codes ............................................... 10, Butylparaben

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=8% in the diet for 12 weeks resulted in 100% mortality before the end of the treatment period in males given such a high dose.; EFFECT=% orally in the diet. Intakes for animals on the 2% diets averaged from 0.9 to 1.2g/kg/day. While the intake of rats on the 8% diets averaged from 5.5 to 5.9 g/kg/day. 8% in the diet for 12 weeks resulted in 100% mortality before the end of the treatment period in males given such a high dose. Females also had many early deaths and showed myocardial depression. The high-dose butylparaben diet also produced a significant decrease in body weight for all animals, while the lower 2% dose produced no toxic effects. The NOEL from this study was in the range 900-1200 mg/kg bw/day (Matthews et al., 1956). In Fisher-344 weanling rats (n=5 male per dose), a diet of 4% butylparaben for nine days acted entirely on the pre-fundic region of the forestomach epithelium adjacent to the fundic mucosa, while oral intubation of butylparaben (0.25 or 50 mg/kg) daily for 13-15 weeks produced no toxic effects (Rodrigues et al., 1986). DNA methylation was investigated within the context of an OECD 407 Test Guideline 28- day study. Male Sprague Dawley; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"8% in the diet for 12 weeks resulted in 100% mortality before the end of the treatment period in males given such a high dose.","duration":"12 weeks","effect":"% orally in the diet. Intakes for animals on the 2% diets averaged from 0.9 to 1.2g/kg/day. While the intake of rats on the 8% diets averaged from 5.5 to 5.9 g/kg/day. 8% in the diet for 12 weeks resulted in 100% mortality before the end of the treatment period in males given such a high dose. Females also had many early deaths and showed myocardial depression. The high-dose butylparaben diet also produced a significant decrease in body weight for all animals, while the lower 2% dose produced no toxic effects. The NOEL from this study was in the range 900-1200 mg/kg bw/day (Matthews et al., 1956). In Fisher-344 weanling rats (n=5 male per dose), a diet of 4% butylparaben for nine days acted entirely on the pre-fundic region of the forestomach epithelium adjacent to the fundic mucosa, while oral intubation of butylparaben (0.25 or 50 mg/kg) daily for 13-15 weeks produced no toxic effects (Rodrigues et al., 1986). DNA methylation was investigated within the context of an OECD 407 Test Guideline 28- day study. Male Sprague Dawley","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"2","page":36,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_005"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==2; DOSE=2 mg/ kg bw /day, n= 6.; EFFECT=weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) Kang et al., 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben (purity not reported) Wistar rats Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) Fisher et al., 1999 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"2 mg/ kg bw /day, n= 6.","duration":"","effect":"weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) Kang et al., 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben (purity not reported) Wistar rats Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) Fisher et al., 1999 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"=2","page":96,"route":"","species":"rat","study_id":"sccs_o_275_noael_037"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 2; DOSE=Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day | Fisher et al.; EFFECT=Unlabeled table on page 41: Butylparaben | Wistar rat Non GLP Non guideline | Effects of neonatal exposure to butylparaben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2-18). Other substances tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol. | Effects of neonatal exposure to butylparaben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2- 18). Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day | Fisher et al. 1999; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day | Fisher et al.","duration":"17 days","effect":"Unlabeled table on page 41: Butylparaben | Wistar rat Non GLP Non guideline | Effects of neonatal exposure to butylparaben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2-18). Other substances tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol. | Effects of neonatal exposure to butylparaben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2- 18). Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day | Fisher et al. 1999","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 2","page":41,"route":"","species":"rat","study_id":"sccs_o_275_noael_051"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); EFFECT=Unlabeled table on page 96: Butyl- paraben (purity not reported) | Wistar rats | Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","duration":"","effect":"Unlabeled table on page 96: Butyl- paraben (purity not reported) | Wistar rats | Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/ kg bw /day","noael_value":"2","page":96,"route":"","species":"rat","study_id":"sccs_o_275_noael_062"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==2; DOSE=2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); EFFECT=Unlabeled table on page 96: Butyl- paraben (purity not reported) | Wistar rats | Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","duration":"","effect":"Unlabeled table on page 96: Butyl- paraben (purity not reported) | Wistar rats | Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. | Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) | Fisher et al., 1999 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"=2","page":96,"route":"","species":"rat","study_id":"sccs_o_275_noael_064"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 10; DOSE=PD 22: higher number of TEBs in two highest dose groups (100, 500 mg/kg bw/day).; EFFECT=ps. Genes (cell markers, receptors (Ar, Fshr, Lhr), steroidogenesis) were investigated in testis PD 16 and in adulthood. Down regulation of Cyp19a1 in all exposure groups was seen on PD16. Not other effects seen on gene expression. Hormone levels (estradiol measured PD16 males and PD 22 females): no effect. Mammary gland was investigated in females. PD 22: higher number of TEBs in two highest dose groups (100, 500 mg/kg bw/day). Increased outgrowth towards the lymphnode in 100 mg/kg bw/day. Adult: no clear effects NOAEL = 10 mg/kg bw/day (decrease in AGD) Boberg et al., 2016 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"PD 22: higher number of TEBs in two highest dose groups (100, 500 mg/kg bw/day).","duration":"","effect":"ps. Genes (cell markers, receptors (Ar, Fshr, Lhr), steroidogenesis) were investigated in testis PD 16 and in adulthood. Down regulation of Cyp19a1 in all exposure groups was seen on PD16. Not other effects seen on gene expression. Hormone levels (estradiol measured PD16 males and PD 22 females): no effect. Mammary gland was investigated in females. PD 22: higher number of TEBs in two highest dose groups (100, 500 mg/kg bw/day). Increased outgrowth towards the lymphnode in 100 mg/kg bw/day. Adult: no clear effects NOAEL = 10 mg/kg bw/day (decrease in AGD) Boberg et al., 2016 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 10","page":99,"route":"","species":"","study_id":"sccs_o_275_noael_040"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 10; DOSE=202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 105 effects seen at both 100 and 1000 mg/kg bw/day.; EFFECT=SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 105 effects seen at both 100 and 1000 mg/kg bw/day. Ovarian gene expression of ERα and Star was upregulated (100 mg/kg bw/day. Weight of adrenal gland, hypothalamus, pituitary, ovary, uterus were all affected at different ages. NOAEL = 10 mg/kg bw/day (estrous cycling); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 105 effects seen at both 100 and 1000 mg/kg bw/day.","duration":"","effect":"SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 105 effects seen at both 100 and 1000 mg/kg bw/day. Ovarian gene expression of ERα and Star was upregulated (100 mg/kg bw/day. Weight of adrenal gland, hypothalamus, pituitary, ovary, uterus were all affected at different ages. NOAEL = 10 mg/kg bw/day (estrous cycling)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 10","page":105,"route":"","species":"","study_id":"sccs_o_275_noael_043"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 10; DOSE=0, 10, 50, 100 mg/kg bw, n ≥ 5.; EFFECT=Unlabeled table on page 103: Butylparab en | Swiss albino mice | Effects on uterus, subcutaneous , 7 days (adult). Dose: 0, 10, 50, 100 mg/kg bw, n ≥ 5. Estradiol used as positive control (0.001mg/kg bw) | Uterine glands ↑ Uterine weight ↑ Endometrial and mycometrium thickness ↑ Total tissue protein ↑ Histological alterations LOEL = 10 mg/kg bw (uterine effects) | Goswami & Kalita 2016 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"0, 10, 50, 100 mg/kg bw, n ≥ 5.","duration":"7 days","effect":"Unlabeled table on page 103: Butylparab en | Swiss albino mice | Effects on uterus, subcutaneous , 7 days (adult). Dose: 0, 10, 50, 100 mg/kg bw, n ≥ 5. Estradiol used as positive control (0.001mg/kg bw) | Uterine glands ↑ Uterine weight ↑ Endometrial and mycometrium thickness ↑ Total tissue protein ↑ Histological alterations LOEL = 10 mg/kg bw (uterine effects) | Goswami & Kalita 2016 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 10","page":103,"route":"","species":"mouse","study_id":"sccs_o_275_noael_071"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=26.9; DOSE=1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group.; EFFECT=e/testis/spe rm) Garcia et al., 2017 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben CF1 mice Pharmacokineti c effects E2, subcutaneous (one injection). Dose: 1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. Urinary estradiol concentrations were measured (both sexes) after BP exposure. In males E2 levels were increased after 3 mg exposure at 8 h. In females’ estradiol levels were increased after 3 mg exposure at 6, 8, and 10 h. NOAEL = 1 mg (26.9 mg/kg in males) Pollock et al., 2017 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butylparab en Swiss albino mice Effects on uterus, subcutaneous , 7 days (adult). Dose: 0, 10, 50, 100 mg/kg bw, n ≥ 5. Estradiol used as positive control (0.001mg/kg bw) Uterine glands ↑ Uterine weight ↑ Endometrial and mycometrium thickness ↑ Total tissue protein ↑ Histological alterations LOEL = 10 mg/kg bw (uterine effects) Goswami & Kalita 2016 Boberg et al., 2020 (The Danish Envi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group.","duration":"7 days","effect":"e/testis/spe rm) Garcia et al., 2017 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben CF1 mice Pharmacokineti c effects E2, subcutaneous (one injection). Dose: 1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. Urinary estradiol concentrations were measured (both sexes) after BP exposure. In males E2 levels were increased after 3 mg exposure at 8 h. In females’ estradiol levels were increased after 3 mg exposure at 6, 8, and 10 h. NOAEL = 1 mg (26.9 mg/kg in males) Pollock et al., 2017 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butylparab en Swiss albino mice Effects on uterus, subcutaneous , 7 days (adult). Dose: 0, 10, 50, 100 mg/kg bw, n ≥ 5. Estradiol used as positive control (0.001mg/kg bw) Uterine glands ↑ Uterine weight ↑ Endometrial and mycometrium thickness ↑ Total tissue protein ↑ Histological alterations LOEL = 10 mg/kg bw (uterine effects) Goswami & Kalita 2016 Boberg et al., 2020 (The Danish Envi","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"26.9","page":103,"route":"","species":"mouse","study_id":"sccs_o_275_noael_042"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=26.9; DOSE=1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure.; EFFECT=Unlabeled table on page 103: Butyl- paraben | CF1 mice | Pharmacokineti c effects E2, subcutaneous (one injection). Dose: 1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure. In males E2 levels were increased after 3 mg exposure at 8 h. In females’ estradiol levels were increased after 3 mg exposure at 6, 8, and 10 h. NOAEL = 1 mg (26.9 mg/kg in males) | Pollock et al., 2017 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure.","duration":"","effect":"Unlabeled table on page 103: Butyl- paraben | CF1 mice | Pharmacokineti c effects E2, subcutaneous (one injection). Dose: 1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure. In males E2 levels were increased after 3 mg exposure at 8 h. In females’ estradiol levels were increased after 3 mg exposure at 6, 8, and 10 h. NOAEL = 1 mg (26.9 mg/kg in males) | Pollock et al., 2017 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"26.9","page":103,"route":"","species":"mouse","study_id":"sccs_o_275_noael_070"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=unclear:Unlabeled table on page 93: n-Butyl- paraben | Wistar rats Non-GLP | Study of the effect of parabens on steroidogenesi s in rats and their offspring when dams are subcutaneou sly exposed to 200 - 400 mg butyl- paraben/kg/da y from gestation day 7 to 21. | Butylparaben did not show any treatment related effects on plasma hormone levels (T3, T4, 17α- hydroxyprogesterone) testosterone production, anogenital distance, or testicular histopathology. Butyl- paraben caused a decrease in the mRNA β-ER expression level in fetal ovaries, and in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose- dependency. No NOAEL defined. | Taxvig et al., 2008 | Applicant dossier; DOSE=However, these effects show no dose- dependency.; EFFECT=Unlabeled table on page 93: n-Butyl- paraben | Wistar rats Non-GLP | Study of the effect of parabens on steroidogenesi s in rats and their offspring when dams are subcutaneou sly exposed to 200 - 400 mg butyl- paraben/kg/da y from gestation day 7 to 21. | Butylparaben did not show any treatment related effects on plasma hormone levels (T3, T4, 17α- hydroxyprogesterone) testosterone production, anogenital distance, or testicular histopathology. Butyl- paraben caused a decrease in the mRNA β-ER expression level in fetal ovaries, and in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose- dependency. No NOAEL defined. | Taxvig et al., 2008 | Applicant dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"However, these effects show no dose- dependency.","duration":"","effect":"Unlabeled table on page 93: n-Butyl- paraben | Wistar rats Non-GLP | Study of the effect of parabens on steroidogenesi s in rats and their offspring when dams are subcutaneou sly exposed to 200 - 400 mg butyl- paraben/kg/da y from gestation day 7 to 21. | Butylparaben did not show any treatment related effects on plasma hormone levels (T3, T4, 17α- hydroxyprogesterone) testosterone production, anogenital distance, or testicular histopathology. Butyl- paraben caused a decrease in the mRNA β-ER expression level in fetal ovaries, and in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose- dependency. No NOAEL defined. | Taxvig et al., 2008 | Applicant dossier","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 93: n-Butyl- paraben | Wistar rats Non-GLP | Study of the effect of parabens on steroidogenesi s in rats and their offspring when dams are subcutaneou sly exposed to 200 - 400 mg butyl- paraben/kg/da y from gestation day 7 to 21. | Butylparaben did not show any treatment related effects on plasma hormone levels (T3, T4, 17α- hydroxyprogesterone) testosterone production, anogenital distance, or testicular histopathology. Butyl- paraben caused a decrease in the mRNA β-ER expression level in fetal ovaries, and in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose- dependency. No NOAEL defined. | Taxvig et al., 2008 | Applicant dossier","page":93,"route":"","species":"rat","study_id":"sccs_o_275_noael_056"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==100; DOSE=100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats).; EFFECT=days administration, PND 18-20 in both species). Dose: 100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats). Estradiol used as positive control (0.1 mg/kg bw/day) for both species No effects on utrine weight in mice (s.c.). In rats, 400 mg/kg bw/day increased uterus wet weight but not weight mg/bw. However, 600 mg/kg increased both wet weight and relative weight. Statistically significant increase in uterus weight at a subcutaneous dose of 600 mg/kg. Positive control significantly increased the uterus weights. NOAEL=100mg/kg bw/day (uterine Hossaini et al. 2000 Applicant dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats).","duration":"","effect":"days administration, PND 18-20 in both species). Dose: 100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats). Estradiol used as positive control (0.1 mg/kg bw/day) for both species No effects on utrine weight in mice (s.c.). In rats, 400 mg/kg bw/day increased uterus wet weight but not weight mg/bw. However, 600 mg/kg increased both wet weight and relative weight. Statistically significant increase in uterus weight at a subcutaneous dose of 600 mg/kg. Positive control significantly increased the uterus weights. NOAEL=100mg/kg bw/day (uterine Hossaini et al. 2000 Applicant dossier","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"=100","page":91,"route":"","species":"rat","study_id":"sccs_o_275_noael_032"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=100; DOSE=100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats).; EFFECT=Unlabeled table on page 91: n-Butyl- paraben | B6D2F1 mice Appears compliant with OECD Test Guideline 440 Non-GLP | Uterotrophic assay, s.c. (3 days administration, PND 18-20 in both species). Dose: 100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats). Estradiol used as positive control (0.1 mg/kg bw/day) for both species | No effects on utrine weight in mice (s.c.). In rats, 400 mg/kg bw/day increased uterus wet weight but not weight mg/bw. However, 600 mg/kg increased both wet weight and relative weight. Statistically significant increase in uterus weight at a subcutaneous dose of 600 mg/kg. Positive control significantly increased the uterus weights. NOAEL=100mg/kg bw/day (uterine | Hossaini et al. 2000 | Applicant dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats).","duration":"3 days","effect":"Unlabeled table on page 91: n-Butyl- paraben | B6D2F1 mice Appears compliant with OECD Test Guideline 440 Non-GLP | Uterotrophic assay, s.c. (3 days administration, PND 18-20 in both species). Dose: 100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats). Estradiol used as positive control (0.1 mg/kg bw/day) for both species | No effects on utrine weight in mice (s.c.). In rats, 400 mg/kg bw/day increased uterus wet weight but not weight mg/bw. However, 600 mg/kg increased both wet weight and relative weight. Statistically significant increase in uterus weight at a subcutaneous dose of 600 mg/kg. Positive control significantly increased the uterus weights. NOAEL=100mg/kg bw/day (uterine | Hossaini et al. 2000 | Applicant dossier","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"100","page":91,"route":"","species":"rat","study_id":"sccs_o_275_noael_053"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 150; DOSE=0 (Both naÏve control and vehicle exposed control), 150, 300, 600 mg/kg bw/day, n = 8-10. | NOTE: naïve control used for stat analysis Prostate weight ↑ Sperm numbers (affected, ↓↑) Sperm morphology:; LOAEL_VALUE=150 mg/kg bw/day; EFFECT=Unlabeled table on page 103: Butyl- paraben | Sprague- Dawley rats | Sperm parameters, s.c. 57 days, 3 alternating days per week (start 6 weeks old). Dose: 0 (Both naÏve control and vehicle exposed control), 150, 300, 600 mg/kg bw/day, n = 8-10. | NOTE: naïve control used for stat analysis Prostate weight ↑ Sperm numbers (affected, ↓↑) Sperm morphology: Normal ↓ Abnormal ↑ LOAEL = 150 mg/kg bw/day (prostate/testis/spe rm) | Garcia et al., 2017 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"0 (Both naÏve control and vehicle exposed control), 150, 300, 600 mg/kg bw/day, n = 8-10. | NOTE: naïve control used for stat analysis Prostate weight ↑ Sperm numbers (affected, ↓↑) Sperm morphology:","duration":"57 days","effect":"Unlabeled table on page 103: Butyl- paraben | Sprague- Dawley rats | Sperm parameters, s.c. 57 days, 3 alternating days per week (start 6 weeks old). Dose: 0 (Both naÏve control and vehicle exposed control), 150, 300, 600 mg/kg bw/day, n = 8-10. | NOTE: naïve control used for stat analysis Prostate weight ↑ Sperm numbers (affected, ↓↑) Sperm morphology: Normal ↓ Abnormal ↑ LOAEL = 150 mg/kg bw/day (prostate/testis/spe rm) | Garcia et al., 2017 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"150 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 150","page":103,"route":"","species":"rat","study_id":"sccs_o_275_noael_069"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=310; DOSE=1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure.; EFFECT=Unlabeled table on page 103: Butyl- paraben | CF1 mice | Pharmacokineti c effects E2, subcutaneous (one injection). Dose: 1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure. In males E2 levels were increased after 3 mg exposure at 8 h. In females’ estradiol levels were increased after 3 mg exposure at 6, 8, and 10 h. NOAEL = 1 mg (26.9 mg/kg in males) | Pollock et al., 2017 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure.","duration":"","effect":"Unlabeled table on page 103: Butyl- paraben | CF1 mice | Pharmacokineti c effects E2, subcutaneous (one injection). Dose: 1, 3, 9, mg (35, 103.3, 310 mg/kg, females) (26.9, 79.5, 242.1 mg/kg, males), n = 10/group. | Urinary estradiol concentrations were measured (both sexes) after BP exposure. In males E2 levels were increased after 3 mg exposure at 8 h. In females’ estradiol levels were increased after 3 mg exposure at 6, 8, and 10 h. NOAEL = 1 mg (26.9 mg/kg in males) | Pollock et al., 2017 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"310","page":103,"route":"","species":"mouse","study_id":"sccs_o_275_noael_068"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=325; DOSE=cant differences in the treated animals.; EFFECT=cant differences in the treated animals. It has been reported that spontaneous amyloidosis is common in aged mice (Soret et al. 1977). The maximum ingested dose of butylparaben that was considered to be non-tumourigenic was approximately 40 mg/mouse, which was equivalent to 65.8g/day in a human. For a 70 kg adult, this would suggest a NOEL of 940 mg/kg bw/day. Inai et al. (1985) Rat study - Liver effects: as observed in a multigenerational continuous breeding study. See study description in section 3.4.5 below. A NOAEL of 325 mg/kg bw/day was established in adult female rats of the F1 generation that showed some signs of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"cant differences in the treated animals.","duration":"","effect":"cant differences in the treated animals. It has been reported that spontaneous amyloidosis is common in aged mice (Soret et al. 1977). The maximum ingested dose of butylparaben that was considered to be non-tumourigenic was approximately 40 mg/mouse, which was equivalent to 65.8g/day in a human. For a 70 kg adult, this would suggest a NOEL of 940 mg/kg bw/day. Inai et al. (1985) Rat study - Liver effects: as observed in a multigenerational continuous breeding study. See study description in section 3.4.5 below. A NOAEL of 325 mg/kg bw/day was established in adult female rats of the F1 generation that showed some signs of","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"325","page":37,"route":"","species":"rat","study_id":"sccs_o_275_noael_009"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=400; DOSE=Butylparaben was administered on PND 21-22 once daily for 3 consecutive days at the following dosage levels: butylparaben oral and subcutaneou s at 40, 200, 400, 600, 800, 1000 and 1200 mg/kg bw/day Uterotrophic assay with ovariectomized (OVX)rats (8- 10 weeks old): butylparaben oral and subcutaneou s at 800, 1000 and 1200 mg/kg bw/day | Immatur...; EFFECT=Unlabeled table on page 91: n-Butyl- paraben | Immature female Alpk:AP rats and ovariectomiz ed (OVX) rats, same strain Non GLP | Uterotrophic assay with immature rats. Butylparaben was administered on PND 21-22 once daily for 3 consecutive days at the following dosage levels: butylparaben oral and subcutaneou s at 40, 200, 400, 600, 800, 1000 and 1200 mg/kg bw/day Uterotrophic assay with ovariectomized (OVX)rats (8- 10 weeks old): butylparaben oral and subcutaneou s at 800, 1000 and 1200 mg/kg bw/day | Immature rat model: 1) No effects were seen after oral dosing with butylparaben. 2)Subcutaneous administration significantly increased uterus wet weights at dosages ≥ 400 mg/kg bw/day (experiment 3). OVX rat model: increased uterus weights only at ≥ 600 mg/kg (experiment 4) or ≥ 800 (experiment 5) mg/kg butylparaben (sc). The positive control oestradiol exerted its effects at an oral dose of 0.4 mg/kg or 0.04 mg/kg bw/day (sc). | Routledg e et al., 1998 | Applicant dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Butylparaben was administered on PND 21-22 once daily for 3 consecutive days at the following dosage levels: butylparaben oral and subcutaneou s at 40, 200, 400, 600, 800, 1000 and 1200 mg/kg bw/day Uterotrophic assay with ovariectomized (OVX)rats (8- 10 weeks old): butylparaben oral and subcutaneou s at 800, 1000 and 1200 mg/kg bw/day | Immatur...","duration":"10 weeks","effect":"Unlabeled table on page 91: n-Butyl- paraben | Immature female Alpk:AP rats and ovariectomiz ed (OVX) rats, same strain Non GLP | Uterotrophic assay with immature rats. Butylparaben was administered on PND 21-22 once daily for 3 consecutive days at the following dosage levels: butylparaben oral and subcutaneou s at 40, 200, 400, 600, 800, 1000 and 1200 mg/kg bw/day Uterotrophic assay with ovariectomized (OVX)rats (8- 10 weeks old): butylparaben oral and subcutaneou s at 800, 1000 and 1200 mg/kg bw/day | Immature rat model: 1) No effects were seen after oral dosing with butylparaben. 2)Subcutaneous administration significantly increased uterus wet weights at dosages ≥ 400 mg/kg bw/day (experiment 3). OVX rat model: increased uterus weights only at ≥ 600 mg/kg (experiment 4) or ≥ 800 (experiment 5) mg/kg butylparaben (sc). The positive control oestradiol exerted its effects at an oral dose of 0.4 mg/kg or 0.04 mg/kg bw/day (sc). | Routledg e et al., 1998 | Applicant dossier","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":91,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_054"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=400; DOSE=100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats).; EFFECT=Unlabeled table on page 91: n-Butyl- paraben | B6D2F1 mice Appears compliant with OECD Test Guideline 440 Non-GLP | Uterotrophic assay, s.c. (3 days administration, PND 18-20 in both species). Dose: 100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats). Estradiol used as positive control (0.1 mg/kg bw/day) for both species | No effects on utrine weight in mice (s.c.). In rats, 400 mg/kg bw/day increased uterus wet weight but not weight mg/bw. However, 600 mg/kg increased both wet weight and relative weight. Statistically significant increase in uterus weight at a subcutaneous dose of 600 mg/kg. Positive control significantly increased the uterus weights. NOAEL=100mg/kg bw/day (uterine | Hossaini et al. 2000 | Applicant dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats).","duration":"3 days","effect":"Unlabeled table on page 91: n-Butyl- paraben | B6D2F1 mice Appears compliant with OECD Test Guideline 440 Non-GLP | Uterotrophic assay, s.c. (3 days administration, PND 18-20 in both species). Dose: 100 mg/kg bw/ day (mice) 400, 600 mg/kg bw/day (rats). Estradiol used as positive control (0.1 mg/kg bw/day) for both species | No effects on utrine weight in mice (s.c.). In rats, 400 mg/kg bw/day increased uterus wet weight but not weight mg/bw. However, 600 mg/kg increased both wet weight and relative weight. Statistically significant increase in uterus weight at a subcutaneous dose of 600 mg/kg. Positive control significantly increased the uterus weights. NOAEL=100mg/kg bw/day (uterine | Hossaini et al. 2000 | Applicant dossier","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":91,"route":"","species":"rat","study_id":"sccs_o_275_noael_055"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=900; DOSE=Deaths occurred within the first two weeks in those given the two highest doses (5 or 10%; >7500 mg/kg bw/day).; EFFECT=control groups. Deaths occurred within the first two weeks in those given the two highest doses (5 or 10%; >7500 mg/kg bw/day). Body weight gain was approximately the same as controls at a dose of 900 mg/kg bw/day. At levels greater than 900 mg/kg bw/day, there was significant atrophy of lymphoid tissue in the spleen, thymus, and lymph nodes and multifocal degeneration and necrosis in the liver parenchyma. No significant lesions or adverse effects were seen at a dose of 900 mg/kg bw/day butylparaben, therefore the NOEL in this study was 900 mg/kg bw/day (Inai et al., 1985) Fifty healthy female Swiss strain albino mice weighing 30-35g were divided equally in five different groups (n = 10). Animals received three different doses of butylparaben (13.33 (low dose LD), 20 (mid dose (MD) and 40 (high dose HD) mg/kg/day) in 200μl of olive oil. Oral treatments were given to all the animals for 30 days using a feeding tube attached to hypodermic syringe. Animals were sacrificed on Day 31 by cervical dislocation and the liver was quickly; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Deaths occurred within the first two weeks in those given the two highest doses (5 or 10%; >7500 mg/kg bw/day).","duration":"30 days","effect":"control groups. Deaths occurred within the first two weeks in those given the two highest doses (5 or 10%; >7500 mg/kg bw/day). Body weight gain was approximately the same as controls at a dose of 900 mg/kg bw/day. At levels greater than 900 mg/kg bw/day, there was significant atrophy of lymphoid tissue in the spleen, thymus, and lymph nodes and multifocal degeneration and necrosis in the liver parenchyma. No significant lesions or adverse effects were seen at a dose of 900 mg/kg bw/day butylparaben, therefore the NOEL in this study was 900 mg/kg bw/day (Inai et al., 1985) Fifty healthy female Swiss strain albino mice weighing 30-35g were divided equally in five different groups (n = 10). Animals received three different doses of butylparaben (13.33 (low dose LD), 20 (mid dose (MD) and 40 (high dose HD) mg/kg/day) in 200μl of olive oil. Oral treatments were given to all the animals for 30 days using a feeding tube attached to hypodermic syringe. Animals were sacrificed on Day 31 by cervical dislocation and the liver was quickly","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"900","page":36,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_006"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=900-1200; DOSE=All male animals died before 12 weeks at the 8% dose of butyl paraben.; EFFECT=consumption was determined. Food and butylparaben intake remained fairly constant throughout the course of experiment. At the end of the experiments, animals that survived were killed and kidney, liver, heart, lung, spleen and pancreas were removed for microscopic examinations. All male animals died before 12 weeks at the 8% dose of butyl paraben. Females also showed signs of toxicity at this dose but details were not specified. There were no toxic effects at the 2% diet 900-1200 mg/kg bw/day of butylparaben. The NOEL in this study was therefore 900-1200 mg/kg bw/day (Matthews et al.,1956). Mouse study: Eight-week-old ICR/Jcl mice (n=50 male; n=50 female) were given butylparaben orally (0.15, 0.3, or 0.6%) in the diet for 102 weeks. 0.6% butylparaben was defined as the maximum tolerated dose. N=50 males and n=50 females were also used in control groups with a basal diet. Body weights were measured once a week for the first 6 weeks, once every other week for the next 24 weeks and once every 4 weeks to the end of the study. Food; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"All male animals died before 12 weeks at the 8% dose of butyl paraben.","duration":"12 weeks","effect":"consumption was determined. Food and butylparaben intake remained fairly constant throughout the course of experiment. At the end of the experiments, animals that survived were killed and kidney, liver, heart, lung, spleen and pancreas were removed for microscopic examinations. All male animals died before 12 weeks at the 8% dose of butyl paraben. Females also showed signs of toxicity at this dose but details were not specified. There were no toxic effects at the 2% diet 900-1200 mg/kg bw/day of butylparaben. The NOEL in this study was therefore 900-1200 mg/kg bw/day (Matthews et al.,1956). Mouse study: Eight-week-old ICR/Jcl mice (n=50 male; n=50 female) were given butylparaben orally (0.15, 0.3, or 0.6%) in the diet for 102 weeks. 0.6% butylparaben was defined as the maximum tolerated dose. N=50 males and n=50 females were also used in control groups with a basal diet. Body weights were measured once a week for the first 6 weeks, once every other week for the next 24 weeks and once every 4 weeks to the end of the study. Food","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"900-1200","page":37,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_007"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=940; DOSE=Tumours were present in treated and control animals alike and there were no significant differences in the treated animals.; EFFECT=les, respectively, that survived for >78 weeks or died with tumours during the experimental period. Tumours were present in treated and control animals alike and there were no significant differences in the treated animals. It has been reported that spontaneous amyloidosis is common in aged mice (Soret et al. 1977). The maximum ingested dose of butylparaben that was considered to be non-tumourigenic was approximately 40 mg/mouse, which was equivalent to 65.8g/day in a human. For a 70 kg adult, this would suggest a NOEL of 940 mg/kg bw/day. Inai et al. (1985) Rat study - Liver effects: as observed in a multigenerational continuous breeding study. See study description in section 3.4.5 below. A NOAEL of 325 mg/kg bw/day was established in adult female rats of the F1 generation that showed some signs of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Tumours were present in treated and control animals alike and there were no significant differences in the treated animals.","duration":"78 weeks","effect":"les, respectively, that survived for >78 weeks or died with tumours during the experimental period. Tumours were present in treated and control animals alike and there were no significant differences in the treated animals. It has been reported that spontaneous amyloidosis is common in aged mice (Soret et al. 1977). The maximum ingested dose of butylparaben that was considered to be non-tumourigenic was approximately 40 mg/mouse, which was equivalent to 65.8g/day in a human. For a 70 kg adult, this would suggest a NOEL of 940 mg/kg bw/day. Inai et al. (1985) Rat study - Liver effects: as observed in a multigenerational continuous breeding study. See study description in section 3.4.5 below. A NOAEL of 325 mg/kg bw/day was established in adult female rats of the F1 generation that showed some signs of","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"940","page":37,"route":"","species":"rat","study_id":"sccs_o_275_noael_008"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=949; DOSE=However, these effects show no dose- dependency.; EFFECT=200 - 400 mg butyl- paraben/kg/da y from gestation day 7 to 21. Butylparaben did not show any treatment related effects on plasma hormone levels (T3, T4, 17α- hydroxyprogesterone) testosterone production, anogenital distance, or testicular histopathology. Butyl- paraben caused a decrease in the mRNA β-ER expression level in fetal ovaries, and in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose- dependency. No NOAEL defined. Taxvig et al., 2008 Applicant dossier n- Butylparab en 17β- oestradiol CF-1 and CD-1 female mice Non-GLP Non OECD Test Guideline No mention of group size Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice. Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation. Additional uterotrophic assay with butyl- paraben at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administer; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"However, these effects show no dose- dependency.","duration":"","effect":"200 - 400 mg butyl- paraben/kg/da y from gestation day 7 to 21. Butylparaben did not show any treatment related effects on plasma hormone levels (T3, T4, 17α- hydroxyprogesterone) testosterone production, anogenital distance, or testicular histopathology. Butyl- paraben caused a decrease in the mRNA β-ER expression level in fetal ovaries, and in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose- dependency. No NOAEL defined. Taxvig et al., 2008 Applicant dossier n- Butylparab en 17β- oestradiol CF-1 and CD-1 female mice Non-GLP Non OECD Test Guideline No mention of group size Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice. Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation. Additional uterotrophic assay with butyl- paraben at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administer","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"949","page":93,"route":"","species":"mouse","study_id":"sccs_o_275_noael_033"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=949; DOSE=Additional uterotrophic assay with BP at 0, 20, 200, 949 mg/kg bw/day in two different mice strains.; EFFECT=Unlabeled table on page 39: Butylparaben 17β-oestradiol | CF-1 and CD-1 female mice Non- GLP, No guideline, No mention of group size | Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice; subcutaneous injection of 0, 1.4, 14, 271,407, 542, 813, 949 mg BP/kg/day, on day 1 to 4 of gestation. Additional uterotrophic assay with BP at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administered as positive control in both assays. | Butylparaben had no impact on the number of implantation sites and measured parameters, e.g. number of pups born, litter weights, pup weight and survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol terminated all pregnancies. A uterotrophic assay was conducted to re-evaluate in vivo data | Shaw and de Catanzaro, 2009; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Additional uterotrophic assay with BP at 0, 20, 200, 949 mg/kg bw/day in two different mice strains.","duration":"","effect":"Unlabeled table on page 39: Butylparaben 17β-oestradiol | CF-1 and CD-1 female mice Non- GLP, No guideline, No mention of group size | Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice; subcutaneous injection of 0, 1.4, 14, 271,407, 542, 813, 949 mg BP/kg/day, on day 1 to 4 of gestation. Additional uterotrophic assay with BP at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administered as positive control in both assays. | Butylparaben had no impact on the number of implantation sites and measured parameters, e.g. number of pups born, litter weights, pup weight and survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol terminated all pregnancies. A uterotrophic assay was conducted to re-evaluate in vivo data | Shaw and de Catanzaro, 2009","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"949","page":39,"route":"","species":"mouse","study_id":"sccs_o_275_noael_046"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=949; DOSE=Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation.; EFFECT=Unlabeled table on page 93: n- Butylparab en 17β- oestradiol | CF-1 and CD-1 female mice Non-GLP Non OECD Test Guideline No mention of group size | Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice. Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation. Additional uterotrophic assay with butyl- paraben at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administered as positive control in both assays. | Butylparaben had no impact on the number of implantation sites observed and did not affect any of the measured parameters, such as the number of pups born, litter weights, individual pup weight and pup survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol (500 ng/animal/day) terminated all pregnancies. A uterotrophic assay was conducted to re- evaluate the in vivo estrogenicity of butylparabens. BP did not affect uterine wet or dry mass at any dose in either strain. 17βoestradiol consistently increased uterine mass in both stra...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation.","duration":"","effect":"Unlabeled table on page 93: n- Butylparab en 17β- oestradiol | CF-1 and CD-1 female mice Non-GLP Non OECD Test Guideline No mention of group size | Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice. Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation. Additional uterotrophic assay with butyl- paraben at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administered as positive control in both assays. | Butylparaben had no impact on the number of implantation sites observed and did not affect any of the measured parameters, such as the number of pups born, litter weights, individual pup weight and pup survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol (500 ng/animal/day) terminated all pregnancies. A uterotrophic assay was conducted to re- evaluate the in vivo estrogenicity of butylparabens. BP did not affect uterine wet or dry mass at any dose in either strain. 17βoestradiol consistently increased uterine mass in both stra...","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"949","page":93,"route":"","species":"mouse","study_id":"sccs_o_275_noael_057"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=950; DOSE=BP did not affect uterine wet or dry mass at any dose in either strain.; EFFECT=implantation sites observed and did not affect any of the measured parameters, such as the number of pups born, litter weights, individual pup weight and pup survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol (500 ng/animal/day) terminated all pregnancies. A uterotrophic assay was conducted to re- evaluate the in vivo estrogenicity of butylparabens. BP did not affect uterine wet or dry mass at any dose in either strain. 17βoestradiol consistently increased uterine mass in both strains NOEL = 35 mg/animal/day or 950 mg/kg bw/day Shaw and de Catanzar o 2009 Applicant dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"BP did not affect uterine wet or dry mass at any dose in either strain.","duration":"","effect":"implantation sites observed and did not affect any of the measured parameters, such as the number of pups born, litter weights, individual pup weight and pup survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol (500 ng/animal/day) terminated all pregnancies. A uterotrophic assay was conducted to re- evaluate the in vivo estrogenicity of butylparabens. BP did not affect uterine wet or dry mass at any dose in either strain. 17βoestradiol consistently increased uterine mass in both strains NOEL = 35 mg/animal/day or 950 mg/kg bw/day Shaw and de Catanzar o 2009 Applicant dossier","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"950","page":93,"route":"","species":"","study_id":"sccs_o_275_noael_034"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=950; DOSE=Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation.; EFFECT=Unlabeled table on page 93: n- Butylparab en 17β- oestradiol | CF-1 and CD-1 female mice Non-GLP Non OECD Test Guideline No mention of group size | Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice. Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation. Additional uterotrophic assay with butyl- paraben at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administered as positive control in both assays. | Butylparaben had no impact on the number of implantation sites observed and did not affect any of the measured parameters, such as the number of pups born, litter weights, individual pup weight and pup survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol (500 ng/animal/day) terminated all pregnancies. A uterotrophic assay was conducted to re- evaluate the in vivo estrogenicity of butylparabens. BP did not affect uterine wet or dry mass at any dose in either strain. 17βoestradiol consistently increased uterine mass in both stra...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation.","duration":"","effect":"Unlabeled table on page 93: n- Butylparab en 17β- oestradiol | CF-1 and CD-1 female mice Non-GLP Non OECD Test Guideline No mention of group size | Evaluation of the effects of butyl- paraben on success of implantation in fertilised mice. Subcutaneous injection of 0, 1.4, 14, 271, 407, 542, 813, 949 mg/kg/day on day 1 to 4 of gestation. Additional uterotrophic assay with butyl- paraben at 0, 20, 200, 949 mg/kg bw/day in two different mice strains. 14 mg/kg bw/day 17β- oestradiol was administered as positive control in both assays. | Butylparaben had no impact on the number of implantation sites observed and did not affect any of the measured parameters, such as the number of pups born, litter weights, individual pup weight and pup survival, number of intrauterine blastocyst implantation sites. 17β-oestradiol (500 ng/animal/day) terminated all pregnancies. A uterotrophic assay was conducted to re- evaluate the in vivo estrogenicity of butylparabens. BP did not affect uterine wet or dry mass at any dose in either strain. 17βoestradiol consistently increased uterine mass in both stra...","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"950","page":93,"route":"","species":"mouse","study_id":"sccs_o_275_noael_058"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1000; DOSE=Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days.; EFFECT=Unlabeled table on page 94: n- Butylparab en 17α- ethinyl oestradiol | Sprague Dawley immature female rats Non GLP Non- OECD test guideline | Uterotrophic assay. Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days. Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic effects. | Subcutaneous injection of 1000 mg/kg bw/day (highest dose) induced increased uterine wet weight for butylparaben (also for pos. control at 1 mg/kg bw/day). The effect was blocked by addition of anti- estrogen fulvestrant, indicating estrogen receptordependent pathway. NOAEL=250 mg/kg bw/day (increase uterine weight) | Vo and Jeung 2009 | Applicant dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days.","duration":"3 days","effect":"Unlabeled table on page 94: n- Butylparab en 17α- ethinyl oestradiol | Sprague Dawley immature female rats Non GLP Non- OECD test guideline | Uterotrophic assay. Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days. Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic effects. | Subcutaneous injection of 1000 mg/kg bw/day (highest dose) induced increased uterine wet weight for butylparaben (also for pos. control at 1 mg/kg bw/day). The effect was blocked by addition of anti- estrogen fulvestrant, indicating estrogen receptordependent pathway. NOAEL=250 mg/kg bw/day (increase uterine weight) | Vo and Jeung 2009 | Applicant dossier","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":94,"route":"","species":"rat","study_id":"sccs_o_275_noael_059"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1504; DOSE=14.4, 146, 1504 mg/kg bw/day. | NOAEL =14.4 mg/kgbw/day.; EFFECT=Unlabeled table on page 41: 14.4, 146, 1504 mg/kg bw/day. | NOAEL =14.4 mg/kgbw/day.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"14.4, 146, 1504 mg/kg bw/day. | NOAEL =14.4 mg/kgbw/day.","duration":"","effect":"Unlabeled table on page 41: 14.4, 146, 1504 mg/kg bw/day. | NOAEL =14.4 mg/kgbw/day.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1504","page":41,"route":"","species":"","study_id":"sccs_o_275_noael_050"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=5,000; DOSE=The highest dose at which only such non-adverse changes occur should be identified as the NOAEL.; EFFECT=ertrophy leading to less than 15% increased mean absolute or relative liver weight, should not be regarded as adverse, and should not be used for the purpose of defining the LOAEL for that specific study, in the demonstrated absence of other histopathological findings such as necrosis, inflammation, fibrosis, vacuolation, pigmentation, degeneration, hyperplasia, or other effects that are indicative of specific liver toxicity. The highest dose at which only such non-adverse changes occur should be identified as the NOAEL. Therefore, the NOAEL from this study, based on liver effects in adult females, is defined at 5,000 ppm (325 – 740 mg/kg/day). The lower value of 325 mg/kg bw/day was selected as a conservative PoD. To ensure that the lack of any adverse findings in offpring in the RACB study was not due to insufficient test article exposure, a study was performed (live phase completed in 2012) to assess exposure and effects in pups. Roberts et al. (2016) – A Supporting study to Hubbard et al. 2020 The objective of this investiga; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"The highest dose at which only such non-adverse changes occur should be identified as the NOAEL.","duration":"","effect":"ertrophy leading to less than 15% increased mean absolute or relative liver weight, should not be regarded as adverse, and should not be used for the purpose of defining the LOAEL for that specific study, in the demonstrated absence of other histopathological findings such as necrosis, inflammation, fibrosis, vacuolation, pigmentation, degeneration, hyperplasia, or other effects that are indicative of specific liver toxicity. The highest dose at which only such non-adverse changes occur should be identified as the NOAEL. Therefore, the NOAEL from this study, based on liver effects in adult females, is defined at 5,000 ppm (325 – 740 mg/kg/day). The lower value of 325 mg/kg bw/day was selected as a conservative PoD. To ensure that the lack of any adverse findings in offpring in the RACB study was not due to insufficient test article exposure, a study was performed (live phase completed in 2012) to assess exposure and effects in pups. Roberts et al. (2016) – A Supporting study to Hubbard et al. 2020 The objective of this investiga","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"5,000","page":44,"route":"","species":"","study_id":"sccs_o_275_noael_025"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=5,000; DOSE=The highest dose at which only such non-adverse changes occur should be identified as the NOAEL.; EFFECT=ss than 15% increased mean absolute or relative liver weight, should not be regarded as adverse, and should not be used for the purpose of defining the LOAEL for that specific study, in the demonstrated absence of other histopathological findings such as necrosis, inflammation, fibrosis, vacuolation, pigmentation, degeneration, hyperplasia, or other effects that are indicative of specific liver toxicity. The highest dose at which only such non-adverse changes occur should be identified as the NOAEL. Therefore, the NOAEL from this study, based on liver effects in adult females, is defined at 5,000 ppm (325 – 740 mg/kg/day). The lower value of 325 mg/kg bw/day was selected as a conservative PoD. To ensure that the lack of any adverse findings in offpring in the RACB study was not due to insufficient test article exposure, a study was performed (live phase completed in 2012) to assess exposure and effects in pups. Roberts et al. (2016) – A Supporting study to Hubbard et al. 2020 The objective of this investigation was to elucidate; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"The highest dose at which only such non-adverse changes occur should be identified as the NOAEL.","duration":"","effect":"ss than 15% increased mean absolute or relative liver weight, should not be regarded as adverse, and should not be used for the purpose of defining the LOAEL for that specific study, in the demonstrated absence of other histopathological findings such as necrosis, inflammation, fibrosis, vacuolation, pigmentation, degeneration, hyperplasia, or other effects that are indicative of specific liver toxicity. The highest dose at which only such non-adverse changes occur should be identified as the NOAEL. Therefore, the NOAEL from this study, based on liver effects in adult females, is defined at 5,000 ppm (325 – 740 mg/kg/day). The lower value of 325 mg/kg bw/day was selected as a conservative PoD. To ensure that the lack of any adverse findings in offpring in the RACB study was not due to insufficient test article exposure, a study was performed (live phase completed in 2012) to assess exposure and effects in pups. Roberts et al. (2016) – A Supporting study to Hubbard et al. 2020 The objective of this investigation was to elucidate","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"5,000","page":44,"route":"","species":"","study_id":"sccs_o_275_noael_026"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=10,000; DOSE=Butylparaben | Wistar rat GLP Non guideline | Repetition of the Oishi study (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone | There...; EFFECT=Unlabeled table on page 40: Butylparaben | Wistar rat GLP Non guideline | Repetition of the Oishi study (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone | There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi (2001), sperm parameters were found unaffected. With both MeP and Butylparaben, the highest dose level in food corresponds to a NOAEL of 10,000 ppm, NOAEL=1100 mg/kgbw/day | Hoberman et al. 2008; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Butylparaben | Wistar rat GLP Non guideline | Repetition of the Oishi study (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone | There...","duration":"","effect":"Unlabeled table on page 40: Butylparaben | Wistar rat GLP Non guideline | Repetition of the Oishi study (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone | There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi (2001), sperm parameters were found unaffected. With both MeP and Butylparaben, the highest dose level in food corresponds to a NOAEL of 10,000 ppm, NOAEL=1100 mg/kgbw/day | Hoberman et al. 2008","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"10,000","page":40,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_048"}

sccs_o_275.pdf

{"dose":"202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day.","effect":"SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day. NOAEL =14.4 mg/kgbw/day. Butylparaben Wistar rat Non GLP Non guideline Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from","page":41,"pdf":"sccs_o_275.pdf","row_type":"noael_study","study_id":"sccs_o_275_noael_016"}

sccs_o_275.pdf

{"dose":"202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day.","effect":"SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day. NOAEL =14.4 mg/kgbw/day. Butylparaben Wistar rat Non GLP Non guideline Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from","page":41,"pdf":"sccs_o_275.pdf","row_type":"noael_study","study_id":"sccs_o_275_noael_016"}

sccs_o_275.pdf

{"dose":"202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day.","effect":"SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day. NOAEL =14.4 mg/kgbw/day. Butylparaben Wistar rat Non GLP Non guideline Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from","page":41,"pdf":"sccs_o_275.pdf","row_type":"noael_study","study_id":"sccs_o_275_noael_016"}

sccs_o_275.pdf

{"dose":"202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day.","effect":"SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day. NOAEL =14.4 mg/kgbw/day. Butylparaben Wistar rat Non GLP Non guideline Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from","page":41,"pdf":"sccs_o_275.pdf","row_type":"noael_study","study_id":"sccs_o_275_noael_016"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==160; EFFECT=21, 35, 49, 90, 180. Male offspring: sex ratio affected (fewer males) Bw decreased from PND 0-49, but not affected PND 90-180. Weight of testis, epididmis and seminal vesicles decreasedàover laps with reduced BW and relative weights not reported. AGD shortened on PND1 and 21 (also coincides with reduced BW). Testis histopathology affected on PND 21 and 90 with, fex, reduced and loosely arranged germ cells, reduced layers of seminiferous tubules, reduced numbers of spermatocytes. No obvious effects on Leydig cells. NOAEL=160mg/kg bw/day (male reproduction and developmental toxicity in rats Zhang et al., 2014 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"","duration":"developmental","effect":"21, 35, 49, 90, 180. Male offspring: sex ratio affected (fewer males) Bw decreased from PND 0-49, but not affected PND 90-180. Weight of testis, epididmis and seminal vesicles decreasedàover laps with reduced BW and relative weights not reported. AGD shortened on PND1 and 21 (also coincides with reduced BW). Testis histopathology affected on PND 21 and 90 with, fex, reduced and loosely arranged germ cells, reduced layers of seminiferous tubules, reduced numbers of spermatocytes. No obvious effects on Leydig cells. NOAEL=160mg/kg bw/day (male reproduction and developmental toxicity in rats Zhang et al., 2014 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"developmental toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"=160","page":97,"route":"","species":"rat","study_id":"sccs_o_275_noael_038"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1000; DOSE=Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19.; EFFECT=Unlabeled table on page 39: Butylparaben | Sprague Dawley rats | Developmental study according to OECD test guideline and GLP. Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19. Foetuses examination on gestational day 20; developmental parameters measured | At the highest dose, maternal food consumption reduced during exposure time, weight gain reduced on days 18-20. No developmental parameters changed. Developmental (oral) NOAEL: 1000 mg/kg bw/day. | Daston, 2004; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19.","duration":"Developmental","effect":"Unlabeled table on page 39: Butylparaben | Sprague Dawley rats | Developmental study according to OECD test guideline and GLP. Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19. Foetuses examination on gestational day 20; developmental parameters measured | At the highest dose, maternal food consumption reduced during exposure time, weight gain reduced on days 18-20. No developmental parameters changed. Developmental (oral) NOAEL: 1000 mg/kg bw/day. | Daston, 2004","endpoint":"developmental toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":39,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_045"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=Acute intraperitoneal toxicity The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956).; EFFECT=d subcutaneously to groups of five mice. The reported LD50 was 2.5 g/kg (Adler-Hradecky & Kelentey, 1960). 3.4.3.5. Acute intraperitoneal toxicity The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956). SCCS overall conclusion on acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. 3.4.4 Repeated dose toxicity In the former SCCS Opinion on parabens (SCCS/1514/13), no adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Appl; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Acute intraperitoneal toxicity The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956).","duration":"","effect":"d subcutaneously to groups of five mice. The reported LD50 was 2.5 g/kg (Adler-Hradecky & Kelentey, 1960). 3.4.3.5. Acute intraperitoneal toxicity The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956). SCCS overall conclusion on acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. 3.4.4 Repeated dose toxicity In the former SCCS Opinion on parabens (SCCS/1514/13), no adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Appl","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":35,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_001"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956).; EFFECT=The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956). SCCS overall conclusion on acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. 3.4.4 Repeated dose toxicity In the former SCCS Opinion on parabens (SCCS/1514/13), no adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Applicant argued that from the general reviews of paraben safety over the past 5 decades of use, there have been no concerns expressed about the gener; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956).","duration":"","effect":"The intraperitoneal (i.p.) LD50 of the sodium salt of butylparaben was 230 mg/kg bw in mice and lacrimation was seen in the eyes of mice (Matthews et al., 1956). SCCS overall conclusion on acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. 3.4.4 Repeated dose toxicity In the former SCCS Opinion on parabens (SCCS/1514/13), no adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Applicant argued that from the general reviews of paraben safety over the past 5 decades of use, there have been no concerns expressed about the gener","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":35,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_002"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=SCCS/1514/13), no adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Applicant argued that from the general reviews of paraben safety over the past 5 decades of use, there have been no concerns expressed about the general toxicity per se of parabens (Soni et al. (2001, 2005), CIR 2008/2012, and CIR 2019). As stated in CIR 2008, “subchronic and chronic oral studies indicate that [all] parabens are practically non- toxic”. It is furthermore noted that in more recent years, there has been more focus on reproductive and developmental studies, which are discusse; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"subchronic","effect":"SCCS/1514/13), no adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Applicant argued that from the general reviews of paraben safety over the past 5 decades of use, there have been no concerns expressed about the general toxicity per se of parabens (Soni et al. (2001, 2005), CIR 2008/2012, and CIR 2019). As stated in CIR 2008, “subchronic and chronic oral studies indicate that [all] parabens are practically non- toxic”. It is furthermore noted that in more recent years, there has been more focus on reproductive and developmental studies, which are discusse","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":35,"route":"oral","species":"","study_id":"sccs_o_275_noael_003"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Applicant argued that from the general reviews of paraben safety over the past 5 decades of use, there have been no concerns expressed about the general toxicity per se of parabens (Soni et al. (2001, 2005), CIR 2008/2012, and CIR 2019). As stated in CIR 2008, “subchronic and chronic oral studies indicate that [all] parabens are practically non- toxic”. It is furthermore noted that in more recent years, there has been more focus on reproductive and developmental studies, which are discussed in detail in sect; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"subchronic","effect":"adequate NO(A)EL-value for the paraben esters under consideration could be retrieved from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasized that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. The Applicant argued that from the general reviews of paraben safety over the past 5 decades of use, there have been no concerns expressed about the general toxicity per se of parabens (Soni et al. (2001, 2005), CIR 2008/2012, and CIR 2019). As stated in CIR 2008, “subchronic and chronic oral studies indicate that [all] parabens are practically non- toxic”. It is furthermore noted that in more recent years, there has been more focus on reproductive and developmental studies, which are discussed in detail in sect","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":35,"route":"oral","species":"","study_id":"sccs_o_275_noael_004"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=~40; DOSE=Decrease of corpora lutea, increase in the number of cystic follicles (~40%) at 62.5 mg/kg bw/d), not dose dependent. but significant.; EFFECT=Unlabeled table on page 94: n-Butyl- paraben 17α-ethinyl oestradiol | Mated Sprague Dawley female rats; Prepubertal (8week-old) females, N=200, n=10/group, 20 groups. 0, 62.5, 250 or 1000 mg/kgbw/day in corn oil (vehicle), by oral gavage. Non GLP NonOECD test guideline | In vivo assay to investigate whether oral- subacute exposure to butylparaben may induce suppressive effects on reproductive organs in female rats during the critical juvenile-peri- pubertal stage. Oral- subacute administration by gavage of paraben from postnatal day 21 to 40. Investigation of Calbindin-D9-k biomarker for estrogenic effects. | No significant changes to estradiol, prolactin and T4 levels. Significant increase in uterus thickness at all doses. Decrease of corpora lutea, increase in the number of cystic follicles (~40%) at 62.5 mg/kg bw/d), not dose dependent. but significant. No effect on vaginal opening. No significant change to estrous cycle. The highest dosage (1000mg/kg bw/day) of butylparaben significantly increased uterine wet weight. Paraben- induced increases in uterine weights were blocked b...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Decrease of corpora lutea, increase in the number of cystic follicles (~40%) at 62.5 mg/kg bw/d), not dose dependent. but significant.","duration":"8week","effect":"Unlabeled table on page 94: n-Butyl- paraben 17α-ethinyl oestradiol | Mated Sprague Dawley female rats; Prepubertal (8week-old) females, N=200, n=10/group, 20 groups. 0, 62.5, 250 or 1000 mg/kgbw/day in corn oil (vehicle), by oral gavage. Non GLP NonOECD test guideline | In vivo assay to investigate whether oral- subacute exposure to butylparaben may induce suppressive effects on reproductive organs in female rats during the critical juvenile-peri- pubertal stage. Oral- subacute administration by gavage of paraben from postnatal day 21 to 40. Investigation of Calbindin-D9-k biomarker for estrogenic effects. | No significant changes to estradiol, prolactin and T4 levels. Significant increase in uterus thickness at all doses. Decrease of corpora lutea, increase in the number of cystic follicles (~40%) at 62.5 mg/kg bw/d), not dose dependent. but significant. No effect on vaginal opening. No significant change to estrous cycle. The highest dosage (1000mg/kg bw/day) of butylparaben significantly increased uterine wet weight. Paraben- induced increases in uterine weights were blocked b...","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"~40","page":94,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_060"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=50; DOSE=Butyl- paraben | Wistar rats | Repeated dose, oral (p.o.) (start PND 19- 21, 8 weeks).; EFFECT=Unlabeled table on page 101: Butyl- paraben | Wistar rats | Repeated dose, oral (p.o.) (start PND 19- 21, 8 weeks). Dose: 50 mg/kg n = 6. | Weight: Testis Prostate Seminal vesicle Sperm: Sperm numbers ↓ Sperm motility ↓ Hormones: Testosterone ↓ Estradiol ↑ LH ↓ FSH ↓ Testosterone/LH ↓ Testosterone/Estradi ol ↓ Testis DNA damage ↑ Histopathology testis (affected) | Riad et al., 2018 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Butyl- paraben | Wistar rats | Repeated dose, oral (p.o.) (start PND 19- 21, 8 weeks).","duration":"8 weeks","effect":"Unlabeled table on page 101: Butyl- paraben | Wistar rats | Repeated dose, oral (p.o.) (start PND 19- 21, 8 weeks). Dose: 50 mg/kg n = 6. | Weight: Testis Prostate Seminal vesicle Sperm: Sperm numbers ↓ Sperm motility ↓ Hormones: Testosterone ↓ Estradiol ↑ LH ↓ FSH ↓ Testosterone/LH ↓ Testosterone/Estradi ol ↓ Testis DNA damage ↑ Histopathology testis (affected) | Riad et al., 2018 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"50","page":101,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_067"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=67.8; DOSE=Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22.; EFFECT=Unlabeled table on page 101: Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22. Continued for 8 weeks). Dose: 10.9 ± 0.4, 109.3 ± 8.2, 1087.6 ± 67.8 mg/kg bw/day, n=8. | Weight: Testis Epididymis Prostate Seminal vesicle Sperm: Numbers Motility Morphology Histopathology: Epididymis Testis Prostate Seminal vesicle Hormones: Testosterone ↓ FSH ↑ LH ↓ NOAEL = 1086.6 mg/kg bw/day (10000 ppm) (effects on hormone levels) | Hoberma n et al., 2008 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22.","duration":"8 weeks","effect":"Unlabeled table on page 101: Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22. Continued for 8 weeks). Dose: 10.9 ± 0.4, 109.3 ± 8.2, 1087.6 ± 67.8 mg/kg bw/day, n=8. | Weight: Testis Epididymis Prostate Seminal vesicle Sperm: Numbers Motility Morphology Histopathology: Epididymis Testis Prostate Seminal vesicle Hormones: Testosterone ↓ FSH ↑ LH ↓ NOAEL = 1086.6 mg/kg bw/day (10000 ppm) (effects on hormone levels) | Hoberma n et al., 2008 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"67.8","page":101,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_065"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==250; DOSE=Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days.; EFFECT=ol Sprague Dawley immature female rats Non GLP Non- OECD test guideline Uterotrophic assay. Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days. Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic effects. Subcutaneous injection of 1000 mg/kg bw/day (highest dose) induced increased uterine wet weight for butylparaben (also for pos. control at 1 mg/kg bw/day). The effect was blocked by addition of anti- estrogen fulvestrant, indicating estrogen receptordependent pathway. NOAEL=250 mg/kg bw/day (increase uterine weight) Vo and Jeung 2009 Applicant dossier n-Butyl- paraben 17α-ethinyl oestradiol Mated Sprague Dawley female rats; Prepubertal (8week-old) females, N=200, n=10/group, 20 groups. 0, 62.5, 250 or 1000 mg/kgbw/day in corn oil (vehicle), by oral gavage. Non GLP NonOECD test guideline In vivo assay to investigate whether oral- subacute exposure to butylparaben may induce suppressive effects on reproductive organs in female rats during the critical juvenile-peri- pubertal stage.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days.","duration":"3 days","effect":"ol Sprague Dawley immature female rats Non GLP Non- OECD test guideline Uterotrophic assay. Subcutaneous injection of 62.5, 250, 1000 mg/kg bw/day of paraben for 3 days. Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic effects. Subcutaneous injection of 1000 mg/kg bw/day (highest dose) induced increased uterine wet weight for butylparaben (also for pos. control at 1 mg/kg bw/day). The effect was blocked by addition of anti- estrogen fulvestrant, indicating estrogen receptordependent pathway. NOAEL=250 mg/kg bw/day (increase uterine weight) Vo and Jeung 2009 Applicant dossier n-Butyl- paraben 17α-ethinyl oestradiol Mated Sprague Dawley female rats; Prepubertal (8week-old) females, N=200, n=10/group, 20 groups. 0, 62.5, 250 or 1000 mg/kgbw/day in corn oil (vehicle), by oral gavage. Non GLP NonOECD test guideline In vivo assay to investigate whether oral- subacute exposure to butylparaben may induce suppressive effects on reproductive organs in female rats during the critical juvenile-peri- pubertal stage.","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"=250","page":94,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_035"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=325; DOSE=Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d.; EFFECT=No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 64 Skin sensitisation Butylparaben is not sensitising in animals and has in humans only a mild sensitising potential. Acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d. Reproductive toxicity The SCCS has carefully considered and agrees with the Applicant’s argumentation with respect to the available in vivo reproductive and developmental studies to determine a NOAEL value of 325 mg/kg bw/d. Mutagenicity / genotoxicity The SCCS did not agree with the Applicant’s conclusions of ‘no mutagenicity’ and ‘no genotoxicity’ because an Ames test according to OECD 471 recommended bacterial strain combination was not included and a valid; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d.","duration":"developmental","effect":"No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 64 Skin sensitisation Butylparaben is not sensitising in animals and has in humans only a mild sensitising potential. Acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d. Reproductive toxicity The SCCS has carefully considered and agrees with the Applicant’s argumentation with respect to the available in vivo reproductive and developmental studies to determine a NOAEL value of 325 mg/kg bw/d. Mutagenicity / genotoxicity The SCCS did not agree with the Applicant’s conclusions of ‘no mutagenicity’ and ‘no genotoxicity’ because an Ames test according to OECD 471 recommended bacterial strain combination was not included and a valid","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kgbw/d","noael_value":"325","page":64,"route":"","species":"human","study_id":"sccs_o_275_noael_030"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=325; DOSE=Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d.; EFFECT=not sensitising in animals and has in humans only a mild sensitising potential. Acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d. Reproductive toxicity The SCCS has carefully considered and agrees with the Applicant’s argumentation with respect to the available in vivo reproductive and developmental studies to determine a NOAEL value of 325 mg/kg bw/d. Mutagenicity / genotoxicity The SCCS did not agree with the Applicant’s conclusions of ‘no mutagenicity’ and ‘no genotoxicity’ because an Ames test according to OECD 471 recommended bacterial strain combination was not included and a valid in vitro micronucleus/ chromosomal aberration study was not provided. Both tests were subsequently requested (in the presence and absence of S9) and were delivered. The SCCS carried out a systematic literature search with respect to mutagenicity/ genoto; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d.","duration":"developmental","effect":"not sensitising in animals and has in humans only a mild sensitising potential. Acute toxicity The SCCS is of the opinion that butylparaben has no acute toxicity. Repeated dose toxicity The SCCS agrees with the Applicant that the target organ is the liver and the NOAEL from repeated dose toxicity study is 325 mg/kgbw/d. Reproductive toxicity The SCCS has carefully considered and agrees with the Applicant’s argumentation with respect to the available in vivo reproductive and developmental studies to determine a NOAEL value of 325 mg/kg bw/d. Mutagenicity / genotoxicity The SCCS did not agree with the Applicant’s conclusions of ‘no mutagenicity’ and ‘no genotoxicity’ because an Ames test according to OECD 471 recommended bacterial strain combination was not included and a valid in vitro micronucleus/ chromosomal aberration study was not provided. Both tests were subsequently requested (in the presence and absence of S9) and were delivered. The SCCS carried out a systematic literature search with respect to mutagenicity/ genoto","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"325","page":64,"route":"","species":"human","study_id":"sccs_o_275_noael_031"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 1086.6; DOSE=Testosterone ↓ LOAEL = 14.4 mg/kg bw/day (elongated spermatid counts were significantly lower) Oishi 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben Wistar rats Repeated dose, oral (diet) (Start PND22.; LOAEL_VALUE=14.4 mg/kg bw/day; EFFECT=Testosterone ↓ LOAEL = 14.4 mg/kg bw/day (elongated spermatid counts were significantly lower) Oishi 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben Wistar rats Repeated dose, oral (diet) (Start PND22. Continued for 8 weeks). Dose: 10.9 ± 0.4, 109.3 ± 8.2, 1087.6 ± 67.8 mg/kg bw/day, n=8. Weight: Testis Epididymis Prostate Seminal vesicle Sperm: Numbers Motility Morphology Histopathology: Epididymis Testis Prostate Seminal vesicle Hormones: Testosterone ↓ FSH ↑ LH ↓ NOAEL = 1086.6 mg/kg bw/day (10000 ppm) (effects on hormone levels) Hoberma n et al., 2008 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben Wistar rats Repeated dose, oral (p.o.) (start PND 19- 21, 8 weeks). Dose: 50 mg/kg n = 6. Weight: Testis Prostate Seminal vesicle Sperm: Sperm numbers ↓ Sperm motility ↓ Hormones: Testosterone ↓ Estradiol ↑ LH ↓ FSH ↓ Testosterone/LH ↓ Testosterone/Estradi ol ↓ Testis DNA damage ↑ Histopathology testis (affected) Riad et al., 2018 Boberg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Testosterone ↓ LOAEL = 14.4 mg/kg bw/day (elongated spermatid counts were significantly lower) Oishi 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben Wistar rats Repeated dose, oral (diet) (Start PND22.","duration":"8 weeks","effect":"Testosterone ↓ LOAEL = 14.4 mg/kg bw/day (elongated spermatid counts were significantly lower) Oishi 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben Wistar rats Repeated dose, oral (diet) (Start PND22. Continued for 8 weeks). Dose: 10.9 ± 0.4, 109.3 ± 8.2, 1087.6 ± 67.8 mg/kg bw/day, n=8. Weight: Testis Epididymis Prostate Seminal vesicle Sperm: Numbers Motility Morphology Histopathology: Epididymis Testis Prostate Seminal vesicle Hormones: Testosterone ↓ FSH ↑ LH ↓ NOAEL = 1086.6 mg/kg bw/day (10000 ppm) (effects on hormone levels) Hoberma n et al., 2008 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben Wistar rats Repeated dose, oral (p.o.) (start PND 19- 21, 8 weeks). Dose: 50 mg/kg n = 6. Weight: Testis Prostate Seminal vesicle Sperm: Sperm numbers ↓ Sperm motility ↓ Hormones: Testosterone ↓ Estradiol ↑ LH ↓ FSH ↓ Testosterone/LH ↓ Testosterone/Estradi ol ↓ Testis DNA damage ↑ Histopathology testis (affected) Riad et al., 2018 Boberg","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"14.4 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 1086.6","page":101,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_041"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 1086.6; DOSE=Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22.; EFFECT=Unlabeled table on page 101: Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22. Continued for 8 weeks). Dose: 10.9 ± 0.4, 109.3 ± 8.2, 1087.6 ± 67.8 mg/kg bw/day, n=8. | Weight: Testis Epididymis Prostate Seminal vesicle Sperm: Numbers Motility Morphology Histopathology: Epididymis Testis Prostate Seminal vesicle Hormones: Testosterone ↓ FSH ↑ LH ↓ NOAEL = 1086.6 mg/kg bw/day (10000 ppm) (effects on hormone levels) | Hoberma n et al., 2008 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22.","duration":"8 weeks","effect":"Unlabeled table on page 101: Butyl- paraben | Wistar rats | Repeated dose, oral (diet) (Start PND22. Continued for 8 weeks). Dose: 10.9 ± 0.4, 109.3 ± 8.2, 1087.6 ± 67.8 mg/kg bw/day, n=8. | Weight: Testis Epididymis Prostate Seminal vesicle Sperm: Numbers Motility Morphology Histopathology: Epididymis Testis Prostate Seminal vesicle Hormones: Testosterone ↓ FSH ↑ LH ↓ NOAEL = 1086.6 mg/kg bw/day (10000 ppm) (effects on hormone levels) | Hoberma n et al., 2008 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 1086.6","page":101,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_066"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 2; DOSE=Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day Fisher et al.; EFFECT=araben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2-18). Other substances tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol. Effects of neonatal exposure to butylparaben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2- 18). Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day Fisher et al. 1999 *) reproductive assessment by continuous breeding The Applicant provided extensive argumentation against the use of the PoD selected in the former SCCS opinion on parabens (SCCS/1514/13). The PoD was based on the study by Fisher et al. (1999). The arguments were taken from the 2019 CIR report on the safety of parabens and were summarised as follows: “i) this study involves a subcutaneous route of exposure, which results in chemicals circumventing the physiological barriers and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day Fisher et al.","duration":"17 days","effect":"araben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2-18). Other substances tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol. Effects of neonatal exposure to butylparaben on development of rat testis after a single subcutaneous administration of 2 mg butyl- paraben/kg/day for 17 days (postnatal days 2- 18). Also tested were diethylstilbestrol ethinyloestradiol bisphenol A, genistein, octylphenol NOEL = 2 mg/kg bw/day Fisher et al. 1999 *) reproductive assessment by continuous breeding The Applicant provided extensive argumentation against the use of the PoD selected in the former SCCS opinion on parabens (SCCS/1514/13). The PoD was based on the study by Fisher et al. (1999). The arguments were taken from the 2019 CIR report on the safety of parabens and were summarised as follows: “i) this study involves a subcutaneous route of exposure, which results in chemicals circumventing the physiological barriers and","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 2","page":41,"route":"","species":"rat","study_id":"sccs_o_275_noael_017"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=aben to pregnant rats while examining toxicity in the male offspring); and v) typical DART end points were not covered, such as AGD, PPS (preputional separation), weight of the epididymis and seminal vesicle, sperm counts, reproductive hormone levels, and so on.” SCCS comment The SCCS agrees with the provided limitations of the Fisher et al. (1999) study for use in the risk assessment of cosmetics, taken from the CIR (2019) report. The former SCCS opinion on parabens (SCCS/1514/13) could not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the A; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"","effect":"aben to pregnant rats while examining toxicity in the male offspring); and v) typical DART end points were not covered, such as AGD, PPS (preputional separation), weight of the epididymis and seminal vesicle, sperm counts, reproductive hormone levels, and so on.” SCCS comment The SCCS agrees with the provided limitations of the Fisher et al. (1999) study for use in the risk assessment of cosmetics, taken from the CIR (2019) report. The former SCCS opinion on parabens (SCCS/1514/13) could not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the A","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":42,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_018"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=D, PPS (preputional separation), weight of the epididymis and seminal vesicle, sperm counts, reproductive hormone levels, and so on.” SCCS comment The SCCS agrees with the provided limitations of the Fisher et al. (1999) study for use in the risk assessment of cosmetics, taken from the CIR (2019) report. The former SCCS opinion on parabens (SCCS/1514/13) could not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the Applicant: Further argumentation was provided by the Applicant for each study included in Table 5. An academic study in mice by; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"","effect":"D, PPS (preputional separation), weight of the epididymis and seminal vesicle, sperm counts, reproductive hormone levels, and so on.” SCCS comment The SCCS agrees with the provided limitations of the Fisher et al. (1999) study for use in the risk assessment of cosmetics, taken from the CIR (2019) report. The former SCCS opinion on parabens (SCCS/1514/13) could not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the Applicant: Further argumentation was provided by the Applicant for each study included in Table 5. An academic study in mice by","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":42,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_019"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=CCS/1514/13) could not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the Applicant: Further argumentation was provided by the Applicant for each study included in Table 5. An academic study in mice by Kang et al. (2002) investigated the effects of butylparaben in F1 male offspring after pregnant females were subcutaneously injected with 100 or 200 mg/kg/day. This too was not an OECD Test Guideline study nor a comprehensive assessment of reproductive and developmental effects. As noted above, some observations relating to sperm effects and m; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"developmental","effect":"CCS/1514/13) could not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the Applicant: Further argumentation was provided by the Applicant for each study included in Table 5. An academic study in mice by Kang et al. (2002) investigated the effects of butylparaben in F1 male offspring after pregnant females were subcutaneously injected with 100 or 200 mg/kg/day. This too was not an OECD Test Guideline study nor a comprehensive assessment of reproductive and developmental effects. As noted above, some observations relating to sperm effects and m","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":42,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_020"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the Applicant: Further argumentation was provided by the Applicant for each study included in Table 5. An academic study in mice by Kang et al. (2002) investigated the effects of butylparaben in F1 male offspring after pregnant females were subcutaneously injected with 100 or 200 mg/kg/day. This too was not an OECD Test Guideline study nor a comprehensive assessment of reproductive and developmental effects. As noted above, some observations relating to sperm effects and male reproductive or; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"developmental","effect":"not determine an adequate NO(A)EL-value for the paraben esters under consideration from the studies listed in Appendix 1 of SCCS/1514/13. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999), was determined to be a conservative choice for the calculation of the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration but emphasised that 2 mg/kg bw/day clearly represents a NOEL instead of a NOAEL. Further reasoning by the Applicant: Further argumentation was provided by the Applicant for each study included in Table 5. An academic study in mice by Kang et al. (2002) investigated the effects of butylparaben in F1 male offspring after pregnant females were subcutaneously injected with 100 or 200 mg/kg/day. This too was not an OECD Test Guideline study nor a comprehensive assessment of reproductive and developmental effects. As noted above, some observations relating to sperm effects and male reproductive or","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":42,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_021"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=unclear:Table 5: summary of DART (developmental and reproductive toxicology) studies on: disruption NOAEL; EFFECT=Table 5: summary of DART (developmental and reproductive toxicology) studies on: disruption NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"","duration":"developmental","effect":"Table 5: summary of DART (developmental and reproductive toxicology) studies on: disruption NOAEL","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Table 5: summary of DART (developmental and reproductive toxicology) studies on: disruption NOAEL","page":38,"route":"","species":"","study_id":"sccs_o_275_noael_044"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=10.4; DOSE=Butylparaben | Wistar rat Non GLP Non guideline | Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. | There were no treatment related effects on testes, ventral prostates and preputial glands in...; EFFECT=Unlabeled table on page 41: Butylparaben | Wistar rat Non GLP Non guideline | Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. | There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from 10.4 mg/kg bw/day onwards (LOAEL). | Oishi 2001; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Butylparaben | Wistar rat Non GLP Non guideline | Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. | There were no treatment related effects on testes, ventral prostates and preputial glands in...","duration":"21 days","effect":"Unlabeled table on page 41: Butylparaben | Wistar rat Non GLP Non guideline | Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. | There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from 10.4 mg/kg bw/day onwards (LOAEL). | Oishi 2001","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10.4","page":41,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_052"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==14.4; DOSE=202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day.; EFFECT=SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day. NOAEL =14.4 mg/kgbw/day. Butylparaben Wistar rat Non GLP Non guideline Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day.","duration":"21 days","effect":"SCCS/1651/23 Final Opinion Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 41 14.4, 146, 1504 mg/kg bw/day. NOAEL =14.4 mg/kgbw/day. Butylparaben Wistar rat Non GLP Non guideline Study of the potential reproductive effects of butyl- paraben on male rats (19-21 days old), receiving butyl- paraben through the oral route for 8 weeks at dosage levels of 10.4, 103, 1026 mg/kg bw/day. There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Decreases in cauda epididymal sperm reserve, sperm count, daily sperm production and in serum testosterone concentration were observed from","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kgbw/day","noael_value":"=14.4","page":41,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_016"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==100; DOSE=Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression Pups:; EFFECT=________________________________________________________________________________ 96 protein (StAR) and CYP11a1. utyl- paraben (purity not reported) Sprague- Dawley rats Development of male reproductive system, s.c. (GD6-PND20). Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression Pups: Live births ↓ Surviving to weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) Kang et al., 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben (purity not reported) Wistar rats Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) Fisher et al., 1999 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression Pups:","duration":"","effect":"________________________________________________________________________________ 96 protein (StAR) and CYP11a1. utyl- paraben (purity not reported) Sprague- Dawley rats Development of male reproductive system, s.c. (GD6-PND20). Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression Pups: Live births ↓ Surviving to weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) Kang et al., 2002 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA) Butyl- paraben (purity not reported) Wistar rats Neonatal repeated, s.c injection (PND 2-18). Dose: 2 mg/ kg bw /day, n= 6. Testis weight Testis histopathology (no significant effects) NOEL=2 mg/kg bw/day (no effects) Fisher et al., 1999 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"=100","page":96,"route":"","species":"rat","study_id":"sccs_o_275_noael_036"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT==100; DOSE=Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups:; EFFECT=Unlabeled table on page 96: utyl- paraben (purity not reported) | Sprague- Dawley rats | Development of male reproductive system, s.c. (GD6-PND20). Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups: Live births ↓ Surviving to weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) | Kang et al., 2002 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups:","duration":"","effect":"Unlabeled table on page 96: utyl- paraben (purity not reported) | Sprague- Dawley rats | Development of male reproductive system, s.c. (GD6-PND20). Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups: Live births ↓ Surviving to weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) | Kang et al., 2002 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"=100","page":96,"route":"","species":"rat","study_id":"sccs_o_275_noael_063"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 160; DOSE=64, 160, 400, 1000 mg/kg bw/day, n = 7- 8.; EFFECT=__________________________________________________ 98 Butyl- paraben Wistar rats Mechanisms of ED and reproductive disorders, oral (gavage) (GD7- PND21). Dose: 64, 160, 400, 1000 mg/kg bw/day, n = 7- 8. Body weight ↓ Weight: Testis Epididymis ↓ Seminal vesicle Hormones: Testosterone ↓ Estradiol ↑ Gene expression: Star, P450scc, Sult1e1 (affected) Gene and protein expression: Erα, Erβ, Ar (affected) Methylation of Erα promoter ↓ Histopathology testis (affected) ! may be partially same study as Zhang et al., 2014 NOAEL = 160 mg/kg bw/day (effects are seen at protein level at this dose) Zhang et al., 2016 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"64, 160, 400, 1000 mg/kg bw/day, n = 7- 8.","duration":"","effect":"__________________________________________________ 98 Butyl- paraben Wistar rats Mechanisms of ED and reproductive disorders, oral (gavage) (GD7- PND21). Dose: 64, 160, 400, 1000 mg/kg bw/day, n = 7- 8. Body weight ↓ Weight: Testis Epididymis ↓ Seminal vesicle Hormones: Testosterone ↓ Estradiol ↑ Gene expression: Star, P450scc, Sult1e1 (affected) Gene and protein expression: Erα, Erβ, Ar (affected) Methylation of Erα promoter ↓ Histopathology testis (affected) ! may be partially same study as Zhang et al., 2014 NOAEL = 160 mg/kg bw/day (effects are seen at protein level at this dose) Zhang et al., 2016 Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 160","page":98,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_039"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=200; DOSE=Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups:; EFFECT=Unlabeled table on page 96: utyl- paraben (purity not reported) | Sprague- Dawley rats | Development of male reproductive system, s.c. (GD6-PND20). Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups: Live births ↓ Surviving to weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) | Kang et al., 2002 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups:","duration":"","effect":"Unlabeled table on page 96: utyl- paraben (purity not reported) | Sprague- Dawley rats | Development of male reproductive system, s.c. (GD6-PND20). Dose 110, 200 mg/ kg bw/day, n = 5- 7 for organ weight/histolog y, 5 form sperm parameters and 3 for gene expression | Pups: Live births ↓ Surviving to weaning ↓ AGD Weight: Testis ↓↑ Prostate ↓ Seminal vesicle ↓ Sperm: Numbers ↓ Motility ↓ Morphology ↓ ERα and ERβ expression in testis ↓↑ NOAEL=100mg/kg bw/day (Effects on, testes, seminal vesicles, prostate glands sperm count and motility) | Kang et al., 2002 | Boberg et al., 2020 (The Danish Environmen tal Protection Agency (DK-EPA)","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/ kg bw/day","noael_value":"200","page":96,"route":"","species":"rat","study_id":"sccs_o_275_noael_061"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=325; DOSE=Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day.; EFFECT=any of the studies in this section were dosed at very high levels. Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day. In a multi- generation continuous breeding study, performed by the US NTP in 2011 (and published later in Hubbard et al. 2020), adult rats were seen to display adaptive effects in the liver, hence the liver was regarded as a target organ in this study and a conservative NOAEL was established at 325 mg/kg bw/day. 3.4.5 Reproductive toxicity In vivo animal reproductive and developmental studies that are available for use in a cosmetic safety assessment for butylparaben are summarised in Table 5 Table 5: summary of DART (developmental and reproductive toxicology) studies on butylparaben Test substances Test system Test principle(s) Result(s) and conclusion(s) Reference A) in vivo experiments - female effect Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c par; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day.","duration":"developmental","effect":"any of the studies in this section were dosed at very high levels. Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day. In a multi- generation continuous breeding study, performed by the US NTP in 2011 (and published later in Hubbard et al. 2020), adult rats were seen to display adaptive effects in the liver, hence the liver was regarded as a target organ in this study and a conservative NOAEL was established at 325 mg/kg bw/day. 3.4.5 Reproductive toxicity In vivo animal reproductive and developmental studies that are available for use in a cosmetic safety assessment for butylparaben are summarised in Table 5 Table 5: summary of DART (developmental and reproductive toxicology) studies on butylparaben Test substances Test system Test principle(s) Result(s) and conclusion(s) Reference A) in vivo experiments - female effect Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c par","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"325","page":38,"route":"","species":"rat","study_id":"sccs_o_275_noael_011"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=325; DOSE=Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose.; EFFECT=(2004), Hoberman et al. (2008) and Shaw & deCantazaro et al. (2009). A supporting study in Roberts et al. (2016) confirms that pups and dams in Hubbard et al. (2020) were sufficiently exposed to parent butylparaben in the RACB study and there were no effects in pups. Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose. Based on the observed effects in liver in Hubbard et al. (2020), a conservative NOAEL of 325 mg/kg/day can be used in a safety evaluation. SCCS comment The SCCS has closely looked to the argumentation of the applicant with respect to the in vivo reproductive and developmental studies available to determine a suitable NOAEL value and agrees with a conservative NOAEL value of 325 mg/kg bw/d. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro The applicant provided an overview of the available in vitro mutagenicity/genotoxicity studies on butylparaben, see Table 7. Tab; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose.","duration":"developmental","effect":"(2004), Hoberman et al. (2008) and Shaw & deCantazaro et al. (2009). A supporting study in Roberts et al. (2016) confirms that pups and dams in Hubbard et al. (2020) were sufficiently exposed to parent butylparaben in the RACB study and there were no effects in pups. Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose. Based on the observed effects in liver in Hubbard et al. (2020), a conservative NOAEL of 325 mg/kg/day can be used in a safety evaluation. SCCS comment The SCCS has closely looked to the argumentation of the applicant with respect to the in vivo reproductive and developmental studies available to determine a suitable NOAEL value and agrees with a conservative NOAEL value of 325 mg/kg bw/d. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro The applicant provided an overview of the available in vitro mutagenicity/genotoxicity studies on butylparaben, see Table 7. Tab","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"325","page":45,"route":"","species":"","study_id":"sccs_o_275_noael_027"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=325; DOSE=Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose.; EFFECT=ere were no effects in pups. Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose. Based on the observed effects in liver in Hubbard et al. (2020), a conservative NOAEL of 325 mg/kg/day can be used in a safety evaluation. SCCS comment The SCCS has closely looked to the argumentation of the applicant with respect to the in vivo reproductive and developmental studies available to determine a suitable NOAEL value and agrees with a conservative NOAEL value of 325 mg/kg bw/d. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro The applicant provided an overview of the available in vitro mutagenicity/genotoxicity studies on butylparaben, see Table 7. Table 7: In vitro assays for butylparaben Methods Test Article Results Reference Bacterial gene mutation assays S.typhimurium TA97, TA98, TA100, TA1535; OECD Test Guidelines Ames Test 1, 3, 10, 33, 100, 166, 333, 1000, 3333 µg BP/plate Non-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose.","duration":"developmental","effect":"ere were no effects in pups. Some adaptive effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose. Based on the observed effects in liver in Hubbard et al. (2020), a conservative NOAEL of 325 mg/kg/day can be used in a safety evaluation. SCCS comment The SCCS has closely looked to the argumentation of the applicant with respect to the in vivo reproductive and developmental studies available to determine a suitable NOAEL value and agrees with a conservative NOAEL value of 325 mg/kg bw/d. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro The applicant provided an overview of the available in vitro mutagenicity/genotoxicity studies on butylparaben, see Table 7. Table 7: In vitro assays for butylparaben Methods Test Article Results Reference Bacterial gene mutation assays S.typhimurium TA97, TA98, TA100, TA1535; OECD Test Guidelines Ames Test 1, 3, 10, 33, 100, 166, 333, 1000, 3333 µg BP/plate Non-","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"325","page":45,"route":"","species":"","study_id":"sccs_o_275_noael_028"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=325; DOSE=effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose.; EFFECT=effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose. Based on the observed effects in liver in Hubbard et al. (2020), a conservative NOAEL of 325 mg/kg/day can be used in a safety evaluation. SCCS comment The SCCS has closely looked to the argumentation of the applicant with respect to the in vivo reproductive and developmental studies available to determine a suitable NOAEL value and agrees with a conservative NOAEL value of 325 mg/kg bw/d. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro The applicant provided an overview of the available in vitro mutagenicity/genotoxicity studies on butylparaben, see Table 7. Table 7: In vitro assays for butylparaben Methods Test Article Results Reference Bacterial gene mutation assays S.typhimurium TA97, TA98, TA100, TA1535; OECD Test Guidelines Ames Test 1, 3, 10, 33, 100, 166, 333, 1000, 3333 µg BP/plate Non-mutagenic (with and without S9) NTP (2018); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose.","duration":"developmental","effect":"effects in the liver were seen in female adults, and some non-neoplastic lesions, suggesting the liver as a potential target organ of toxicity at high dose. Based on the observed effects in liver in Hubbard et al. (2020), a conservative NOAEL of 325 mg/kg/day can be used in a safety evaluation. SCCS comment The SCCS has closely looked to the argumentation of the applicant with respect to the in vivo reproductive and developmental studies available to determine a suitable NOAEL value and agrees with a conservative NOAEL value of 325 mg/kg bw/d. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro The applicant provided an overview of the available in vitro mutagenicity/genotoxicity studies on butylparaben, see Table 7. Table 7: In vitro assays for butylparaben Methods Test Article Results Reference Bacterial gene mutation assays S.typhimurium TA97, TA98, TA100, TA1535; OECD Test Guidelines Ames Test 1, 3, 10, 33, 100, 166, 333, 1000, 3333 µg BP/plate Non-mutagenic (with and without S9) NTP (2018)","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"325","page":45,"route":"","species":"","study_id":"sccs_o_275_noael_029"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=900; DOSE=Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day.; EFFECT=Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 38 adaptive liver effects in this study (NTP, 2011; published subsequently in Hubbard et al., 2020). Conclusion by the applicant Many of the studies in this section were dosed at very high levels. Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day. In a multi- generation continuous breeding study, performed by the US NTP in 2011 (and published later in Hubbard et al. 2020), adult rats were seen to display adaptive effects in the liver, hence the liver was regarded as a target organ in this study and a conservative NOAEL was established at 325 mg/kg bw/day. 3.4.5 Reproductive toxicity In vivo animal reproductive and developmental studies that are available for use; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day.","duration":"developmental","effect":"Opinion on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7) _________________________________________________________________________________________ _________________________________________________________________________________________ 38 adaptive liver effects in this study (NTP, 2011; published subsequently in Hubbard et al., 2020). Conclusion by the applicant Many of the studies in this section were dosed at very high levels. Based on the results from these studies investigating repeat-dose toxicity, the NOAEL from general repeat-dose toxicity studies of butylparaben was observed to be ≥900 mg/kg bw/day. In a multi- generation continuous breeding study, performed by the US NTP in 2011 (and published later in Hubbard et al. 2020), adult rats were seen to display adaptive effects in the liver, hence the liver was regarded as a target organ in this study and a conservative NOAEL was established at 325 mg/kg bw/day. 3.4.5 Reproductive toxicity In vivo animal reproductive and developmental studies that are available for use","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"900","page":38,"route":"","species":"rat","study_id":"sccs_o_275_noael_010"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1000; DOSE=Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19.; EFFECT=l pregnancies. A uterotrophic assay was conducted to re-evaluate in vivo data Shaw and de Catanzaro, 2009 Butylparaben Sprague Dawley rats Developmental study according to OECD test guideline and GLP. Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19. Foetuses examination on gestational day 20; developmental parameters measured At the highest dose, maternal food consumption reduced during exposure time, weight gain reduced on days 18-20. No developmental parameters changed. Developmental (oral) NOAEL: 1000 mg/kg bw/day. Daston, 2004 B) In vivo experiments: male effects Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged12-13 wks) n = 26-40) RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. No male reproductive or developmental effects observed at any dose. NTP (live phase completed 2011); Hubbard et al. 2020. Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) RACB study to GLP: supplemen; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19.","duration":"Developmental","effect":"l pregnancies. A uterotrophic assay was conducted to re-evaluate in vivo data Shaw and de Catanzaro, 2009 Butylparaben Sprague Dawley rats Developmental study according to OECD test guideline and GLP. Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6- 19. Foetuses examination on gestational day 20; developmental parameters measured At the highest dose, maternal food consumption reduced during exposure time, weight gain reduced on days 18-20. No developmental parameters changed. Developmental (oral) NOAEL: 1000 mg/kg bw/day. Daston, 2004 B) In vivo experiments: male effects Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged12-13 wks) n = 26-40) RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. No male reproductive or developmental effects observed at any dose. NTP (live phase completed 2011); Hubbard et al. 2020. Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) RACB study to GLP: supplemen","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":39,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_013"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1000; DOSE=The highest dose level of 1000 mg/kg bw/day produced decreases in maternal weight gain during some of the treatment intervals (reaching statistical significance during the gestation day 18–20 interval), as well as a significant decrease in food consumption measured over the entire 15-day treatment period.; EFFECT=00 mg/kg bw/day. The highest dose level of 1000 mg/kg bw/day produced decreases in maternal weight gain during some of the treatment intervals (reaching statistical significance during the gestation day 18–20 interval), as well as a significant decrease in food consumption measured over the entire 15-day treatment period. However, the observed decreases in maternal weight gain did not follow a dose response. A benchmark dose model was further submitted by the applicant, using the data to illustrate this point. The NOAEL for adult females from this study was taken as 1000 mg/kg/day and the developmental NOAEL was also 1000 mg/kg/day. The observations in Daston (2004) were confirmed in mice by Shaw and deCantanzaro (2009), who saw no effects on female reproductive parameters at subcutaneous doses of up to 949 mg/kg bw/day and no effects in an uterotrophic assay conducted in two different strains of mice. Hoberman et al. (2008) specifically investigated the putative effects on male reproduction and sperm in rats, in a study designe; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"The highest dose level of 1000 mg/kg bw/day produced decreases in maternal weight gain during some of the treatment intervals (reaching statistical significance during the gestation day 18–20 interval), as well as a significant decrease in food consumption measured over the entire 15-day treatment period.","duration":"15-day","effect":"00 mg/kg bw/day. The highest dose level of 1000 mg/kg bw/day produced decreases in maternal weight gain during some of the treatment intervals (reaching statistical significance during the gestation day 18–20 interval), as well as a significant decrease in food consumption measured over the entire 15-day treatment period. However, the observed decreases in maternal weight gain did not follow a dose response. A benchmark dose model was further submitted by the applicant, using the data to illustrate this point. The NOAEL for adult females from this study was taken as 1000 mg/kg/day and the developmental NOAEL was also 1000 mg/kg/day. The observations in Daston (2004) were confirmed in mice by Shaw and deCantanzaro (2009), who saw no effects on female reproductive parameters at subcutaneous doses of up to 949 mg/kg bw/day and no effects in an uterotrophic assay conducted in two different strains of mice. Hoberman et al. (2008) specifically investigated the putative effects on male reproduction and sperm in rats, in a study designe","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":42,"route":"","species":"rat","study_id":"sccs_o_275_noael_022"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1000; DOSE=However, the observed decreases in maternal weight gain did not follow a dose response.; EFFECT=l weight gain during some of the treatment intervals (reaching statistical significance during the gestation day 18–20 interval), as well as a significant decrease in food consumption measured over the entire 15-day treatment period. However, the observed decreases in maternal weight gain did not follow a dose response. A benchmark dose model was further submitted by the applicant, using the data to illustrate this point. The NOAEL for adult females from this study was taken as 1000 mg/kg/day and the developmental NOAEL was also 1000 mg/kg/day. The observations in Daston (2004) were confirmed in mice by Shaw and deCantanzaro (2009), who saw no effects on female reproductive parameters at subcutaneous doses of up to 949 mg/kg bw/day and no effects in an uterotrophic assay conducted in two different strains of mice. Hoberman et al. (2008) specifically investigated the putative effects on male reproduction and sperm in rats, in a study designed with the aim of reproducing the observations seen by Oishi (2001). The dosing regimen, d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"However, the observed decreases in maternal weight gain did not follow a dose response.","duration":"15-day","effect":"l weight gain during some of the treatment intervals (reaching statistical significance during the gestation day 18–20 interval), as well as a significant decrease in food consumption measured over the entire 15-day treatment period. However, the observed decreases in maternal weight gain did not follow a dose response. A benchmark dose model was further submitted by the applicant, using the data to illustrate this point. The NOAEL for adult females from this study was taken as 1000 mg/kg/day and the developmental NOAEL was also 1000 mg/kg/day. The observations in Daston (2004) were confirmed in mice by Shaw and deCantanzaro (2009), who saw no effects on female reproductive parameters at subcutaneous doses of up to 949 mg/kg bw/day and no effects in an uterotrophic assay conducted in two different strains of mice. Hoberman et al. (2008) specifically investigated the putative effects on male reproduction and sperm in rats, in a study designed with the aim of reproducing the observations seen by Oishi (2001). The dosing regimen, d","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":42,"route":"","species":"rat","study_id":"sccs_o_275_noael_023"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1000; DOSE=There were no effects seen up to the highest dose tested of 1000 mg/kg bw/day in any of the parameters measured.; EFFECT=left testes, right and left epididymis, seminal vesicles, and prostate) were weighed and retained for histology. Sperm concentration and motility was evaluated. There were no effects seen up to the highest dose tested of 1000 mg/kg bw/day in any of the parameters measured. Body weight increased as per the control group over the duration of the study. There were no effects on male sperm motility, count or daily sperm production. There were no adverse histological findings in any of the organs and glands tested. The NOEL in this study was 1000 mg/kg bw/day. To add further confidence that there are no reproductive or developmental effects for butylparaben, a large multigenerational reproductive assessment by continuous breeding study was performed by the US NTP (live phase completed in 2011), as published by Hubbard et al. (2020). The Applicant considered this the pivotal study to derive the POD for the safety evaluation and is detailed below. Pivotal Study – Hubbard et al. 2020 A multigenerational reproductive assessment by conti; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"There were no effects seen up to the highest dose tested of 1000 mg/kg bw/day in any of the parameters measured.","duration":"developmental","effect":"left testes, right and left epididymis, seminal vesicles, and prostate) were weighed and retained for histology. Sperm concentration and motility was evaluated. There were no effects seen up to the highest dose tested of 1000 mg/kg bw/day in any of the parameters measured. Body weight increased as per the control group over the duration of the study. There were no effects on male sperm motility, count or daily sperm production. There were no adverse histological findings in any of the organs and glands tested. The NOEL in this study was 1000 mg/kg bw/day. To add further confidence that there are no reproductive or developmental effects for butylparaben, a large multigenerational reproductive assessment by continuous breeding study was performed by the US NTP (live phase completed in 2011), as published by Hubbard et al. (2020). The Applicant considered this the pivotal study to derive the POD for the safety evaluation and is detailed below. Pivotal Study – Hubbard et al. 2020 A multigenerational reproductive assessment by conti","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":43,"route":"","species":"","study_id":"sccs_o_275_noael_024"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=1504; DOSE=Mice (25- 27 days old) received butyl- paraben through the oral route for 10 weeks at dosage levels of | Administration of butylparaben at 146 and 1504 mg/kg bw/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. | Oishi 2002; EFFECT=Unlabeled table on page 40: Butylparaben | CD-1 ICR mice Non GLP Non guideline | Study of the effects of butyl- paraben on general function of the male mouse reproductive system. Mice (25- 27 days old) received butyl- paraben through the oral route for 10 weeks at dosage levels of | Administration of butylparaben at 146 and 1504 mg/kg bw/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. | Oishi 2002; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Mice (25- 27 days old) received butyl- paraben through the oral route for 10 weeks at dosage levels of | Administration of butylparaben at 146 and 1504 mg/kg bw/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. | Oishi 2002","duration":"27 days","effect":"Unlabeled table on page 40: Butylparaben | CD-1 ICR mice Non GLP Non guideline | Study of the effects of butyl- paraben on general function of the male mouse reproductive system. Mice (25- 27 days old) received butyl- paraben through the oral route for 10 weeks at dosage levels of | Administration of butylparaben at 146 and 1504 mg/kg bw/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. | Oishi 2002","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1504","page":40,"route":"oral","species":"mouse","study_id":"sccs_o_275_noael_049"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT== 5000; DOSE=rague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged 12-13 weeks, n =26-40) RACB*) study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm.; EFFECT=rague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged 12-13 weeks, n =26-40) RACB*) study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. No female reproductive or developmental effects observed at any dose in any generation. Increases in liver weights, and some incidences of non- neoplastic liver lesions suggest the liver is a target organ. No findings were observed that would support any mechanism of BP- induced endocrine disruption NOAEL = 5000 ppm, equivalent to 325 – 740 mg/kg/day (observations in liver in adult F1 females only) NTP (live phase completed 2011); Hubbard et al., 2020 Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, No female reproductive or developmental effects. Showed exposure to the test article to NTP (live phase completed 2012);; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"rague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged 12-13 weeks, n =26-40) RACB*) study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm.","duration":"11 weeks","effect":"rague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged 12-13 weeks, n =26-40) RACB*) study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. No female reproductive or developmental effects observed at any dose in any generation. Increases in liver weights, and some incidences of non- neoplastic liver lesions suggest the liver is a target organ. No findings were observed that would support any mechanism of BP- induced endocrine disruption NOAEL = 5000 ppm, equivalent to 325 – 740 mg/kg/day (observations in liver in adult F1 females only) NTP (live phase completed 2011); Hubbard et al., 2020 Butylparaben Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, No female reproductive or developmental effects. Showed exposure to the test article to NTP (live phase completed 2012);","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"= 5000","page":38,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_012"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=10,000; DOSE=udy (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputi...; EFFECT=udy (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi (2001), sperm parameters were found unaffected. With both MeP and Butylparaben, the highest dose level in food corresponds to a NOAEL of 10,000 ppm, NOAEL=1100 mg/kgbw/day Hoberman et al. 2008 Butylparaben Sprague Dawley rats Non GLP Non guideline Study of the effect of butyl- paraben on the development of the reproductive organs of F1 offspring when pregnant rats are subcutaneously injected with 100 or 200 mg butyl- paraben/kg/day from gestation day 6 to postnatal day 20 (lactation period). At both dosage levels, the weights of testes, seminal vesicles and prostate glands were decreased, together with the sperm count and the sperm motile activi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"udy (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputi...","duration":"","effect":"udy (2001) under GLP with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi (2001), sperm parameters were found unaffected. With both MeP and Butylparaben, the highest dose level in food corresponds to a NOAEL of 10,000 ppm, NOAEL=1100 mg/kgbw/day Hoberman et al. 2008 Butylparaben Sprague Dawley rats Non GLP Non guideline Study of the effect of butyl- paraben on the development of the reproductive organs of F1 offspring when pregnant rats are subcutaneously injected with 100 or 200 mg butyl- paraben/kg/day from gestation day 6 to postnatal day 20 (lactation period). At both dosage levels, the weights of testes, seminal vesicles and prostate glands were decreased, together with the sperm count and the sperm motile activi","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"10,000","page":40,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_014"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=10,000; DOSE=with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputial glands in any of t...; EFFECT=with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi (2001), sperm parameters were found unaffected. With both MeP and Butylparaben, the highest dose level in food corresponds to a NOAEL of 10,000 ppm, NOAEL=1100 mg/kgbw/day Hoberman et al. 2008 Butylparaben Sprague Dawley rats Non GLP Non guideline Study of the effect of butyl- paraben on the development of the reproductive organs of F1 offspring when pregnant rats are subcutaneously injected with 100 or 200 mg butyl- paraben/kg/day from gestation day 6 to postnatal day 20 (lactation period). At both dosage levels, the weights of testes, seminal vesicles and prostate glands were decreased, together with the sperm count and the sperm motile activity in the epididymis.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputial glands in any of t...","duration":"","effect":"with MeP or Butylparaben using the same strain of rats but 16 instead of 8 animals per dose group, same oral route dosage levels of 0, 100, 1000 and 10,000 ppm in food. blood samples were weekly taken for the analysis of LH, FSH and testosterone There were no treatment related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi (2001), sperm parameters were found unaffected. With both MeP and Butylparaben, the highest dose level in food corresponds to a NOAEL of 10,000 ppm, NOAEL=1100 mg/kgbw/day Hoberman et al. 2008 Butylparaben Sprague Dawley rats Non GLP Non guideline Study of the effect of butyl- paraben on the development of the reproductive organs of F1 offspring when pregnant rats are subcutaneously injected with 100 or 200 mg butyl- paraben/kg/day from gestation day 6 to postnatal day 20 (lactation period). At both dosage levels, the weights of testes, seminal vesicles and prostate glands were decreased, together with the sperm count and the sperm motile activity in the epididymis.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"10,000","page":40,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_015"}

sccs_o_275.pdf

SOURCE_SUBDIR=sccs_o_275; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Butylparaben (CAS No. 94-26-8, EC No. 202-318-7); OPINION_NUMBER=SCCS/1651/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 26 October 2023; VALUE_TEXT=40000; DOSE=Butylparaben | Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged12-13 wks) n = 26-40) | RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. | No male reproductive or developmental effects observed at any dose. | NTP (live phase completed 2011);; EFFECT=Unlabeled table on page 39: Butylparaben | Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged12-13 wks) n = 26-40) | RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. | No male reproductive or developmental effects observed at any dose. | NTP (live phase completed 2011); Hubbard et al. 2020.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-26-8","citation":"","dose":"Butylparaben | Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged12-13 wks) n = 26-40) | RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. | No male reproductive or developmental effects observed at any dose. | NTP (live phase completed 2011);","duration":"11 weeks","effect":"Unlabeled table on page 39: Butylparaben | Sprague Dawley rats, F0 (aged 11 weeks, n=22/sex/group) and F1c parental (F1cP) animals (aged12-13 wks) n = 26-40) | RACB study to GLP: supplementation in NIH-07 powdered feed at levels of 0, 5000, 15000, or 40000 ppm. | No male reproductive or developmental effects observed at any dose. | NTP (live phase completed 2011); Hubbard et al. 2020.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"40000","page":39,"route":"oral","species":"rat","study_id":"sccs_o_275_noael_047"}

sccs_o_275.pdf