, and this warrants further, Benzophenone-3

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=0.50; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"0.50","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_039"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=unclear:Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS; DOSE=Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"","noael_value":"unclear:Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_033"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV cream | 6% | whole body | 1.782 | 0 | 0 | 1.782 | 67.9 | 38; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV cream | 6% | whole body | 1.782 | 0 | 0 | 1.782 | 67.9 | 38","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_034"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV aerosolised spray | 6% | whole body | 1.782 | 0.105 | 0 | 1.887 | 67.9 | 36; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV aerosolised spray | 6% | whole body | 1.782 | 0.105 | 0 | 1.887 | 67.9 | 36","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_035"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV pump spray | 6% | whole body | 1.782 | 0.001053 | 0 | 1.783 | 67.9 | 38; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV pump spray | 6% | whole body | 1.782 | 0.001053 | 0 | 1.783 | 67.9 | 38","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_036"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV face cream | 6% | face | 0.152 | 0 | 0 | 0.152 | 67.9 | 447; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV face cream | 6% | face | 0.152 | 0 | 0 | 0.152 | 67.9 | 447","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_037"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV hand cream | 6% | hand | 0.214 | 0 | 0 | 0.214 | 67.9 | 317; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV hand cream | 6% | hand | 0.214 | 0 | 0 | 0.214 | 67.9 | 317","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_038"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: Lipstick | 6% | lips | 0.000 | 0 | 0.054 | 0.054 | 67.9 | 1257; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Lipstick | 6% | lips | 0.000 | 0 | 0.054 | 0.054 | 67.9 | 1257","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_040"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=unclear:Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments; DOSE=Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments; EFFECT=Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","duration":"","effect":"Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","page":62,"route":"","species":"","study_id":"sccs_o_247_noael_041"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.; EFFECT=al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","duration":"","effect":"al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":47,"route":"oral","species":"","study_id":"sccs_o_247_noael_009"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.; EFFECT=_________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Con; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","duration":"","effect":"_________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Con","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":47,"route":"oral","species":"","study_id":"sccs_o_247_noael_010"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.; EFFECT=toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.00; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","duration":"","effect":"toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.00","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":47,"route":"oral","species":"","study_id":"sccs_o_247_noael_011"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=>99; DOSE=The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.; EFFECT=housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.","duration":"5 weeks","effect":"housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":">99","page":40,"route":"","species":"mouse","study_id":"sccs_o_247_noael_008"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 364; DOSE=Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm; EFFECT=Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm","duration":"","effect":"Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 364","page":67,"route":"dermal","species":"mouse","study_id":"sccs_o_247_noael_054"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 411; DOSE=om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...; EFFECT=om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...","duration":"39 days","effect":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg/ day","noael_value":"= 411","page":65,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_028"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 411; DOSE=Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day; EFFECT=Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day","duration":"","effect":"Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg/ day","noael_value":"= 411","page":65,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_049"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.; LOAEL_VALUE=67.9 mg /kg bw/day; EFFECT=reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.","duration":"","effect":"reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation)","endpoint":"","ingredient":", and this warrants further","loael_value":"67.9 mg /kg bw/day","noael_unit":"ppm","noael_value":"1000","page":39,"route":"","species":"","study_id":"sccs_o_247_noael_007"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=unclear:SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°; EFFECT=SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"route":"","species":"rat","study_id":"sccs_o_247_noael_013"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3448.2; DOSE=Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...; LOAEL_VALUE=68 mg /kg bw/day; EFFECT=Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...","duration":"","effect":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day)","endpoint":"","ingredient":", and this warrants further","loael_value":"68 mg /kg bw/day","noael_unit":"mg/kg/day","noael_value":"3448.2","page":63,"route":"","species":"","study_id":"sccs_o_247_noael_045"}

sccs_o_247.pdf

{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}

sccs_o_247.pdf

{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}

sccs_o_247.pdf

{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}

sccs_o_247.pdf

{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}

sccs_o_247.pdf

{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}

sccs_o_247.pdf

{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}

sccs_o_247.pdf

{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}

sccs_o_247.pdf

{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products.; LOAEL_VALUE=67.9 mg /kg bw/day; EFFECT=ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al. (2015) study. The SCCS has estimated the margin of safety (MoS) as 38 for the use of BP-3 at a concentration of 6% as a UV-filter in sunscreens for the whole body application (in the form of cream/lotion or pump spray, and 36 for sunscreen propellant spray), and 447 for the face, 317 for the hand and 1257 for lipstick application. The MoS has been estimated at 585 for the use of BP-3 at 0.5% to protect cosmetic formulations against sunlight. The SCCS assessment did not c; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products.","duration":"","effect":"ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al. (2015) study. The SCCS has estimated the margin of safety (MoS) as 38 for the use of BP-3 at a concentration of 6% as a UV-filter in sunscreens for the whole body application (in the form of cream/lotion or pump spray, and 36 for sunscreen propellant spray), and 447 for the face, 317 for the hand and 1257 for lipstick application. The MoS has been estimated at 585 for the use of BP-3 at 0.5% to protect cosmetic formulations against sunlight. The SCCS assessment did not c","endpoint":"dermal absorption","ingredient":", and this warrants further","loael_value":"67.9 mg /kg bw/day","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":51,"route":"dermal","species":"","study_id":"sccs_o_247_noael_017"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; DOSE=Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.; EFFECT=et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.","duration":"prenatal","effect":"et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_012"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...; EFFECT=study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","duration":"","effect":"study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_019"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...; EFFECT=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","duration":"","effect":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_020"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at...; EFFECT=d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at...","duration":"2 years","effect":"d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":64,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_025"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal...; EFFECT=ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal...","duration":"2 years","effect":"ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":64,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_026"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence...; EFFECT=s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence...","duration":"2 years","effect":"s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":64,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_027"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...; EFFECT=Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No","dose":"WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...","duration":"Prenatal","effect":"Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_044"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 242; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...; EFFECT=SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","duration":"","effect":"SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 242","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_023"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 242; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...; EFFECT=SCCS-rejected applicant NOAEL: tudy period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","duration":"","effect":"SCCS-rejected applicant NOAEL: tudy period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 242","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_024"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 242; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...; EFFECT=SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","duration":"","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 242","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_047"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=660; DOSE=2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...; EFFECT=Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...","duration":"105 weeks","effect":"Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg","noael_value":"660","page":64,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_048"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...; EFFECT=SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","duration":"Prenatal","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_018"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocy...; LOAEL_VALUE=68 mg /kg bw/day; EFFECT=aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variatio; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocy...","duration":"","effect":"aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variatio","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"68 mg /kg bw/day","noael_unit":"ppm","noael_value":"1000","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_022"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...; EFFECT=Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No","dose":"WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...","duration":"Prenatal","effect":"Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_042"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3000; DOSE=However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.; EFFECT=ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","duration":"developmental","effect":"ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"ppm","noael_value":"3000","page":27,"route":"","species":"","study_id":"sccs_o_247_noael_005"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3000; DOSE=, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.; EFFECT=, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":", and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","duration":"developmental","effect":", and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"ppm","noael_value":"3000","page":27,"route":"","species":"","study_id":"sccs_o_247_noael_006"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3689; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...; EFFECT=SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","duration":"","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg","noael_value":"3689","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_046"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1; DOSE=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...; EFFECT=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","duration":"Sub-chronic","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"1","page":66,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_050"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 100; DOSE=at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...; EFFECT=at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...","duration":"Sub-chronic","effect":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 100","page":66,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_029"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 100; DOSE=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...; EFFECT=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","duration":"Sub-chronic","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 100","page":66,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_051"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":25,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_002"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.; EFFECT=ved relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.","duration":"developmental","effect":"ved relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":50,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_014"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.; EFFECT=ive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3 in the diet displayed slight decreases in GD 6–21 body weight gain (~10%) r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.","duration":"developmental","effect":"ive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3 in the diet displayed slight decreases in GD 6–21 body weight gain (~10%) r","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":50,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_015"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in subm...; EFFECT=kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in subm...","duration":"Sub-chronic","effect":"kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 200","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_031"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; EFFECT=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","duration":"Sub-chronic","effect":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_053"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; EFFECT=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","duration":"Sub-chronic","effect":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 200","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_055"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 364; DOSE=based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...; EFFECT=based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...","duration":"Sub-chronic","effect":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 364","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_032"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=411; DOSE=Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"411","page":25,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_001"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 1246; DOSE=___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...; EFFECT=___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...","duration":"Sub-chronic","effect":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw /day","noael_value":"= 1246","page":67,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_030"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=50000; DOSE=Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...; EFFECT=Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...","duration":"Sub-chronic","effect":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"ppm","noael_value":"50000","page":67,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_052"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=000; DOSE=i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...; LOAEL_VALUE=1798 mg/kg/d; EFFECT=i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...","duration":"","effect":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"1798 mg/kg/d","noael_unit":"ppm","noael_value":"000","page":62,"route":"","species":"","study_id":"sccs_o_247_noael_021"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=000; DOSE=35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean...; LOAEL_VALUE=1798 mg/kg/d; EFFECT=Unlabeled table on page 62: - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live | One foetus with hydrocephaly at 50 000 ppm but no other malformations observed | In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher | NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) | It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean...","duration":"","effect":"Unlabeled table on page 62: - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live | One foetus with hydrocephaly at 50 000 ppm but no other malformations observed | In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher | NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) | It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"1798 mg/kg/d","noael_unit":"ppm","noael_value":"000","page":62,"route":"","species":"rat","study_id":"sccs_o_247_noael_043"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=study male rat livers from the 10,000 ppm and control groups.; EFFECT=study male rat livers from the 10,000 ppm and control groups. The observed effects on transcription were consistent with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"study male rat livers from the 10,000 ppm and control groups.","duration":"Chronic","effect":"study male rat livers from the 10,000 ppm and control groups. The observed effects on transcription were consistent with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":26,"route":"","species":"rat","study_id":"sccs_o_247_noael_003"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘.; EFFECT=with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of BP-3 and also on some ED properties. This study is therefore described in this section and also in more detail in th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘.","duration":"Chronic","effect":"with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of BP-3 and also on some ED properties. This study is therefore described in this section and also in more detail in th","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":26,"route":"","species":"rat","study_id":"sccs_o_247_noael_004"}

sccs_o_247.pdf

SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the cal...; LOAEL_VALUE=67.9 mg /kg bw/day; EFFECT=igh doses that can only be considered far beyond the human exposure range. The study from Nakamura et al. (2015) that determined the effects of maternal and lactational exposure to BP-3 on development and reproductive organs of offspring of time-mated female Harlan Sprague-Dawley rats has been selected by the SCCS as the key study to be used for the calculation of the MoS. Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the cal...","duration":"","effect":"igh doses that can only be considered far beyond the human exposure range. The study from Nakamura et al. (2015) that determined the effects of maternal and lactational exposure to BP-3 on development and reproductive organs of offspring of time-mated female Harlan Sprague-Dawley rats has been selected by the SCCS as the key study to be used for the calculation of the MoS. Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al.","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"67.9 mg /kg bw/day","noael_unit":"ppm","noael_value":"1000","page":51,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_016"}

sccs_o_247.pdf