, or to derive a toxicological point of departure based, codes ............................................... 10, Propylparaben

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=PB did not affect CaBP-9k gene expression.; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: PB did not affect CaBP-9k gene expression.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: PB did not affect CaBP-9k gene expression.","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"PB did not affect CaBP-9k gene expression.","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_050"}

SCCS Opinion

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=Doses : 0-949-1084 mg PrPB/kg bw/day on day 1 to 4 of gestation.; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Non guideline | Doses : 0-949-1084 mg PrPB/kg bw/day on day 1 to 4 of gestation.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Non guideline | Doses : 0-949-1084 mg PrPB/kg bw/day on day 1 to 4 of gestation.","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"Doses : 0-949-1084 mg PrPB/kg bw/day on day 1 to 4 of gestation.","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_046"}

SCCS Opinion

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=0.036 mmol/kg),; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Non-GLP | 0.036 mmol/kg),; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Non-GLP | 0.036 mmol/kg),","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"0.036 mmol/kg),","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_044"}

SCCS Opinion

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=ovariectomized (Ovx) CD1 mice. Subcutaneous route (sc) Treated; DOSE=Subcutaneous route (sc) Treated | 2004; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: compliant with | ovariectomized (Ovx) CD1 mice. Subcutaneous route (sc) Treated | 2004; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Subcutaneous route (sc) Treated | 2004","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: compliant with | ovariectomized (Ovx) CD1 mice. Subcutaneous route (sc) Treated | 2004","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"ovariectomized (Ovx) CD1 mice. Subcutaneous route (sc) Treated","page":35,"route":"","species":"mouse","study_id":"sccs_o_243_noael_042"}

SCCS Opinion

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=In the estrogen receptor binding assay, PP competed with E2 and Ki; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: In the estrogen receptor binding assay, PP competed with E2 and Ki; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: In the estrogen receptor binding assay, PP competed with E2 and Ki","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"In the estrogen receptor binding assay, PP competed with E2 and Ki","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_040"}

SCCS Opinion

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=NOELs for uterotrophic activity of PBs in immature mice were 6.5, in; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: assay | NOELs for uterotrophic activity of PBs in immature mice were 6.5, in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: assay | NOELs for uterotrophic activity of PBs in immature mice were 6.5, in","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"NOELs for uterotrophic activity of PBs in immature mice were 6.5, in","page":35,"route":"","species":"mouse","study_id":"sccs_o_243_noael_038"}

SCCS Opinion

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=Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: immature | Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: immature | Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"Investigation of Calbindin-D9-k (CaBP-9k), biomarker for estrogenic","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_049"}

SCCS Opinion

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=12.4; DOSE=Significant histopathological changes were limited to the treated skin site.; EFFECT=brain, heart, liver, spleen and adrenal weights and increased relative brain, lung and testes weights were observed. In females, absolute liver and relative heart and liver weights were increased and absolute and relative spleen weight were decreased. No treatment-related abnormalities were noticed at necropsy. Significant histopathological changes were limited to the treated skin site. All observations were regarded as non-adverse and not treatment related and the only dose tested (12.4 mg/kg/day) is stated as a NOAEL from this study. SCCS comment In the REACH dossier, the reliability of this study is considered as low because the test substance was one of the ingredients of a formulation (reliability 4 – not assignable). Therefore this study has not been used by the SCCS in the current safety assessment.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Significant histopathological changes were limited to the treated skin site.","duration":"","effect":"brain, heart, liver, spleen and adrenal weights and increased relative brain, lung and testes weights were observed. In females, absolute liver and relative heart and liver weights were increased and absolute and relative spleen weight were decreased. No treatment-related abnormalities were noticed at necropsy. Significant histopathological changes were limited to the treated skin site. All observations were regarded as non-adverse and not treatment related and the only dose tested (12.4 mg/kg/day) is stated as a NOAEL from this study. SCCS comment In the REACH dossier, the reliability of this study is considered as low because the test substance was one of the ingredients of a formulation (reliability 4 – not assignable). Therefore this study has not been used by the SCCS in the current safety assessment.","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"12.4","page":22,"route":"","species":"","study_id":"sccs_o_243_noael_003"}

SCCS Opinion

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=17; DOSE=Non GLP | was 7 μg/kg bw (Im or Ovx), ED50 of PB were from 17 mg/kg | 2003; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Non GLP | was 7 μg/kg bw (Im or Ovx), ED50 of PB were from 17 mg/kg | 2003; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Non GLP | was 7 μg/kg bw (Im or Ovx), ED50 of PB were from 17 mg/kg | 2003","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Non GLP | was 7 μg/kg bw (Im or Ovx), ED50 of PB were from 17 mg/kg | 2003","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"17","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_034"}

SCCS Opinion

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=those of 17β-estradiol; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: those of 17β-estradiol; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: those of 17β-estradiol","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"those of 17β-estradiol","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_041"}

SCCS Opinion

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=17β-oestradiol terminated all pregnancies.; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: 17β-oestradiol terminated all pregnancies.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: 17β-oestradiol terminated all pregnancies.","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"17β-oestradiol terminated all pregnancies.","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_047"}

SCCS Opinion

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=20; DOSE=An overview of all studies related to the endocrine activity of propylparaben in vivo: ovariectomized mice 7, and in immature rats 20 mg/kg bw,; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: ovariectomized mice 7, and in immature rats 20 mg/kg bw,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"An overview of all studies related to the endocrine activity of propylparaben in vivo: ovariectomized mice 7, and in immature rats 20 mg/kg bw,","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: ovariectomized mice 7, and in immature rats 20 mg/kg bw,","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw","noael_value":"20","page":35,"route":"","species":"rat","study_id":"sccs_o_243_noael_039"}

SCCS Opinion

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=33; DOSE=Uterotrophic | was 10,3 μg/kg bw ED50 of PB were from 33 mg/kg bw.; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Uterotrophic | was 10,3 μg/kg bw ED50 of PB were from 33 mg/kg bw.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Uterotrophic | was 10,3 μg/kg bw ED50 of PB were from 33 mg/kg bw.","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Uterotrophic | was 10,3 μg/kg bw ED50 of PB were from 33 mg/kg bw.","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw","noael_value":"33","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_037"}

SCCS Opinion

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=38 to 76; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: effects (38 to 76%) compared to E2 effects (100%) in Luminal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: effects (38 to 76%) compared to E2 effects (100%) in Luminal","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"%","noael_value":"38 to 76","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_045"}

SCCS Opinion

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=43; DOSE=CD1 mice | bw (Im) or 43 mg/kg bw (Ovx).; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: CD1 mice | bw (Im) or 43 mg/kg bw (Ovx).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"CD1 mice | bw (Im) or 43 mg/kg bw (Ovx).","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: CD1 mice | bw (Im) or 43 mg/kg bw (Ovx).","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw","noael_value":"43","page":35,"route":"","species":"mouse","study_id":"sccs_o_243_noael_035"}

SCCS Opinion

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=In mice, ED50 of 17β-oestradiol (E2) for increase in uterine weight; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: OECD 440 | In mice, ED50 of 17β-oestradiol (E2) for increase in uterine weight | Lemini et al.,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: OECD 440 | In mice, ED50 of 17β-oestradiol (E2) for increase in uterine weight | Lemini et al.,","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"In mice, ED50 of 17β-oestradiol (E2) for increase in uterine weight","page":35,"route":"","species":"mouse","study_id":"sccs_o_243_noael_033"}

SCCS Opinion

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=In rats, ED50 of 17β-oestradiol (E2) for increase in uterine weight; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Wistar rats | In rats, ED50 of 17β-oestradiol (E2) for increase in uterine weight; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Wistar rats | In rats, ED50 of 17β-oestradiol (E2) for increase in uterine weight","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"","noael_value":"In rats, ED50 of 17β-oestradiol (E2) for increase in uterine weight","page":35,"route":"","species":"rat","study_id":"sccs_o_243_noael_036"}

SCCS Opinion

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=62.5; DOSE=Neonatal Sprague Dawley female rats (n =5) - Non GLP Non guideline Klimisch 3 | Effects at 62.5 mg/kg/day and above:; EFFECT=Unlabeled table on page 36: Neonatal Sprague Dawley female rats (n =5) - Non GLP Non guideline Klimisch 3 | Effects at 62.5 mg/kg/day and above: MePB, PrPB: mRNA levels of StAR decreased Effects at 250 and 1000 mg/kg/day: CaBP-9k (dose-response relationship) Decreased numbers of early primary follicles (dose response relationship) mRNA levels of AMH (ovarian anti-Mullerian hormone) and FoxI2 (forkhead box protein I2 transcription factor) increased (both not affected by E2) (no dose response relationship) mRNA levels of CYP11a1, mid-dose increased, high dose decreased (no dose-response relationships) Effects only at 1000 mg/kg/day: increased numbers of primordial follicles LO(A)EL (sc): 62.5 mg/kg bw/day Not all data appear consistent. | Ahn et al. 2012; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Neonatal Sprague Dawley female rats (n =5) - Non GLP Non guideline Klimisch 3 | Effects at 62.5 mg/kg/day and above:","duration":"","effect":"Unlabeled table on page 36: Neonatal Sprague Dawley female rats (n =5) - Non GLP Non guideline Klimisch 3 | Effects at 62.5 mg/kg/day and above: MePB, PrPB: mRNA levels of StAR decreased Effects at 250 and 1000 mg/kg/day: CaBP-9k (dose-response relationship) Decreased numbers of early primary follicles (dose response relationship) mRNA levels of AMH (ovarian anti-Mullerian hormone) and FoxI2 (forkhead box protein I2 transcription factor) increased (both not affected by E2) (no dose response relationship) mRNA levels of CYP11a1, mid-dose increased, high dose decreased (no dose-response relationships) Effects only at 1000 mg/kg/day: increased numbers of primordial follicles LO(A)EL (sc): 62.5 mg/kg bw/day Not all data appear consistent. | Ahn et al. 2012","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"62.5","page":36,"route":"","species":"rat","study_id":"sccs_o_243_noael_052"}

SCCS Opinion

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=100; DOSE=NOEL (mice) 100 mg/kg (top dose PrPB tested).; EFFECT=rogen/androgen receptor activation by parent parabens can cause harmful effects in humans (Engeli et al 2017). 3.4.10.3 Endocrine activity. In vivo and other assays Animal data Propylparaben has been investigated for endocrine activity in vivo in numerous studies. Table 6 provides an overview of these studies. Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo Test principle Results and conclusion Reference OECD 440 Non GLP B6D2F1 mice Uterotrophic assay Oral and SC. NOEL (mice) 100 mg/kg (top dose PrPB tested). No change to uterine weights. Hossaini et al 2000 OECD 440 Non GLP CD1 mice Wistar rats Uterotrophic assay In mice, ED50 of 17β-oestradiol (E2) for increase in uterine weight was 7 μg/kg bw (Im or Ovx), ED50 of PB were from 17 mg/kg bw (Im) or 43 mg/kg bw (Ovx). In rats, ED50 of 17β-oestradiol (E2) for increase in uterine weight was 10,3 µg/kg bw ED50 of PB were from 33 mg/kg bw. NOELs for uterotrophic activity of PBs in immature mice were 6.5, in ovariectomized mice 7, an; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"NOEL (mice) 100 mg/kg (top dose PrPB tested).","duration":"","effect":"rogen/androgen receptor activation by parent parabens can cause harmful effects in humans (Engeli et al 2017). 3.4.10.3 Endocrine activity. In vivo and other assays Animal data Propylparaben has been investigated for endocrine activity in vivo in numerous studies. Table 6 provides an overview of these studies. Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo Test principle Results and conclusion Reference OECD 440 Non GLP B6D2F1 mice Uterotrophic assay Oral and SC. NOEL (mice) 100 mg/kg (top dose PrPB tested). No change to uterine weights. Hossaini et al 2000 OECD 440 Non GLP CD1 mice Wistar rats Uterotrophic assay In mice, ED50 of 17β-oestradiol (E2) for increase in uterine weight was 7 μg/kg bw (Im or Ovx), ED50 of PB were from 17 mg/kg bw (Im) or 43 mg/kg bw (Ovx). In rats, ED50 of 17β-oestradiol (E2) for increase in uterine weight was 10,3 µg/kg bw ED50 of PB were from 33 mg/kg bw. NOELs for uterotrophic activity of PBs in immature mice were 6.5, in ovariectomized mice 7, an","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"100","page":35,"route":"oral","species":"rat","study_id":"sccs_o_243_noael_016"}

SCCS Opinion

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=100; DOSE=NOEL (mice) 100 mg/kg (top dose PrPB tested).; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: OECD 440 | Oral and SC. NOEL (mice) 100 mg/kg (top dose PrPB tested). No | Hossaini et al; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"NOEL (mice) 100 mg/kg (top dose PrPB tested).","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: OECD 440 | Oral and SC. NOEL (mice) 100 mg/kg (top dose PrPB tested). No | Hossaini et al","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"100","page":35,"route":"oral","species":"mouse","study_id":"sccs_o_243_noael_032"}

SCCS Opinion

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=195; DOSE=PrPben (65 and 195 mg/kg), E2 (10 mg/kg;; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: OECD 440 | daily for three days: PrPben (65 and 195 mg/kg), E2 (10 mg/kg;; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"PrPben (65 and 195 mg/kg), E2 (10 mg/kg;","duration":"","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: OECD 440 | daily for three days: PrPben (65 and 195 mg/kg), E2 (10 mg/kg;","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"195","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_043"}

SCCS Opinion

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=250-1000; DOSE=62.5-250-1000 mg/kg bw/day of paraben for 3 days. | 2009; EFFECT=Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Dawley | Doses: 62.5-250-1000 mg/kg bw/day of paraben for 3 days. | 2009; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"62.5-250-1000 mg/kg bw/day of paraben for 3 days. | 2009","duration":"3 days","effect":"Table 6: An overview of all studies related to the endocrine activity of propylparaben in vivo: Dawley | Doses: 62.5-250-1000 mg/kg bw/day of paraben for 3 days. | 2009","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250-1000","page":35,"route":"","species":"","study_id":"sccs_o_243_noael_048"}

SCCS Opinion

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=NOAEL of 1000 mg/kg body weight/day was derived from that study.; EFFECT=Unlabeled table on page 22: NOAEL of 1000 mg/kg body weight/day was derived from that study.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"NOAEL of 1000 mg/kg body weight/day was derived from that study.","duration":"","effect":"Unlabeled table on page 22: NOAEL of 1000 mg/kg body weight/day was derived from that study.","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":22,"route":"","species":"","study_id":"sccs_o_243_noael_031"}

SCCS Opinion

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=Negative for estrogen agonism and antagonism NOEL defined at a top dose of 1000 mg/kg/day | Ohta et al 2012; EFFECT=Unlabeled table on page 36: Mouse (C57BL/6J) Klimisch 1 OECD 440 | (Uterotrophic Bioassay in rodents). Ovariectomised female mice 8 weeks of age (n=6/group, 11 groups) were dosed daily for 7 consecutive days by oral gavage and subcutaneous injection. 6 µg/kg bw/day estradiol (E2) was given orally as positive control for agonist and antagonist detection. Negative for estrogen agonism and antagonism NOEL defined at a top dose of 1000 mg/kg/day | Ohta et al 2012; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Negative for estrogen agonism and antagonism NOEL defined at a top dose of 1000 mg/kg/day | Ohta et al 2012","duration":"8 weeks","effect":"Unlabeled table on page 36: Mouse (C57BL/6J) Klimisch 1 OECD 440 | (Uterotrophic Bioassay in rodents). Ovariectomised female mice 8 weeks of age (n=6/group, 11 groups) were dosed daily for 7 consecutive days by oral gavage and subcutaneous injection. 6 µg/kg bw/day estradiol (E2) was given orally as positive control for agonist and antagonist detection. Negative for estrogen agonism and antagonism NOEL defined at a top dose of 1000 mg/kg/day | Ohta et al 2012","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":36,"route":"oral","species":"mouse","study_id":"sccs_o_243_noael_051"}

SCCS Opinion

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=The NOAEL was 1000 mg/kg/day, corresponding to a maximum; EFFECT=Unlabeled table on page 37: The NOAEL was 1000 mg/kg/day, corresponding to a maximum; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"The NOAEL was 1000 mg/kg/day, corresponding to a maximum","duration":"","effect":"Unlabeled table on page 37: The NOAEL was 1000 mg/kg/day, corresponding to a maximum","endpoint":"","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":37,"route":"","species":"","study_id":"sccs_o_243_noael_054"}

SCCS Opinion

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=Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats.; EFFECT=SCCS-rejected applicant NOAEL: Irritation and corrosivity Propylparaben is not expected to be an eye or skin irritant. Skin sensitisation Propylparaben is not considered to be a skin sensitiser. Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats. Repeated dose toxicity The newly submitted repeated dose toxicity studies provide a NOAEL of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females. Reproductive toxicity The newly submitted reproductive and devevelopmenral toxicity studies provide data that support a change of the NOEL of 2 mg/kg body weight per day described in the previous SCCS opinion. Additional studies support a new NOAEL derived from reproductive endpoints to be 1000 mg/kg bw/day. Mutagenicity / genotoxicity Propylparaben has been tested in valid OECD guideline mutagenicity assays for bacterial and mammalian gene mutations assays, aneuploidy and clastogenicity endpoints with negative results. The SCCS is of the opinion that propylparaben does not pose a genotoxic hazard. Carcinogenicity Based on all the available data, t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats.","duration":"","effect":"SCCS-rejected applicant NOAEL: Irritation and corrosivity Propylparaben is not expected to be an eye or skin irritant. Skin sensitisation Propylparaben is not considered to be a skin sensitiser. Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats. Repeated dose toxicity The newly submitted repeated dose toxicity studies provide a NOAEL of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females. Reproductive toxicity The newly submitted reproductive and devevelopmenral toxicity studies provide data that support a change of the NOEL of 2 mg/kg body weight per day described in the previous SCCS opinion. Additional studies support a new NOAEL derived from reproductive endpoints to be 1000 mg/kg bw/day. Mutagenicity / genotoxicity Propylparaben has been tested in valid OECD guideline mutagenicity assays for bacterial and mammalian gene mutations assays, aneuploidy and clastogenicity endpoints with negative results. The SCCS is of the opinion that propylparaben does not pose a genotoxic hazard. Carcinogenicity Based on all the available data, t","endpoint":"repeated dose toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"2","page":42,"route":"","species":"rat","study_id":"sccs_o_243_noael_028"}

SCCS Opinion

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=980; DOSE=Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats.; EFFECT=SCCS-rejected applicant NOAEL: propylparaben, when used together as a binary mixture in the same product. This would be equivalent to a maximum concentration of propylparaben of 0.183% in cosmetic products. Toxicological Evaluation Irritation and corrosivity Propylparaben is not expected to be an eye or skin irritant. Skin sensitisation Propylparaben is not considered to be a skin sensitiser. Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats. Repeated dose toxicity The newly submitted repeated dose toxicity studies provide a NOAEL of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females. Reproductive toxicity The newly submitted reproductive and devevelopmenral toxicity studies provide data that support a change of the NOEL of 2 mg/kg body weight per day described in the previous SCCS opinion. Additional studies support a new NOAEL derived from reproductive endpoints to be 1000 mg/kg bw/day. Mutagenicity / genotoxicity Propylparaben has been tested in valid OECD guideline mutagenicity assays for bacterial and mammalian gene mutations a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats.","duration":"","effect":"SCCS-rejected applicant NOAEL: propylparaben, when used together as a binary mixture in the same product. This would be equivalent to a maximum concentration of propylparaben of 0.183% in cosmetic products. Toxicological Evaluation Irritation and corrosivity Propylparaben is not expected to be an eye or skin irritant. Skin sensitisation Propylparaben is not considered to be a skin sensitiser. Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats. Repeated dose toxicity The newly submitted repeated dose toxicity studies provide a NOAEL of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females. Reproductive toxicity The newly submitted reproductive and devevelopmenral toxicity studies provide data that support a change of the NOEL of 2 mg/kg body weight per day described in the previous SCCS opinion. Additional studies support a new NOAEL derived from reproductive endpoints to be 1000 mg/kg bw/day. Mutagenicity / genotoxicity Propylparaben has been tested in valid OECD guideline mutagenicity assays for bacterial and mammalian gene mutations a","endpoint":"repeated dose toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"980","page":42,"route":"","species":"rat","study_id":"sccs_o_243_noael_027"}

SCCS Opinion

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=Control, low-, mid- and high-dose group rats received the dose at 0, 100, 300 and 1000 mg/kg/day respectively, as a repeated dose at the dose volume of 5 mL/kg.; EFFECT=le control group received 1% aqueous hydroxyethyl-cellulose, the vehicle used in this study. The 4 groups were comprised of 10 male and 10 female Wistar rats. Control, low-, mid- and high-dose group rats received the dose at 0, 100, 300 and 1000 mg/kg/day respectively, as a repeated dose at the dose volume of 5 mL/kg. All animals in the recovery group were observed for a period of 28 days following the last administration. There were no adverse effects or effect of toxicological relevance recorded in this study. A NOAEL of 1000 mg/kg body weight/day was derived from that study. SCCS comment This study was performed after the animal testing ban for cosmetics but was obtained and accepted by the SCCS because it was performed to comply with the requirements under REACH regulation. (https://echa.europa.eu/documents/10162/f8e15bd5-5139-0e1a-8b55- c7136afd4ccf). Dermal route A dermal repeated-dose toxicity study performed in 1981 is reported in the REACH dossier for propylparaben (in 2018 - cited in ECHA REACH dossier). A medicated l; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Control, low-, mid- and high-dose group rats received the dose at 0, 100, 300 and 1000 mg/kg/day respectively, as a repeated dose at the dose volume of 5 mL/kg.","duration":"28 days","effect":"le control group received 1% aqueous hydroxyethyl-cellulose, the vehicle used in this study. The 4 groups were comprised of 10 male and 10 female Wistar rats. Control, low-, mid- and high-dose group rats received the dose at 0, 100, 300 and 1000 mg/kg/day respectively, as a repeated dose at the dose volume of 5 mL/kg. All animals in the recovery group were observed for a period of 28 days following the last administration. There were no adverse effects or effect of toxicological relevance recorded in this study. A NOAEL of 1000 mg/kg body weight/day was derived from that study. SCCS comment This study was performed after the animal testing ban for cosmetics but was obtained and accepted by the SCCS because it was performed to comply with the requirements under REACH regulation. (https://echa.europa.eu/documents/10162/f8e15bd5-5139-0e1a-8b55- c7136afd4ccf). Dermal route A dermal repeated-dose toxicity study performed in 1981 is reported in the REACH dossier for propylparaben (in 2018 - cited in ECHA REACH dossier). A medicated l","endpoint":"repeated dose toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":22,"route":"dermal","species":"rat","study_id":"sccs_o_243_noael_002"}

SCCS Opinion

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=Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats.; EFFECT=SCCS-rejected applicant NOAEL: ropylparaben is not considered to be a skin sensitiser. Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats. Repeated dose toxicity The newly submitted repeated dose toxicity studies provide a NOAEL of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females. Reproductive toxicity The newly submitted reproductive and devevelopmenral toxicity studies provide data that support a change of the NOEL of 2 mg/kg body weight per day described in the previous SCCS opinion. Additional studies support a new NOAEL derived from reproductive endpoints to be 1000 mg/kg bw/day. Mutagenicity / genotoxicity Propylparaben has been tested in valid OECD guideline mutagenicity assays for bacterial and mammalian gene mutations assays, aneuploidy and clastogenicity endpoints with negative results. The SCCS is of the opinion that propylparaben does not pose a genotoxic hazard. Carcinogenicity Based on all the available data, the SCCS considers propylparaben to have no carcinogenic potential. Photo-induced toxicity Propylparaben is co; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats.","duration":"","effect":"SCCS-rejected applicant NOAEL: ropylparaben is not considered to be a skin sensitiser. Acute toxicity The LD50 is >5000 mg/kg bw for male and female rats. Repeated dose toxicity The newly submitted repeated dose toxicity studies provide a NOAEL of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females. Reproductive toxicity The newly submitted reproductive and devevelopmenral toxicity studies provide data that support a change of the NOEL of 2 mg/kg body weight per day described in the previous SCCS opinion. Additional studies support a new NOAEL derived from reproductive endpoints to be 1000 mg/kg bw/day. Mutagenicity / genotoxicity Propylparaben has been tested in valid OECD guideline mutagenicity assays for bacterial and mammalian gene mutations assays, aneuploidy and clastogenicity endpoints with negative results. The SCCS is of the opinion that propylparaben does not pose a genotoxic hazard. Carcinogenicity Based on all the available data, the SCCS considers propylparaben to have no carcinogenic potential. Photo-induced toxicity Propylparaben is co","endpoint":"repeated dose toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":42,"route":"","species":"rat","study_id":"sccs_o_243_noael_029"}

SCCS Opinion

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 Opinion

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=980; DOSE=observed in males or females at any dose level following repeat daily dosing.; EFFECT=observed in males or females at any dose level following repeat daily dosing. At the dose level of 1076 mg/kg/d ppm in males, reduced body weight gain was noted in the absence of statistically significant changes in absolute body weights and an increase in plasma triglicerydes concentration was noted in the absence of any histopathological or other changes related to the finding. No further test item-related effects were noted in males or females at any dose level. SCCS comment The SCCS concludes that respective NOAEL values for general toxicity and reproduction (fertility) of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females should be considered for propylparaben.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"observed in males or females at any dose level following repeat daily dosing.","duration":"","effect":"observed in males or females at any dose level following repeat daily dosing. At the dose level of 1076 mg/kg/d ppm in males, reduced body weight gain was noted in the absence of statistically significant changes in absolute body weights and an increase in plasma triglicerydes concentration was noted in the absence of any histopathological or other changes related to the finding. No further test item-related effects were noted in males or females at any dose level. SCCS comment The SCCS concludes that respective NOAEL values for general toxicity and reproduction (fertility) of 980 mg/kg bw/d for males and 1076 mg/kg bw/d for females should be considered for propylparaben.","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"980","page":21,"route":"","species":"","study_id":"sccs_o_243_noael_001"}

SCCS Opinion

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 Opinion

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 Opinion

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 Opinion

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=he numbers of corpora lutea, implantation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males.; EFFECT=he numbers of corpora lutea, implantation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males. No propylparaben- related reproductive organ weight changes were noted at end-of-dose or end-of-recovery necropsies and no gross findings or microscopic findings were recorded at the end-of-dose or end-of-recovery necropsies. No treatment-related changes in hematology, coagulation, serum chemistry, or urinalysis parameters were noted. The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. An extended One-Generation Reproductive Toxicity Study was performed after oral administration in male and female Wistar Rats at dose levels of 100, 300, and 1000 mg/kg body weight day (day (Clariant GMBH; 2019) General toxicity: There were no mortalities/morbidities related to the propylparaben treatment. There were no clinical signs of toxicological relevance observed in the treatment groups. Body weight and food consumption were not affected by treat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"he numbers of corpora lutea, implantation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males.","duration":"","effect":"he numbers of corpora lutea, implantation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males. No propylparaben- related reproductive organ weight changes were noted at end-of-dose or end-of-recovery necropsies and no gross findings or microscopic findings were recorded at the end-of-dose or end-of-recovery necropsies. No treatment-related changes in hematology, coagulation, serum chemistry, or urinalysis parameters were noted. The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. An extended One-Generation Reproductive Toxicity Study was performed after oral administration in male and female Wistar Rats at dose levels of 100, 300, and 1000 mg/kg body weight day (day (Clariant GMBH; 2019) General toxicity: There were no mortalities/morbidities related to the propylparaben treatment. There were no clinical signs of toxicological relevance observed in the treatment groups. Body weight and food consumption were not affected by treat","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":24,"route":"oral","species":"rat","study_id":"sccs_o_243_noael_008"}

SCCS Opinion

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=ntation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males.; EFFECT=ntation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males. No propylparaben- related reproductive organ weight changes were noted at end-of-dose or end-of-recovery necropsies and no gross findings or microscopic findings were recorded at the end-of-dose or end-of-recovery necropsies. No treatment-related changes in hematology, coagulation, serum chemistry, or urinalysis parameters were noted. The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. An extended One-Generation Reproductive Toxicity Study was performed after oral administration in male and female Wistar Rats at dose levels of 100, 300, and 1000 mg/kg body weight day (day (Clariant GMBH; 2019) General toxicity: There were no mortalities/morbidities related to the propylparaben treatment. There were no clinical signs of toxicological relevance observed in the treatment groups. Body weight and food consumption were not affected by treatment. A; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"ntation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males.","duration":"","effect":"ntation sites, live embryos, dead embryos, early resorptions, or pre- and postimplantation losses in naïve females paired with PP-treated males. No propylparaben- related reproductive organ weight changes were noted at end-of-dose or end-of-recovery necropsies and no gross findings or microscopic findings were recorded at the end-of-dose or end-of-recovery necropsies. No treatment-related changes in hematology, coagulation, serum chemistry, or urinalysis parameters were noted. The No-Observed-Adverse-Effect-Level (NOAEL) can be derived at 1,000 mg/kg/day from this study. An extended One-Generation Reproductive Toxicity Study was performed after oral administration in male and female Wistar Rats at dose levels of 100, 300, and 1000 mg/kg body weight day (day (Clariant GMBH; 2019) General toxicity: There were no mortalities/morbidities related to the propylparaben treatment. There were no clinical signs of toxicological relevance observed in the treatment groups. Body weight and food consumption were not affected by treatment. A","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":24,"route":"oral","species":"rat","study_id":"sccs_o_243_noael_009"}

SCCS Opinion

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=No morphometric changes were observed in dose groups compared to controls.; EFFECT=re was no indication of endocrine disruptive properties of the test item in this study. Neurotoxicity: There was no test-item related effects on learning and memory, auditory startle response, clinical and functional observations and motor activity. Histopathologically, there were no indications of morphological abnormalities in the brain. No morphometric changes were observed in dose groups compared to controls. Immunotoxicity: There was no sign of immunotoxicity in this study. According to the applicant, the NOAEL of the study for male reproductive endpoints is 1000 mg/kg bw/day for the treatment period of 8 weeks. The present study did not confirm the effects on the reproductive functions reported by Oishi (2002a) and is regarded of sufficient quality to overturn the findings by Oishi, which is a study that suffers from numerous limitations as mentioned above. SCCS comment The SCCS considers that the results of these two additional studies support the derivation of NOAEL for reproductive endpoints to be at 1000 mg/kg bw/d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"No morphometric changes were observed in dose groups compared to controls.","duration":"8 weeks","effect":"re was no indication of endocrine disruptive properties of the test item in this study. Neurotoxicity: There was no test-item related effects on learning and memory, auditory startle response, clinical and functional observations and motor activity. Histopathologically, there were no indications of morphological abnormalities in the brain. No morphometric changes were observed in dose groups compared to controls. Immunotoxicity: There was no sign of immunotoxicity in this study. According to the applicant, the NOAEL of the study for male reproductive endpoints is 1000 mg/kg bw/day for the treatment period of 8 weeks. The present study did not confirm the effects on the reproductive functions reported by Oishi (2002a) and is regarded of sufficient quality to overturn the findings by Oishi, which is a study that suffers from numerous limitations as mentioned above. SCCS comment The SCCS considers that the results of these two additional studies support the derivation of NOAEL for reproductive endpoints to be at 1000 mg/kg bw/d","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":25,"route":"","species":"","study_id":"sccs_o_243_noael_010"}

SCCS Opinion

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=According to the applicant, the NOAEL of the study for male reproductive endpoints is 1000 mg/kg bw/day for the treatment period of 8 weeks.; EFFECT=ity in this study. According to the applicant, the NOAEL of the study for male reproductive endpoints is 1000 mg/kg bw/day for the treatment period of 8 weeks. The present study did not confirm the effects on the reproductive functions reported by Oishi (2002a) and is regarded of sufficient quality to overturn the findings by Oishi, which is a study that suffers from numerous limitations as mentioned above. SCCS comment The SCCS considers that the results of these two additional studies support the derivation of NOAEL for reproductive endpoints to be at 1000 mg/kg bw/day. 3.4.5.2 Developmental Toxicity In a Prenatal Developmental Toxicity study according to OECD 414 and GLP, propylparaben was administrated by oral gavage to 52 males and 104 females (cited in ECHA REACH dossier 2018). The doses evaluated were 0, 100, 300 and 1000 mg/kg body weight/day. No mortality was observed in the study and there were no clinical signs of toxicological relevance observed in the treatment groups. The body weight, food consumption, prenatal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"According to the applicant, the NOAEL of the study for male reproductive endpoints is 1000 mg/kg bw/day for the treatment period of 8 weeks.","duration":"8 weeks","effect":"ity in this study. According to the applicant, the NOAEL of the study for male reproductive endpoints is 1000 mg/kg bw/day for the treatment period of 8 weeks. The present study did not confirm the effects on the reproductive functions reported by Oishi (2002a) and is regarded of sufficient quality to overturn the findings by Oishi, which is a study that suffers from numerous limitations as mentioned above. SCCS comment The SCCS considers that the results of these two additional studies support the derivation of NOAEL for reproductive endpoints to be at 1000 mg/kg bw/day. 3.4.5.2 Developmental Toxicity In a Prenatal Developmental Toxicity study according to OECD 414 and GLP, propylparaben was administrated by oral gavage to 52 males and 104 females (cited in ECHA REACH dossier 2018). The doses evaluated were 0, 100, 300 and 1000 mg/kg body weight/day. No mortality was observed in the study and there were no clinical signs of toxicological relevance observed in the treatment groups. The body weight, food consumption, prenatal","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":25,"route":"oral","species":"","study_id":"sccs_o_243_noael_011"}

SCCS Opinion

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=No effects of propylparaben on females and foetuses were found at dose levels up to 1000 mg/kg body weight/day.; EFFECT=SCCS-rejected applicant NOAEL: reduced ossification of some bones and few other skeletal findings were well within the historical control data range for this strain of rats and not considered to be a substance related effect. Generally delayed ossification is not regarded to persist postnatally and not associated with long-term consequences on survival, general growth and development and therefore is not considered to be adverse. No effects of propylparaben on females and foetuses were found at dose levels up to 1000 mg/kg body weight/day. The NOAEL for both maternal toxicity and foetal toxicity is considered to be 1000 mg/kg body weight/day in this study. Conclusions from reproductive and developmental studies: It can be concluded from the Gazin et al (2013) study and as supported by an OECD guideline 422 study (Harlan, 2012), an OECD guideline 414 (cited in ECHA REACH dossier 2018), an EMA (CHMP), US FDA and the ICH S3a guidelines (Sivaraman et al, 2018) and Clariant GMBH (2019), that the NOAEL for reproductive and developmental effects in males and female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"No effects of propylparaben on females and foetuses were found at dose levels up to 1000 mg/kg body weight/day.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: reduced ossification of some bones and few other skeletal findings were well within the historical control data range for this strain of rats and not considered to be a substance related effect. Generally delayed ossification is not regarded to persist postnatally and not associated with long-term consequences on survival, general growth and development and therefore is not considered to be adverse. No effects of propylparaben on females and foetuses were found at dose levels up to 1000 mg/kg body weight/day. The NOAEL for both maternal toxicity and foetal toxicity is considered to be 1000 mg/kg body weight/day in this study. Conclusions from reproductive and developmental studies: It can be concluded from the Gazin et al (2013) study and as supported by an OECD guideline 422 study (Harlan, 2012), an OECD guideline 414 (cited in ECHA REACH dossier 2018), an EMA (CHMP), US FDA and the ICH S3a guidelines (Sivaraman et al, 2018) and Clariant GMBH (2019), that the NOAEL for reproductive and developmental effects in males and female","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":25,"route":"","species":"rat","study_id":"sccs_o_243_noael_012"}

SCCS Opinion

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=ere found at dose levels up to 1000 mg/kg body weight/day.; EFFECT=ere found at dose levels up to 1000 mg/kg body weight/day. The NOAEL for both maternal toxicity and foetal toxicity is considered to be 1000 mg/kg body weight/day in this study. Conclusions from reproductive and developmental studies: It can be concluded from the Gazin et al (2013) study and as supported by an OECD guideline 422 study (Harlan, 2012), an OECD guideline 414 (cited in ECHA REACH dossier 2018), an EMA (CHMP), US FDA and the ICH S3a guidelines (Sivaraman et al, 2018) and Clariant GMBH (2019), that the NOAEL for reproductive and developmental effects in males and females with; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"ere found at dose levels up to 1000 mg/kg body weight/day.","duration":"developmental","effect":"ere found at dose levels up to 1000 mg/kg body weight/day. The NOAEL for both maternal toxicity and foetal toxicity is considered to be 1000 mg/kg body weight/day in this study. Conclusions from reproductive and developmental studies: It can be concluded from the Gazin et al (2013) study and as supported by an OECD guideline 422 study (Harlan, 2012), an OECD guideline 414 (cited in ECHA REACH dossier 2018), an EMA (CHMP), US FDA and the ICH S3a guidelines (Sivaraman et al, 2018) and Clariant GMBH (2019), that the NOAEL for reproductive and developmental effects in males and females with","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":25,"route":"","species":"","study_id":"sccs_o_243_noael_013"}

SCCS Opinion

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

SCCS Opinion

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

SCCS Opinion

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=only at 1000 mg/kg/day: increased numbers of primordial follicles LO(A)EL (sc):; LOAEL_VALUE=12.4 mg/kg; EFFECT=only at 1000 mg/kg/day: increased numbers of primordial follicles LO(A)EL (sc): 62.5 mg/kg bw/day Not all data appear consistent. Ahn et al. 2012 Mouse (C57BL/6J) Klimisch 1 OECD 440 (Uterotrophic Bioassay in rodents). Ovariectomised female mice 8 weeks of age (n=6/group, 11 groups) were dosed daily for 7 consecutive days by oral gavage and subcutaneous injection. 6 µg/kg bw/day estradiol (E2) was given orally as positive control for agonist and antagonist detection. Negative for estrogen agonism and antagonism NOEL defined at a top dose of 1000 mg/kg/day Ohta et al 2012 Wistar rat Non GLP Non guideline Klimisch 3 Study of the effects on general function of the male rat reproductive system. Rats (19-21 days old) received PP through the oral route (diet) for 4 weeks at dosage levels of 12.4, 125 and 1290 mg/kg/day. At all three dosage levels, a decrease in cauda epididymal sperm reserve, sperm count and daily sperm production was observed and from 125 mg/kg/day serum testosterone concentration was decreased. LOAEL: 12.4 mg/kg/; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"only at 1000 mg/kg/day: increased numbers of primordial follicles LO(A)EL (sc):","duration":"8 weeks","effect":"only at 1000 mg/kg/day: increased numbers of primordial follicles LO(A)EL (sc): 62.5 mg/kg bw/day Not all data appear consistent. Ahn et al. 2012 Mouse (C57BL/6J) Klimisch 1 OECD 440 (Uterotrophic Bioassay in rodents). Ovariectomised female mice 8 weeks of age (n=6/group, 11 groups) were dosed daily for 7 consecutive days by oral gavage and subcutaneous injection. 6 µg/kg bw/day estradiol (E2) was given orally as positive control for agonist and antagonist detection. Negative for estrogen agonism and antagonism NOEL defined at a top dose of 1000 mg/kg/day Ohta et al 2012 Wistar rat Non GLP Non guideline Klimisch 3 Study of the effects on general function of the male rat reproductive system. Rats (19-21 days old) received PP through the oral route (diet) for 4 weeks at dosage levels of 12.4, 125 and 1290 mg/kg/day. At all three dosage levels, a decrease in cauda epididymal sperm reserve, sperm count and daily sperm production was observed and from 125 mg/kg/day serum testosterone concentration was decreased. LOAEL: 12.4 mg/kg/","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"12.4 mg/kg","noael_unit":"mg/kg/day","noael_value":"1000","page":36,"route":"oral","species":"rat","study_id":"sccs_o_243_noael_017"}

SCCS Opinion

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=ation included Klimisch 1 PP orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day for 8 weeks starting on PND21.; EFFECT=ation included Klimisch 1 PP orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day for 8 weeks starting on PND21. A first subgroup of 10 males/dose was necropsied immediately after the 8-week exposure period; a second subgroup of 10 males/dose was necropsied after a 26-week washout period. GLP. There was no evidence of an effect of PrP on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The NOAEL was 1000 mg/kg/day, corresponding to a maximum plasma concentration of 12,030 ng/ml and exposure to 47 760 ng · h/ml (AUC0-8 h) at the end of the treatment. Ricerca Biosciences 2012d (Written up in Gazin et al 2013) Immature male Wistar rats Guideline: OPPTS 890.1400 Hershberger bioassay PP was orally administered by gavage to immature Wistar male rats at doses of 10, 250, or 750 mg/kg/day for 10 days. The Hershberger bioassay serves as an in vivo screening method for androgen agonists or antagonists and other 5α-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"ation included Klimisch 1 PP orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day for 8 weeks starting on PND21.","duration":"8 weeks","effect":"ation included Klimisch 1 PP orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day for 8 weeks starting on PND21. A first subgroup of 10 males/dose was necropsied immediately after the 8-week exposure period; a second subgroup of 10 males/dose was necropsied after a 26-week washout period. GLP. There was no evidence of an effect of PrP on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The NOAEL was 1000 mg/kg/day, corresponding to a maximum plasma concentration of 12,030 ng/ml and exposure to 47 760 ng · h/ml (AUC0-8 h) at the end of the treatment. Ricerca Biosciences 2012d (Written up in Gazin et al 2013) Immature male Wistar rats Guideline: OPPTS 890.1400 Hershberger bioassay PP was orally administered by gavage to immature Wistar male rats at doses of 10, 250, or 750 mg/kg/day for 10 days. The Hershberger bioassay serves as an in vivo screening method for androgen agonists or antagonists and other 5α-","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":37,"route":"oral","species":"rat","study_id":"sccs_o_243_noael_018"}

SCCS Opinion

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=An oral (gavage at a dose volume of 10 ml/kg) administration of propylparaben (0, 3, 10, 100, or 1000 mg/kg/day) performed on male Wistar rats for 8 weeks, initiating on PND 21, had no effects on reproductive organ weights, sperm count or motility, or hormone levels (LH, FSH and testosterone).; EFFECT=Biosciences (2012; written up in Gazin et al 2013). An oral (gavage at a dose volume of 10 ml/kg) administration of propylparaben (0, 3, 10, 100, or 1000 mg/kg/day) performed on male Wistar rats for 8 weeks, initiating on PND 21, had no effects on reproductive organ weights, sperm count or motility, or hormone levels (LH, FSH and testosterone). Importantly, this study was robustly powered and GLP compliant, with confirmation of systemic propylparaben exposures (Gazin et al., 2013). Gazin et al., 2013 determined a No observed adverse effect level for males of 1000 mg/kg/day. SCCS comment Hass et al. (2012), based on in vitro and in vivo studies, considered propylparaben as a suspected endocrine disrupter, as there is evidence of an estrogenic mode of action in vivo that is suspected to be linked to adverse effects in vivo. Conversely, the additional studies requested in the context of the REACH registration process for propylparaben, and provided by Clariant, were analyzed for all measured parameters and endpoints that can be used for the evaluation of po; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"An oral (gavage at a dose volume of 10 ml/kg) administration of propylparaben (0, 3, 10, 100, or 1000 mg/kg/day) performed on male Wistar rats for 8 weeks, initiating on PND 21, had no effects on reproductive organ weights, sperm count or motility, or hormone levels (LH, FSH and testosterone).","duration":"8 weeks","effect":"Biosciences (2012; written up in Gazin et al 2013). An oral (gavage at a dose volume of 10 ml/kg) administration of propylparaben (0, 3, 10, 100, or 1000 mg/kg/day) performed on male Wistar rats for 8 weeks, initiating on PND 21, had no effects on reproductive organ weights, sperm count or motility, or hormone levels (LH, FSH and testosterone). Importantly, this study was robustly powered and GLP compliant, with confirmation of systemic propylparaben exposures (Gazin et al., 2013). Gazin et al., 2013 determined a No observed adverse effect level for males of 1000 mg/kg/day. SCCS comment Hass et al. (2012), based on in vitro and in vivo studies, considered propylparaben as a suspected endocrine disrupter, as there is evidence of an estrogenic mode of action in vivo that is suspected to be linked to adverse effects in vivo. Conversely, the additional studies requested in the context of the REACH registration process for propylparaben, and provided by Clariant, were analyzed for all measured parameters and endpoints that can be used for the evaluation of po","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":38,"route":"oral","species":"rat","study_id":"sccs_o_243_noael_019"}

SCCS Opinion

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=Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7.; EFFECT=rine disrupter based on current EU classification criteria (ECHA/EFSA, 2018). Female endocrine effects: an uterotrophic study that followed OECD guidelines and was performed to GLP (Ohta et al 2012). In vivo, propylparaben is negative for estrogen agonism and antagonism and no estrogenicity was observed. Propylparaben did not modify levels of 17β-estradiol. Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7. The No-Observed-Adverse-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for ma; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7.","duration":"","effect":"rine disrupter based on current EU classification criteria (ECHA/EFSA, 2018). Female endocrine effects: an uterotrophic study that followed OECD guidelines and was performed to GLP (Ohta et al 2012). In vivo, propylparaben is negative for estrogen agonism and antagonism and no estrogenicity was observed. Propylparaben did not modify levels of 17β-estradiol. Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7. The No-Observed-Adverse-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for ma","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":39,"route":"","species":"","study_id":"sccs_o_243_noael_020"}

SCCS Opinion

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=Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7.; EFFECT=classification criteria (ECHA/EFSA, 2018). Female endocrine effects: an uterotrophic study that followed OECD guidelines and was performed to GLP (Ohta et al 2012). In vivo, propylparaben is negative for estrogen agonism and antagonism and no estrogenicity was observed. Propylparaben did not modify levels of 17β-estradiol. Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7. The No-Observed-Adverse-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7.","duration":"","effect":"classification criteria (ECHA/EFSA, 2018). Female endocrine effects: an uterotrophic study that followed OECD guidelines and was performed to GLP (Ohta et al 2012). In vivo, propylparaben is negative for estrogen agonism and antagonism and no estrogenicity was observed. Propylparaben did not modify levels of 17β-estradiol. Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7. The No-Observed-Adverse-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is","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":39,"route":"","species":"","study_id":"sccs_o_243_noael_021"}

SCCS Opinion

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) for females is a top dose at 1,000 mg/kg/day.; EFFECT=on PND 7. The No-Observed-Adverse-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day. A risk assessment can be performed based on no adverse effects in males and females using the NOAEL of 1000 mg/kg/day from the pivotal studies in female and male animals. A BMD cannot be calculated from these studies as there were no quantifiable observed effects with a dose-response. Overall SCCS conclusions on endocrine disruption properties of propylparaben The SCCS has analysed all the relevant information provided in the dossier and available in the publis; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"The No-Observed-Adverse-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day.","duration":"","effect":"on PND 7. The No-Observed-Adverse-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day. A risk assessment can be performed based on no adverse effects in males and females using the NOAEL of 1000 mg/kg/day from the pivotal studies in female and male animals. A BMD cannot be calculated from these studies as there were no quantifiable observed effects with a dose-response. Overall SCCS conclusions on endocrine disruption properties of propylparaben The SCCS has analysed all the relevant information provided in the dossier and available in the publis","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":39,"route":"","species":"","study_id":"sccs_o_243_noael_022"}

SCCS Opinion

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=-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day.; EFFECT=-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day. A risk assessment can be performed based on no adverse effects in males and females using the NOAEL of 1000 mg/kg/day from the pivotal studies in female and male animals. A BMD cannot be calculated from these studies as there were no quantifiable observed effects with a dose-response. Overall SCCS conclusions on endocrine disruption properties of propylparaben The SCCS has analysed all the relevant information provided in the dossier and available in the published lit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day.","duration":"","effect":"-Effect-Level (NOAEL) for females is a top dose at 1,000 mg/kg/day. Male endocrine effects: the pivotal study covering the potential for adverse effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day. A risk assessment can be performed based on no adverse effects in males and females using the NOAEL of 1000 mg/kg/day from the pivotal studies in female and male animals. A BMD cannot be calculated from these studies as there were no quantifiable observed effects with a dose-response. Overall SCCS conclusions on endocrine disruption properties of propylparaben The SCCS has analysed all the relevant information provided in the dossier and available in the published lit","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":39,"route":"","species":"","study_id":"sccs_o_243_noael_023"}

SCCS Opinion

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=The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day.; EFFECT=effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day. A risk assessment can be performed based on no adverse effects in males and females using the NOAEL of 1000 mg/kg/day from the pivotal studies in female and male animals. A BMD cannot be calculated from these studies as there were no quantifiable observed effects with a dose-response. Overall SCCS conclusions on endocrine disruption properties of propylparaben The SCCS has analysed all the relevant information provided in the dossier and available in the published literature for safety asesesment of propylparaben with an emphasis on its potential endcrine effects (CIR (2019), ECHA (Reach dossier, 2018), Centre; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day.","duration":"","effect":"effects in the intact organism is by Gazin et al. (2013), which is the published write up of Ricerca Biosciences 2012 study. In this in vivo study there was no evidence of an effect of propylparaben on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels (LH, FSH or testosterone), or histopathology. The No-Observed-Adverse-Effect-Level (NOAEL) for males is a top dose of 1,000 mg/kg/day. A risk assessment can be performed based on no adverse effects in males and females using the NOAEL of 1000 mg/kg/day from the pivotal studies in female and male animals. A BMD cannot be calculated from these studies as there were no quantifiable observed effects with a dose-response. Overall SCCS conclusions on endocrine disruption properties of propylparaben The SCCS has analysed all the relevant information provided in the dossier and available in the published literature for safety asesesment of propylparaben with an emphasis on its potential endcrine effects (CIR (2019), ECHA (Reach dossier, 2018), Centre","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":39,"route":"","species":"","study_id":"sccs_o_243_noael_024"}

SCCS Opinion

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=Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben.; EFFECT=ne disrupting substance or to derive a specific endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) Toxicological Point of Departure from Animal Data The point of departure for use in safety assessment is derived from reproductive effects of propylparaben, as described in section 3.4.5. Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben. These include Harlan (2012), Gazin et al (2013), Sivaraman et al. (2018), the OECD guideline 414 study cited in ECHA REACH dossier (2018) and Clariant GMBH study (2019). The POD as an oral NOAEL for use in risk assessment is 1000 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben.","duration":"","effect":"ne disrupting substance or to derive a specific endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) Toxicological Point of Departure from Animal Data The point of departure for use in safety assessment is derived from reproductive effects of propylparaben, as described in section 3.4.5. Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben. These include Harlan (2012), Gazin et al (2013), Sivaraman et al. (2018), the OECD guideline 414 study cited in ECHA REACH dossier (2018) and Clariant GMBH study (2019). The POD as an oral NOAEL for use in risk assessment is 1000 mg/kg/day","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":39,"route":"oral","species":"","study_id":"sccs_o_243_noael_025"}

SCCS Opinion

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=Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben.; EFFECT=ata The point of departure for use in safety assessment is derived from reproductive effects of propylparaben, as described in section 3.4.5. Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben. These include Harlan (2012), Gazin et al (2013), Sivaraman et al. (2018), the OECD guideline 414 study cited in ECHA REACH dossier (2018) and Clariant GMBH study (2019). The POD as an oral NOAEL for use in risk assessment is 1000 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben.","duration":"","effect":"ata The point of departure for use in safety assessment is derived from reproductive effects of propylparaben, as described in section 3.4.5. Pivotal study for calculating the oral POD The finding of five good quality GLP studies (detailed in sections 3.4.4 and 3.4.5) support a NOAEL of 1000 mg/kg/day for propylparaben. These include Harlan (2012), Gazin et al (2013), Sivaraman et al. (2018), the OECD guideline 414 study cited in ECHA REACH dossier (2018) and Clariant GMBH study (2019). The POD as an oral NOAEL for use in risk assessment is 1000 mg/kg/day","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":39,"route":"oral","species":"","study_id":"sccs_o_243_noael_026"}

SCCS Opinion

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=A NOAEL of 1000 mg/kg bw/day has been derived from the pivotal study covering the potential for adverse effects in the intact organism by Gazin et (2013) and is used for this safety assessment.; EFFECT=studies have indicated weak associations between increased paraben exposure and the markers for human reproductive health. Special investigations Endocrine activity The SCCS is of the view that, although the available data on propylparaben provide some indications for potential endocrine effects, the current level of evidence is not sufficient to conclusively regard it as an endocrine disrupting substance, or to derive a specific endocrine- related toxicological point of departure for use in safety assessment. A NOAEL of 1000 mg/kg bw/day has been derived from the pivotal study covering the potential for adverse effects in the intact organism by Gazin et (2013) and is used for this safety assessment. The SCCS mandates do not address environmental aspects. Therefore this assessment did not cover the safety of Propylparaben for the environment.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"A NOAEL of 1000 mg/kg bw/day has been derived from the pivotal study covering the potential for adverse effects in the intact organism by Gazin et (2013) and is used for this safety assessment.","duration":"","effect":"studies have indicated weak associations between increased paraben exposure and the markers for human reproductive health. Special investigations Endocrine activity The SCCS is of the view that, although the available data on propylparaben provide some indications for potential endocrine effects, the current level of evidence is not sufficient to conclusively regard it as an endocrine disrupting substance, or to derive a specific endocrine- related toxicological point of departure for use in safety assessment. A NOAEL of 1000 mg/kg bw/day has been derived from the pivotal study covering the potential for adverse effects in the intact organism by Gazin et (2013) and is used for this safety assessment. The SCCS mandates do not address environmental aspects. Therefore this assessment did not cover the safety of Propylparaben for the environment.","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":43,"route":"","species":"human","study_id":"sccs_o_243_noael_030"}

SCCS Opinion

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=1290; DOSE=Rats (19-21 days old) received PP through the oral route (diet) for 4 weeks at dosage levels of 12.4, 125 and 1290 mg/kg/day.; LOAEL_VALUE=12.4 mg/kg/day; EFFECT=Unlabeled table on page 36: Wistar rat Non GLP Non guideline Klimisch 3 | Study of the effects on general function of the male rat reproductive system. Rats (19-21 days old) received PP through the oral route (diet) for 4 weeks at dosage levels of 12.4, 125 and 1290 mg/kg/day. At all three dosage levels, a decrease in cauda epididymal sperm reserve, sperm count and daily sperm production was observed and from 125 mg/kg/day serum testosterone concentration was decreased. LOAEL: 12.4 mg/kg/day. Recent toxicokinetic data indicate low systemic exposure to PrPB even at high doses and raise doubt on the relevance of the study for risk assessment. Shortcomings:  control values outside normal range, not consistent with literature data and other Oishi studies,  absence of dose-response for Daily Sperm Production,  small group size, full study protocol and raw data not available | Oishi 2002; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"94-13-3","citation":"","dose":"Rats (19-21 days old) received PP through the oral route (diet) for 4 weeks at dosage levels of 12.4, 125 and 1290 mg/kg/day.","duration":"21 days","effect":"Unlabeled table on page 36: Wistar rat Non GLP Non guideline Klimisch 3 | Study of the effects on general function of the male rat reproductive system. Rats (19-21 days old) received PP through the oral route (diet) for 4 weeks at dosage levels of 12.4, 125 and 1290 mg/kg/day. At all three dosage levels, a decrease in cauda epididymal sperm reserve, sperm count and daily sperm production was observed and from 125 mg/kg/day serum testosterone concentration was decreased. LOAEL: 12.4 mg/kg/day. Recent toxicokinetic data indicate low systemic exposure to PrPB even at high doses and raise doubt on the relevance of the study for risk assessment. Shortcomings:  control values outside normal range, not consistent with literature data and other Oishi studies,  absence of dose-response for Daily Sperm Production,  small group size, full study protocol and raw data not available | Oishi 2002","endpoint":"reproductive toxicity","ingredient":", or to derive a toxicological point of departure based","loael_value":"12.4 mg/kg/day","noael_unit":"mg/kg/day","noael_value":"1290","page":36,"route":"oral","species":"rat","study_id":"sccs_o_243_noael_053"}

SCCS Opinion

{"absorption_percent":"11.9%; 15%; 25.8%; 3.7%","basis":"applied dose (AD) (receptor fluid) + 11.9%AD (as measured within the skin), at 4 hours (SD was not reported). Overall, a conservative and expectedly worst-case estimate of 15% skin absorption of unmetabolised Methylparaben can be used in the risk assessment for the following reasons: • this value is from an experiment using a penetration enhancing vehicle, • the extent of metabolism is expected to increase beyond 4h following application to the skin, • following dermal application of Methylparaben for 6 hours to rats only up to 25.8% of the applied radioactivity was found in the urine which may be far less in humans taking into account that the skin of rats may be up to 10 times more permeable compared to human skin (van Ravenzwaay & Leibold, 2004), • the SCCS considered a dermal absorption rate of 3.7% for the close analogue Propylparaben (SCCS/1623/20).","concentration_tested":"applied dose (AD) (receptor fluid) + 11.9%AD (as measured within the skin), at 4 hours (SD was not reported).","page":16,"pdf":"sccs_o_276.pdf","row_type":"dermal_absorption_study"}

SCCS Opinion

{"absorption_percent":"11.9%; 15%; 25.8%; 3.7%","basis":"applied dose (AD) (receptor fluid) + 11.9%AD (as measured within the skin), at 4 hours (SD was not reported). Overall, a conservative and expectedly worst-case estimate of 15% skin absorption of unmetabolised Methylparaben can be used in the risk assessment for the following reasons: • this value is from an experiment using a penetration enhancing vehicle, • the extent of metabolism is expected to increase beyond 4h following application to the skin, • following dermal application of Methylparaben for 6 hours to rats only up to 25.8% of the applied radioactivity was found in the urine which may be far less in humans taking into account that the skin of rats may be up to 10 times more permeable compared to human skin (van Ravenzwaay & Leibold, 2004), • the SCCS considered a dermal absorption rate of 3.7% for the close analogue Propylparaben (SCCS/1623/20).","concentration_tested":"applied dose (AD) (receptor fluid) + 11.9%AD (as measured within the skin), at 4 hours (SD was not reported).","page":16,"pdf":"sccs_o_276.pdf","row_type":"dermal_absorption_study"}

SCCS Opinion

{"absorption_percent":"11.9%; 15%; 25.8%; 3.7%","basis":"applied dose (AD) (receptor fluid) + 11.9%AD (as measured within the skin), at 4 hours (SD was not reported). Overall, a conservative and expectedly worst-case estimate of 15% skin absorption of unmetabolised Methylparaben can be used in the risk assessment for the following reasons: • this value is from an experiment using a penetration enhancing vehicle, • the extent of metabolism is expected to increase beyond 4h following application to the skin, • following dermal application of Methylparaben for 6 hours to rats only up to 25.8% of the applied radioactivity was found in the urine which may be far less in humans taking into account that the skin of rats may be up to 10 times more permeable compared to human skin (van Ravenzwaay & Leibold, 2004), • the SCCS considered a dermal absorption rate of 3.7% for the close analogue Propylparaben (SCCS/1623/20).","concentration_tested":"applied dose (AD) (receptor fluid) + 11.9%AD (as measured within the skin), at 4 hours (SD was not reported).","page":16,"pdf":"sccs_o_276.pdf","row_type":"dermal_absorption_study"}

SCCS Opinion