NOAEL Studies Cosmetic Ingredient

Methyl Benzoate NOAEL Studies

INCI: METHYL BENZOATE (BENZOIC ACID, METHYL ESTER)

CAS: 93-58-3

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 32 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
CIR_vision_codex NOAEL =1230 mg/m3 rat oral 24 months inhalation toxicity {"citation":"60; (0, 1; 2","dose":"735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102;","effect":"s 60% in the control group). Sodium benzoate (0, 1%, or 2%; 735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102; 50 males, 52 females) for 18 to 24 months.73 There were no dif- ferences in mortality between groups. Necropsies were unremarkable. Alcohols. Amyl alcohol (0, 50, 150, 100 mg/kg/d) was admi- nistered orally to ASH/CSE rats (n ¼ 30; 15/sex) for 13 weeks.74 The rats were killed and necropsied 24 hours after the last treat- ment. No adverse effects were observed at any dose. The no observed adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) for the inhalation of isopropyl alcohol was 1230 mg/m3 and 3690 mg/m3, respec- tively, in Fischer 344 rats and CD-1 mice (n ¼ 10/sex) exposed (0, 1230, 3690, or 12 300 mg/m3) 6 h/d, 5 d/week for 13 weeks.75 Adverse effects observed at the LOAEL included narcosis in rats and mice, hematological changes in rats, and increased liver weights in mice. An NOAEL of 1230 mg/m3 for rats and mice was reported (based on kidney and testicular effects) in a study in which Fischer 344 rats (n ¼ 6...","page":11,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_001"}
CIR_vision_codex NOAEL =125 mg/kg/d rat oral 11 days repeated dose toxicity {"citation":"100; 150; 9","dose":"The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose.","effect":"caused transient erythema of the treated skin. The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose. NOAELs ranged from 100 to 150 mg/kg body weight/day in several studies in which mice or rats were exposed orally for 9 to 11 days to ethylhexyl alcohol by gavage, in drinking water, or in feed.80–84 Doses \u0006330 mg/kg body weight/day produced CNS depression, lacrimation, and decreased food consumption and body weights. The NOAEL was 125 mg/kg/d for male and female F344 rats and B6C3Fl mice treated daily with ethylhexyl alcohol (0, 25, 125, 250, or 500 mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aeroso...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_002"}
CIR_vision_codex NOAEL =200 mg/kg/d rat oral 13 weeks repeated dose toxicity {"citation":"13; 85; 60","dose":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male...","effect":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aerosolized 2-ethyl-l-hexanol (15, 40, or 120 mL/m3; purity 99.9%).87 The oral NOAEL for noncancer systemic toxicity end points were 200 and 50 mg/kg/d in mice and rats, respectively, exposed chronically to ethylhexyl alcohol.88 Ocular/Mucosal Irritation Methyl benzoate. Methyl benzoate (100%) was administered to the center of the cornea while the lids were retracted in rabbits (n ¼ 5).53 The eye lids were released after *1 minute. The eyes were scored after 18 to 24 hours in day- light and with staining. Methyl benzoate was given a grade 1 (iritis, slight internal congestion). Ethyl benzoate. The above experiment was repeated with ethyl benzoate (...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_003"}
CIR_vision_codex NOAEL =1 % rat oral 8 weeks developmental toxicity {"citation":"4; (0, 1; 2","dose":"There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum.","effect":"re no differences between treatment groups and controls with regard to fertility index, precoital interval, and copulatory index com- pared to controls. There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum. Histopathological examina- tion of the ovaries and testes (including the stage in the sper- matogenic cycle) did not reveal any differences between the treated and control animals. The authors concluded that 1000 mg/kg/d was the NOAEL. Benzoic Acid and Sodium Benzoate Sodium benzoate (0, 1%, 2%, 4%, or 8%; 0, 667, 1333, 1600, or 710 [sic] mg/kg/d) was administered in the feed of female Wistar rats (n ¼ 27-30) during gestation (number of days not provided).117 On day 20, 20 to 25 rats of each group were killed and necropsied. The rest were allowed to live through preg- nancy and nurse for 3 or 8 weeks and then were killed. Half of the pups were then killed at each of these times and necropsied. The 2 highest dose groups had an increase in the number of dead fetuses and resorbed embryos. The body...","page":15,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_004"}
CIR_vision_codex NOAEL =175 mg/kg rat oral gestation days 6-10 developmental toxicity {"citation":"175; 20); 21","dose":"The fetal and mater- nal NOAEL was 175 mg/kg.","effect":"delivered by Caesarean section. There were no differences in the types or incidences of abnormalities observed in any of the treatment groups compared to the control. The fetal and mater- nal NOAEL was 175 mg/kg. The study above was repeated using mice (n ¼ 20), hamsters (n ¼ 21-22; gestation days 6-10), and rabbits (n ¼ 10). Similar results were reported. In oral teratogenicity studies, benzoic acid administered on gestation days 6 to 10 increased the number of resorptions at \u000630 mg/kg/d and increased the number of fetal malformations at >600 mg/kg/d in hamsters. Results for benzoic acid were negative in 2 oral rat studies up to 500 mg/kg/d.120 Crossbred white mice (n ¼ 50; 25/sex) were orally adminis- tered benzoic acid (40 mg/kg/d) for 8 months before breed- ing.72 This was continued for 5 generations. The parental and F1","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_005"}
CIR_vision_codex NOAEL =130 mg/kg/d rat - - developmental toxicity {"citation":"131,132; 25); 2","dose":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliat...","effect":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliation, crusting, and erythema at the site of application, and doses \u00061680 mg/kg/d were associ- ated with decreased maternal weight gain. Maternal and developmental NOAEL was found to be 130 mg/kg/d in Wistar rats (n ¼ 10) orally exposed to ethylhexyl alcohol (0, 130, 650, and 1300 mg/kg/d) on days 6 to 19 of gestation.134 The pups of Charles River CD-l mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingestin...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_006"}
CIR_vision_codex NOAEL =850 mg/m3 rat oral - developmental toxicity {"citation":"50); 2; 1","dose":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity.","effect":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingesting microencapsu- lated ethylhexyl alcohol (0.13, 43, and 129 mg/kg/d; >99% pure) in the diet on days 0 to 17 of pregnancy.136,137 The NOAEL for maternal and developmental toxicity was 850 mg/m3 (160 mL/m3) aerosolized ethylhexyl alcohol in Sprague-Dawley rats (n ¼ 15) exposed (whole body) 7 h/d on gestation days 0 to 19.123 Genotoxicity Methyl Benzoate In an Ames test using Salmonella typhimurium (TA97, TA98, TA100, TA1535, and TA1537), methyl benzoate (6666 mg/ plate) was not mutagenic with or without metabolic activa- tion.138 Methyl benzoate (dose not reported) was not found to be mutagenic in Escherichia coli (Sd-4-73).139 Ethyl Benzoate In an Ames test using S typhimurium (TA98, TA100, TA102, TA15...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_007"}
CIR_vision_codex NOAEL =1000 mg/kg/d rat oral - oral toxicity {"citation":"15; 100; 10","dose":"One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum.","effect":"bbits. C12-15 alkyl benzoate was a mild dermal irritant to rabbits at 100% and was found to be irritating in an in vitro test. In guinea pigs, methyl benzoate up to 10%, ethyl benzoate up to 8%, amyl benzoate up to 6%, C12-15 alkyl benzoate up to 10%, and isobutyl benzoate up to 2% were nonsensitizing to guinea pigs. One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum. The NOAEL was 1000 mg/kg/d. In Ames tests, methyl benzoate, ethyl benzoate, and C12-15 alkyl benzoate were not genotoxic. Isononyl benzoate adminis- tered orally at 2000 mg/kg to rats did not induce micronuclei in the polychromatic erythrocytes. Ethylhexyl benzoate was not an ocular irritant to humans in a sunscreen at 3.5%. 362S International Journal of Toxicology 31(Supplement 3)","page":21,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_008"}
CIR_vision_codex NOAEL =1230 mg/m3 rat oral 24 months inhalation toxicity {"citation":"60; (0, 1; 2","dose":"735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102;","effect":"s 60% in the control group). Sodium benzoate (0, 1%, or 2%; 735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102; 50 males, 52 females) for 18 to 24 months.73 There were no dif- ferences in mortality between groups. Necropsies were unremarkable. Alcohols. Amyl alcohol (0, 50, 150, 100 mg/kg/d) was admi- nistered orally to ASH/CSE rats (n ¼ 30; 15/sex) for 13 weeks.74 The rats were killed and necropsied 24 hours after the last treat- ment. No adverse effects were observed at any dose. The no observed adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) for the inhalation of isopropyl alcohol was 1230 mg/m3 and 3690 mg/m3, respec- tively, in Fischer 344 rats and CD-1 mice (n ¼ 10/sex) exposed (0, 1230, 3690, or 12 300 mg/m3) 6 h/d, 5 d/week for 13 weeks.75 Adverse effects observed at the LOAEL included narcosis in rats and mice, hematological changes in rats, and increased liver weights in mice. An NOAEL of 1230 mg/m3 for rats and mice was reported (based on kidney and testicular effects) in a study in which Fischer 344 rats (n ¼ 6...","page":11,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_001"}
CIR_vision_codex NOAEL =125 mg/kg/d rat oral 11 days repeated dose toxicity {"citation":"100; 150; 9","dose":"The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose.","effect":"caused transient erythema of the treated skin. The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose. NOAELs ranged from 100 to 150 mg/kg body weight/day in several studies in which mice or rats were exposed orally for 9 to 11 days to ethylhexyl alcohol by gavage, in drinking water, or in feed.80–84 Doses \u0006330 mg/kg body weight/day produced CNS depression, lacrimation, and decreased food consumption and body weights. The NOAEL was 125 mg/kg/d for male and female F344 rats and B6C3Fl mice treated daily with ethylhexyl alcohol (0, 25, 125, 250, or 500 mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aeroso...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_002"}
CIR_vision_codex NOAEL =200 mg/kg/d rat oral 13 weeks repeated dose toxicity {"citation":"13; 85; 60","dose":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male...","effect":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aerosolized 2-ethyl-l-hexanol (15, 40, or 120 mL/m3; purity 99.9%).87 The oral NOAEL for noncancer systemic toxicity end points were 200 and 50 mg/kg/d in mice and rats, respectively, exposed chronically to ethylhexyl alcohol.88 Ocular/Mucosal Irritation Methyl benzoate. Methyl benzoate (100%) was administered to the center of the cornea while the lids were retracted in rabbits (n ¼ 5).53 The eye lids were released after *1 minute. The eyes were scored after 18 to 24 hours in day- light and with staining. Methyl benzoate was given a grade 1 (iritis, slight internal congestion). Ethyl benzoate. The above experiment was repeated with ethyl benzoate (...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_003"}
CIR_vision_codex NOAEL =1 % rat oral 8 weeks developmental toxicity {"citation":"4; (0, 1; 2","dose":"There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum.","effect":"re no differences between treatment groups and controls with regard to fertility index, precoital interval, and copulatory index com- pared to controls. There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum. Histopathological examina- tion of the ovaries and testes (including the stage in the sper- matogenic cycle) did not reveal any differences between the treated and control animals. The authors concluded that 1000 mg/kg/d was the NOAEL. Benzoic Acid and Sodium Benzoate Sodium benzoate (0, 1%, 2%, 4%, or 8%; 0, 667, 1333, 1600, or 710 [sic] mg/kg/d) was administered in the feed of female Wistar rats (n ¼ 27-30) during gestation (number of days not provided).117 On day 20, 20 to 25 rats of each group were killed and necropsied. The rest were allowed to live through preg- nancy and nurse for 3 or 8 weeks and then were killed. Half of the pups were then killed at each of these times and necropsied. The 2 highest dose groups had an increase in the number of dead fetuses and resorbed embryos. The body...","page":15,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_004"}
CIR_vision_codex NOAEL =175 mg/kg rat oral gestation days 6-10 developmental toxicity {"citation":"175; 20); 21","dose":"The fetal and mater- nal NOAEL was 175 mg/kg.","effect":"delivered by Caesarean section. There were no differences in the types or incidences of abnormalities observed in any of the treatment groups compared to the control. The fetal and mater- nal NOAEL was 175 mg/kg. The study above was repeated using mice (n ¼ 20), hamsters (n ¼ 21-22; gestation days 6-10), and rabbits (n ¼ 10). Similar results were reported. In oral teratogenicity studies, benzoic acid administered on gestation days 6 to 10 increased the number of resorptions at \u000630 mg/kg/d and increased the number of fetal malformations at >600 mg/kg/d in hamsters. Results for benzoic acid were negative in 2 oral rat studies up to 500 mg/kg/d.120 Crossbred white mice (n ¼ 50; 25/sex) were orally adminis- tered benzoic acid (40 mg/kg/d) for 8 months before breed- ing.72 This was continued for 5 generations. The parental and F1","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_005"}
CIR_vision_codex NOAEL =130 mg/kg/d rat - - developmental toxicity {"citation":"131,132; 25); 2","dose":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliat...","effect":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliation, crusting, and erythema at the site of application, and doses \u00061680 mg/kg/d were associ- ated with decreased maternal weight gain. Maternal and developmental NOAEL was found to be 130 mg/kg/d in Wistar rats (n ¼ 10) orally exposed to ethylhexyl alcohol (0, 130, 650, and 1300 mg/kg/d) on days 6 to 19 of gestation.134 The pups of Charles River CD-l mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingestin...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_006"}
CIR_vision_codex NOAEL =850 mg/m3 rat oral - developmental toxicity {"citation":"50); 2; 1","dose":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity.","effect":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingesting microencapsu- lated ethylhexyl alcohol (0.13, 43, and 129 mg/kg/d; >99% pure) in the diet on days 0 to 17 of pregnancy.136,137 The NOAEL for maternal and developmental toxicity was 850 mg/m3 (160 mL/m3) aerosolized ethylhexyl alcohol in Sprague-Dawley rats (n ¼ 15) exposed (whole body) 7 h/d on gestation days 0 to 19.123 Genotoxicity Methyl Benzoate In an Ames test using Salmonella typhimurium (TA97, TA98, TA100, TA1535, and TA1537), methyl benzoate (6666 mg/ plate) was not mutagenic with or without metabolic activa- tion.138 Methyl benzoate (dose not reported) was not found to be mutagenic in Escherichia coli (Sd-4-73).139 Ethyl Benzoate In an Ames test using S typhimurium (TA98, TA100, TA102, TA15...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_007"}
CIR_vision_codex NOAEL =1000 mg/kg/d rat oral - oral toxicity {"citation":"15; 100; 10","dose":"One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum.","effect":"bbits. C12-15 alkyl benzoate was a mild dermal irritant to rabbits at 100% and was found to be irritating in an in vitro test. In guinea pigs, methyl benzoate up to 10%, ethyl benzoate up to 8%, amyl benzoate up to 6%, C12-15 alkyl benzoate up to 10%, and isobutyl benzoate up to 2% were nonsensitizing to guinea pigs. One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum. The NOAEL was 1000 mg/kg/d. In Ames tests, methyl benzoate, ethyl benzoate, and C12-15 alkyl benzoate were not genotoxic. Isononyl benzoate adminis- tered orally at 2000 mg/kg to rats did not induce micronuclei in the polychromatic erythrocytes. Ethylhexyl benzoate was not an ocular irritant to humans in a sunscreen at 3.5%. 362S International Journal of Toxicology 31(Supplement 3)","page":21,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_008"}
CIR_vision_codex NOAEL =1230 mg/m3 rat oral 24 months inhalation toxicity {"citation":"60; (0, 1; 2","dose":"735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102;","effect":"s 60% in the control group). Sodium benzoate (0, 1%, or 2%; 735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102; 50 males, 52 females) for 18 to 24 months.73 There were no dif- ferences in mortality between groups. Necropsies were unremarkable. Alcohols. Amyl alcohol (0, 50, 150, 100 mg/kg/d) was admi- nistered orally to ASH/CSE rats (n ¼ 30; 15/sex) for 13 weeks.74 The rats were killed and necropsied 24 hours after the last treat- ment. No adverse effects were observed at any dose. The no observed adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) for the inhalation of isopropyl alcohol was 1230 mg/m3 and 3690 mg/m3, respec- tively, in Fischer 344 rats and CD-1 mice (n ¼ 10/sex) exposed (0, 1230, 3690, or 12 300 mg/m3) 6 h/d, 5 d/week for 13 weeks.75 Adverse effects observed at the LOAEL included narcosis in rats and mice, hematological changes in rats, and increased liver weights in mice. An NOAEL of 1230 mg/m3 for rats and mice was reported (based on kidney and testicular effects) in a study in which Fischer 344 rats (n ¼ 6...","page":11,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_001"}
CIR_vision_codex NOAEL =125 mg/kg/d rat oral 11 days repeated dose toxicity {"citation":"100; 150; 9","dose":"The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose.","effect":"caused transient erythema of the treated skin. The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose. NOAELs ranged from 100 to 150 mg/kg body weight/day in several studies in which mice or rats were exposed orally for 9 to 11 days to ethylhexyl alcohol by gavage, in drinking water, or in feed.80–84 Doses \u0006330 mg/kg body weight/day produced CNS depression, lacrimation, and decreased food consumption and body weights. The NOAEL was 125 mg/kg/d for male and female F344 rats and B6C3Fl mice treated daily with ethylhexyl alcohol (0, 25, 125, 250, or 500 mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aeroso...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_002"}
CIR_vision_codex NOAEL =200 mg/kg/d rat oral 13 weeks repeated dose toxicity {"citation":"13; 85; 60","dose":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male...","effect":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aerosolized 2-ethyl-l-hexanol (15, 40, or 120 mL/m3; purity 99.9%).87 The oral NOAEL for noncancer systemic toxicity end points were 200 and 50 mg/kg/d in mice and rats, respectively, exposed chronically to ethylhexyl alcohol.88 Ocular/Mucosal Irritation Methyl benzoate. Methyl benzoate (100%) was administered to the center of the cornea while the lids were retracted in rabbits (n ¼ 5).53 The eye lids were released after *1 minute. The eyes were scored after 18 to 24 hours in day- light and with staining. Methyl benzoate was given a grade 1 (iritis, slight internal congestion). Ethyl benzoate. The above experiment was repeated with ethyl benzoate (...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_003"}
CIR_vision_codex NOAEL =1 % rat oral 8 weeks developmental toxicity {"citation":"4; (0, 1; 2","dose":"There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum.","effect":"re no differences between treatment groups and controls with regard to fertility index, precoital interval, and copulatory index com- pared to controls. There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum. Histopathological examina- tion of the ovaries and testes (including the stage in the sper- matogenic cycle) did not reveal any differences between the treated and control animals. The authors concluded that 1000 mg/kg/d was the NOAEL. Benzoic Acid and Sodium Benzoate Sodium benzoate (0, 1%, 2%, 4%, or 8%; 0, 667, 1333, 1600, or 710 [sic] mg/kg/d) was administered in the feed of female Wistar rats (n ¼ 27-30) during gestation (number of days not provided).117 On day 20, 20 to 25 rats of each group were killed and necropsied. The rest were allowed to live through preg- nancy and nurse for 3 or 8 weeks and then were killed. Half of the pups were then killed at each of these times and necropsied. The 2 highest dose groups had an increase in the number of dead fetuses and resorbed embryos. The body...","page":15,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_004"}
CIR_vision_codex NOAEL =175 mg/kg rat oral gestation days 6-10 developmental toxicity {"citation":"175; 20); 21","dose":"The fetal and mater- nal NOAEL was 175 mg/kg.","effect":"delivered by Caesarean section. There were no differences in the types or incidences of abnormalities observed in any of the treatment groups compared to the control. The fetal and mater- nal NOAEL was 175 mg/kg. The study above was repeated using mice (n ¼ 20), hamsters (n ¼ 21-22; gestation days 6-10), and rabbits (n ¼ 10). Similar results were reported. In oral teratogenicity studies, benzoic acid administered on gestation days 6 to 10 increased the number of resorptions at \u000630 mg/kg/d and increased the number of fetal malformations at >600 mg/kg/d in hamsters. Results for benzoic acid were negative in 2 oral rat studies up to 500 mg/kg/d.120 Crossbred white mice (n ¼ 50; 25/sex) were orally adminis- tered benzoic acid (40 mg/kg/d) for 8 months before breed- ing.72 This was continued for 5 generations. The parental and F1","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_005"}
CIR_vision_codex NOAEL =130 mg/kg/d rat - - developmental toxicity {"citation":"131,132; 25); 2","dose":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliat...","effect":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliation, crusting, and erythema at the site of application, and doses \u00061680 mg/kg/d were associ- ated with decreased maternal weight gain. Maternal and developmental NOAEL was found to be 130 mg/kg/d in Wistar rats (n ¼ 10) orally exposed to ethylhexyl alcohol (0, 130, 650, and 1300 mg/kg/d) on days 6 to 19 of gestation.134 The pups of Charles River CD-l mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingestin...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_006"}
CIR_vision_codex NOAEL =850 mg/m3 rat oral - developmental toxicity {"citation":"50); 2; 1","dose":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity.","effect":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingesting microencapsu- lated ethylhexyl alcohol (0.13, 43, and 129 mg/kg/d; >99% pure) in the diet on days 0 to 17 of pregnancy.136,137 The NOAEL for maternal and developmental toxicity was 850 mg/m3 (160 mL/m3) aerosolized ethylhexyl alcohol in Sprague-Dawley rats (n ¼ 15) exposed (whole body) 7 h/d on gestation days 0 to 19.123 Genotoxicity Methyl Benzoate In an Ames test using Salmonella typhimurium (TA97, TA98, TA100, TA1535, and TA1537), methyl benzoate (6666 mg/ plate) was not mutagenic with or without metabolic activa- tion.138 Methyl benzoate (dose not reported) was not found to be mutagenic in Escherichia coli (Sd-4-73).139 Ethyl Benzoate In an Ames test using S typhimurium (TA98, TA100, TA102, TA15...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_007"}
CIR_vision_codex NOAEL =1000 mg/kg/d rat oral - oral toxicity {"citation":"15; 100; 10","dose":"One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum.","effect":"bbits. C12-15 alkyl benzoate was a mild dermal irritant to rabbits at 100% and was found to be irritating in an in vitro test. In guinea pigs, methyl benzoate up to 10%, ethyl benzoate up to 8%, amyl benzoate up to 6%, C12-15 alkyl benzoate up to 10%, and isobutyl benzoate up to 2% were nonsensitizing to guinea pigs. One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum. The NOAEL was 1000 mg/kg/d. In Ames tests, methyl benzoate, ethyl benzoate, and C12-15 alkyl benzoate were not genotoxic. Isononyl benzoate adminis- tered orally at 2000 mg/kg to rats did not induce micronuclei in the polychromatic erythrocytes. Ethylhexyl benzoate was not an ocular irritant to humans in a sunscreen at 3.5%. 362S International Journal of Toxicology 31(Supplement 3)","page":21,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_008"}
CIR_vision_codex NOAEL =1230 mg/m3 rat oral 24 months inhalation toxicity {"citation":"60; (0, 1; 2","dose":"735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102;","effect":"s 60% in the control group). Sodium benzoate (0, 1%, or 2%; 735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102; 50 males, 52 females) for 18 to 24 months.73 There were no dif- ferences in mortality between groups. Necropsies were unremarkable. Alcohols. Amyl alcohol (0, 50, 150, 100 mg/kg/d) was admi- nistered orally to ASH/CSE rats (n ¼ 30; 15/sex) for 13 weeks.74 The rats were killed and necropsied 24 hours after the last treat- ment. No adverse effects were observed at any dose. The no observed adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) for the inhalation of isopropyl alcohol was 1230 mg/m3 and 3690 mg/m3, respec- tively, in Fischer 344 rats and CD-1 mice (n ¼ 10/sex) exposed (0, 1230, 3690, or 12 300 mg/m3) 6 h/d, 5 d/week for 13 weeks.75 Adverse effects observed at the LOAEL included narcosis in rats and mice, hematological changes in rats, and increased liver weights in mice. An NOAEL of 1230 mg/m3 for rats and mice was reported (based on kidney and testicular effects) in a study in which Fischer 344 rats (n ¼ 6...","page":11,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_001"}
CIR_vision_codex NOAEL =125 mg/kg/d rat oral 11 days repeated dose toxicity {"citation":"100; 150; 9","dose":"The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose.","effect":"caused transient erythema of the treated skin. The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose. NOAELs ranged from 100 to 150 mg/kg body weight/day in several studies in which mice or rats were exposed orally for 9 to 11 days to ethylhexyl alcohol by gavage, in drinking water, or in feed.80–84 Doses \u0006330 mg/kg body weight/day produced CNS depression, lacrimation, and decreased food consumption and body weights. The NOAEL was 125 mg/kg/d for male and female F344 rats and B6C3Fl mice treated daily with ethylhexyl alcohol (0, 25, 125, 250, or 500 mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aeroso...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_002"}
CIR_vision_codex NOAEL =200 mg/kg/d rat oral 13 weeks repeated dose toxicity {"citation":"13; 85; 60","dose":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male...","effect":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aerosolized 2-ethyl-l-hexanol (15, 40, or 120 mL/m3; purity 99.9%).87 The oral NOAEL for noncancer systemic toxicity end points were 200 and 50 mg/kg/d in mice and rats, respectively, exposed chronically to ethylhexyl alcohol.88 Ocular/Mucosal Irritation Methyl benzoate. Methyl benzoate (100%) was administered to the center of the cornea while the lids were retracted in rabbits (n ¼ 5).53 The eye lids were released after *1 minute. The eyes were scored after 18 to 24 hours in day- light and with staining. Methyl benzoate was given a grade 1 (iritis, slight internal congestion). Ethyl benzoate. The above experiment was repeated with ethyl benzoate (...","page":13,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_003"}
CIR_vision_codex NOAEL =1 % rat oral 8 weeks developmental toxicity {"citation":"4; (0, 1; 2","dose":"There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum.","effect":"re no differences between treatment groups and controls with regard to fertility index, precoital interval, and copulatory index com- pared to controls. There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum. Histopathological examina- tion of the ovaries and testes (including the stage in the sper- matogenic cycle) did not reveal any differences between the treated and control animals. The authors concluded that 1000 mg/kg/d was the NOAEL. Benzoic Acid and Sodium Benzoate Sodium benzoate (0, 1%, 2%, 4%, or 8%; 0, 667, 1333, 1600, or 710 [sic] mg/kg/d) was administered in the feed of female Wistar rats (n ¼ 27-30) during gestation (number of days not provided).117 On day 20, 20 to 25 rats of each group were killed and necropsied. The rest were allowed to live through preg- nancy and nurse for 3 or 8 weeks and then were killed. Half of the pups were then killed at each of these times and necropsied. The 2 highest dose groups had an increase in the number of dead fetuses and resorbed embryos. The body...","page":15,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_004"}
CIR_vision_codex NOAEL =175 mg/kg rat oral gestation days 6-10 developmental toxicity {"citation":"175; 20); 21","dose":"The fetal and mater- nal NOAEL was 175 mg/kg.","effect":"delivered by Caesarean section. There were no differences in the types or incidences of abnormalities observed in any of the treatment groups compared to the control. The fetal and mater- nal NOAEL was 175 mg/kg. The study above was repeated using mice (n ¼ 20), hamsters (n ¼ 21-22; gestation days 6-10), and rabbits (n ¼ 10). Similar results were reported. In oral teratogenicity studies, benzoic acid administered on gestation days 6 to 10 increased the number of resorptions at \u000630 mg/kg/d and increased the number of fetal malformations at >600 mg/kg/d in hamsters. Results for benzoic acid were negative in 2 oral rat studies up to 500 mg/kg/d.120 Crossbred white mice (n ¼ 50; 25/sex) were orally adminis- tered benzoic acid (40 mg/kg/d) for 8 months before breed- ing.72 This was continued for 5 generations. The parental and F1","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_005"}
CIR_vision_codex NOAEL =130 mg/kg/d rat - - developmental toxicity {"citation":"131,132; 25); 2","dose":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliat...","effect":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliation, crusting, and erythema at the site of application, and doses \u00061680 mg/kg/d were associ- ated with decreased maternal weight gain. Maternal and developmental NOAEL was found to be 130 mg/kg/d in Wistar rats (n ¼ 10) orally exposed to ethylhexyl alcohol (0, 130, 650, and 1300 mg/kg/d) on days 6 to 19 of gestation.134 The pups of Charles River CD-l mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingestin...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_006"}
CIR_vision_codex NOAEL =850 mg/m3 rat oral - developmental toxicity {"citation":"50); 2; 1","dose":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity.","effect":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingesting microencapsu- lated ethylhexyl alcohol (0.13, 43, and 129 mg/kg/d; >99% pure) in the diet on days 0 to 17 of pregnancy.136,137 The NOAEL for maternal and developmental toxicity was 850 mg/m3 (160 mL/m3) aerosolized ethylhexyl alcohol in Sprague-Dawley rats (n ¼ 15) exposed (whole body) 7 h/d on gestation days 0 to 19.123 Genotoxicity Methyl Benzoate In an Ames test using Salmonella typhimurium (TA97, TA98, TA100, TA1535, and TA1537), methyl benzoate (6666 mg/ plate) was not mutagenic with or without metabolic activa- tion.138 Methyl benzoate (dose not reported) was not found to be mutagenic in Escherichia coli (Sd-4-73).139 Ethyl Benzoate In an Ames test using S typhimurium (TA98, TA100, TA102, TA15...","page":16,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_007"}
CIR_vision_codex NOAEL =1000 mg/kg/d rat oral - oral toxicity {"citation":"15; 100; 10","dose":"One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum.","effect":"bbits. C12-15 alkyl benzoate was a mild dermal irritant to rabbits at 100% and was found to be irritating in an in vitro test. In guinea pigs, methyl benzoate up to 10%, ethyl benzoate up to 8%, amyl benzoate up to 6%, C12-15 alkyl benzoate up to 10%, and isobutyl benzoate up to 2% were nonsensitizing to guinea pigs. One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum. The NOAEL was 1000 mg/kg/d. In Ames tests, methyl benzoate, ethyl benzoate, and C12-15 alkyl benzoate were not genotoxic. Isononyl benzoate adminis- tered orally at 2000 mg/kg to rats did not induce micronuclei in the polychromatic erythrocytes. Ethylhexyl benzoate was not an ocular irritant to humans in a sunscreen at 3.5%. 362S International Journal of Toxicology 31(Supplement 3)","page":21,"pdf":"PRS578.pdf","row_type":"noael_study","study_id":"PRS578_noael_008"}
NTP_ICE_acute_oral 5 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_oral LD50 =3400 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_11548; row=8890; data_type=In Vivo; mixture=Chemical; chemical_name=Methyl benzoate; preferred_name=Methyl benzoate; dtxsid=DTXSID5025572; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID5025572; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =2000 mg/kg bw Rat oral acute Rat Acute Oral Toxicity record_id=acute_oral_11546; row=8891; data_type=In Vivo; mixture=Chemical; chemical_name=Methyl benzoate; preferred_name=Methyl benzoate; dtxsid=DTXSID5025572; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID5025572; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =1625 mg/kg bw Rat oral acute Rat Acute Oral Toxicity ECHA ChemProp (undated); record_id=acute_oral_11542; row=8893; data_type=In Vivo; mixture=Chemical; chemical_name=Methyl benzoate; preferred_name=Methyl benzoate; dtxsid=DTXSID5025572; url=https://echa.europa.eu/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID5025572; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 =1177 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_11540; row=8894; data_type=In Vivo; mixture=Chemical; chemical_name=Methyl benzoate; preferred_name=Methyl benzoate; dtxsid=DTXSID5025572; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID5025572; source_file=acute_oral.xlsx
NTP_ICE_acute_oral LD50 <4000 mg/kg bw Rat oral acute Rat Acute Oral Toxicity record_id=acute_oral_11550; row=8895; data_type=In Vivo; mixture=Chemical; chemical_name=Methyl benzoate; preferred_name=Methyl benzoate; dtxsid=DTXSID5025572; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID5025572; source_file=acute_oral.xlsx
NTP_ICE_skin_sensitization 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_skin_sensitization Incidence of positive responses 0 % Human Dermal - In Vivo; HPPT2020WIP; Human Maximization Test sheet=Data_invivo; excel_row=11108; Record_ID=skin_sensitization_invivo_2430; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=4.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025572; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=0; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1970: report to RIFM|RIFM 1970; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Opdyke 1974; Not available; 10.1016/0015-6264(74)90193-X; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025572
NTP_ICE_skin_sensitization Induction dose per skin area 2592 ug/cm2 Human Dermal - In Vivo; HPPT2020WIP; Human Maximization Test sheet=Data_invivo; excel_row=11107; Record_ID=skin_sensitization_invivo_2430; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=4.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025572; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=2592; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1970: report to RIFM|RIFM 1970; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Opdyke 1974; Not available; 10.1016/0015-6264(74)90193-X; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025572
NTP_ICE_skin_sensitization Relative reliability score 3 unitless Human Dermal - In Vivo; HPPT2020WIP; Human Maximization Test sheet=Data_invivo; excel_row=11110; Record_ID=skin_sensitization_invivo_2430; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=4.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025572; Assay=Human Maximization Test; Endpoint=Relative reliability score; Response=3; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=Kligman 1970: report to RIFM|RIFM 1970; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Opdyke 1974; Not available; 10.1016/0015-6264(74)90193-X; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025572; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025572
ToxValDB_GESTIS_DNEL 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL systemic =39.3 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:15633308:-:--; 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_490727a2417859f8553738d9d3221d1b
UnifiedCodex:CIR:beta.noael_studies 8 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:CIR:beta.noael_studies developmental toxicity 1 % rat oral 8 weeks developmental toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=1; DOSE=There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum.; EFFECT=re no differences between treatment groups and controls with regard to fertility index, precoital interval, and copulatory index com- pared to controls. There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum. Histopathological examina- tion of the ovaries and testes (including the stage in the sper- matogenic cycle) did not reveal any differences between the treated and control animals. The authors concluded that 1000 mg/kg/d was the NOAEL. Benzoic Acid and Sodium Benzoate Sodium benzoate (0, 1%, 2%, 4%, or 8%; 0, 667, 1333, 1600, or 710 [sic] mg/kg/d) was administered in the feed of female Wistar rats (n ¼ 27-30) during gestation (number of days not provided).117 On day 20, 20 to 25 rats of each group were killed and necropsied. The rest were allowed to live through preg- nancy and nurse for 3 or 8 weeks and then were killed. Half of the pups were then killed at each of these times and necropsied. The 2 highest dose groups had an increase in the number of dead fetuses and resorbed embryos. The body...; CITATION=4; (0, 1; 2; CITATION_NUMBERS=[4,1,2]; REFERENCE=4; (0, 1; 2; DETAILS_JSON={"cas_number":"93-58-3","citation":"4; (0, 1; 2","dose":"There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum.","duration":"8 weeks","effect":"re no differences between treatment groups and controls with regard to fertility index, precoital interval, and copulatory index com- pared to controls. There was a slight decrease in mean pup weights and consequently in litter weights in high-dose females at birth and on day 4 postpartum. Histopathological examina- tion of the ovaries and testes (including the stage in the sper- matogenic cycle) did not reveal any differences between the treated and control animals. The authors concluded that 1000 mg/kg/d was the NOAEL. Benzoic Acid and Sodium Benzoate Sodium benzoate (0, 1%, 2%, 4%, or 8%; 0, 667, 1333, 1600, or 710 [sic] mg/kg/d) was administered in the feed of female Wistar rats (n ¼ 27-30) during gestation (number of days not provided).117 On day 20, 20 to 25 rats of each group were killed and necropsied. The rest were allowed to live through preg- nancy and nurse for 3 or 8 weeks and then were killed. Half of the pups were then killed at each of these times and necropsied. The 2 highest dose groups had an increase in the number of dead fetuses and resorbed embryos. The body...","endpoint":"developmental toxicity","ingredient":"Alkyl Benzoates","loael_value":"","noael_unit":"%","noael_value":"1","page":15,"route":"oral","species":"rat","study_id":"PRS578_noael_004"}
UnifiedCodex:CIR:beta.noael_studies developmental toxicity 175 mg/kg rat oral gestation days 6-10 developmental toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=175; DOSE=The fetal and mater- nal NOAEL was 175 mg/kg.; EFFECT=delivered by Caesarean section. There were no differences in the types or incidences of abnormalities observed in any of the treatment groups compared to the control. The fetal and mater- nal NOAEL was 175 mg/kg. The study above was repeated using mice (n ¼ 20), hamsters (n ¼ 21-22; gestation days 6-10), and rabbits (n ¼ 10). Similar results were reported. In oral teratogenicity studies, benzoic acid administered on gestation days 6 to 10 increased the number of resorptions at 30 mg/kg/d and increased the number of fetal malformations at >600 mg/kg/d in hamsters. Results for benzoic acid were negative in 2 oral rat studies up to 500 mg/kg/d.120 Crossbred white mice (n ¼ 50; 25/sex) were orally adminis- tered benzoic acid (40 mg/kg/d) for 8 months before breed- ing.72 This was continued for 5 generations. The parental and F1; CITATION=175; 20); 21; CITATION_NUMBERS=[175,20,21]; REFERENCE=175; 20); 21; DETAILS_JSON={"cas_number":"93-58-3","citation":"175; 20); 21","dose":"The fetal and mater- nal NOAEL was 175 mg/kg.","duration":"gestation days 6-10","effect":"delivered by Caesarean section. There were no differences in the types or incidences of abnormalities observed in any of the treatment groups compared to the control. The fetal and mater- nal NOAEL was 175 mg/kg. The study above was repeated using mice (n ¼ 20), hamsters (n ¼ 21-22; gestation days 6-10), and rabbits (n ¼ 10). Similar results were reported. In oral teratogenicity studies, benzoic acid administered on gestation days 6 to 10 increased the number of resorptions at \u000630 mg/kg/d and increased the number of fetal malformations at >600 mg/kg/d in hamsters. Results for benzoic acid were negative in 2 oral rat studies up to 500 mg/kg/d.120 Crossbred white mice (n ¼ 50; 25/sex) were orally adminis- tered benzoic acid (40 mg/kg/d) for 8 months before breed- ing.72 This was continued for 5 generations. The parental and F1","endpoint":"developmental toxicity","ingredient":"Alkyl Benzoates","loael_value":"","noael_unit":"mg/kg","noael_value":"175","page":16,"route":"oral","species":"rat","study_id":"PRS578_noael_005"}
UnifiedCodex:CIR:beta.noael_studies developmental toxicity 130 mg/kg/d rat - - developmental toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=130; DOSE=not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at 840 mg/ kg/d included persistent exfoliat...; EFFECT=not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at 840 mg/ kg/d included persistent exfoliation, crusting, and erythema at the site of application, and doses 1680 mg/kg/d were associ- ated with decreased maternal weight gain. Maternal and developmental NOAEL was found to be 130 mg/kg/d in Wistar rats (n ¼ 10) orally exposed to ethylhexyl alcohol (0, 130, 650, and 1300 mg/kg/d) on days 6 to 19 of gestation.134 The pups of Charles River CD-l mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingestin...; CITATION=131,132; 25); 2; CITATION_NUMBERS=[131,132,25,2]; REFERENCE=131,132; 25); 2; DETAILS_JSON={"cas_number":"93-58-3","citation":"131,132; 25); 2","dose":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliat...","duration":"","effect":"not affected.131,132 No treatment-related increases in the incidences of malfor- mations or variations were found in F344 rats (n ¼ 25) der- mally exposed (clipped dorsal skin) to 2-ethyl-1-1hexanol (0, 252, 420, 840, 1680 or 2520 mg/kg/d, 6 h/d, occlusive) on gestation days 6 to 15.41,124,133 Maternal effects at \u0006840 mg/ kg/d included persistent exfoliation, crusting, and erythema at the site of application, and doses \u00061680 mg/kg/d were associ- ated with decreased maternal weight gain. Maternal and developmental NOAEL was found to be 130 mg/kg/d in Wistar rats (n ¼ 10) orally exposed to ethylhexyl alcohol (0, 130, 650, and 1300 mg/kg/d) on days 6 to 19 of gestation.134 The pups of Charles River CD-l mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingestin...","endpoint":"developmental toxicity","ingredient":"Alkyl Benzoates","loael_value":"","noael_unit":"mg/kg/d","noael_value":"130","page":16,"route":"","species":"rat","study_id":"PRS578_noael_006"}
UnifiedCodex:CIR:beta.noael_studies developmental toxicity 850 mg/m3 rat oral - developmental toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=850; DOSE=mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity.; EFFECT=mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingesting microencapsu- lated ethylhexyl alcohol (0.13, 43, and 129 mg/kg/d; >99% pure) in the diet on days 0 to 17 of pregnancy.136,137 The NOAEL for maternal and developmental toxicity was 850 mg/m3 (160 mL/m3) aerosolized ethylhexyl alcohol in Sprague-Dawley rats (n ¼ 15) exposed (whole body) 7 h/d on gestation days 0 to 19.123 Genotoxicity Methyl Benzoate In an Ames test using Salmonella typhimurium (TA97, TA98, TA100, TA1535, and TA1537), methyl benzoate (6666 mg/ plate) was not mutagenic with or without metabolic activa- tion.138 Methyl benzoate (dose not reported) was not found to be mutagenic in Escherichia coli (Sd-4-73).139 Ethyl Benzoate In an Ames test using S typhimurium (TA98, TA100, TA102, TA15...; CITATION=50); 2; 1; CITATION_NUMBERS=[50,2,1]; REFERENCE=50); 2; 1; DETAILS_JSON={"cas_number":"93-58-3","citation":"50); 2; 1","dose":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity.","duration":"","effect":"mice (n ¼ 50) exposed to 2- ethyl-1-1hexanol (1,525 mg/kg/d in corn oil) on days 7 to 14 of pregnancy exhibited reduced viability and body weights on day 3 of lactation.135 Maternal effects included decreased fertility and pregnancy indexes, body weights, and other signs of toxicity. No maternal, reproductive, or developmental toxicities were found in CD-1 Swiss mice (n ¼ 28) ingesting microencapsu- lated ethylhexyl alcohol (0.13, 43, and 129 mg/kg/d; >99% pure) in the diet on days 0 to 17 of pregnancy.136,137 The NOAEL for maternal and developmental toxicity was 850 mg/m3 (160 mL/m3) aerosolized ethylhexyl alcohol in Sprague-Dawley rats (n ¼ 15) exposed (whole body) 7 h/d on gestation days 0 to 19.123 Genotoxicity Methyl Benzoate In an Ames test using Salmonella typhimurium (TA97, TA98, TA100, TA1535, and TA1537), methyl benzoate (6666 mg/ plate) was not mutagenic with or without metabolic activa- tion.138 Methyl benzoate (dose not reported) was not found to be mutagenic in Escherichia coli (Sd-4-73).139 Ethyl Benzoate In an Ames test using S typhimurium (TA98, TA100, TA102, TA15...","endpoint":"developmental toxicity","ingredient":"Alkyl Benzoates","loael_value":"","noael_unit":"mg/m3","noael_value":"850","page":16,"route":"oral","species":"rat","study_id":"PRS578_noael_007"}
UnifiedCodex:CIR:beta.noael_studies inhalation toxicity 1230 mg/m3 rat oral 24 months inhalation toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=1230; DOSE=735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102;; LOAEL_VALUE=1230 mg/m3; EFFECT=s 60% in the control group). Sodium benzoate (0, 1%, or 2%; 735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102; 50 males, 52 females) for 18 to 24 months.73 There were no dif- ferences in mortality between groups. Necropsies were unremarkable. Alcohols. Amyl alcohol (0, 50, 150, 100 mg/kg/d) was admi- nistered orally to ASH/CSE rats (n ¼ 30; 15/sex) for 13 weeks.74 The rats were killed and necropsied 24 hours after the last treat- ment. No adverse effects were observed at any dose. The no observed adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) for the inhalation of isopropyl alcohol was 1230 mg/m3 and 3690 mg/m3, respec- tively, in Fischer 344 rats and CD-1 mice (n ¼ 10/sex) exposed (0, 1230, 3690, or 12 300 mg/m3) 6 h/d, 5 d/week for 13 weeks.75 Adverse effects observed at the LOAEL included narcosis in rats and mice, hematological changes in rats, and increased liver weights in mice. An NOAEL of 1230 mg/m3 for rats and mice was reported (based on kidney and testicular effects) in a study in which Fischer 344 rats (n ¼ 6...; CITATION=60; (0, 1; 2; CITATION_NUMBERS=[60,1,2]; REFERENCE=60; (0, 1; 2; DETAILS_JSON={"cas_number":"93-58-3","citation":"60; (0, 1; 2","dose":"735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102;","duration":"24 months","effect":"s 60% in the control group). Sodium benzoate (0, 1%, or 2%; 735 or 880 mg/kg/d) was incorporated into the feed of Fischer 344 rats (n ¼ 102; 50 males, 52 females) for 18 to 24 months.73 There were no dif- ferences in mortality between groups. Necropsies were unremarkable. Alcohols. Amyl alcohol (0, 50, 150, 100 mg/kg/d) was admi- nistered orally to ASH/CSE rats (n ¼ 30; 15/sex) for 13 weeks.74 The rats were killed and necropsied 24 hours after the last treat- ment. No adverse effects were observed at any dose. The no observed adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) for the inhalation of isopropyl alcohol was 1230 mg/m3 and 3690 mg/m3, respec- tively, in Fischer 344 rats and CD-1 mice (n ¼ 10/sex) exposed (0, 1230, 3690, or 12 300 mg/m3) 6 h/d, 5 d/week for 13 weeks.75 Adverse effects observed at the LOAEL included narcosis in rats and mice, hematological changes in rats, and increased liver weights in mice. An NOAEL of 1230 mg/m3 for rats and mice was reported (based on kidney and testicular effects) in a study in which Fischer 344 rats (n ¼ 6...","endpoint":"inhalation toxicity","ingredient":"Alkyl Benzoates","loael_value":"1230 mg/m3","noael_unit":"mg/m3","noael_value":"1230","page":11,"route":"oral","species":"rat","study_id":"PRS578_noael_001"}
UnifiedCodex:CIR:beta.noael_studies oral toxicity 1000 mg/kg/d rat oral - oral toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=1000; DOSE=One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum.; EFFECT=bbits. C12-15 alkyl benzoate was a mild dermal irritant to rabbits at 100% and was found to be irritating in an in vitro test. In guinea pigs, methyl benzoate up to 10%, ethyl benzoate up to 8%, amyl benzoate up to 6%, C12-15 alkyl benzoate up to 10%, and isobutyl benzoate up to 2% were nonsensitizing to guinea pigs. One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum. The NOAEL was 1000 mg/kg/d. In Ames tests, methyl benzoate, ethyl benzoate, and C12-15 alkyl benzoate were not genotoxic. Isononyl benzoate adminis- tered orally at 2000 mg/kg to rats did not induce micronuclei in the polychromatic erythrocytes. Ethylhexyl benzoate was not an ocular irritant to humans in a sunscreen at 3.5%. 362S International Journal of Toxicology 31(Supplement 3); CITATION=15; 100; 10; CITATION_NUMBERS=[15,100,10]; REFERENCE=15; 100; 10; DETAILS_JSON={"cas_number":"93-58-3","citation":"15; 100; 10","dose":"One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum.","duration":"","effect":"bbits. C12-15 alkyl benzoate was a mild dermal irritant to rabbits at 100% and was found to be irritating in an in vitro test. In guinea pigs, methyl benzoate up to 10%, ethyl benzoate up to 8%, amyl benzoate up to 6%, C12-15 alkyl benzoate up to 10%, and isobutyl benzoate up to 2% were nonsensitizing to guinea pigs. One oral study of the related compound isononyl benzoate resulted in a slight decrease in mean pup weight and conse- quently in litter weight in high-dose females at birth and on day 4 postpartum. The NOAEL was 1000 mg/kg/d. In Ames tests, methyl benzoate, ethyl benzoate, and C12-15 alkyl benzoate were not genotoxic. Isononyl benzoate adminis- tered orally at 2000 mg/kg to rats did not induce micronuclei in the polychromatic erythrocytes. Ethylhexyl benzoate was not an ocular irritant to humans in a sunscreen at 3.5%. 362S International Journal of Toxicology 31(Supplement 3)","endpoint":"oral toxicity","ingredient":"Alkyl Benzoates","loael_value":"","noael_unit":"mg/kg/d","noael_value":"1000","page":21,"route":"oral","species":"rat","study_id":"PRS578_noael_008"}
UnifiedCodex:CIR:beta.noael_studies repeated dose toxicity 125 mg/kg/d rat oral 11 days repeated dose toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=125; DOSE=The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose.; EFFECT=caused transient erythema of the treated skin. The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose. NOAELs ranged from 100 to 150 mg/kg body weight/day in several studies in which mice or rats were exposed orally for 9 to 11 days to ethylhexyl alcohol by gavage, in drinking water, or in feed.80–84 Doses 330 mg/kg body weight/day produced CNS depression, lacrimation, and decreased food consumption and body weights. The NOAEL was 125 mg/kg/d for male and female F344 rats and B6C3Fl mice treated daily with ethylhexyl alcohol (0, 25, 125, 250, or 500 mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses 60 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aeroso...; CITATION=100; 150; 9; CITATION_NUMBERS=[100,150,9]; REFERENCE=100; 150; 9; DETAILS_JSON={"cas_number":"93-58-3","citation":"100; 150; 9","dose":"The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose.","duration":"11 days","effect":"caused transient erythema of the treated skin. The female rats exhibited elevated serum triglycerides at both doses and decreased peripheral blood lymphocytes and spleen weights at the high dose. NOAELs ranged from 100 to 150 mg/kg body weight/day in several studies in which mice or rats were exposed orally for 9 to 11 days to ethylhexyl alcohol by gavage, in drinking water, or in feed.80–84 Doses \u0006330 mg/kg body weight/day produced CNS depression, lacrimation, and decreased food consumption and body weights. The NOAEL was 125 mg/kg/d for male and female F344 rats and B6C3Fl mice treated daily with ethylhexyl alcohol (0, 25, 125, 250, or 500 mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aeroso...","endpoint":"repeated dose toxicity","ingredient":"Alkyl Benzoates","loael_value":"","noael_unit":"mg/kg/d","noael_value":"125","page":13,"route":"oral","species":"rat","study_id":"PRS578_noael_002"}
UnifiedCodex:CIR:beta.noael_studies repeated dose toxicity 200 mg/kg/d rat oral 13 weeks repeated dose toxicity SOURCE_SUBDIR=PRS578; REPORT_TITLE=Safety Assessment of Alkyl Benzoates as Used in Cosmetics Lillian C. ’Becker1, Wilma F. Bergfeld2, Donald V. Belsito2, Ronald A. Hill2, Curtis D. Klaassen2, Daniel Liebler2, James G. Marks Jr2, Ronald C. Shank2, Thomas J. Slaga2, Paul W. Sn; OPINION_NUMBER=PRS578; COMMITTEE=Cosmetic Ingredient Review Expert Panel; REPORT_DATE=4 In 2005; VALUE_TEXT=200; 50; DOSE=mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses 60 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male...; EFFECT=mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses 60 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aerosolized 2-ethyl-l-hexanol (15, 40, or 120 mL/m3; purity 99.9%).87 The oral NOAEL for noncancer systemic toxicity end points were 200 and 50 mg/kg/d in mice and rats, respectively, exposed chronically to ethylhexyl alcohol.88 Ocular/Mucosal Irritation Methyl benzoate. Methyl benzoate (100%) was administered to the center of the cornea while the lids were retracted in rabbits (n ¼ 5).53 The eye lids were released after *1 minute. The eyes were scored after 18 to 24 hours in day- light and with staining. Methyl benzoate was given a grade 1 (iritis, slight internal congestion). Ethyl benzoate. The above experiment was repeated with ethyl benzoate (...; CITATION=13; 85; 60; CITATION_NUMBERS=[13,85,60]; REFERENCE=13; 85; 60; DETAILS_JSON={"cas_number":"93-58-3","citation":"13; 85; 60","dose":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male...","duration":"13 weeks","effect":"mg/kg/d) by gavage for 13 weeks.85 Multiple in vitro and in vivo short-term repeated dose studies showed that ethylhexyl alcohol is a peroxisome prolif- erator and liver enzyme inducer in mice and rats, and that doses \u000660 mg/kg body weight/day can cause these effects and alpha- 2u-nephropathy in male rats.86 No local or systemic effects were found in male and female Wistar rats (n ¼ 20; 10/sex) exposed 6 h/d, 5 days/week, for 90 days to aerosolized 2-ethyl-l-hexanol (15, 40, or 120 mL/m3; purity 99.9%).87 The oral NOAEL for noncancer systemic toxicity end points were 200 and 50 mg/kg/d in mice and rats, respectively, exposed chronically to ethylhexyl alcohol.88 Ocular/Mucosal Irritation Methyl benzoate. Methyl benzoate (100%) was administered to the center of the cornea while the lids were retracted in rabbits (n ¼ 5).53 The eye lids were released after *1 minute. The eyes were scored after 18 to 24 hours in day- light and with staining. Methyl benzoate was given a grade 1 (iritis, slight internal congestion). Ethyl benzoate. The above experiment was repeated with ethyl benzoate (...","endpoint":"repeated dose toxicity","ingredient":"Alkyl Benzoates","loael_value":"","noael_unit":"mg/kg/d","noael_value":"200; 50","page":13,"route":"oral","species":"rat","study_id":"PRS578_noael_003"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier 6618K1VJ9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"6618K1VJ9T"}
openFDA substances FDA UNII substance identifier 6618K1VJ9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"6618K1VJ9T"}
openFDA substances FDA UNII substance identifier 6618K1VJ9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"6618K1VJ9T"}
openFDA substances FDA UNII substance identifier 6618K1VJ9T UNII - - - chemical {"approval_status":null,"molecular_formula":"C8H8O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"6618K1VJ9T"}