, or to derive a toxicological point of departure based, codes ............................................... 10, s are covered by this entry, with the

{"dose":", 500 mg/kg/day propylparaben for 318 to 394 days.","effect":", 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on the toxicokinetics and reproductive toxicity of propylparaben in male juvenile Wistar rats starting from PND 21 we","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_005"}

sccs_o_243.pdf

{"dose":", 500 mg/kg/day propylparaben for 318 to 394 days.","effect":", 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on the toxicokinetics and reproductive toxicity of propylparaben in male juvenile Wistar rats starting from PND 21 we","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_005"}

sccs_o_243.pdf

{"dose":", 500 mg/kg/day propylparaben for 318 to 394 days.","effect":", 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on the toxicokinetics and reproductive toxicity of propylparaben in male juvenile Wistar rats starting from PND 21 we","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_005"}

sccs_o_243.pdf

{"dose":", 500 mg/kg/day propylparaben for 318 to 394 days.","effect":", 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on the toxicokinetics and reproductive toxicity of propylparaben in male juvenile Wistar rats starting from PND 21 we","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_005"}

sccs_o_243.pdf

{"dose":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days.","effect":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_004"}

sccs_o_243.pdf

{"dose":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days.","effect":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_004"}

sccs_o_243.pdf

{"dose":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days.","effect":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_004"}

sccs_o_243.pdf

{"dose":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days.","effect":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on","page":23,"pdf":"sccs_o_243.pdf","row_type":"noael_study","study_id":"sccs_o_243_noael_004"}

sccs_o_243.pdf

SOURCE_SUBDIR=sccs_o_243; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Propylparaben (PP); OPINION_NUMBER=SCCS/1623/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=2; DOSE=, 500 mg/kg/day propylparaben for 318 to 394 days.; EFFECT=, 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on the toxicokinetics and reproductive toxicity of propylparaben in male juvenile Wistar rats starting from PND 21 we; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":", 500 mg/kg/day propylparaben for 318 to 394 days.","duration":"394 days","effect":", 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on the toxicokinetics and reproductive toxicity of propylparaben in male juvenile Wistar rats starting from PND 21 we","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"2","page":23,"route":"","species":"rat","study_id":"sccs_o_243_noael_005"}

sccs_o_243.pdf

SOURCE_SUBDIR=sccs_o_243; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Propylparaben (PP); OPINION_NUMBER=SCCS/1623/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days.; EFFECT=hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days.","duration":"422 days","effect":"hors also dosed weanling dogs as follows: six dogs, 1000 mg/kg/day propylparaben for 378 to 422 days; and three dogs, 500 mg/kg/day propylparaben for 318 to 394 days. Two untreated dogs served as a control group. All dogs were killed for necropsy upon completion of the feeding. No toxicity to the parabens was observed. All animals were in excellent condition throughout the experiment. All tissues were normal. SCCS comment Although this study is old, and from a secondary report from the CIR 2008, it corroborates a NOAEL of 1000 mg/kg/day. 3.4.5 Reproductive toxicity In its Opinion from 2013 (SCCS/1514/13), the SCCS derived a NOEL for butylparaben of 2 mg/kg/day in male juvenile rats from a study by Fisher (1999). 3.4.5.1 Fertility and reproduction toxicity Fertility and reproduction toxicity studies have been extensively reviewed and evaluated in previous Opinions (SCCS/1348/10 and SCCS 2013). In order to confirm or challenge and further characterize the effects by Oishi 2002, in vivo GLP-compliant studies on","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":23,"route":"","species":"rat","study_id":"sccs_o_243_noael_004"}

sccs_o_243.pdf

SOURCE_SUBDIR=sccs_o_243; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Propylparaben (PP); OPINION_NUMBER=SCCS/1623/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=SCCS/1623/20 Final Opinion Opinion on Propylparaben ___________________________________________________________________________________________ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg.; EFFECT=SCCS/1623/20 Final Opinion Opinion on Propylparaben ___________________________________________________________________________________________ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg. Given there are no effects and no dose response, a BMD could not be calculated and therefore the NOAEL value can be used as the toxicological point of departure (POD). SCCS conclusion Based on the studies performed after the publication of previous Opinion (SCCS/1514/13), the SCCS agrees that reproductive toxicity, neurotoxicity and immunotoxicity data (in rats) suggest a NOAEL of 1000 mg/kg/day. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro From the applicant dossier: Available in vitro data for mutagenicity and genotoxicity for propylparaben are presented in Table 4. Table 4; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"SCCS/1623/20 Final Opinion Opinion on Propylparaben ___________________________________________________________________________________________ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg.","duration":"","effect":"SCCS/1623/20 Final Opinion Opinion on Propylparaben ___________________________________________________________________________________________ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg. Given there are no effects and no dose response, a BMD could not be calculated and therefore the NOAEL value can be used as the toxicological point of departure (POD). SCCS conclusion Based on the studies performed after the publication of previous Opinion (SCCS/1514/13), the SCCS agrees that reproductive toxicity, neurotoxicity and immunotoxicity data (in rats) suggest a NOAEL of 1000 mg/kg/day. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro From the applicant dossier: Available in vitro data for mutagenicity and genotoxicity for propylparaben are presented in Table 4. Table 4","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":26,"route":"","species":"rat","study_id":"sccs_o_243_noael_014"}

sccs_o_243.pdf

SOURCE_SUBDIR=sccs_o_243; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Propylparaben (PP); OPINION_NUMBER=SCCS/1623/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=_____ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg.; EFFECT=_____ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg. Given there are no effects and no dose response, a BMD could not be calculated and therefore the NOAEL value can be used as the toxicological point of departure (POD). SCCS conclusion Based on the studies performed after the publication of previous Opinion (SCCS/1514/13), the SCCS agrees that reproductive toxicity, neurotoxicity and immunotoxicity data (in rats) suggest a NOAEL of 1000 mg/kg/day. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro From the applicant dossier: Available in vitro data for mutagenicity and genotoxicity for propylparaben are presented in Table 4. Table 4: In vitro assays for propylparaben Methods Test Article Metabolic activation Results Reference Bacteria S. typhimurium strains TA100, TA98, TA1535, and TA1537 10 to 2000 µg/plate Aroclor 1254- induced rat liver microsomal enzymes (S9) Non mutagenic, with or without metabolic a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"_____ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg.","duration":"","effect":"_____ _________________________________________________________________________________ 26 propylparaben is the top dose tested at 1000 mg/kg. Given there are no effects and no dose response, a BMD could not be calculated and therefore the NOAEL value can be used as the toxicological point of departure (POD). SCCS conclusion Based on the studies performed after the publication of previous Opinion (SCCS/1514/13), the SCCS agrees that reproductive toxicity, neurotoxicity and immunotoxicity data (in rats) suggest a NOAEL of 1000 mg/kg/day. 3.4.6 Mutagenicity / genotoxicity 3.4.6.1 Mutagenicity / genotoxicity in vitro From the applicant dossier: Available in vitro data for mutagenicity and genotoxicity for propylparaben are presented in Table 4. Table 4: In vitro assays for propylparaben Methods Test Article Metabolic activation Results Reference Bacteria S. typhimurium strains TA100, TA98, TA1535, and TA1537 10 to 2000 µg/plate Aroclor 1254- induced rat liver microsomal enzymes (S9) Non mutagenic, with or without metabolic a","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":26,"route":"","species":"rat","study_id":"sccs_o_243_noael_015"}

sccs_o_243.pdf

{"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","page":35,"pdf":"sccs_o_275.pdf","row_type":"noael_study","study_id":"sccs_o_275_noael_001"}

sccs_o_275.pdf

{"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","page":35,"pdf":"sccs_o_275.pdf","row_type":"noael_study","study_id":"sccs_o_275_noael_001"}

sccs_o_275.pdf

{"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","page":35,"pdf":"sccs_o_275.pdf","row_type":"noael_study","study_id":"sccs_o_275_noael_001"}

sccs_o_275.pdf

{"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","page":35,"pdf":"sccs_o_275.pdf","row_type":"noael_study","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=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== 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_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=(1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application.; EFFECT=es of a 5 product. 6 7 3.2 Issues 8 9 3.2.1 Potential endocrine effects of parabens 10 11 Possible effects on the developing organism 12 After considering the main arguments of a recent review of Boberg et al. (2010), the SCCS 13 stated in its Opinion (SCCS/1446/11): The toxicity of parabens, in particular butylparaben, 14 has been investigated in previous and more recent studies, with exposure in utero, during 15 lactation and in juvenile animals (see Appendix 1). The lowest available critical effect level 16 (NOAEL) chosen in the safety assessment (Opinion SCCS/1348/10) was based on such 17 studies. 18 The study chosen by the SCCP/SCCS was that of Fisher et al. (1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application. 21 In other studies in female and male rodents, often (much) higher dose levels (several 22 hundred up to 1200 mg/kg bw) were administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"(1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application.","duration":"","effect":"es of a 5 product. 6 7 3.2 Issues 8 9 3.2.1 Potential endocrine effects of parabens 10 11 Possible effects on the developing organism 12 After considering the main arguments of a recent review of Boberg et al. (2010), the SCCS 13 stated in its Opinion (SCCS/1446/11): The toxicity of parabens, in particular butylparaben, 14 has been investigated in previous and more recent studies, with exposure in utero, during 15 lactation and in juvenile animals (see Appendix 1). The lowest available critical effect level 16 (NOAEL) chosen in the safety assessment (Opinion SCCS/1348/10) was based on such 17 studies. 18 The study chosen by the SCCP/SCCS was that of Fisher et al. (1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application. 21 In other studies in female and male rodents, often (much) higher dose levels (several 22 hundred up to 1200 mg/kg bw) were administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":8,"route":"","species":"rat","study_id":"sccs_o_132_noael_003"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.; EFFECT=SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 10 for the final safety assessment of the parabens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.","duration":"","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 10 for the final safety assessment of the parabens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg","noael_value":"2","page":10,"route":"oral","species":"","study_id":"sccs_o_132_noael_006"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=Neither EtPB nor BuPB showed any treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. BuPB caused a significant decrease as well in the mRNA β-ER expression level in fetal ovaries, as in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose-dependency. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3; DOSE=However, these effects show no dose-dependency.; EFFECT=Unlabeled table on page 37: EtPB BuPB | Wistar rats | Study of the effect of parabens on the steroidogenesis in rats and their offspring when dams are subcutaneously exposed to either: - 400 mg EtPB/kg/day; or - 200 - 400 mg BuPB/kg/day from gestation day 7 to 21. | Neither EtPB nor BuPB showed any treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. BuPB caused a significant decrease as well in the mRNA β-ER expression level in fetal ovaries, as in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose-dependency. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3 | Taxvig et al. 2008; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"However, these effects show no dose-dependency.","duration":"","effect":"Unlabeled table on page 37: EtPB BuPB | Wistar rats | Study of the effect of parabens on the steroidogenesis in rats and their offspring when dams are subcutaneously exposed to either: - 400 mg EtPB/kg/day; or - 200 - 400 mg BuPB/kg/day from gestation day 7 to 21. | Neither EtPB nor BuPB showed any treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. BuPB caused a significant decrease as well in the mRNA β-ER expression level in fetal ovaries, as in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose-dependency. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3 | Taxvig et al. 2008","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"Neither EtPB nor BuPB showed any treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. BuPB caused a significant decrease as well in the mRNA β-ER expression level in fetal ovaries, as in mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. However, these effects show no dose-dependency. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3","page":37,"route":"","species":"rat","study_id":"sccs_o_132_noael_034"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=4.36; DOSE=No dosage level(s) stated. ‘Estimated dose’ is 4.36 mg/kg bw/day | Early exposure to IsoBuPB may increase anxiety, and specifically disturb passive avoidance performance, although the effects are male-specific.; EFFECT=Unlabeled table on page 37: IsoBuPB | Sprague Dawley rats | Study designed to analyze the effects of maternal IsoBuPB treatment on the emotional behavior and learning performance in mature offspring. Exposure occurred via silastic capsule implanted subcutaneously. No dosage level(s) stated. ‘Estimated dose’ is 4.36 mg/kg bw/day | Early exposure to IsoBuPB may increase anxiety, and specifically disturb passive avoidance performance, although the effects are male-specific. Other parameters were unaffected and no signs of overt toxicity were noted. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3 | Kawaguchi et al. 2009b; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"No dosage level(s) stated. ‘Estimated dose’ is 4.36 mg/kg bw/day | Early exposure to IsoBuPB may increase anxiety, and specifically disturb passive avoidance performance, although the effects are male-specific.","duration":"","effect":"Unlabeled table on page 37: IsoBuPB | Sprague Dawley rats | Study designed to analyze the effects of maternal IsoBuPB treatment on the emotional behavior and learning performance in mature offspring. Exposure occurred via silastic capsule implanted subcutaneously. No dosage level(s) stated. ‘Estimated dose’ is 4.36 mg/kg bw/day | Early exposure to IsoBuPB may increase anxiety, and specifically disturb passive avoidance performance, although the effects are male-specific. Other parameters were unaffected and no signs of overt toxicity were noted. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3 | Kawaguchi et al. 2009b","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"4.36","page":37,"route":"","species":"rat","study_id":"sccs_o_132_noael_036"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=unclear:Unlabeled table on page 11: NOEL=2 (mg/kg/day); EFFECT=Unlabeled table on page 11: NOEL=2 (mg/kg/day); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 11: NOEL=2 (mg/kg/day)","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 11: NOEL=2 (mg/kg/day)","page":11,"route":"","species":"","study_id":"sccs_o_132_noael_031"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=unclear:Unlabeled table on page 13: NOEL=2 (mg/kg/day); EFFECT=Unlabeled table on page 13: NOEL=2 (mg/kg/day); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 13: NOEL=2 (mg/kg/day)","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 13: NOEL=2 (mg/kg/day)","page":13,"route":"","species":"","study_id":"sccs_o_132_noael_032"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1100; DOSE=imals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food.; EFFECT=imals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) 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 MePB and BuPB, the highest dose level in food corresponds to approximately 1100 mg/kg bw/day (NOEL). Comment: No guideline study but GLP. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt on the relevance of the study for risk assessment Charles River 2005; later published as Hoberman et al. 2008 1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"imals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food.","duration":"","effect":"imals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) 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 MePB and BuPB, the highest dose level in food corresponds to approximately 1100 mg/kg bw/day (NOEL). Comment: No guideline study but GLP. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt on the relevance of the study for risk assessment Charles River 2005; later published as Hoberman et al. 2008 1","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1100","page":42,"route":"","species":"","study_id":"sccs_o_132_noael_030"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1100; DOSE=MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food.; EFFECT=Unlabeled table on page 42: MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) 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 MePB and BuPB, the highest dose level in food corresponds to approximately 1100 mg/kg bw/day (NOEL). Comment: No guideline study but GLP. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt on the relevance of the study for risk assessment | Charles River 2005; later published as Hoberman et al. 2008; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food.","duration":"","effect":"Unlabeled table on page 42: MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) 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 MePB and BuPB, the highest dose level in food corresponds to approximately 1100 mg/kg bw/day (NOEL). Comment: No guideline study but GLP. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt on the relevance of the study for risk assessment | Charles River 2005; later published as Hoberman et al. 2008","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1100","page":42,"route":"","species":"rat","study_id":"sccs_o_132_noael_040"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=unclear:SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived from human biomonitoring studies. 3 Concentrations in human biological fluids (e.g. urine, blood) account for both dietary intake 4 (e.g. from foods with paraben preservatives) and dermal application of products with 5 parabens; according to Soni et al. (2005) the latter is considered to be the major 6 contributor. Thus, such measurements are of interest as they pro; DOSE=SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived fr...; EFFECT=SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived from human biomonitoring studies. 3 Concentrations in human biological fluids (e.g. urine, blood) account for both dietary intake 4 (e.g. from foods with paraben preservatives) and dermal application of products with 5 parabens; according to Soni et al. (2005) the latter is considered to be the major 6 contributor. Thus, such measurements are of interest as they pro; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived fr...","duration":"","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived from human biomonitoring studies. 3 Concentrations in human biological fluids (e.g. urine, blood) account for both dietary intake 4 (e.g. from foods with paraben preservatives) and dermal application of products with 5 parabens; according to Soni et al. (2005) the latter is considered to be the major 6 contributor. Thus, such measurements are of interest as they pro","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived from human biomonitoring studies. 3 Concentrations in human biological fluids (e.g. urine, blood) account for both dietary intake 4 (e.g. from foods with paraben preservatives) and dermal application of products with 5 parabens; according to Soni et al. (2005) the latter is considered to be the major 6 contributor. Thus, such measurements are of interest as they pro","page":13,"route":"oral","species":"human","study_id":"sccs_o_132_noael_015"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=unclear:SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 15 instead of dietary admixture. Furthermore, a fourth dose level-group (low dose) was 1 included in an attempt to determine a NOAEL. Additional animals were included to evaluate 2 the reversibility of any toxic signs during a 26-week treatment-free period (to cover 3 3 spermatogenic cycles). Toxicokinetic groups were also included to assess systemic exposure 4 under the defined experimental conditions. Additional endpoints such as histopathology and 5 serum LH and FSH levels were included in order to determine the mechanisms of the 6 awaited testicular and epididymal effects. The pathology data and evaluation were 7 subjected to an external re; DOSE=Furthermore, a fourth dose level-group (low dose) was 1 included in an attempt to determine a NOAEL.; EFFECT=SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 15 instead of dietary admixture. Furthermore, a fourth dose level-group (low dose) was 1 included in an attempt to determine a NOAEL. Additional animals were included to evaluate 2 the reversibility of any toxic signs during a 26-week treatment-free period (to cover 3 3 spermatogenic cycles). Toxicokinetic groups were also included to assess systemic exposure 4 under the defined experimental conditions. Additional endpoints such as histopathology and 5 serum LH and FSH levels were included in order to determine the mechanisms of the 6 awaited testicular and epididymal effects. The pathology data and evaluation were 7 subjected to an external re; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Furthermore, a fourth dose level-group (low dose) was 1 included in an attempt to determine a NOAEL.","duration":"26-week","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 15 instead of dietary admixture. Furthermore, a fourth dose level-group (low dose) was 1 included in an attempt to determine a NOAEL. Additional animals were included to evaluate 2 the reversibility of any toxic signs during a 26-week treatment-free period (to cover 3 3 spermatogenic cycles). Toxicokinetic groups were also included to assess systemic exposure 4 under the defined experimental conditions. Additional endpoints such as histopathology and 5 serum LH and FSH levels were included in order to determine the mechanisms of the 6 awaited testicular and epididymal effects. The pathology data and evaluation were 7 subjected to an external re","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 15 instead of dietary admixture. Furthermore, a fourth dose level-group (low dose) was 1 included in an attempt to determine a NOAEL. Additional animals were included to evaluate 2 the reversibility of any toxic signs during a 26-week treatment-free period (to cover 3 3 spermatogenic cycles). Toxicokinetic groups were also included to assess systemic exposure 4 under the defined experimental conditions. Additional endpoints such as histopathology and 5 serum LH and FSH levels were included in order to determine the mechanisms of the 6 awaited testicular and epididymal effects. The pathology data and evaluation were 7 subjected to an external re","page":15,"route":"oral","species":"","study_id":"sccs_o_132_noael_016"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=10,000; DOSE=MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food.; EFFECT=Unlabeled table on page 42: MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) 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 MePB and BuPB, the highest dose level in food corresponds to approximately 1100 mg/kg bw/day (NOEL). Comment: No guideline study but GLP. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt on the relevance of the study for risk assessment | Charles River 2005; later published as Hoberman et al. 2008; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food.","duration":"","effect":"Unlabeled table on page 42: MePB BuPB | Wistar rat | Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) 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 MePB and BuPB, the highest dose level in food corresponds to approximately 1100 mg/kg bw/day (NOEL). Comment: No guideline study but GLP. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt on the relevance of the study for risk assessment | Charles River 2005; later published as Hoberman et al. 2008","endpoint":"","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"ppm","noael_value":"10,000","page":42,"route":"","species":"rat","study_id":"sccs_o_132_noael_039"}

sccs_o_132.pdf

{"dose":"Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 10 for the final safety assessment of the parabens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative","page":10,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_006"}

sccs_o_132.pdf

{"dose":"Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 10 for the final safety assessment of the parabens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative","page":10,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_006"}

sccs_o_132.pdf

{"dose":"Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 10 for the final safety assessment of the parabens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative","page":10,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_006"}

sccs_o_132.pdf

{"dose":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived fr...","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived from human biomonitoring studies. 3 Concentrations in human biological fluids (e.g. urine, blood) account for both dietary intake 4 (e.g. from foods with paraben preservatives) and dermal application of products with 5 parabens; according to Soni et al. (2005) the latter is considered to be the major 6 contributor. Thus, such measurements are of interest as they pro","page":13,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_015"}

sccs_o_132.pdf

{"dose":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived fr...","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived from human biomonitoring studies. 3 Concentrations in human biological fluids (e.g. urine, blood) account for both dietary intake 4 (e.g. from foods with paraben preservatives) and dermal application of products with 5 parabens; according to Soni et al. (2005) the latter is considered to be the major 6 contributor. Thus, such measurements are of interest as they pro","page":13,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_015"}

sccs_o_132.pdf

{"dose":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived fr...","effect":"SCCS/1514/13 Opinion on parabens, updated request on propyl- and butylparaben 13 Retention factor 0.01 0.01 Daily amount 1 g 2.4 g Body weight 5.3 kg 5.3 kg SED (mg/kg/day) 0.0001326 0.000318 NOEL=2 (mg/kg/day) MOS 15078 6282 1 3.2.4 Biomonitoring studies: paraben levels in urine and plasma 2 Information on exposure to parabens can be derived from human biomonitoring studies. 3 Concentrations in human biological fluids (e.g. urine, blood) account for both dietary intake 4 (e.g. from foods with paraben preservatives) and dermal application of products with 5 parabens; according to Soni et al. (2005) the latter is considered to be the major 6 contributor. Thus, such measurements are of interest as they pro","page":13,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_015"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT== 0.0408; DOSE=2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf; EFFECT=of 1.75 m2 for an adult. For a child of 3 months of 29 age (5.3 kg and a surface area 0.31m2)3 the cumulative exposure would then result in 17.4 30 *0.31/1.75= 3.08 g/day. 31 Accordingly, the MOS would then be: 32 Dermal absorption: 3.7% 33 Intended concentration in finished product: 0.19% 34 Typical body weight: 5.3 kg 35 Cumulative exposure to leave-on products: 3.08 g/day 36 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf","duration":"3 months","effect":"of 1.75 m2 for an adult. For a child of 3 months of 29 age (5.3 kg and a surface area 0.31m2)3 the cumulative exposure would then result in 17.4 30 *0.31/1.75= 3.08 g/day. 31 Accordingly, the MOS would then be: 32 Dermal absorption: 3.7% 33 Intended concentration in finished product: 0.19% 34 Typical body weight: 5.3 kg 35 Cumulative exposure to leave-on products: 3.08 g/day 36 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 0.0408","page":10,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_012"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT== 0.043; DOSE=2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%.; EFFECT=ed (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%. 23 24 Based on the exposure calculation made for adults in opinion SCCS/1348/10, an 25 extrapolation has been made for children on the basis of the body surface area, assuming a 26 concentration of 0.19% for butylparaben in the finished cosmetic product. 27 The cumulative exposure to preservatives used in all cosmetic product categories is 28; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%.","duration":"17 days","effect":"ed (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%. 23 24 Based on the exposure calculation made for adults in opinion SCCS/1348/10, an 25 extrapolation has been made for children on the basis of the body surface area, assuming a 26 concentration of 0.19% for butylparaben in the finished cosmetic product. 27 The cumulative exposure to preservatives used in all cosmetic product categories is 28","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 0.043","page":10,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_010"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=0.19; DOSE=21 22 Table 1 23 Leave-on products Body care products Products for buttock area Cream and other products Wipes Dermal absorption 3.7% 3.7% 3.7% concentration 0.19% 0.19% 0.19% Daily amount 0.063 g 1.34 g 0.55 g Body weight 5.3 kg 5.3 kg 5.3 kg SED (mg/kg/day) 0.000836 0.0177 0.0076 NOEL=2 (mg/kg/day) 4 European Cosmetics Association, now Cosmeti...; EFFECT=a 16 - for rinse-off products: 17 1 g/d for rinse-off products for body care 18 2.4 g/d for rinse-off products for nappy area, 19 This results in the following exposure, considering a child of three months of age (5.3 kg 20 bw): 21 22 Table 1 23 Leave-on products Body care products Products for buttock area Cream and other products Wipes Dermal absorption 3.7% 3.7% 3.7% concentration 0.19% 0.19% 0.19% Daily amount 0.063 g 1.34 g 0.55 g Body weight 5.3 kg 5.3 kg 5.3 kg SED (mg/kg/day) 0.000836 0.0177 0.0076 NOEL=2 (mg/kg/day) 4 European Cosmetics Association, now Cosmetics Europe; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"21 22 Table 1 23 Leave-on products Body care products Products for buttock area Cream and other products Wipes Dermal absorption 3.7% 3.7% 3.7% concentration 0.19% 0.19% 0.19% Daily amount 0.063 g 1.34 g 0.55 g Body weight 5.3 kg 5.3 kg 5.3 kg SED (mg/kg/day) 0.000836 0.0177 0.0076 NOEL=2 (mg/kg/day) 4 European Cosmetics Association, now Cosmeti...","duration":"","effect":"a 16 - for rinse-off products: 17 1 g/d for rinse-off products for body care 18 2.4 g/d for rinse-off products for nappy area, 19 This results in the following exposure, considering a child of three months of age (5.3 kg 20 bw): 21 22 Table 1 23 Leave-on products Body care products Products for buttock area Cream and other products Wipes Dermal absorption 3.7% 3.7% 3.7% concentration 0.19% 0.19% 0.19% Daily amount 0.063 g 1.34 g 0.55 g Body weight 5.3 kg 5.3 kg 5.3 kg SED (mg/kg/day) 0.000836 0.0177 0.0076 NOEL=2 (mg/kg/day) 4 European Cosmetics Association, now Cosmetics Europe","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"%","noael_value":"0.19","page":11,"route":"dermal","species":"","study_id":"sccs_o_132_noael_013"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=32 • The risk assessment was done for the most lipophilic compound butylparaben using 33 the very low NOEL value of 2 mg/kg bw/day derived from a study where juvenile 34 rats were exposed after subcutaneous administration of 2 mg butylparaben/kg/day 35 for 17 days (postnatal days 2-18;; EFFECT=e an inactive metabolite (rationale is given in the Opinion SCCS/1446/11). 27 28 In humans, on the other hand it is possible that parent (un-metabolized) parabens become 29 systemically available, even if in limited amounts. As properly conducted dermal absorption 30 and/or toxicokinetic studies in humans were lacking, a quantitative risk assessment was 31 carried out incorporating several layers of conservatism: 32 • The risk assessment was done for the most lipophilic compound butylparaben using 33 the very low NOEL value of 2 mg/kg bw/day derived from a study where juvenile 34 rats were exposed after subcutaneous administration of 2 mg butylparaben/kg/day 35 for 17 days (postnatal days 2-18; (Fisher et al. 1999), 36 • a high dermal absorption value of 3.7% and 37 • a cumulative human exposure value of 17.4 g/day to cosmetic products containing 38 lipophilic parabens. 39 As a consequence, the use of propylparaben and butylparaben as preservatives in cosmetic 40 products was considered as safe to the consumer as long as the su; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"32 • The risk assessment was done for the most lipophilic compound butylparaben using 33 the very low NOEL value of 2 mg/kg bw/day derived from a study where juvenile 34 rats were exposed after subcutaneous administration of 2 mg butylparaben/kg/day 35 for 17 days (postnatal days 2-18;","duration":"17 days","effect":"e an inactive metabolite (rationale is given in the Opinion SCCS/1446/11). 27 28 In humans, on the other hand it is possible that parent (un-metabolized) parabens become 29 systemically available, even if in limited amounts. As properly conducted dermal absorption 30 and/or toxicokinetic studies in humans were lacking, a quantitative risk assessment was 31 carried out incorporating several layers of conservatism: 32 • The risk assessment was done for the most lipophilic compound butylparaben using 33 the very low NOEL value of 2 mg/kg bw/day derived from a study where juvenile 34 rats were exposed after subcutaneous administration of 2 mg butylparaben/kg/day 35 for 17 days (postnatal days 2-18; (Fisher et al. 1999), 36 • a high dermal absorption value of 3.7% and 37 • a cumulative human exposure value of 17.4 g/day to cosmetic products containing 38 lipophilic parabens. 39 As a consequence, the use of propylparaben and butylparaben as preservatives in cosmetic 40 products was considered as safe to the consumer as long as the su","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":6,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_002"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=(1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application.; EFFECT=guments of a recent review of Boberg et al. (2010), the SCCS 13 stated in its Opinion (SCCS/1446/11): The toxicity of parabens, in particular butylparaben, 14 has been investigated in previous and more recent studies, with exposure in utero, during 15 lactation and in juvenile animals (see Appendix 1). The lowest available critical effect level 16 (NOAEL) chosen in the safety assessment (Opinion SCCS/1348/10) was based on such 17 studies. 18 The study chosen by the SCCP/SCCS was that of Fisher et al. (1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application. 21 In other studies in female and male rodents, often (much) higher dose levels (several 22 hundred up to 1200 mg/kg bw) were administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test substance was chosen, which does not reflect 24 human exposure. Dermal absorption and skin metabolism were, as such, not taken into 25 consideration. Furthermore, when; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"(1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application.","duration":"","effect":"guments of a recent review of Boberg et al. (2010), the SCCS 13 stated in its Opinion (SCCS/1446/11): The toxicity of parabens, in particular butylparaben, 14 has been investigated in previous and more recent studies, with exposure in utero, during 15 lactation and in juvenile animals (see Appendix 1). The lowest available critical effect level 16 (NOAEL) chosen in the safety assessment (Opinion SCCS/1348/10) was based on such 17 studies. 18 The study chosen by the SCCP/SCCS was that of Fisher et al. (1999) with a NOEL of 19 2 mg/kg bw/day for butylparaben (no other doses studied) in male juvenile rats after 20 repeated subcutaneous application. 21 In other studies in female and male rodents, often (much) higher dose levels (several 22 hundred up to 1200 mg/kg bw) were administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test substance was chosen, which does not reflect 24 human exposure. Dermal absorption and skin metabolism were, as such, not taken into 25 consideration. Furthermore, when","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":8,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_004"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.; EFFECT=sessment of the parabens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative value of 17.4 g/day was used (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.","duration":"","effect":"sessment of the parabens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative value of 17.4 g/day was used (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":10,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_007"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.; EFFECT=abens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative value of 17.4 g/day was used (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al.","duration":"17 days","effect":"abens: 1 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 2 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 3 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 4 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 5 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 6 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative value of 17.4 g/day was used (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":10,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_008"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2.0; DOSE=2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%.; EFFECT=ay clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative value of 17.4 g/day was used (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%. 23 24 Based on the exposure calculation made for adults in opinion SCCS/1348/10, an 25 extrapolation has been made for children on the basis of the body surface area, assuming a 26 concentration of 0.19% for butylpara; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%.","duration":"17 days","effect":"ay clearly represents a NOEL instead of an NOAEL. 7 8 For the calculation of the SED the cumulative value of 17.4 g/day was used (SCCS Notes of 9 Guidance, SCCS/1416/11), assuming that parabens were used as preservatives in all 10 cosmetic products. 11 Thus, the following parameters for the final calculation of the MoS of butylparaben were 12 used: 13 14 Dermal absorption: 3.7% 15 Intended concentration in finished product: 0.4% 16 Typical body weight: 60 kg 17 Cumulative exposure to preservatives: 17.4 g/day 18 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 19 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 20 21 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 22 finished cosmetic product would need to be reduced to 0.19%. 23 24 Based on the exposure calculation made for adults in opinion SCCS/1348/10, an 25 extrapolation has been made for children on the basis of the body surface area, assuming a 26 concentration of 0.19% for butylpara","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.0","page":10,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_009"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2.0; DOSE=2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf; EFFECT=roduct. 27 The cumulative exposure to preservatives used in all cosmetic product categories is 28 considered to be 17.4 g/day on a surface of 1.75 m2 for an adult. For a child of 3 months of 29 age (5.3 kg and a surface area 0.31m2)3 the cumulative exposure would then result in 17.4 30 *0.31/1.75= 3.08 g/day. 31 Accordingly, the MOS would then be: 32 Dermal absorption: 3.7% 33 Intended concentration in finished product: 0.19% 34 Typical body weight: 5.3 kg 35 Cumulative exposure to leave-on products: 3.08 g/day 36 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf","duration":"3 months","effect":"roduct. 27 The cumulative exposure to preservatives used in all cosmetic product categories is 28 considered to be 17.4 g/day on a surface of 1.75 m2 for an adult. For a child of 3 months of 29 age (5.3 kg and a surface area 0.31m2)3 the cumulative exposure would then result in 17.4 30 *0.31/1.75= 3.08 g/day. 31 Accordingly, the MOS would then be: 32 Dermal absorption: 3.7% 33 Intended concentration in finished product: 0.19% 34 Typical body weight: 5.3 kg 35 Cumulative exposure to leave-on products: 3.08 g/day 36 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 37 SED = 3080 mg/day * 0.19/100 * (3.7/100* 5.3) kg = 0.0408mg/kg bw/day 38 39 MoS = NOEL / SED = 49 40 3 http://www.rivm.nl/bibliotheek/rapporten/320005005.pdf","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.0","page":10,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_011"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.; EFFECT=n its previous opinions, the SCCS takes the following parameters into account for the 14 final safety assessment of the parabens: 15 Until a properly conducted dermal absorption and toxicokinetic study in humans will allow 16 the assignment of a more scientifically solid value, the SCCS will use a dermal absorption 17 value of 3.7% in its MoS safety calculations. 18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.","duration":"","effect":"n its previous opinions, the SCCS takes the following parameters into account for the 14 final safety assessment of the parabens: 15 Until a properly conducted dermal absorption and toxicokinetic study in humans will allow 16 the assignment of a more scientifically solid value, the SCCS will use a dermal absorption 17 value of 3.7% in its MoS safety calculations. 18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg","noael_value":"2","page":20,"route":"oral","species":"human","study_id":"sccs_o_132_noael_019"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.; EFFECT=afety calculations. 18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.","duration":"17 d","effect":"afety calculations. 18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 d","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":20,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_020"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.; EFFECT=18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.","duration":"17 days","effect":"18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/d","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":20,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_021"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=3.7; EFFECT=ether it is appropriate to extrapolate from adult use to children. 13 14 In conclusion, the range of results obtained by the different approaches demonstrates the 15 uncertainty in the exposure data and urges the need for children specific exposure 16 information. A realistic exposure is expected to be inside this range and the MOS is 17 considered sufficient despite the uncertainties with regard to the metabolic capacity of the 18 skin of newborns and early infants, as the value for the dermal absorption and the NOEL are 19 conservative. 20 21 Leave-on products used in the nappy area: 22 A specific calculation has been made for products used for the nappy area. For this area it is 23 expected that, especially in the case of irritated skin (see specific section on cosmetics 24 products used in the nappy area, SCCS/1446/11, sections 3.2.1 and 3.3.3), the dermal 25 absorption might be higher than the 3.7% used in the calculation above. In combination 26 with the uncertainty associated with the exposure data, the likely simultane; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"ether it is appropriate to extrapolate from adult use to children. 13 14 In conclusion, the range of results obtained by the different approaches demonstrates the 15 uncertainty in the exposure data and urges the need for children specific exposure 16 information. A realistic exposure is expected to be inside this range and the MOS is 17 considered sufficient despite the uncertainties with regard to the metabolic capacity of the 18 skin of newborns and early infants, as the value for the dermal absorption and the NOEL are 19 conservative. 20 21 Leave-on products used in the nappy area: 22 A specific calculation has been made for products used for the nappy area. For this area it is 23 expected that, especially in the case of irritated skin (see specific section on cosmetics 24 products used in the nappy area, SCCS/1446/11, sections 3.2.1 and 3.3.3), the dermal 25 absorption might be higher than the 3.7% used in the calculation above. In combination 26 with the uncertainty associated with the exposure data, the likely simultane","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"%","noael_value":"3.7","page":12,"route":"dermal","species":"","study_id":"sccs_o_132_noael_014"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=3.7; DOSE=Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.; EFFECT=cover the potentially sensitive period after birth until 8 PND 21. 9 10 11 3.4 Safety evaluation 12 13 As in its previous opinions, the SCCS takes the following parameters into account for the 14 final safety assessment of the parabens: 15 Until a properly conducted dermal absorption and toxicokinetic study in humans will allow 16 the assignment of a more scientifically solid value, the SCCS will use a dermal absorption 17 value of 3.7% in its MoS safety calculations. 18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al.","duration":"","effect":"cover the potentially sensitive period after birth until 8 PND 21. 9 10 11 3.4 Safety evaluation 12 13 As in its previous opinions, the SCCS takes the following parameters into account for the 14 final safety assessment of the parabens: 15 Until a properly conducted dermal absorption and toxicokinetic study in humans will allow 16 the assignment of a more scientifically solid value, the SCCS will use a dermal absorption 17 value of 3.7% in its MoS safety calculations. 18 The SCCS could not determine an adequate NO(A)EL-value for the paraben esters under 19 consideration from the studies in Appendix 1. Consequently, the NOEL value of 2 mg/kg 20 bw/day, based on Fisher et al. (1999) remains the conservative choice for the calculation of 21 the MoS of propyl- and butylparaben. The Committee acknowledged the fact that the Fisher 22 et al. (1999) study involves subcutaneous instead of oral administration, but emphasized 23 that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumu","endpoint":"dermal absorption","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"%","noael_value":"3.7","page":20,"route":"oral","species":"human","study_id":"sccs_o_132_noael_018"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=100; DOSE=Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6-19.; EFFECT=paraben ___________________________________________________________________________________________ 37 BuPB Sprague Dawley rats Developmental study according to OECD guideline. 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 NOEL: 1000 mg/kg/day. Maternal NOAEL: 100 mg/kg/day SCCS comment: Guideline study. Study valid for risk assessment of developmental effects. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt about the study. Daston ert al. 2004 EtPB BuPB Wistar rats Study of the effect of parabens on the steroidogenesis in rats and their offspring when dams are subcutaneously exposed to either: - 400 mg EtPB/kg/day; or - 200 - 400 mg BuPB/kg/day from gestation day 7 to 21. Neither EtPB nor BuPB showed any treatment-re; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6-19.","duration":"Developmental","effect":"paraben ___________________________________________________________________________________________ 37 BuPB Sprague Dawley rats Developmental study according to OECD guideline. 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 NOEL: 1000 mg/kg/day. Maternal NOAEL: 100 mg/kg/day SCCS comment: Guideline study. Study valid for risk assessment of developmental effects. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt about the study. Daston ert al. 2004 EtPB BuPB Wistar rats Study of the effect of parabens on the steroidogenesis in rats and their offspring when dams are subcutaneously exposed to either: - 400 mg EtPB/kg/day; or - 200 - 400 mg BuPB/kg/day from gestation day 7 to 21. Neither EtPB nor BuPB showed any treatment-re","endpoint":"developmental toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":37,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_027"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1000; DOSE=Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6-19.; EFFECT=ed request on propyl- and butylparaben ___________________________________________________________________________________________ 37 BuPB Sprague Dawley rats Developmental study according to OECD guideline. 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 NOEL: 1000 mg/kg/day. Maternal NOAEL: 100 mg/kg/day SCCS comment: Guideline study. Study valid for risk assessment of developmental effects. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt about the study. Daston ert al. 2004 EtPB BuPB Wistar rats Study of the effect of parabens on the steroidogenesis in rats and their offspring when dams are subcutaneously exposed to either: - 400 mg EtPB/kg/day; or - 200 - 400 mg BuPB/kg/day from gestation day 7 to 21. Neither EtPB; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Oral gavage, 0, 10, 100 and 1000 mg/kg bw/day on gestation days 6-19.","duration":"Developmental","effect":"ed request on propyl- and butylparaben ___________________________________________________________________________________________ 37 BuPB Sprague Dawley rats Developmental study according to OECD guideline. 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 NOEL: 1000 mg/kg/day. Maternal NOAEL: 100 mg/kg/day SCCS comment: Guideline study. Study valid for risk assessment of developmental effects. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt about the study. Daston ert al. 2004 EtPB BuPB Wistar rats Study of the effect of parabens on the steroidogenesis in rats and their offspring when dams are subcutaneously exposed to either: - 400 mg EtPB/kg/day; or - 200 - 400 mg BuPB/kg/day from gestation day 7 to 21. Neither EtPB","endpoint":"developmental toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":37,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_026"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; 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 37: BuPB | Sprague Dawley rats | Developmental study according to OECD guideline. 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 NOEL: 1000 mg/kg/day. Maternal NOAEL: 100 mg/kg/day SCCS comment: Guideline study. Study valid for risk assessment of developmental effects. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt about the study. | Daston ert al. 2004; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","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 37: BuPB | Sprague Dawley rats | Developmental study according to OECD guideline. 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 NOEL: 1000 mg/kg/day. Maternal NOAEL: 100 mg/kg/day SCCS comment: Guideline study. Study valid for risk assessment of developmental effects. Recent toxicokinetic data indicate low systemic exposure to BuPB even at high doses and raise doubt about the study. | Daston ert al. 2004","endpoint":"developmental toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":37,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_033"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT== 0.043; DOSE=2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%.; EFFECT=used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%. 38 39 40 3.5 Discussion 41 42 3.5.1 Evaluation of the recent study on the reproductive toxicity of 43 propylparaben and its toxicokinetics in male juvenile Wistar rats 44 45; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%.","duration":"17 days","effect":"used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%. 38 39 40 3.5 Discussion 41 42 3.5.1 Evaluation of the recent study on the reproductive toxicity of 43 propylparaben and its toxicokinetics in male juvenile Wistar rats 44 45","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 0.043","page":20,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_023"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=unclear:e administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test substance was chosen, which does not reflect 24 human exposure. Dermal absorption and skin metabolism were, as such, not taken into 25 consideration. Furthermore, when hormone levels or endocrine functions are found to be 26 changed in vitro or in vivo it is often not clear whether the effects are adverse to the 27 organism or not. These circumstances (and not the lack of any studies) make it difficult to 28 derive a NO(A)EL. Although a multigeneration OECD guideline study is missing, the main 29 endpoints of reproductive toxicity are covered by the available studies. 30 The SCCS considered that the question of possibly increased susceptibility of children is 31 sufficiently covered by the available data on reproductive toxicity. Potential remaining 32 uncertainties have been addressed by introducing several layers of conservative 33 assumptions in the assessment (summarized in the final conclusions). 34 In its Opinion (SCCS/1446/11),; DOSE=e administered (see Appendix 1).; EFFECT=e administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test substance was chosen, which does not reflect 24 human exposure. Dermal absorption and skin metabolism were, as such, not taken into 25 consideration. Furthermore, when hormone levels or endocrine functions are found to be 26 changed in vitro or in vivo it is often not clear whether the effects are adverse to the 27 organism or not. These circumstances (and not the lack of any studies) make it difficult to 28 derive a NO(A)EL. Although a multigeneration OECD guideline study is missing, the main 29 endpoints of reproductive toxicity are covered by the available studies. 30 The SCCS considered that the question of possibly increased susceptibility of children is 31 sufficiently covered by the available data on reproductive toxicity. Potential remaining 32 uncertainties have been addressed by introducing several layers of conservative 33 assumptions in the assessment (summarized in the final conclusions). 34 In its Opinion (SCCS/1446/11),; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"e administered (see Appendix 1).","duration":"","effect":"e administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test substance was chosen, which does not reflect 24 human exposure. Dermal absorption and skin metabolism were, as such, not taken into 25 consideration. Furthermore, when hormone levels or endocrine functions are found to be 26 changed in vitro or in vivo it is often not clear whether the effects are adverse to the 27 organism or not. These circumstances (and not the lack of any studies) make it difficult to 28 derive a NO(A)EL. Although a multigeneration OECD guideline study is missing, the main 29 endpoints of reproductive toxicity are covered by the available studies. 30 The SCCS considered that the question of possibly increased susceptibility of children is 31 sufficiently covered by the available data on reproductive toxicity. Potential remaining 32 uncertainties have been addressed by introducing several layers of conservative 33 assumptions in the assessment (summarized in the final conclusions). 34 In its Opinion (SCCS/1446/11),","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"unclear:e administered (see Appendix 1). In some of these 23 studies, subcutaneous application of the test substance was chosen, which does not reflect 24 human exposure. Dermal absorption and skin metabolism were, as such, not taken into 25 consideration. Furthermore, when hormone levels or endocrine functions are found to be 26 changed in vitro or in vivo it is often not clear whether the effects are adverse to the 27 organism or not. These circumstances (and not the lack of any studies) make it difficult to 28 derive a NO(A)EL. Although a multigeneration OECD guideline study is missing, the main 29 endpoints of reproductive toxicity are covered by the available studies. 30 The SCCS considered that the question of possibly increased susceptibility of children is 31 sufficiently covered by the available data on reproductive toxicity. Potential remaining 32 uncertainties have been addressed by introducing several layers of conservative 33 assumptions in the assessment (summarized in the final conclusions). 34 In its Opinion (SCCS/1446/11),","page":8,"route":"dermal","species":"human","study_id":"sccs_o_132_noael_005"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=2.0; DOSE=2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%.; EFFECT=day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%. 38 39 40 3.5 Discussion 41 42 3.5.1 Evaluation of the recent study on the reproductive toxicity of 43 propylparaben and its toxicokinetics in male juvenile Wistar rats 44 45; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%.","duration":"17 days","effect":"day clearly represents a NOEL instead of an NOAEL For the calculation 24 of the SED. 25 The cumulative value of 17.4 g/day was used (SCCS Notes of Guidance, SCCS/1416/11), 26 assuming that parabens were used as preservatives in all cosmetic products. 27 Thus, the following parameters for the final calculation of the MoS of butylparaben were 28 used: 29 30 Dermal absorption: 3.7% 31 Intended concentration in finished product: 0.4% 32 Typical body weight: 60 kg 33 Cumulative exposure to preservatives: 17.4 g/day 34 NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 35 SED = 17400 mg/day * 0.4/100 * 3.7/100 = 0.043 mg/kg bw/day 60 kg MoS = NOEL / SED = 46.6 36 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the 37 finished cosmetic product would need to be reduced to 0.19%. 38 39 40 3.5 Discussion 41 42 3.5.1 Evaluation of the recent study on the reproductive toxicity of 43 propylparaben and its toxicokinetics in male juvenile Wistar rats 44 45","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.0","page":20,"route":"dermal","species":"rat","study_id":"sccs_o_132_noael_022"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=Maternal exposure to IsoBuPB showed to decrease the plasma corticosterone concentration and to increase the uterus weight in dams as well as the uterine sensitivity to estrogen in adult female offspring. All other indices examined were unaffected by the treatment. No positive control was included. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3; EFFECT=Unlabeled table on page 37: IsoBuPB | Sprague Dawley rats | Study designed to clarify the estrogenic effects during gestation and lactation on the endocrine systems of dams and offspring by measuring - in dams: plasma hormone concentrations and organ weights - in offspring: ratio of male pups, anogenital distance, organ weights and plasma hormone concentrations, puberty, estrous cycle and response of organ weight and plasma hormone concentrations to estrogen in adult females, and reproductive and adrenal function in adult males. Exposure occurred via silastic capsule implanted subcutaneously. No dosage level(s) stated. | Maternal exposure to IsoBuPB showed to decrease the plasma corticosterone concentration and to increase the uterus weight in dams as well as the uterine sensitivity to estrogen in adult female offspring. All other indices examined were unaffected by the treatment. No positive control was included. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3 | Kawaguchi et al. 2009; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 37: IsoBuPB | Sprague Dawley rats | Study designed to clarify the estrogenic effects during gestation and lactation on the endocrine systems of dams and offspring by measuring - in dams: plasma hormone concentrations and organ weights - in offspring: ratio of male pups, anogenital distance, organ weights and plasma hormone concentrations, puberty, estrous cycle and response of organ weight and plasma hormone concentrations to estrogen in adult females, and reproductive and adrenal function in adult males. Exposure occurred via silastic capsule implanted subcutaneously. No dosage level(s) stated. | Maternal exposure to IsoBuPB showed to decrease the plasma corticosterone concentration and to increase the uterus weight in dams as well as the uterine sensitivity to estrogen in adult female offspring. All other indices examined were unaffected by the treatment. No positive control was included. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3 | Kawaguchi et al. 2009","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"Maternal exposure to IsoBuPB showed to decrease the plasma corticosterone concentration and to increase the uterus weight in dams as well as the uterine sensitivity to estrogen in adult female offspring. All other indices examined were unaffected by the treatment. No positive control was included. SCCS comment: No guideline study. Effects observed after s.c. application. See discussion, section 3.5.3","page":37,"route":"","species":"rat","study_id":"sccs_o_132_noael_035"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=14.4; DOSE=Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day.; EFFECT=pyl- and butylparaben ___________________________________________________________________________________________ 42 BuPB CD-1 ICR mice Study of the effects of BuPB on general function of the male mouse reproductive system. Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day. Administration of BuPB at 146 and 1504 mg/kg/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. The NOAEL is stated to be 14.4 mg/kg/day. Comment: No guideline study. Refuted studies in rats raise doubts on the methodology of the study. No data on toxicokinetics of parabens in mice available. Oishi 2002b MePB EtPB Wistar rat Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day. Rats were 25-27 days old and received the parabens for 8 weeks. MePB and EtPB did not affect the ma; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day.","duration":"27 days","effect":"pyl- and butylparaben ___________________________________________________________________________________________ 42 BuPB CD-1 ICR mice Study of the effects of BuPB on general function of the male mouse reproductive system. Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day. Administration of BuPB at 146 and 1504 mg/kg/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. The NOAEL is stated to be 14.4 mg/kg/day. Comment: No guideline study. Refuted studies in rats raise doubts on the methodology of the study. No data on toxicokinetics of parabens in mice available. Oishi 2002b MePB EtPB Wistar rat Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day. Rats were 25-27 days old and received the parabens for 8 weeks. MePB and EtPB did not affect the ma","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg/day","noael_value":"14.4","page":42,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_028"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=unclear:n used in 17 combination) is considered safe for human health. 18 Concerns were expressed with respect to the potential endocrine modifying effects and 19 potential endocrine related toxicity of propylparaben 1, butylparaben as well as their related 20 iso compounds and benzylparaben as these properties appeared to increase with increasing 21 chain length. For the frequently used compounds, propylparaben and butylparaben, 22 considered as having a weak endocrine modifying potential, the deduction of an adequate 23 NO(A)EL value was hampered by considerable shortcomings of the reproductive toxicity 24 studies carried out in rodents. In rats it was found that longer chain parabens are 25 metabolized in a fast and complete way into p- hydroxybenzoic acid (PHBA) which is 26 considered to be an inactive metabolite (rationale is given in the Opinion SCCS/1446/11). 27 28 In humans, on the other hand it is possible that parent (un-metabolized) parabens become 29 systemically available, even if in limited amounts. As properly conducted der; EFFECT=n used in 17 combination) is considered safe for human health. 18 Concerns were expressed with respect to the potential endocrine modifying effects and 19 potential endocrine related toxicity of propylparaben 1, butylparaben as well as their related 20 iso compounds and benzylparaben as these properties appeared to increase with increasing 21 chain length. For the frequently used compounds, propylparaben and butylparaben, 22 considered as having a weak endocrine modifying potential, the deduction of an adequate 23 NO(A)EL value was hampered by considerable shortcomings of the reproductive toxicity 24 studies carried out in rodents. In rats it was found that longer chain parabens are 25 metabolized in a fast and complete way into p- hydroxybenzoic acid (PHBA) which is 26 considered to be an inactive metabolite (rationale is given in the Opinion SCCS/1446/11). 27 28 In humans, on the other hand it is possible that parent (un-metabolized) parabens become 29 systemically available, even if in limited amounts. As properly conducted der; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"n used in 17 combination) is considered safe for human health. 18 Concerns were expressed with respect to the potential endocrine modifying effects and 19 potential endocrine related toxicity of propylparaben 1, butylparaben as well as their related 20 iso compounds and benzylparaben as these properties appeared to increase with increasing 21 chain length. For the frequently used compounds, propylparaben and butylparaben, 22 considered as having a weak endocrine modifying potential, the deduction of an adequate 23 NO(A)EL value was hampered by considerable shortcomings of the reproductive toxicity 24 studies carried out in rodents. In rats it was found that longer chain parabens are 25 metabolized in a fast and complete way into p- hydroxybenzoic acid (PHBA) which is 26 considered to be an inactive metabolite (rationale is given in the Opinion SCCS/1446/11). 27 28 In humans, on the other hand it is possible that parent (un-metabolized) parabens become 29 systemically available, even if in limited amounts. As properly conducted der","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"","noael_value":"unclear:n used in 17 combination) is considered safe for human health. 18 Concerns were expressed with respect to the potential endocrine modifying effects and 19 potential endocrine related toxicity of propylparaben 1, butylparaben as well as their related 20 iso compounds and benzylparaben as these properties appeared to increase with increasing 21 chain length. For the frequently used compounds, propylparaben and butylparaben, 22 considered as having a weak endocrine modifying potential, the deduction of an adequate 23 NO(A)EL value was hampered by considerable shortcomings of the reproductive toxicity 24 studies carried out in rodents. In rats it was found that longer chain parabens are 25 metabolized in a fast and complete way into p- hydroxybenzoic acid (PHBA) which is 26 considered to be an inactive metabolite (rationale is given in the Opinion SCCS/1446/11). 27 28 In humans, on the other hand it is possible that parent (un-metabolized) parabens become 29 systemically available, even if in limited amounts. As properly conducted der","page":6,"route":"","species":"rat","study_id":"sccs_o_132_noael_001"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1000; DOSE=There was no evidence of any treatment-related effect on testicular and 19 epididymal weights or on sperm count and motility data in any of the treated groups.; EFFECT=rmatogenesis in the right testis. 15 In summary of the pathology investigations, daily oral administration of propylparaben in 16 post-weaning juvenile male Wistar rats for 8 weeks followed by a 26-week treatment-free 17 period did not result in test item-related macroscopic or microscopic changes in the testes 18 and epididymides. There was no evidence of any treatment-related effect on testicular and 19 epididymal weights or on sperm count and motility data in any of the treated groups. 20 21 In conclusion, the NOAEL of the study is 1000 mg/kg bw/day for the treatment period of 22 8 weeks. The present study did not confirm the effects on the reproductive functions 23 reported by Oishi (2002a). 24 25 The satellite toxicokinetic study by the oral route (gavage) in the juvenile rats was 26 performed as follows (Ricerca Biosciences, 2012d): 27 The satellite animals were subjected to the same dosing regime as the main groups from 28 day 0 (PND 21) to day 56 (PND 77). After the first dosing day 0 (PND 21), blood samples of 29 appro; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"There was no evidence of any treatment-related effect on testicular and 19 epididymal weights or on sperm count and motility data in any of the treated groups.","duration":"8 weeks","effect":"rmatogenesis in the right testis. 15 In summary of the pathology investigations, daily oral administration of propylparaben in 16 post-weaning juvenile male Wistar rats for 8 weeks followed by a 26-week treatment-free 17 period did not result in test item-related macroscopic or microscopic changes in the testes 18 and epididymides. There was no evidence of any treatment-related effect on testicular and 19 epididymal weights or on sperm count and motility data in any of the treated groups. 20 21 In conclusion, the NOAEL of the study is 1000 mg/kg bw/day for the treatment period of 22 8 weeks. The present study did not confirm the effects on the reproductive functions 23 reported by Oishi (2002a). 24 25 The satellite toxicokinetic study by the oral route (gavage) in the juvenile rats was 26 performed as follows (Ricerca Biosciences, 2012d): 27 The satellite animals were subjected to the same dosing regime as the main groups from 28 day 0 (PND 21) to day 56 (PND 77). After the first dosing day 0 (PND 21), blood samples of 29 appro","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":16,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_017"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1000; DOSE=for 4 weeks to propylparaben in doses of 12.4, 125 and 1290 mg/kg bw 4 per day in food.; EFFECT=for 4 weeks to propylparaben in doses of 12.4, 125 and 1290 mg/kg bw 4 per day in food. Therefore, a similar study design including the use of the same rat strain 5 was chosen with some modifications (gavage instead of application by food) and additional 6 testing, e.g., some additional hormonal parameters described in Section 3.3. However, 7 virtually no effects on the endocrine or reproductive functions of the rats were found, hence 8 the effects observed in the Oishi study (2002a) could not be confirmed and the NOAEL has 9 been set at 1000 mg/kg bw/day. Although not a guideline study, in agreement with the 10 study objectives, the study can be considered valid with regards to the investigation of 11 reproductive toxicity. However, the relevance 8 of the study for human risk assessment is 12 limited because of the rapid and effective metabolism in rats unlike to humans (for details 13 see Appendix 2 and discussion below). 14 15 Similar results have been obtained in a previous study with butylparaben (Charles River 16 2005; lat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"for 4 weeks to propylparaben in doses of 12.4, 125 and 1290 mg/kg bw 4 per day in food.","duration":"4 weeks","effect":"for 4 weeks to propylparaben in doses of 12.4, 125 and 1290 mg/kg bw 4 per day in food. Therefore, a similar study design including the use of the same rat strain 5 was chosen with some modifications (gavage instead of application by food) and additional 6 testing, e.g., some additional hormonal parameters described in Section 3.3. However, 7 virtually no effects on the endocrine or reproductive functions of the rats were found, hence 8 the effects observed in the Oishi study (2002a) could not be confirmed and the NOAEL has 9 been set at 1000 mg/kg bw/day. Although not a guideline study, in agreement with the 10 study objectives, the study can be considered valid with regards to the investigation of 11 reproductive toxicity. However, the relevance 8 of the study for human risk assessment is 12 limited because of the rapid and effective metabolism in rats unlike to humans (for details 13 see Appendix 2 and discussion below). 14 15 Similar results have been obtained in a previous study with butylparaben (Charles River 16 2005; lat","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":21,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_024"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1000; DOSE=These studies are considered not reliable, as raw data are not 21 available and some studies conducted under similar experimental conditions and under GLP 22 with oral application even at high doses up to 1000 mg/kg; EFFECT=inciple valuable means for 10 determining inherent toxic potentials (hazards) or modes of actions of chemical substances, 11 these studies are not per se considered as suited for quantitative risk assessment (unless 12 the systemic exposure under s.c. conditions has been determined). Usually, subcutaneous 13 studies are not the best choice for performing risk assessment and should be avoided when 14 more adequate data are available. However, in the absence of more adequate data, as in 15 the case for parabens, the NOAEL derived from such subcutaneous studies may be used as 16 it is very conservative. 17 18 Some previous oral studies with propyl- or butylparaben in rodents were reported to show 19 endocrine potential or reproductive toxicity effects at low doses, in particular those of Oishi 20 (2001, 2002a , 2002b). These studies are considered not reliable, as raw data are not 21 available and some studies conducted under similar experimental conditions and under GLP 22 with oral application even at high doses up to 1000 mg/kg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"These studies are considered not reliable, as raw data are not 21 available and some studies conducted under similar experimental conditions and under GLP 22 with oral application even at high doses up to 1000 mg/kg","duration":"","effect":"inciple valuable means for 10 determining inherent toxic potentials (hazards) or modes of actions of chemical substances, 11 these studies are not per se considered as suited for quantitative risk assessment (unless 12 the systemic exposure under s.c. conditions has been determined). Usually, subcutaneous 13 studies are not the best choice for performing risk assessment and should be avoided when 14 more adequate data are available. However, in the absence of more adequate data, as in 15 the case for parabens, the NOAEL derived from such subcutaneous studies may be used as 16 it is very conservative. 17 18 Some previous oral studies with propyl- or butylparaben in rodents were reported to show 19 endocrine potential or reproductive toxicity effects at low doses, in particular those of Oishi 20 (2001, 2002a , 2002b). These studies are considered not reliable, as raw data are not 21 available and some studies conducted under similar experimental conditions and under GLP 22 with oral application even at high doses up to 1000 mg/kg","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":23,"route":"oral","species":"","study_id":"sccs_o_132_noael_025"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1000; DOSE=Oishi 2002b MePB EtPB Wistar rat Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day.; EFFECT=raise doubts on the methodology of the study. No data on toxicokinetics of parabens in mice available. Oishi 2002b MePB EtPB Wistar rat Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day. Rats were 25-27 days old and received the parabens for 8 weeks. MePB and EtPB did not affect the male reproductive system including anti-spermatogenic activity to about 1000 mg/kg/day (NOEL). Oishi 2004 MePB BuPB Wistar rat Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) and testosterone There were no treatment-related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Oishi 2002b MePB EtPB Wistar rat Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day.","duration":"27 days","effect":"raise doubts on the methodology of the study. No data on toxicokinetics of parabens in mice available. Oishi 2002b MePB EtPB Wistar rat Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day. Rats were 25-27 days old and received the parabens for 8 weeks. MePB and EtPB did not affect the male reproductive system including anti-spermatogenic activity to about 1000 mg/kg/day (NOEL). Oishi 2004 MePB BuPB Wistar rat Repetition of the Oishi study (2001) under GLP with MePB or BuPB using the same strain of rats but 16 instead of 8 animals per dose group, same dosage levels of 0, 100, 1000 and 10,000 ppm in food. In addition of the Oishi study, blood samples were weekly taken for the analysis of LH (luteinizing hormone), FSH (follicle-stimulating hormone) and testosterone There were no treatment-related effects on testes, ventral prostates and preputial glands in any of the groups. Unlike Oishi","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":42,"route":"","species":"rat","study_id":"sccs_o_132_noael_029"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1000; DOSE=MePB EtPB | Wistar rat | Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day.; EFFECT=Unlabeled table on page 42: MePB EtPB | Wistar rat | Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day. Rats were 25-27 days old and received the parabens for 8 weeks. | MePB and EtPB did not affect the male reproductive system including anti-spermatogenic activity to about 1000 mg/kg/day (NOEL). | Oishi 2004; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"MePB EtPB | Wistar rat | Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day.","duration":"27 days","effect":"Unlabeled table on page 42: MePB EtPB | Wistar rat | Study of the effects of parabens on testosterone secretion and the function of the male reproductive system in rats receiving the test substances orally at dosage levels of ± 100 and 1000 mg/kg/day. Rats were 25-27 days old and received the parabens for 8 weeks. | MePB and EtPB did not affect the male reproductive system including anti-spermatogenic activity to about 1000 mg/kg/day (NOEL). | Oishi 2004","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":42,"route":"","species":"rat","study_id":"sccs_o_132_noael_038"}

sccs_o_132.pdf

SOURCE_SUBDIR=sccs_o_132; REPORT_TITLE=OPINION ON Parabens Updated request for a scientific opinion on propyl- and butylparaben COLIPA n° P82; OPINION_NUMBER=SCCS/1514/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=3 May 2013; VALUE_TEXT=1504; DOSE=Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day. | Administration of BuPB at 146 and 1504 mg/kg/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration.; EFFECT=Unlabeled table on page 42: BuPB | CD-1 ICR mice | Study of the effects of BuPB on general function of the male mouse reproductive system. Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day. | Administration of BuPB at 146 and 1504 mg/kg/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. The NOAEL is stated to be 14.4 mg/kg/day. Comment: No guideline study. Refuted studies in rats raise doubts on the methodology of the study. No data on toxicokinetics of parabens in mice available. | Oishi 2002b; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day. | Administration of BuPB at 146 and 1504 mg/kg/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration.","duration":"27 days","effect":"Unlabeled table on page 42: BuPB | CD-1 ICR mice | Study of the effects of BuPB on general function of the male mouse reproductive system. Mice (25-27 days old) received BuPB through the oral route for 10 weeks at dosage levels of 14.4, 146 and 1504 mg/kg/day. | Administration of BuPB at 146 and 1504 mg/kg/day caused an increase in epididymal weights, a decrease in testis spermatid count and in serum testosterone concentration. The NOAEL is stated to be 14.4 mg/kg/day. Comment: No guideline study. Refuted studies in rats raise doubts on the methodology of the study. No data on toxicokinetics of parabens in mice available. | Oishi 2002b","endpoint":"reproductive toxicity","ingredient":"s are covered by this entry, with the","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1504","page":42,"route":"oral","species":"rat","study_id":"sccs_o_132_noael_037"}

sccs_o_132.pdf