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

{"absorption_percent":"3.7%","basis":"In the previous safety evaluations of parabens by the SCCS/SCCP (SCCS/1348/10; SCCP/1017/06), a dermal absorption value of 3.7% (for parent paraben based on the available data for butyl paraben) was used. In this new submission, two recent studies with respect to dermal absorption of propyl paraben were included:","page":11,"pdf":"sccs_o_243.pdf","row_type":"dermal_absorption_study"}

sccs_o_243.pdf

{"absorption_percent":"3.7%","basis":"In the previous safety evaluations of parabens by the SCCS/SCCP (SCCS/1348/10; SCCP/1017/06), a dermal absorption value of 3.7% (for parent paraben based on the available data for butyl paraben) was used. In this new submission, two recent studies with respect to dermal absorption of propyl paraben were included:","page":11,"pdf":"sccs_o_243.pdf","row_type":"dermal_absorption_study"}

sccs_o_243.pdf

{"absorption_percent":"3.7%","basis":"In the previous safety evaluations of parabens by the SCCS/SCCP (SCCS/1348/10; SCCP/1017/06), a dermal absorption value of 3.7% (for parent paraben based on the available data for butyl paraben) was used. In this new submission, two recent studies with respect to dermal absorption of propyl paraben were included:","page":11,"pdf":"sccs_o_243.pdf","row_type":"dermal_absorption_study"}

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":", 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=1,000; DOSE=The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study.; EFFECT=ively 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 were conducted in 2010-2012 (Ricerca Biosciences 2011, 2012a, 2012b, 2012c, 2012d). The findings of these studies were published in Gazin et al (2013) and previously reviewed by SCCS (2013) and EMA (2015). The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. The SCCS obtained and reviewed the study by Sivaraman et al (2018).The study by Sivaraman et al (2018) was designed to meet the requirements of the European Medicines Agency (EMA), Committee for Human Medicinal Products (CHMP), the United States Food and Drug Administration (US FDA) Guidance Document and the ICH S3a guidelines. The studies were also conducted in compliance with GLP. Two separate studies on the safety of propylparaben were conducted to ass; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study.","duration":"2012d","effect":"ively 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 were conducted in 2010-2012 (Ricerca Biosciences 2011, 2012a, 2012b, 2012c, 2012d). The findings of these studies were published in Gazin et al (2013) and previously reviewed by SCCS (2013) and EMA (2015). The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. The SCCS obtained and reviewed the study by Sivaraman et al (2018).The study by Sivaraman et al (2018) was designed to meet the requirements of the European Medicines Agency (EMA), Committee for Human Medicinal Products (CHMP), the United States Food and Drug Administration (US FDA) Guidance Document and the ICH S3a guidelines. The studies were also conducted in compliance with GLP. Two separate studies on the safety of propylparaben were conducted to ass","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1,000","page":23,"route":"","species":"rat","study_id":"sccs_o_243_noael_006"}

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=1,000; DOSE=The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study.; EFFECT=evious 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 were conducted in 2010-2012 (Ricerca Biosciences 2011, 2012a, 2012b, 2012c, 2012d). The findings of these studies were published in Gazin et al (2013) and previously reviewed by SCCS (2013) and EMA (2015). The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. The SCCS obtained and reviewed the study by Sivaraman et al (2018).The study by Sivaraman et al (2018) was designed to meet the requirements of the European Medicines Agency (EMA), Committee for Human Medicinal Products (CHMP), the United States Food and Drug Administration (US FDA) Guidance Document and the ICH S3a guidelines. The studies were also conducted in compliance with GLP. Two separate studies on the safety of propylparaben were conducted to assess the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study.","duration":"2012d","effect":"evious 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 were conducted in 2010-2012 (Ricerca Biosciences 2011, 2012a, 2012b, 2012c, 2012d). The findings of these studies were published in Gazin et al (2013) and previously reviewed by SCCS (2013) and EMA (2015). The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. The SCCS obtained and reviewed the study by Sivaraman et al (2018).The study by Sivaraman et al (2018) was designed to meet the requirements of the European Medicines Agency (EMA), Committee for Human Medicinal Products (CHMP), the United States Food and Drug Administration (US FDA) Guidance Document and the ICH S3a guidelines. The studies were also conducted in compliance with GLP. Two separate studies on the safety of propylparaben were conducted to assess the","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1,000","page":23,"route":"","species":"rat","study_id":"sccs_o_243_noael_007"}

sccs_o_243.pdf

{"absorption_percent":"3.7%; 37%","basis":"Dermal absorption studies have been extensively reviewed and evaluated in previous opinions (summarised in SCCS 1348/10, section 3.3.1). The SCCS noted several shortcomings in the data provided and based upon a combination of the three Fasano (2004a, 2004b and 2005) studies, the SCCS derived the value of 3.7% as a worst-case assumption for the dermal absorption of unmetabolised butylparaben. This percentage originated from the mean dermal absorption of 37% measured in split-thickness skin (Fasano 2004b), using a correction factor of 10 to account for skin metabolism as seen in the full thickness skin experiments (Fasano 2004a, 2005). The factor of 10 was considered to be a conservative value as in these studies the measured butylparaben concentration in the receptor fluid was not 10, but 65 to 150 times lower than the metabolite parahydroxy benzoic acid (PHBA) concentration, meaning that butylparaben undergoes extensive metabolism in human skin. The conclusion was: ‘Until a properly...","page":11,"pdf":"sccs_o_275.pdf","row_type":"dermal_absorption_study"}

sccs_o_275.pdf

{"absorption_percent":"3.7%; 37%","basis":"Dermal absorption studies have been extensively reviewed and evaluated in previous opinions (summarised in SCCS 1348/10, section 3.3.1). The SCCS noted several shortcomings in the data provided and based upon a combination of the three Fasano (2004a, 2004b and 2005) studies, the SCCS derived the value of 3.7% as a worst-case assumption for the dermal absorption of unmetabolised butylparaben. This percentage originated from the mean dermal absorption of 37% measured in split-thickness skin (Fasano 2004b), using a correction factor of 10 to account for skin metabolism as seen in the full thickness skin experiments (Fasano 2004a, 2005). The factor of 10 was considered to be a conservative value as in these studies the measured butylparaben concentration in the receptor fluid was not 10, but 65 to 150 times lower than the metabolite parahydroxy benzoic acid (PHBA) concentration, meaning that butylparaben undergoes extensive metabolism in human skin. The conclusion was: ‘Until a properly...","page":11,"pdf":"sccs_o_275.pdf","row_type":"dermal_absorption_study"}

sccs_o_275.pdf

{"absorption_percent":"3.7%; 37%","basis":"Dermal absorption studies have been extensively reviewed and evaluated in previous opinions (summarised in SCCS 1348/10, section 3.3.1). The SCCS noted several shortcomings in the data provided and based upon a combination of the three Fasano (2004a, 2004b and 2005) studies, the SCCS derived the value of 3.7% as a worst-case assumption for the dermal absorption of unmetabolised butylparaben. This percentage originated from the mean dermal absorption of 37% measured in split-thickness skin (Fasano 2004b), using a correction factor of 10 to account for skin metabolism as seen in the full thickness skin experiments (Fasano 2004a, 2005). The factor of 10 was considered to be a conservative value as in these studies the measured butylparaben concentration in the receptor fluid was not 10, but 65 to 150 times lower than the metabolite parahydroxy benzoic acid (PHBA) concentration, meaning that butylparaben undergoes extensive metabolism in human skin. The conclusion was: ‘Until a properly...","page":11,"pdf":"sccs_o_275.pdf","row_type":"dermal_absorption_study"}

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

{"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","page":10,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_010"}

sccs_o_132.pdf

{"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","page":10,"pdf":"sccs_o_132.pdf","row_type":"noael_study","study_id":"sccs_o_132_noael_010"}

sccs_o_132.pdf

{"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","page":10,"pdf":"sccs_o_132.pdf","row_type":"noael_study","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== 0.043; 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=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=2.0; 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_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al.; EFFECT=__________________ 12 The SCCP concluded that a) the quality of the Oishi studies could not be properly assessed as the full test description and the complete raw data packages were not available, b) with regard to the Industry repeat studies, although the full descriptions and raw data were available and although some of the questions raised by the SCCP were addressed during an Industry hearing, the remaining issues hampered their acceptance as unarguable refutation of the Oishi findings. This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al. (1999) study, was still considered as the NOEL to be used in further calculations. Between 2008 and 2010, additional in vivo data on parabens were published. An overview of the most pertinent ones is given below: - Effects of ethylparaben and butylparaben on steroidogenesis in parental rats and offspring after subcutaneous administration to pregnant rats: Ethylparaben and butylparaben (up to 400 mg/kg/day) showed no treatment-related effects on test; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al.","duration":"","effect":"__________________ 12 The SCCP concluded that a) the quality of the Oishi studies could not be properly assessed as the full test description and the complete raw data packages were not available, b) with regard to the Industry repeat studies, although the full descriptions and raw data were available and although some of the questions raised by the SCCP were addressed during an Industry hearing, the remaining issues hampered their acceptance as unarguable refutation of the Oishi findings. This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al. (1999) study, was still considered as the NOEL to be used in further calculations. Between 2008 and 2010, additional in vivo data on parabens were published. An overview of the most pertinent ones is given below: - Effects of ethylparaben and butylparaben on steroidogenesis in parental rats and offspring after subcutaneous administration to pregnant rats: Ethylparaben and butylparaben (up to 400 mg/kg/day) showed no treatment-related effects on test","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":12,"route":"","species":"rat","study_id":"sccs_o_041_noael_006"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al.; EFFECT=as the full test description and the complete raw data packages were not available, b) with regard to the Industry repeat studies, although the full descriptions and raw data were available and although some of the questions raised by the SCCP were addressed during an Industry hearing, the remaining issues hampered their acceptance as unarguable refutation of the Oishi findings. This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al. (1999) study, was still considered as the NOEL to be used in further calculations. Between 2008 and 2010, additional in vivo data on parabens were published. An overview of the most pertinent ones is given below: - Effects of ethylparaben and butylparaben on steroidogenesis in parental rats and offspring after subcutaneous administration to pregnant rats: Ethylparaben and butylparaben (up to 400 mg/kg/day) showed no treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERβ mRNA expressi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al.","duration":"","effect":"as the full test description and the complete raw data packages were not available, b) with regard to the Industry repeat studies, although the full descriptions and raw data were available and although some of the questions raised by the SCCP were addressed during an Industry hearing, the remaining issues hampered their acceptance as unarguable refutation of the Oishi findings. This also meant that the NOEL of 2 mg/kg bw/day of butylparaben, obtained in the Fisher et al. (1999) study, was still considered as the NOEL to be used in further calculations. Between 2008 and 2010, additional in vivo data on parabens were published. An overview of the most pertinent ones is given below: - Effects of ethylparaben and butylparaben on steroidogenesis in parental rats and offspring after subcutaneous administration to pregnant rats: Ethylparaben and butylparaben (up to 400 mg/kg/day) showed no treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. Butylparaben decreased ERβ mRNA expressi","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":12,"route":"","species":"rat","study_id":"sccs_o_041_noael_007"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=unclear:Table 2 in the appendix to this opinion. The SCCP concluded that the studies displayed a: the Fisher et | al. (1999) | study in the r | at, is still | considered | as the | NOEL to be; EFFECT=Table 2 in the appendix to this opinion. The SCCP concluded that the studies displayed a: the Fisher et | al. (1999) | study in the r | at, is still | considered | as the | NOEL to be; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"Table 2 in the appendix to this opinion. The SCCP concluded that the studies displayed a: the Fisher et | al. (1999) | study in the r | at, is still | considered | as the | NOEL to be","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"","noael_value":"unclear:Table 2 in the appendix to this opinion. The SCCP concluded that the studies displayed a: the Fisher et | al. (1999) | study in the r | at, is still | considered | as the | NOEL to be","page":13,"route":"","species":"","study_id":"sccs_o_041_noael_028"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=unclear:_____________________________________________ 20 4. DISCUSSION Not only Industry and the SCCS, but also other stakeholders expressed their views on the safe use of parabens in cosmetic products. In order to provide an as complete as possible picture on all the available information, the individual points of view of all parties are also summarized below. 4.1 VIEW OF THE INDUSTRY The current Industry submission uses the following argumentation to declare all parabens safe for use: 1. The choice of the reproduction NO(A)EL value: Industry emphasizes that the Oishi (2001) study is not reliable and that the CTFA/Colipa study (Hoberman et al. 2008) is well performed. One of their arguments is that the SCCP (2008) acknowledged the scientific value of the new study. 2. Toxicokinetic aspects related to the risk assessment of parabens: Industry presents a large pharmacokinetic study in the rat using different routes of exposure (Aubert 2009). A major conclusion is that in the rat, independent of the route of exposure, parabens are quickly; EFFECT=_____________________________________________ 20 4. DISCUSSION Not only Industry and the SCCS, but also other stakeholders expressed their views on the safe use of parabens in cosmetic products. In order to provide an as complete as possible picture on all the available information, the individual points of view of all parties are also summarized below. 4.1 VIEW OF THE INDUSTRY The current Industry submission uses the following argumentation to declare all parabens safe for use: 1. The choice of the reproduction NO(A)EL value: Industry emphasizes that the Oishi (2001) study is not reliable and that the CTFA/Colipa study (Hoberman et al. 2008) is well performed. One of their arguments is that the SCCP (2008) acknowledged the scientific value of the new study. 2. Toxicokinetic aspects related to the risk assessment of parabens: Industry presents a large pharmacokinetic study in the rat using different routes of exposure (Aubert 2009). A major conclusion is that in the rat, independent of the route of exposure, parabens are quickly; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"_____________________________________________ 20 4. DISCUSSION Not only Industry and the SCCS, but also other stakeholders expressed their views on the safe use of parabens in cosmetic products. In order to provide an as complete as possible picture on all the available information, the individual points of view of all parties are also summarized below. 4.1 VIEW OF THE INDUSTRY The current Industry submission uses the following argumentation to declare all parabens safe for use: 1. The choice of the reproduction NO(A)EL value: Industry emphasizes that the Oishi (2001) study is not reliable and that the CTFA/Colipa study (Hoberman et al. 2008) is well performed. One of their arguments is that the SCCP (2008) acknowledged the scientific value of the new study. 2. Toxicokinetic aspects related to the risk assessment of parabens: Industry presents a large pharmacokinetic study in the rat using different routes of exposure (Aubert 2009). A major conclusion is that in the rat, independent of the route of exposure, parabens are quickly","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"","noael_value":"unclear:_____________________________________________ 20 4. DISCUSSION Not only Industry and the SCCS, but also other stakeholders expressed their views on the safe use of parabens in cosmetic products. In order to provide an as complete as possible picture on all the available information, the individual points of view of all parties are also summarized below. 4.1 VIEW OF THE INDUSTRY The current Industry submission uses the following argumentation to declare all parabens safe for use: 1. The choice of the reproduction NO(A)EL value: Industry emphasizes that the Oishi (2001) study is not reliable and that the CTFA/Colipa study (Hoberman et al. 2008) is well performed. One of their arguments is that the SCCP (2008) acknowledged the scientific value of the new study. 2. Toxicokinetic aspects related to the risk assessment of parabens: Industry presents a large pharmacokinetic study in the rat using different routes of exposure (Aubert 2009). A major conclusion is that in the rat, independent of the route of exposure, parabens are quickly","page":20,"route":"","species":"rat","study_id":"sccs_o_041_noael_012"}

sccs_o_041.pdf

{"absorption_percent":"3.5%","basis":"3.3.1.1 Dermal absorption in vitro The Norwegian Institute of Public Health published in 2003 a report (Paulsen and Alexander, 2003), briefly summarising the toxicity of the parabens and using in their calculation of the MoS a value of 3.5% dermal absorption, based on in vitro studies with human skin (Cross and Roberts 2000): This document was taken up in the 2005 SCCP opinion on parabens (SCCP/0873/05) and was considered to give a realistic value for dermal absorption. During the commenting period of the present opinion (SCCS/1348/10) however, the SCCS was informed that the value of 3.5% dermal absorption was based on a misinterpretation of the original study results contained in the applicant's dossier and should therefore not be used.","page":13,"pdf":"sccs_o_041.pdf","row_type":"dermal_absorption_study"}

sccs_o_041.pdf

{"absorption_percent":"3.5%","basis":"3.3.1.1 Dermal absorption in vitro The Norwegian Institute of Public Health published in 2003 a report (Paulsen and Alexander, 2003), briefly summarising the toxicity of the parabens and using in their calculation of the MoS a value of 3.5% dermal absorption, based on in vitro studies with human skin (Cross and Roberts 2000): This document was taken up in the 2005 SCCP opinion on parabens (SCCP/0873/05) and was considered to give a realistic value for dermal absorption. During the commenting period of the present opinion (SCCS/1348/10) however, the SCCS was informed that the value of 3.5% dermal absorption was based on a misinterpretation of the original study results contained in the applicant's dossier and should therefore not be used.","page":13,"pdf":"sccs_o_041.pdf","row_type":"dermal_absorption_study"}

sccs_o_041.pdf

{"absorption_percent":"3.5%","basis":"3.3.1.1 Dermal absorption in vitro The Norwegian Institute of Public Health published in 2003 a report (Paulsen and Alexander, 2003), briefly summarising the toxicity of the parabens and using in their calculation of the MoS a value of 3.5% dermal absorption, based on in vitro studies with human skin (Cross and Roberts 2000): This document was taken up in the 2005 SCCP opinion on parabens (SCCP/0873/05) and was considered to give a realistic value for dermal absorption. During the commenting period of the present opinion (SCCS/1348/10) however, the SCCS was informed that the value of 3.5% dermal absorption was based on a misinterpretation of the original study results contained in the applicant's dossier and should therefore not be used.","page":13,"pdf":"sccs_o_041.pdf","row_type":"dermal_absorption_study"}

sccs_o_041.pdf

{"dose":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester.","effect":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester. Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive","page":10,"pdf":"sccs_o_041.pdf","row_type":"noael_study","study_id":"sccs_o_041_noael_002"}

sccs_o_041.pdf

{"dose":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester.","effect":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester. Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive","page":10,"pdf":"sccs_o_041.pdf","row_type":"noael_study","study_id":"sccs_o_041_noael_002"}

sccs_o_041.pdf

{"dose":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester.","effect":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester. Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive","page":10,"pdf":"sccs_o_041.pdf","row_type":"noael_study","study_id":"sccs_o_041_noael_002"}

sccs_o_041.pdf

{"effect":"CCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 7 3. ISSUES Considering the questions raised during the last six years on the safety evaluation of parabens, three separate issues need to be considered: 1) The relationship between the use of parabens in deodorants and the development of breast cancer. 2) The potential in vitro and in vivo endocrine modifying effects of parabens, in particular estrogenic/anti-androgenic activities and the NO(A)EL value to be used for the calculation of the MoS for the different paraben esters. 3) The toxicokinetics (dermal absorption and biotransformation) of the different paraben esters (in humans and rodents). Each issue has been previously discussed and described in a number of publications and/or official reports. The following sections summarise the available data per issue with special emphasis on the remaining problem points. The previous opinions of the SCCP on the subject of parabens, which provide additional info","page":7,"pdf":"sccs_o_041.pdf","row_type":"noael_study","study_id":"sccs_o_041_noael_001"}

sccs_o_041.pdf

{"effect":"CCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 7 3. ISSUES Considering the questions raised during the last six years on the safety evaluation of parabens, three separate issues need to be considered: 1) The relationship between the use of parabens in deodorants and the development of breast cancer. 2) The potential in vitro and in vivo endocrine modifying effects of parabens, in particular estrogenic/anti-androgenic activities and the NO(A)EL value to be used for the calculation of the MoS for the different paraben esters. 3) The toxicokinetics (dermal absorption and biotransformation) of the different paraben esters (in humans and rodents). Each issue has been previously discussed and described in a number of publications and/or official reports. The following sections summarise the available data per issue with special emphasis on the remaining problem points. The previous opinions of the SCCP on the subject of parabens, which provide additional info","page":7,"pdf":"sccs_o_041.pdf","row_type":"noael_study","study_id":"sccs_o_041_noael_001"}

sccs_o_041.pdf

{"effect":"CCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 7 3. ISSUES Considering the questions raised during the last six years on the safety evaluation of parabens, three separate issues need to be considered: 1) The relationship between the use of parabens in deodorants and the development of breast cancer. 2) The potential in vitro and in vivo endocrine modifying effects of parabens, in particular estrogenic/anti-androgenic activities and the NO(A)EL value to be used for the calculation of the MoS for the different paraben esters. 3) The toxicokinetics (dermal absorption and biotransformation) of the different paraben esters (in humans and rodents). Each issue has been previously discussed and described in a number of publications and/or official reports. The following sections summarise the available data per issue with special emphasis on the remaining problem points. The previous opinions of the SCCP on the subject of parabens, which provide additional info","page":7,"pdf":"sccs_o_041.pdf","row_type":"noael_study","study_id":"sccs_o_041_noael_001"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT== 0.043; DOSE=2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.; EFFECT=try, being the dermal absorption value, the NO(A)EL value and the finished product exposure level, only the latter seems acceptable. As explained before, the SCCS uses the following parameters for the final calculation of the MoS of butylparaben: Dermal absorption: 3.7% Intended concentration in finished product: 0.4% Typical body weight: 60 kg Cumulative exposure to preservatives: 17.4 g/day NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.","duration":"17 days","effect":"try, being the dermal absorption value, the NO(A)EL value and the finished product exposure level, only the latter seems acceptable. As explained before, the SCCS uses the following parameters for the final calculation of the MoS of butylparaben: Dermal absorption: 3.7% Intended concentration in finished product: 0.4% Typical body weight: 60 kg Cumulative exposure to preservatives: 17.4 g/day NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 0.043","page":23,"route":"dermal","species":"rat","study_id":"sccs_o_041_noael_024"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=In vivo studies on parabens published between 2008-2010 showed effects with relatively high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters.; EFFECT=(Vo et al. 2010). Sub conclusion 2: In vivo studies on parabens published between 2008-2010 showed effects with relatively high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters. The recent findings do not clarify the diverging results between the Oishi and Hoberman studies in male rats. The shortcomings of the Hoberman study prevent its acceptance. It cannot be used to refute the Oishi findings; these, in turn, cannot be properly assessed due to the unavailability of raw data. This means that the NOEL of 2 mg/kg bw/day for butylparaben, derived from the Fisher et al. (1999) study in the rat, is still considered as the NOEL to be used in further calculations. For the iso-derivatives of butyl- and propylparaben, and for benzyl- or phenylparaben no suitable data are present. 3.3 DERMAL ABSORPTION AND OTHER TOXICOKINETIC DATA 3.3.1 Dermal absorption 3.3.1.1 Dermal absorption in vitro The Norwegian Institute of Public Health published in 2003 a report (Paulsen and Alexander, 2003), briefly summarising the toxicit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"In vivo studies on parabens published between 2008-2010 showed effects with relatively high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters.","duration":"","effect":"(Vo et al. 2010). Sub conclusion 2: In vivo studies on parabens published between 2008-2010 showed effects with relatively high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters. The recent findings do not clarify the diverging results between the Oishi and Hoberman studies in male rats. The shortcomings of the Hoberman study prevent its acceptance. It cannot be used to refute the Oishi findings; these, in turn, cannot be properly assessed due to the unavailability of raw data. This means that the NOEL of 2 mg/kg bw/day for butylparaben, derived from the Fisher et al. (1999) study in the rat, is still considered as the NOEL to be used in further calculations. For the iso-derivatives of butyl- and propylparaben, and for benzyl- or phenylparaben no suitable data are present. 3.3 DERMAL ABSORPTION AND OTHER TOXICOKINETIC DATA 3.3.1 Dermal absorption 3.3.1.1 Dermal absorption in vitro The Norwegian Institute of Public Health published in 2003 a report (Paulsen and Alexander, 2003), briefly summarising the toxicit","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":13,"route":"dermal","species":"rat","study_id":"sccs_o_041_noael_008"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters.; EFFECT=high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters. The recent findings do not clarify the diverging results between the Oishi and Hoberman studies in male rats. The shortcomings of the Hoberman study prevent its acceptance. It cannot be used to refute the Oishi findings; these, in turn, cannot be properly assessed due to the unavailability of raw data. This means that the NOEL of 2 mg/kg bw/day for butylparaben, derived from the Fisher et al. (1999) study in the rat, is still considered as the NOEL to be used in further calculations. For the iso-derivatives of butyl- and propylparaben, and for benzyl- or phenylparaben no suitable data are present. 3.3 DERMAL ABSORPTION AND OTHER TOXICOKINETIC DATA 3.3.1 Dermal absorption 3.3.1.1 Dermal absorption in vitro The Norwegian Institute of Public Health published in 2003 a report (Paulsen and Alexander, 2003), briefly summarising the toxicity of the parabens and using in their calculation of the MoS a value of 3.5% dermal absorption, based on in vitro studies wit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters.","duration":"","effect":"high dosage levels (mainly about 1000 mg/kg bw/day) of paraben esters. The recent findings do not clarify the diverging results between the Oishi and Hoberman studies in male rats. The shortcomings of the Hoberman study prevent its acceptance. It cannot be used to refute the Oishi findings; these, in turn, cannot be properly assessed due to the unavailability of raw data. This means that the NOEL of 2 mg/kg bw/day for butylparaben, derived from the Fisher et al. (1999) study in the rat, is still considered as the NOEL to be used in further calculations. For the iso-derivatives of butyl- and propylparaben, and for benzyl- or phenylparaben no suitable data are present. 3.3 DERMAL ABSORPTION AND OTHER TOXICOKINETIC DATA 3.3.1 Dermal absorption 3.3.1.1 Dermal absorption in vitro The Norwegian Institute of Public Health published in 2003 a report (Paulsen and Alexander, 2003), briefly summarising the toxicity of the parabens and using in their calculation of the MoS a value of 3.5% dermal absorption, based on in vitro studies wit","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":13,"route":"dermal","species":"rat","study_id":"sccs_o_041_noael_009"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=table. Therefore the SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylparaben to cause similar effects at about the same dosage levels after subcutaneous or oral administration (Routledge et al. 1998). ¾ With regard to the toxicokinetic aspects related to parabens, the SCCP not only requested sound in vitro dermal absorption data, but also the performance of a human study in order to obtain adequate and detailed information on the absorption and metabolism of paraben esters in human skin. This request was based upon the fact that; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"","effect":"table. Therefore the SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylparaben to cause similar effects at about the same dosage levels after subcutaneous or oral administration (Routledge et al. 1998). ¾ With regard to the toxicokinetic aspects related to parabens, the SCCP not only requested sound in vitro dermal absorption data, but also the performance of a human study in order to obtain adequate and detailed information on the absorption and metabolism of paraben esters in human skin. This request was based upon the fact that","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":22,"route":"oral","species":"human","study_id":"sccs_o_041_noael_018"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=e SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylparaben to cause similar effects at about the same dosage levels after subcutaneous or oral administration (Routledge et al. 1998). ¾ With regard to the toxicokinetic aspects related to parabens, the SCCP not only requested sound in vitro dermal absorption data, but also the performance of a human study in order to obtain adequate and detailed information on the absorption and metabolism of paraben esters in human skin. This request was based upon the fact that the observed in vit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"","effect":"e SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylparaben to cause similar effects at about the same dosage levels after subcutaneous or oral administration (Routledge et al. 1998). ¾ With regard to the toxicokinetic aspects related to parabens, the SCCP not only requested sound in vitro dermal absorption data, but also the performance of a human study in order to obtain adequate and detailed information on the absorption and metabolism of paraben esters in human skin. This request was based upon the fact that the observed in vit","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":22,"route":"oral","species":"human","study_id":"sccs_o_041_noael_019"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2.0; DOSE=2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.; EFFECT=levance for this risk assessment is not clear. Of the three assumptions present in the MoS calculation proposed by the Industry, being the dermal absorption value, the NO(A)EL value and the finished product exposure level, only the latter seems acceptable. As explained before, the SCCS uses the following parameters for the final calculation of the MoS of butylparaben: Dermal absorption: 3.7% Intended concentration in finished product: 0.4% Typical body weight: 60 kg Cumulative exposure to preservatives: 17.4 g/day NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.","duration":"17 days","effect":"levance for this risk assessment is not clear. Of the three assumptions present in the MoS calculation proposed by the Industry, being the dermal absorption value, the NO(A)EL value and the finished product exposure level, only the latter seems acceptable. As explained before, the SCCS uses the following parameters for the final calculation of the MoS of butylparaben: Dermal absorption: 3.7% Intended concentration in finished product: 0.4% Typical body weight: 60 kg Cumulative exposure to preservatives: 17.4 g/day NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obtain a MoS ≥ 100, the concentration of butylparaben in the finished cosmetic product needs to be reduced to 0.19%.","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.0","page":23,"route":"dermal","species":"rat","study_id":"sccs_o_041_noael_023"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=3.7; DOSE=2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obta; EFFECT=toxicity NO(A)EL is based on a study with insufficient scientific reliability. Using the in vivo estrogenicity studies and applying additional safety factors is not feasible either, as all studies are performed either through subcutaneous or oral route, meaning that skin metabolism is avoided. Therefore, with the current level of knowledge, their relevance for this risk assessment is not clear. Of the three assumptions present in the MoS calculation proposed by the Industry, being the dermal absorption value, the NO(A)EL value and the finished product exposure level, only the latter seems acceptable. As explained before, the SCCS uses the following parameters for the final calculation of the MoS of butylparaben: Dermal absorption: 3.7% Intended concentration in finished product: 0.4% Typical body weight: 60 kg Cumulative exposure to preservatives: 17.4 g/day NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obta; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obta","duration":"17 days","effect":"toxicity NO(A)EL is based on a study with insufficient scientific reliability. Using the in vivo estrogenicity studies and applying additional safety factors is not feasible either, as all studies are performed either through subcutaneous or oral route, meaning that skin metabolism is avoided. Therefore, with the current level of knowledge, their relevance for this risk assessment is not clear. Of the three assumptions present in the MoS calculation proposed by the Industry, being the dermal absorption value, the NO(A)EL value and the finished product exposure level, only the latter seems acceptable. As explained before, the SCCS uses the following parameters for the final calculation of the MoS of butylparaben: Dermal absorption: 3.7% Intended concentration in finished product: 0.4% Typical body weight: 60 kg Cumulative exposure to preservatives: 17.4 g/day NOEL (subcutaneous, rat, 17 days): 2.0 mg/kg bw/day 17400 mg/day * 0.4/100 * 3.7/100 SED = 60 kg = 0.043 mg/kg bw/day MoS = NOEL / SED = 46.6 This means that, in order to obta","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"%","noael_value":"3.7","page":23,"route":"oral","species":"rat","study_id":"sccs_o_041_noael_022"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=1000; DOSE=(2008) value of 1000 mg/kg/day. - For the calculation of the SED, the cumulative value of 17.4 g/day is used (SCCS Notes of Guidance, SCCS/1416/11), assuming that parabens may be used as a preservative in all cosmetic products. - Only 1% of the paraben level is assumed to become systemically available, due to the hydrolysis of the parent compoun...; EFFECT=exposure, parabens are quickly hydrolysed and only occur in the systemic circulation in the form of the metabolite PHBA. In addition, excretion is rapid and mainly occurs via the urine. Total dermal absorption (parent compound + metabolites) in the rat is estimated to be around 27%. 3. With regard to the requested human toxicokinetic study: Industry decided not to perform it (arguments stated under 3.3.2.2). 4. For the final safety assessment of the parabens, the following parameters are taken into account: - The NO(A)EL used for all paraben esters is the Hoberman et al. (2008) value of 1000 mg/kg/day. - For the calculation of the SED, the cumulative value of 17.4 g/day is used (SCCS Notes of Guidance, SCCS/1416/11), assuming that parabens may be used as a preservative in all cosmetic products. - Only 1% of the paraben level is assumed to become systemically available, due to the hydrolysis of the parent compound into PHBA (based upon Schepky et al. 2009). The MoS values obtained are 83,300 for the individual paraben esters and 41; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"(2008) value of 1000 mg/kg/day. - For the calculation of the SED, the cumulative value of 17.4 g/day is used (SCCS Notes of Guidance, SCCS/1416/11), assuming that parabens may be used as a preservative in all cosmetic products. - Only 1% of the paraben level is assumed to become systemically available, due to the hydrolysis of the parent compoun...","duration":"","effect":"exposure, parabens are quickly hydrolysed and only occur in the systemic circulation in the form of the metabolite PHBA. In addition, excretion is rapid and mainly occurs via the urine. Total dermal absorption (parent compound + metabolites) in the rat is estimated to be around 27%. 3. With regard to the requested human toxicokinetic study: Industry decided not to perform it (arguments stated under 3.3.2.2). 4. For the final safety assessment of the parabens, the following parameters are taken into account: - The NO(A)EL used for all paraben esters is the Hoberman et al. (2008) value of 1000 mg/kg/day. - For the calculation of the SED, the cumulative value of 17.4 g/day is used (SCCS Notes of Guidance, SCCS/1416/11), assuming that parabens may be used as a preservative in all cosmetic products. - Only 1% of the paraben level is assumed to become systemically available, due to the hydrolysis of the parent compound into PHBA (based upon Schepky et al. 2009). The MoS values obtained are 83,300 for the individual paraben esters and 41","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":20,"route":"dermal","species":"rat","study_id":"sccs_o_041_noael_013"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=unclear:CCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 7 3. ISSUES Considering the questions raised during the last six years on the safety evaluation of parabens, three separate issues need to be considered: 1) The relationship between the use of parabens in deodorants and the development of breast cancer. 2) The potential in vitro and in vivo endocrine modifying effects of parabens, in particular estrogenic/anti-androgenic activities and the NO(A)EL value to be used for the calculation of the MoS for the different paraben esters. 3) The toxicokinetics (dermal absorption and biotransformation) of the different paraben esters (in humans and rodents). Each issue has been previously discussed and described in a number of publications and/or official reports. The following sections summarise the available data per issue with special emphasis on the remaining problem points. The previous opinions of the SCCP on the subject of parabens, which provide additional info; EFFECT=CCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 7 3. ISSUES Considering the questions raised during the last six years on the safety evaluation of parabens, three separate issues need to be considered: 1) The relationship between the use of parabens in deodorants and the development of breast cancer. 2) The potential in vitro and in vivo endocrine modifying effects of parabens, in particular estrogenic/anti-androgenic activities and the NO(A)EL value to be used for the calculation of the MoS for the different paraben esters. 3) The toxicokinetics (dermal absorption and biotransformation) of the different paraben esters (in humans and rodents). Each issue has been previously discussed and described in a number of publications and/or official reports. The following sections summarise the available data per issue with special emphasis on the remaining problem points. The previous opinions of the SCCP on the subject of parabens, which provide additional info; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"CCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 7 3. ISSUES Considering the questions raised during the last six years on the safety evaluation of parabens, three separate issues need to be considered: 1) The relationship between the use of parabens in deodorants and the development of breast cancer. 2) The potential in vitro and in vivo endocrine modifying effects of parabens, in particular estrogenic/anti-androgenic activities and the NO(A)EL value to be used for the calculation of the MoS for the different paraben esters. 3) The toxicokinetics (dermal absorption and biotransformation) of the different paraben esters (in humans and rodents). Each issue has been previously discussed and described in a number of publications and/or official reports. The following sections summarise the available data per issue with special emphasis on the remaining problem points. The previous opinions of the SCCP on the subject of parabens, which provide additional info","endpoint":"dermal absorption","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"","noael_value":"unclear:CCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 7 3. ISSUES Considering the questions raised during the last six years on the safety evaluation of parabens, three separate issues need to be considered: 1) The relationship between the use of parabens in deodorants and the development of breast cancer. 2) The potential in vitro and in vivo endocrine modifying effects of parabens, in particular estrogenic/anti-androgenic activities and the NO(A)EL value to be used for the calculation of the MoS for the different paraben esters. 3) The toxicokinetics (dermal absorption and biotransformation) of the different paraben esters (in humans and rodents). Each issue has been previously discussed and described in a number of publications and/or official reports. The following sections summarise the available data per issue with special emphasis on the remaining problem points. The previous opinions of the SCCP on the subject of parabens, which provide additional info","page":7,"route":"dermal","species":"human","study_id":"sccs_o_041_noael_001"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al.; LOAEL_VALUE=10 mg/kg bw/day; EFFECT=in vitro data show an increasing potential for endocrine modifying effects with increasing chain length. PHBA, a common metabolite of all paraben esters, however, appears to exhibit no endocrine modifying effects. 2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al. 2008) are controversial and provide very divergent critical effect levels for butylparaben ranging from a LOAEL of 10 mg/kg bw/day to a NOAEL 1000 mg/kg bw/day, respectively. Older data on butylparaben revealed a reproductive NOEL of 2 mg/kg bw/day in the rat (Fisher et al. 1999). The latter will be used as a conservative value in further calculations. 3) The presented in vivo pharmacokinetic studies on methylparaben, propylparaben and butylparaben in the rat (oral, dermal, subcutaneous administration) show that these parabens are rapidly absorbed and eliminated in this species. Available in vitro dermal absorption study results point towards a potential difference not only in dermal absorption (Fasano 2004b, Pape and Skepky 2009) but also; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al.","duration":"","effect":"in vitro data show an increasing potential for endocrine modifying effects with increasing chain length. PHBA, a common metabolite of all paraben esters, however, appears to exhibit no endocrine modifying effects. 2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al. 2008) are controversial and provide very divergent critical effect levels for butylparaben ranging from a LOAEL of 10 mg/kg bw/day to a NOAEL 1000 mg/kg bw/day, respectively. Older data on butylparaben revealed a reproductive NOEL of 2 mg/kg bw/day in the rat (Fisher et al. 1999). The latter will be used as a conservative value in further calculations. 3) The presented in vivo pharmacokinetic studies on methylparaben, propylparaben and butylparaben in the rat (oral, dermal, subcutaneous administration) show that these parabens are rapidly absorbed and eliminated in this species. Available in vitro dermal absorption study results point towards a potential difference not only in dermal absorption (Fasano 2004b, Pape and Skepky 2009) but also","endpoint":"repeated dose toxicity","ingredient":"s, toys, textiles,","loael_value":"10 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"2","page":19,"route":"oral","species":"rat","study_id":"sccs_o_041_noael_011"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=1000; DOSE=2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al.; LOAEL_VALUE=10 mg/kg bw/day; EFFECT=e metabolite PHBA. 3.4 SUMMARY OF CONCLUSIONS RELATED TO ISSUES 3.1-3.3 1) Human-based in vitro data show an increasing potential for endocrine modifying effects with increasing chain length. PHBA, a common metabolite of all paraben esters, however, appears to exhibit no endocrine modifying effects. 2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al. 2008) are controversial and provide very divergent critical effect levels for butylparaben ranging from a LOAEL of 10 mg/kg bw/day to a NOAEL 1000 mg/kg bw/day, respectively. Older data on butylparaben revealed a reproductive NOEL of 2 mg/kg bw/day in the rat (Fisher et al. 1999). The latter will be used as a conservative value in further calculations. 3) The presented in vivo pharmacokinetic studies on methylparaben, propylparaben and butylparaben in the rat (oral, dermal, subcutaneous administration) show that these parabens are rapidly absorbed and eliminated in this species. Available in vitro dermal absorption study results point towards a potentia; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al.","duration":"","effect":"e metabolite PHBA. 3.4 SUMMARY OF CONCLUSIONS RELATED TO ISSUES 3.1-3.3 1) Human-based in vitro data show an increasing potential for endocrine modifying effects with increasing chain length. PHBA, a common metabolite of all paraben esters, however, appears to exhibit no endocrine modifying effects. 2) The major repeated dose studies in rat (Oishi 2001 and 2002, Hoberman et al. 2008) are controversial and provide very divergent critical effect levels for butylparaben ranging from a LOAEL of 10 mg/kg bw/day to a NOAEL 1000 mg/kg bw/day, respectively. Older data on butylparaben revealed a reproductive NOEL of 2 mg/kg bw/day in the rat (Fisher et al. 1999). The latter will be used as a conservative value in further calculations. 3) The presented in vivo pharmacokinetic studies on methylparaben, propylparaben and butylparaben in the rat (oral, dermal, subcutaneous administration) show that these parabens are rapidly absorbed and eliminated in this species. Available in vitro dermal absorption study results point towards a potentia","endpoint":"repeated dose toxicity","ingredient":"s, toys, textiles,","loael_value":"10 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"1000","page":19,"route":"oral","species":"rat","study_id":"sccs_o_041_noael_010"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=1; EFFECT=7% dermal absorption value derived from the results of three in vitro dermal absorption studies (full rationale under 3.4). The limited data available for human in vivo studies support the assumption of an absorption value for unmetabolised parabens in the lower one-digit percentage range. This value is a more conservative estimate than the 1% proposed by Industry and the 2% value proposed by the Danish Technical University (2010) ¾ The MoS calculation as proposed by Industry, based upon the Hoberman et al. (2008) NO(A)EL value and a 1% dermal absorption is not acceptable for the following reasons: - the 1% value of systemic availability results from a re-analysed ‘preliminary’ dermal absorption study (Pape and Schepky 2009), of poor quality. In case parabens are completely hydrolyzed into PHBA, the latter will become systemically available. - the reproductive toxicity NO(A)EL is based on a study with insufficient scientific reliability. Using the in vivo estrogenicity studies and applying additional safety factors is not feasible; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"7% dermal absorption value derived from the results of three in vitro dermal absorption studies (full rationale under 3.4). The limited data available for human in vivo studies support the assumption of an absorption value for unmetabolised parabens in the lower one-digit percentage range. This value is a more conservative estimate than the 1% proposed by Industry and the 2% value proposed by the Danish Technical University (2010) ¾ The MoS calculation as proposed by Industry, based upon the Hoberman et al. (2008) NO(A)EL value and a 1% dermal absorption is not acceptable for the following reasons: - the 1% value of systemic availability results from a re-analysed ‘preliminary’ dermal absorption study (Pape and Schepky 2009), of poor quality. In case parabens are completely hydrolyzed into PHBA, the latter will become systemically available. - the reproductive toxicity NO(A)EL is based on a study with insufficient scientific reliability. Using the in vivo estrogenicity studies and applying additional safety factors is not feasible","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"%","noael_value":"1","page":23,"route":"dermal","species":"human","study_id":"sccs_o_041_noael_020"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=1; EFFECT=stry and the 2% value proposed by the Danish Technical University (2010) ¾ The MoS calculation as proposed by Industry, based upon the Hoberman et al. (2008) NO(A)EL value and a 1% dermal absorption is not acceptable for the following reasons: - the 1% value of systemic availability results from a re-analysed ‘preliminary’ dermal absorption study (Pape and Schepky 2009), of poor quality. In case parabens are completely hydrolyzed into PHBA, the latter will become systemically available. - the reproductive toxicity NO(A)EL is based on a study with insufficient scientific reliability. Using the in vivo estrogenicity studies and applying additional safety factors is not feasible either, as all studies are performed either through subcutaneous or oral route, meaning that skin metabolism is avoided. Therefore, with the current level of knowledge, their relevance for this risk assessment is not clear. Of the three assumptions present in the MoS calculation proposed by the Industry, being the dermal absorption value, the NO(A)EL value and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"stry and the 2% value proposed by the Danish Technical University (2010) ¾ The MoS calculation as proposed by Industry, based upon the Hoberman et al. (2008) NO(A)EL value and a 1% dermal absorption is not acceptable for the following reasons: - the 1% value of systemic availability results from a re-analysed ‘preliminary’ dermal absorption study (Pape and Schepky 2009), of poor quality. In case parabens are completely hydrolyzed into PHBA, the latter will become systemically available. - the reproductive toxicity NO(A)EL is based on a study with insufficient scientific reliability. Using the in vivo estrogenicity studies and applying additional safety factors is not feasible either, as all studies are performed either through subcutaneous or oral route, meaning that skin metabolism is avoided. Therefore, with the current level of knowledge, their relevance for this risk assessment is not clear. Of the three assumptions present in the MoS calculation proposed by the Industry, being the dermal absorption value, the NO(A)EL value and","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"%","noael_value":"1","page":23,"route":"oral","species":"","study_id":"sccs_o_041_noael_021"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004).; EFFECT=ter. Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days. Out of this study a NOEL of 2 mg/kg bw/day could be extracted for butylparaben (Fisher et al. 1999). Since Industry considered both the NOEL of 2 mg/kg bw/day for butylparaben (Fisher et al. 1999) and the NO(A)EL of 10 mg/kg bw/day for propylparaben (Oishi 2002) an overestimation of the reproductive hazard of the parabens under study, the applicant decided to repeat the Oishi assay in male rats with a more robust study design. Butylparaben and methylparaben were chosen as test compounds as they were considered to bracket the chain lengths; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004).","duration":"","effect":"ter. Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days. Out of this study a NOEL of 2 mg/kg bw/day could be extracted for butylparaben (Fisher et al. 1999). Since Industry considered both the NOEL of 2 mg/kg bw/day for butylparaben (Fisher et al. 1999) and the NO(A)EL of 10 mg/kg bw/day for propylparaben (Oishi 2002) an overestimation of the reproductive hazard of the parabens under study, the applicant decided to repeat the Oishi assay in male rats with a more robust study design. Butylparaben and methylparaben were chosen as test compounds as they were considered to bracket the chain lengths","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":10,"route":"","species":"rat","study_id":"sccs_o_041_noael_003"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=ctive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004).; EFFECT=ctive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days. Out of this study a NOEL of 2 mg/kg bw/day could be extracted for butylparaben (Fisher et al. 1999). Since Industry considered both the NOEL of 2 mg/kg bw/day for butylparaben (Fisher et al. 1999) and the NO(A)EL of 10 mg/kg bw/day for propylparaben (Oishi 2002) an overestimation of the reproductive hazard of the parabens under study, the applicant decided to repeat the Oishi assay in male rats with a more robust study design. Butylparaben and methylparaben were chosen as test compounds as they were considered to bracket the chain lengths of all parabens used and to allow interpolation of the results for ethylparaben and propylparaben. The full study r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"ctive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004).","duration":"","effect":"ctive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days. Out of this study a NOEL of 2 mg/kg bw/day could be extracted for butylparaben (Fisher et al. 1999). Since Industry considered both the NOEL of 2 mg/kg bw/day for butylparaben (Fisher et al. 1999) and the NO(A)EL of 10 mg/kg bw/day for propylparaben (Oishi 2002) an overestimation of the reproductive hazard of the parabens under study, the applicant decided to repeat the Oishi assay in male rats with a more robust study design. Butylparaben and methylparaben were chosen as test compounds as they were considered to bracket the chain lengths of all parabens used and to allow interpolation of the results for ethylparaben and propylparaben. The full study r","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":10,"route":"","species":"rat","study_id":"sccs_o_041_noael_004"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=e use of parabens in cosmetics. Therefore, the availability of a sound in vivo reproductive toxicity study is essential in the hazard assessment of the different esters. However, no unequivocal conclusion can be drawn from the available male reproductive toxicity studies of Hoberman et al. (2008) and Oishi (2001; 2002a,b; 2004) with butylparaben and/or propylparaben. They deliver contradictory results and neither of them is considered to be scientifically acceptable. Therefore the SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylpar; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"","effect":"e use of parabens in cosmetics. Therefore, the availability of a sound in vivo reproductive toxicity study is essential in the hazard assessment of the different esters. However, no unequivocal conclusion can be drawn from the available male reproductive toxicity studies of Hoberman et al. (2008) and Oishi (2001; 2002a,b; 2004) with butylparaben and/or propylparaben. They deliver contradictory results and neither of them is considered to be scientifically acceptable. Therefore the SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylpar","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":22,"route":"oral","species":"","study_id":"sccs_o_041_noael_016"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.; EFFECT=icity study is essential in the hazard assessment of the different esters. However, no unequivocal conclusion can be drawn from the available male reproductive toxicity studies of Hoberman et al. (2008) and Oishi (2001; 2002a,b; 2004) with butylparaben and/or propylparaben. They deliver contradictory results and neither of them is considered to be scientifically acceptable. Therefore the SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylparaben to cause similar effects at about the same dosage levels after subcutaneous or oral adm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al.","duration":"","effect":"icity study is essential in the hazard assessment of the different esters. However, no unequivocal conclusion can be drawn from the available male reproductive toxicity studies of Hoberman et al. (2008) and Oishi (2001; 2002a,b; 2004) with butylparaben and/or propylparaben. They deliver contradictory results and neither of them is considered to be scientifically acceptable. Therefore the SCCS cannot determine an adequate NO(A)EL-value for the paraben esters under consideration from these studies. Consequently, the NOEL value of 2 mg/kg bw/day, based on Fisher et al. (1999) and also mentioned by Oishi (2001), remains the conservative choice for the calculation of the MoS of butyl- and propylparaben. The Committee acknowledges the fact that the Fisher et al. (1999) study involves subcutaneous instead of oral administration, but emphasizes that 2 mg/kg bw/day clearly represents a NOEL instead of an NOAEL and that another study shows butylparaben to cause similar effects at about the same dosage levels after subcutaneous or oral adm","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":22,"route":"oral","species":"","study_id":"sccs_o_041_noael_017"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=2; DOSE=As the two male reproductive toxicity studies in rodents are of insufficient scientific quality, the NOEL of the Fisher 1999 study (2 mg/kg bw/day) is used as the most conservative value by the SCCS.; EFFECT=as potentially systemically available, however not to an unlimited extent. Due to the lack of properly conducted dermal absorption and/or toxicokinetic studies in humans, the SCCS derived the conservative value of 3.7% dermal absorption for butylparaben. This leads to a MoS of 47 for both butylparaben and propylparaben at the intended use concentration of 0.4% (applying a read-across approach for these two esters). As the two male reproductive toxicity studies in rodents are of insufficient scientific quality, the NOEL of the Fisher 1999 study (2 mg/kg bw/day) is used as the most conservative value by the SCCS. Based upon the above, the SCCS considers the use of butylparaben and propylparaben as preservatives in finished cosmetic products as safe to the consumer, as long as the sum of their individual concentrations does not exceed 0.19%. This conclusion is based on the lack of scientifically sound data on the pivotal link between dermal absorption in rats and humans, in particular with regard to the metabolism of the parent co; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"As the two male reproductive toxicity studies in rodents are of insufficient scientific quality, the NOEL of the Fisher 1999 study (2 mg/kg bw/day) is used as the most conservative value by the SCCS.","duration":"","effect":"as potentially systemically available, however not to an unlimited extent. Due to the lack of properly conducted dermal absorption and/or toxicokinetic studies in humans, the SCCS derived the conservative value of 3.7% dermal absorption for butylparaben. This leads to a MoS of 47 for both butylparaben and propylparaben at the intended use concentration of 0.4% (applying a read-across approach for these two esters). As the two male reproductive toxicity studies in rodents are of insufficient scientific quality, the NOEL of the Fisher 1999 study (2 mg/kg bw/day) is used as the most conservative value by the SCCS. Based upon the above, the SCCS considers the use of butylparaben and propylparaben as preservatives in finished cosmetic products as safe to the consumer, as long as the sum of their individual concentrations does not exceed 0.19%. This conclusion is based on the lack of scientifically sound data on the pivotal link between dermal absorption in rats and humans, in particular with regard to the metabolism of the parent co","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2","page":24,"route":"dermal","species":"rat","study_id":"sccs_o_041_noael_026"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=unclear:of higher chain length including propylparaben, butylparaben and related iso compounds. Benzylparaben was also of concern. Based upon the currently available in vitro data and in vivo rodent test results, the SCCS agrees that the estrogenic properties displayed by parabens appear to increase with increasing chain length. Nevertheless, the SCCS stresses that the displayed potency levels remain about 3 to 6 orders of magnitude lower than the potency of the positive controls. It is difficult to determine an adequate NO(A)EL value for the observed reproductive effects of butylparaben or propylparaben in rodents, as each of the two available key (sets of) oral studies suffered serious shortcomings. Industry attempted to resolve this issue by providing data to suggest the complete skin metabolism of parabens into the non-endocrine modifying and non-reproductive toxic metabolite p-hydroxybenzoic acid (PHBA). Unfortunately, this data consisted of pharmacokinetic results from rodent studies only, whereas other reports clearly pointed towar; EFFECT=of higher chain length including propylparaben, butylparaben and related iso compounds. Benzylparaben was also of concern. Based upon the currently available in vitro data and in vivo rodent test results, the SCCS agrees that the estrogenic properties displayed by parabens appear to increase with increasing chain length. Nevertheless, the SCCS stresses that the displayed potency levels remain about 3 to 6 orders of magnitude lower than the potency of the positive controls. It is difficult to determine an adequate NO(A)EL value for the observed reproductive effects of butylparaben or propylparaben in rodents, as each of the two available key (sets of) oral studies suffered serious shortcomings. Industry attempted to resolve this issue by providing data to suggest the complete skin metabolism of parabens into the non-endocrine modifying and non-reproductive toxic metabolite p-hydroxybenzoic acid (PHBA). Unfortunately, this data consisted of pharmacokinetic results from rodent studies only, whereas other reports clearly pointed towar; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"of higher chain length including propylparaben, butylparaben and related iso compounds. Benzylparaben was also of concern. Based upon the currently available in vitro data and in vivo rodent test results, the SCCS agrees that the estrogenic properties displayed by parabens appear to increase with increasing chain length. Nevertheless, the SCCS stresses that the displayed potency levels remain about 3 to 6 orders of magnitude lower than the potency of the positive controls. It is difficult to determine an adequate NO(A)EL value for the observed reproductive effects of butylparaben or propylparaben in rodents, as each of the two available key (sets of) oral studies suffered serious shortcomings. Industry attempted to resolve this issue by providing data to suggest the complete skin metabolism of parabens into the non-endocrine modifying and non-reproductive toxic metabolite p-hydroxybenzoic acid (PHBA). Unfortunately, this data consisted of pharmacokinetic results from rodent studies only, whereas other reports clearly pointed towar","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"","noael_value":"unclear:of higher chain length including propylparaben, butylparaben and related iso compounds. Benzylparaben was also of concern. Based upon the currently available in vitro data and in vivo rodent test results, the SCCS agrees that the estrogenic properties displayed by parabens appear to increase with increasing chain length. Nevertheless, the SCCS stresses that the displayed potency levels remain about 3 to 6 orders of magnitude lower than the potency of the positive controls. It is difficult to determine an adequate NO(A)EL value for the observed reproductive effects of butylparaben or propylparaben in rodents, as each of the two available key (sets of) oral studies suffered serious shortcomings. Industry attempted to resolve this issue by providing data to suggest the complete skin metabolism of parabens into the non-endocrine modifying and non-reproductive toxic metabolite p-hydroxybenzoic acid (PHBA). Unfortunately, this data consisted of pharmacokinetic results from rodent studies only, whereas other reports clearly pointed towar","page":24,"route":"oral","species":"","study_id":"sccs_o_041_noael_025"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=10; DOSE=SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester.; EFFECT=SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester. Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester.","duration":"","effect":"SCCS/1348/10 Opinion on parabens ___________________________________________________________________________________________ 10 noted at the 10 mg/kg bw/day level, which was further considered the NOAEL value for that paraben ester. Methylparaben and ethylparaben were shown not to adversely affect the secretion of sex hormones or male reproductive function, up to dose levels of about 1000 mg/kg bw/day (Oishi 2004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":10,"route":"","species":"rat","study_id":"sccs_o_041_noael_002"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=10; DOSE=At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days.; EFFECT=004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days. Out of this study a NOEL of 2 mg/kg bw/day could be extracted for butylparaben (Fisher et al. 1999). Since Industry considered both the NOEL of 2 mg/kg bw/day for butylparaben (Fisher et al. 1999) and the NO(A)EL of 10 mg/kg bw/day for propylparaben (Oishi 2002) an overestimation of the reproductive hazard of the parabens under study, the applicant decided to repeat the Oishi assay in male rats with a more robust study design. Butylparaben and methylparaben were chosen as test compounds as they were considered to bracket the chain lengths of all parabens used and to allow interpolation of the results for ethylparaben and propylparaben. The full study report was submitted to the SCCP in 2006 and was later published (Hoberma; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days.","duration":"","effect":"004). At the time of the 2005 SCCP opinion, the only in vivo study in which the lowest (and only) dosage level of butylparaben did not cause any adverse effect on the male reproductive parameters measured, was a rat assay in which the ester was subcutaneously administered to neonatal rats for 17 consecutive days. Out of this study a NOEL of 2 mg/kg bw/day could be extracted for butylparaben (Fisher et al. 1999). Since Industry considered both the NOEL of 2 mg/kg bw/day for butylparaben (Fisher et al. 1999) and the NO(A)EL of 10 mg/kg bw/day for propylparaben (Oishi 2002) an overestimation of the reproductive hazard of the parabens under study, the applicant decided to repeat the Oishi assay in male rats with a more robust study design. Butylparaben and methylparaben were chosen as test compounds as they were considered to bracket the chain lengths of all parabens used and to allow interpolation of the results for ethylparaben and propylparaben. The full study report was submitted to the SCCP in 2006 and was later published (Hoberma","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":10,"route":"","species":"rat","study_id":"sccs_o_041_noael_005"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=14.4; DOSE=sperm production was observed and from 125 mg/kg/day on, serum testosterone concentration was decreased.; EFFECT=sperm production was observed and from 125 mg/kg/day on, serum testosterone concentration was decreased. Oishi 2002a 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. Oishi 2002b; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"sperm production was observed and from 125 mg/kg/day on, serum testosterone concentration was decreased.","duration":"27 days","effect":"sperm production was observed and from 125 mg/kg/day on, serum testosterone concentration was decreased. Oishi 2002a 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. Oishi 2002b","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg/day","noael_value":"14.4","page":29,"route":"oral","species":"mouse","study_id":"sccs_o_041_noael_027"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=1000; DOSE=For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al.; EFFECT=raben mixture. An additional calculation takes into account aggregate exposure through non-cosmetic use of parabens as described by Cowan-Ellsberry and Robison (2009), but this does not add to the current discussion. 4.2 VIEW OF THE COSMETIC INGREDIENT REVIEW PANEL (CIR) In 2008, the CIR Expert Panel reviewed the safety assessment of methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl- and benzylparaben in cosmetic products (CIR, 2008). For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al. (2008) study, which was considered as the “most statistically powerful and well-conducted study on the effects of butylparaben on the male reproductive system”. 4.3 VIEW OF THE EUROPEAN FOOD SAFETY AUTHORITY (EFSA) The EFSA review panel used the 1000 mg/kg/day level for methyl- and ethylparaben, but considered more data necessary to determine a NO(A)EL value for propylparaben (EFSA, 2004).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al.","duration":"","effect":"raben mixture. An additional calculation takes into account aggregate exposure through non-cosmetic use of parabens as described by Cowan-Ellsberry and Robison (2009), but this does not add to the current discussion. 4.2 VIEW OF THE COSMETIC INGREDIENT REVIEW PANEL (CIR) In 2008, the CIR Expert Panel reviewed the safety assessment of methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl- and benzylparaben in cosmetic products (CIR, 2008). For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al. (2008) study, which was considered as the “most statistically powerful and well-conducted study on the effects of butylparaben on the male reproductive system”. 4.3 VIEW OF THE EUROPEAN FOOD SAFETY AUTHORITY (EFSA) The EFSA review panel used the 1000 mg/kg/day level for methyl- and ethylparaben, but considered more data necessary to determine a NO(A)EL value for propylparaben (EFSA, 2004).","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":20,"route":"","species":"","study_id":"sccs_o_041_noael_014"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; VALUE_TEXT=1000; DOSE=For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al.; EFFECT=d benzylparaben in cosmetic products (CIR, 2008). For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al. (2008) study, which was considered as the “most statistically powerful and well-conducted study on the effects of butylparaben on the male reproductive system”. 4.3 VIEW OF THE EUROPEAN FOOD SAFETY AUTHORITY (EFSA) The EFSA review panel used the 1000 mg/kg/day level for methyl- and ethylparaben, but considered more data necessary to determine a NO(A)EL value for propylparaben (EFSA, 2004).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al.","duration":"","effect":"d benzylparaben in cosmetic products (CIR, 2008). For their MoS calculations for the whole range of parabens, they used the NOAEL of 1000 mg/kg/day of the Hoberman et al. (2008) study, which was considered as the “most statistically powerful and well-conducted study on the effects of butylparaben on the male reproductive system”. 4.3 VIEW OF THE EUROPEAN FOOD SAFETY AUTHORITY (EFSA) The EFSA review panel used the 1000 mg/kg/day level for methyl- and ethylparaben, but considered more data necessary to determine a NO(A)EL value for propylparaben (EFSA, 2004).","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":20,"route":"","species":"","study_id":"sccs_o_041_noael_015"}

sccs_o_041.pdf

SOURCE_SUBDIR=sccs_o_041; REPORT_TITLE=OPINION ON Parabens COLIPA n° P82; OPINION_NUMBER=SCCS/1348/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 March 2011; 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 29: 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. | 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 29: 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. | Oishi 2002b","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1504","page":29,"route":"oral","species":"mouse","study_id":"sccs_o_041_noael_029"}

sccs_o_041.pdf