/d for 70 days before pairing, continuing through pregnancy (n= 47 females) and a single administration of BHA on GD 9, 11 or 13 (n=111 females) to Albino rats. BHA also administered at 500 mg/kg bw/d Porton SPF rats for 7 weeks before pairing continuin","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_004"}
SCCS_vision_codex NOAEL =0.082 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"bw/d is used as a PoD for risk assessment. As explained in section 3.2.1 (Dermal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_006"}
SCCS_vision_codex NOAEL =0.079 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"rmal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_008"}
SCCS_vision_codex NOAEL =0.0029 mg/kg bw/d - - - NOAEL study {"dose":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_011"}
SCCS_vision_codex NOAEL =55 mg/kg bw/d rat oral 104 wk NOAEL study {"dose":"0.5, 50, 250 mg/kg bw/d), diet NOAEL:","effect":"pronounced hyperplasia: 1/14; hyperkeratosis: 1/14 close to esophagus: moderate hyperplasia: 1/14; hyperkeratosis 5/14 Species, Strain, number of animals per group Exposure Findings Reference Rat, Norway Hooded; Each 20 ♂, ♀ 8 mo 0; 0,001; 0,1; 0,5% BHA (ca. 0.5, 50, 250 mg/kg bw/d), diet NOAEL: 50 mg/kg bw/d 250 mg/kg bw/d: increased liver weight (investigated tissues: liver, kidney, spleen, testes) Brown et al., 1959 Rat, F344 50 ♂ 104 wk 0; 0,125; 0,25; 0,5; 1; 2% BHA (55, 110, 230, 428, 1323 mg/kg bw/d), diet NOAEL: 55 mg/kg bw/d from 110 mg/kg bw/d: decreased bw gain; forestomach hyperplasia at 230 and 428 mg/kg bw/d: hyperplasia of liver (not dose- dependent) Ito et al., 1986a Rat, F344 up to 31 ♂ 104 wk 0; 0,4% BHA (0 and ca. 200 mg/kg bw/d), diet At 200 mg/kg bw/d: Rel. liver and kidney weight increased Hirose et al., 1997 Rat, F344 27 ♂ 110 wk 0 and 12000mg BHA/kg diet (ca. 600 mg/kg bw/d) At 600 mg/kg bw/d: liver weight affected, liver effects, forestomach hyperplasia Williams et al., 1990b Rat, F344 50 ♂ 2 years 0, 1%","page":60,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_018"}
SCCS_vision_codex NOAEL =55 mg/kg bw/d rat oral 104 wk NOAEL study {"dose":"0.5, 50, 250 mg/kg bw/d), diet NOAEL:","effect":"pronounced hyperplasia: 1/14; hyperkeratosis: 1/14 close to esophagus: moderate hyperplasia: 1/14; hyperkeratosis 5/14 Species, Strain, number of animals per group Exposure Findings Reference Rat, Norway Hooded; Each 20 ♂, ♀ 8 mo 0; 0,001; 0,1; 0,5% BHA (ca. 0.5, 50, 250 mg/kg bw/d), diet NOAEL: 50 mg/kg bw/d 250 mg/kg bw/d: increased liver weight (investigated tissues: liver, kidney, spleen, testes) Brown et al., 1959 Rat, F344 50 ♂ 104 wk 0; 0,125; 0,25; 0,5; 1; 2% BHA (55, 110, 230, 428, 1323 mg/kg bw/d), diet NOAEL: 55 mg/kg bw/d from 110 mg/kg bw/d: decreased bw gain; forestomach hyperplasia at 230 and 428 mg/kg bw/d: hyperplasia of liver (not dose- dependent) Ito et al., 1986a Rat, F344 up to 31 ♂ 104 wk 0; 0,4% BHA (0 and ca. 200 mg/kg bw/d), diet At 200 mg/kg bw/d: Rel. liver and kidney weight increased Hirose et al., 1997 Rat, F344 27 ♂ 110 wk 0 and 12000mg BHA/kg diet (ca. 600 mg/kg bw/d) At 600 mg/kg bw/d: liver weight affected, liver effects, forestomach hyperplasia Williams et al., 1990b Rat, F344 50 ♂ 2 years 0, 1%","page":60,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_018"}
SCCS_vision_codex NOAEL =50 mg/kg bw/d rat oral 4 weeks repeated dose toxicity {"citation":"Ref.: Miyakawa et al","dose":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx.","effect":"0 female CD1 mice were epicutaneously administered 0.1 ml of a solution of 30 mg BHA (approx. 1000 mg/kg body weight) in DMSO three times a week for 4 weeks. Repeated dermal dosing did not result in lethality or lung toxicity. Ref.: Miyakawa et al. 1986 SCCS conclusion on repeated dose toxicity After oral administration, the forestomach and liver were identified as target organs in oral repeat-dose studies in various animal species over different durations (see Annex I). The totality of these studies points to an NOAEL of 50 mg/kg bw/d based on liver effects. Systemic effects were not observed after repeated dermal application of BHA. Therefore, the SCCS will use 50 mg/kg bw/d as a point of departure (PoD) for MoS calculation. 3.4.5 Reproductive toxicity 3.4.5.1 Fertility and reproduction toxicity Fertility and toxicity to reproduction was investigated in a study similar to OECD TG 415. Groups of 12 male and 12 female Sprague-Dawley rats each received 0, 10, 100 or 500 mg BHA/kg bw/d (purity 99.9%) by gavage, dissolved in co","page":22,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_001"}
SCCS_vision_codex NOAEL =400 mg/kg bw/day rabbit oral 7 to day reproductive toxicity {"citation":"Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt p","dose":"There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters).","effect":"tokes and Scudder, 1974, quoted from EFSA, 2011 Doses of 0, 50, 200 or 400 mg BHA/kg bw/day were given orally by gavage to groups of pregnant New Zealand white rabbits from day 7 to day 18 of pregnancy. There were no observed differences between the treated groups and controls in the parameters measured (body weight, incidence of soft tissue or skeletal abnormalities, number of foetuses born dead or alive, number of corpora lutea and implantations, general reproductive parameters). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study. Ref.: Hansen and Meyer (1978), quoted from EFSA, 2011 A diet containing the equivalent of 0, 50, 200, or 400 mg BHA/kg bw/day was given to groups of 10 young adult Danish Landrace gilt pigs The pigs were maintained on the diet for three weeks and then artificially inseminated. Resulting numbers of pregnant animals were: 9 in the 0 mg/kg bw/day dose group, 11 in the 50 mg/kg bw/day dose group, 13 in the 200 mg/kg bw/day dose group and 1","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_002"}
SCCS_vision_codex NOAEL =200 mg/kg bw/day rat - developmental reproductive toxicity {"citation":"Ref.: Hansen et al","dose":"increased relative to the control at all dose levels tested.","effect":"increased relative to the control at all dose levels tested. There was no effect of BHA on the reproductive and developmental parameters. Anses noted that the histological picture of the thyroid indicated a reduced activity which was not confirmed by other parameters. In this study, it was not clear when the dosing period started (on the day of insemination or at the start of pregnancy). The EFSA Panel concluded that a NOAEL for developmental toxicity of 400 mg/kg bw/day can be derived from this study and that the NOAEL for maternal toxicity is 200 mg/kg bw/day. Ref.: Hansen et al., 1982, quoted from EFSA, 2011 and Anses, 2024 Anses (2024) mentions a further, poorly reported study (Clegg, 1965) administering BHA at 750 mg/kg bw/d BHA on GD 1-20 (n=32 females), BHA at 750 mg/kg bw/d for 70 days before pairing, continuing through pregnancy (n= 47 females) and a single administration of BHA on GD 9, 11 or 13 (n=111 females) to Albino rats. BHA also administered at 500 mg/kg bw/d Porton SPF rats for 7 weeks before pairing continuin","page":24,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_004"}
SCCS_vision_codex NOAEL =0.082 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"bw/d is used as a PoD for risk assessment. As explained in section 3.2.1 (Dermal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_006"}
SCCS_vision_codex NOAEL =0.079 mg/kg bw/d - oral - dermal absorption {"dose":"No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"rmal/percutaneous absorption), a default of 50 % is used as dermal absorption percentage. No correction is made for oral absorption (see section 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_008"}
SCCS_vision_codex NOAEL =0.0029 mg/kg bw/d - - - NOAEL study {"dose":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated.","effect":"n 3.2.) As explained in section 3.3.2, SEDs of 0.082 mg/kg bw/d (for leave-on and rinse-off products combined), 0.0029 mg/kg bw/d for rinse-off products and 0.079 mg/kg bw/d for leave-on products were calculated. Safety calculations: Leave-on and rinse-off products combined: SED: 0.082 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 610 Leave-on products alone: SED: 0.079 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 632 Rinse-off products alone: SED: 0.0029 mg/kg bw/d NOAEL (not adjusted): 50 mg/kg bw/d Margin of Safety (NOAEL/SED) adjusted NOAEL/SED = 17251","page":45,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_011"}
SCCS_vision_codex NOAEL =55 mg/kg bw/d rat oral 104 wk NOAEL study {"dose":"0.5, 50, 250 mg/kg bw/d), diet NOAEL:","effect":"pronounced hyperplasia: 1/14; hyperkeratosis: 1/14 close to esophagus: moderate hyperplasia: 1/14; hyperkeratosis 5/14 Species, Strain, number of animals per group Exposure Findings Reference Rat, Norway Hooded; Each 20 ♂, ♀ 8 mo 0; 0,001; 0,1; 0,5% BHA (ca. 0.5, 50, 250 mg/kg bw/d), diet NOAEL: 50 mg/kg bw/d 250 mg/kg bw/d: increased liver weight (investigated tissues: liver, kidney, spleen, testes) Brown et al., 1959 Rat, F344 50 ♂ 104 wk 0; 0,125; 0,25; 0,5; 1; 2% BHA (55, 110, 230, 428, 1323 mg/kg bw/d), diet NOAEL: 55 mg/kg bw/d from 110 mg/kg bw/d: decreased bw gain; forestomach hyperplasia at 230 and 428 mg/kg bw/d: hyperplasia of liver (not dose- dependent) Ito et al., 1986a Rat, F344 up to 31 ♂ 104 wk 0; 0,4% BHA (0 and ca. 200 mg/kg bw/d), diet At 200 mg/kg bw/d: Rel. liver and kidney weight increased Hirose et al., 1997 Rat, F344 27 ♂ 110 wk 0 and 12000mg BHA/kg diet (ca. 600 mg/kg bw/d) At 600 mg/kg bw/d: liver weight affected, liver effects, forestomach hyperplasia Williams et al., 1990b Rat, F344 50 ♂ 2 years 0, 1%","page":60,"pdf":"sccs_o_306.pdf","row_type":"noael_study","study_id":"sccs_o_306_noael_018"}
ToxValDB_ECOTOX 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECOTOX LOEL =500 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_15607592_15607593:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=0a9b557befd14cc3f3710b072e45e203
ToxValDB_ECOTOX NOEL =0.75 % w/v Mouse oral short-term; 8.0833 days short-term LONG_REF=Toxicol. Appl. Pharmacol.87(3): 389-392 Ketterman,A.J., S.M. Pond, and C.E. Becker The Effects of Differential Induction of Cytochrome P-450, Carboxylesterase and Glutathione S-Transferase Activities on Malathion Toxicity in Mice 1987; TITLE=The Effects of Differential Induction of Cytochrome P-450, Carboxylesterase and Glutathione S-Transferase Activities on Malathion Toxicity in Mice; AUTHOR=Ketterman,A.J., S.M. Pond, and C.E. Becker; DOI=10.1016/0041-008x(87)90243-2; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=88919; 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=1987; ORIGINAL_YEAR=1987; TOXICOLOGICAL_EFFECT=Enzyme(s): Acetylcholinesterase|Enzyme(s): Cytochrome P-450|Enzyme(s): Malathion carboxylesterase; TOXICOLOGICAL_EFFECT_CATEGORY=enzyme activity|neurotransmitter; STUDY_GROUP=ECOTOX_dup_EPA ORD_15595130_15596728:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=290206b7fb741beb64a2e9506b0c1ba8
ToxValDB_ECOTOX NOEL =2 % Rat oral subchronic; 56 days subchronic LONG_REF=Toxicol. Appl. Pharmacol.99(1): 37-49 Shibata,M.A., M. Yamada, H. Tanaka, M. Kagawa, and S. Fukushima Changes in Urine Composition, Bladder Epithelial Morphology, and DNA Synthesis in Male F344 Rats in Response to Ingestion of Bladder Tumor Promoters 1989; TITLE=Changes in Urine Composition, Bladder Epithelial Morphology, and DNA Synthesis in Male F344 Rats in Response to Ingestion of Bladder Tumor Promoters; AUTHOR=Shibata,M.A., M. Yamada, H. Tanaka, M. Kagawa, and S. Fukushima; DOI=10.1016/0041-008x(89)90109-9; QUALITY=Control type: Multiple entries; EXTERNAL_SOURCE_ID=106692; 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=1989; ORIGINAL_YEAR=1989; TOXICOLOGICAL_EFFECT=Biochemistry: Phosphorus content|Physiology: Osmolality; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|urinalysis; STUDY_GROUP=ECOTOX_dup_EPA ORD_15606152_15606153:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=9e32b962490f3ab16295ff87c645719c
ToxValDB_ECOTOX NOEL =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_15607592_15607593:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=37769999adf9ad5df3f5d820fc2dd8ba
ToxValDB_EFSA 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_EFSA NOAEL =100 mg/kg bw/day Rat oral - developmental LONG_REF=EFSA ANS (2011). Scientific Opinion on the re-evaluation of butylated hydroxyanisole BHA (E 320) as a food additive. doi:10.2903/j.efsa.2011.2392.; TITLE=Scientific Opinion on the re-evaluation of butylated hydroxyanisole BHA (E 320) as a food additive; AUTHOR=EFSA ANS; DOI=doi:10.2903/j.efsa.2011.2392; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65201d30e4b0f0a60ddd1165; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://zenodo.org/record/5076033#.Y9fEoXbMI2z; YEAR=2011; ORIGINAL_YEAR=2011; TOXICOLOGICAL_EFFECT=development; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=EFSA_dup_-_15614341_15614342_15614343:-:--; 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_f4860a914ce41c83c6db2710fbad625e
ToxValDB_WHO_JECFA_ADI 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_WHO_JECFA_ADI ADI <=0.5 mg/kg Human oral - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/650afb36e4b0d99f5a87a669; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://apps.who.int/food-additives-contaminants-jecfa-database/; SUBSOURCE_URL=https://apps.who.int/food-additives-contaminants-jecfa-database/Home/Chemical/1910; YEAR=1988; ORIGINAL_YEAR=1988; STUDY_GROUP=WHO JECFA ADI:15715345:-:--; 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_40ef5fb290354b51ced1628598a40bd2
UnifiedCodex:CIR:beta.noael_studies 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:CIR:beta.noael_studies oral toxicity 100 mg/kg bw/d rat oral - oral toxicity SOURCE_SUBDIR=TR890; REPORT_TITLE=Amended Safety Assessment of BHA as Used in Cosmetics Status: Tentative Amended Report for Public Comment Last Panel Review:; OPINION_NUMBER=TR890; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=Review 1620; VALUE_TEXT=100; DOSE=In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased...; EFFECT=contact and food packaging materials, including: as a pressure-sensitive adhesive (21CFR175.125), as an antioxidant in resinous and polymeric coatings (21CFR175.300), as a defoaming agent (21CFR176.210), and as a component of polyethylene film (21CFR179.45). In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased mortality and behavioral effects in rat pups at higher dose levels, and using an uncertainty factor of 100, the EFSA Panel on Food Additives and Nutrient Sources added to Food revised the acceptable daily intake (ADI) of BHA from 0.5 mg/kg bw/d to 1 mg/kg bw/d.11 TOXICOKINETIC STUDIES Dermal Absorption In Vitro The dermal absorption of BHA was measured in an in vitro preparation of human skin.12 After a 16-h continuous application of 0.07% BHA, approximately 30% of the applie...; CITATION=125); 300); 210); CITATION_NUMBERS=[125,300,210]; REFERENCE=125); 300); 210); DETAILS_JSON={"cas_number":"25013-16-5","citation":"125); 300); 210)","dose":"In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased...","duration":"","effect":"contact and food packaging materials, including: as a pressure-sensitive adhesive (21CFR175.125), as an antioxidant in resinous and polymeric coatings (21CFR175.300), as a defoaming agent (21CFR176.210), and as a component of polyethylene film (21CFR179.45). In 2019, the European Food Safety Authority (EFSA) determined that the maximum authorized BHA content in animal feed (all animals, except cats), either alone, or in combination with butylated hydroxytoluene and/or ethoxyquin is 150 mg/kg.10 In 2011, based on a no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw/d BHA for growth retardation, increased mortality and behavioral effects in rat pups at higher dose levels, and using an uncertainty factor of 100, the EFSA Panel on Food Additives and Nutrient Sources added to Food revised the acceptable daily intake (ADI) of BHA from 0.5 mg/kg bw/d to 1 mg/kg bw/d.11 TOXICOKINETIC STUDIES Dermal Absorption In Vitro The dermal absorption of BHA was measured in an in vitro preparation of human skin.12 After a 16-h continuous application of 0.07% BHA, approximately 30% of the applie...","endpoint":"oral toxicity","ingredient":"BHA","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"100","page":6,"route":"oral","species":"rat","study_id":"TR890_noael_001"}
UnifiedCodex:CIR:beta.noael_studies reproductive toxicity 420 mg/kg/d rat oral 13 wk reproductive toxicity SOURCE_SUBDIR=TR890; REPORT_TITLE=Amended Safety Assessment of BHA as Used in Cosmetics Status: Tentative Amended Report for Public Comment Last Panel Review:; OPINION_NUMBER=TR890; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=Review 1620; VALUE_TEXT=420; DOSE=een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk.; LOAEL_VALUE=420 mg/kg/d; EFFECT=een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.; CITATION=100; 500; 13; CITATION_NUMBERS=[100,500,13]; REFERENCE=100; 500; 13; DETAILS_JSON={"cas_number":"25013-16-5","citation":"100; 500; 13","dose":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk.","duration":"13 wk","effect":"een, vagina, testes, and ventral prostate were decreased in the F1 (filial) generation rats exposed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","endpoint":"reproductive toxicity","ingredient":"BHA","loael_value":"420 mg/kg/d","noael_unit":"mg/kg/d","noael_value":"420","page":10,"route":"oral","species":"rat","study_id":"TR890_noael_002"}
UnifiedCodex:CIR:beta.noael_studies reproductive toxicity 220 mg/kg/d rat oral 13 wk reproductive toxicity SOURCE_SUBDIR=TR890; REPORT_TITLE=Amended Safety Assessment of BHA as Used in Cosmetics Status: Tentative Amended Report for Public Comment Last Panel Review:; OPINION_NUMBER=TR890; COMMITTEE=Expert Panel for Cosmetic Ingredient Safety; REPORT_DATE=Review 1620; VALUE_TEXT=220; DOSE=posed to 100 or 500 mg/kg BHA for 13 wk.; LOAEL_VALUE=420 mg/kg/d; EFFECT=posed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.; CITATION=100; 500; 13; CITATION_NUMBERS=[100,500,13]; REFERENCE=100; 500; 13; DETAILS_JSON={"cas_number":"25013-16-5","citation":"100; 500; 13","dose":"posed to 100 or 500 mg/kg BHA for 13 wk.","duration":"13 wk","effect":"posed to 100 or 500 mg/kg BHA for 13 wk. Additionally, reduced velocity of sperm motion and number, lowered serum levels of thyroxine and testosterone, slightly shortened estrous cycle length, and effects in the follicular epithelial cells of the thyroid were observed in F1 rats exposed to 500 mg/kg BHA. In another reproductive toxicity study, male and female rats received 0, 110, 220, or 420 mg/kg/d BHA, in the diet; the NOAEL for maternal toxicity was determined to be 420 mg/kg/d for.15 For offspring toxicity, a NOAEL of 220 mg/kg/d BHA and a LOAEL of 420 mg/kg/d BHA was established, based on the reduced weight of progeny during lactation and increasing peri-weaning mortality.","endpoint":"reproductive toxicity","ingredient":"BHA","loael_value":"420 mg/kg/d","noael_unit":"mg/kg/d","noael_value":"220","page":10,"route":"oral","species":"rat","study_id":"TR890_noael_003"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier REK4960K2U UNII - - - mixture {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"mixture","unii_code":"REK4960K2U"}
openFDA substances FDA UNII substance identifier REK4960K2U UNII - - - mixture {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"mixture","unii_code":"REK4960K2U"}
openFDA substances FDA UNII substance identifier REK4960K2U UNII - - - mixture {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"mixture","unii_code":"REK4960K2U"}
openFDA substances FDA UNII substance identifier REK4960K2U UNII - - - mixture {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"mixture","unii_code":"REK4960K2U"}