by other scientific bodies (e.g. under REACH) should also be, Butylphenyl Methylpropional

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT== 0.0281; DOSE=SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.; EFFECT=SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.","duration":"","effect":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,","endpoint":"","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.0281","page":48,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_016"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT== 0.0281; DOSE=SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.; EFFECT=SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.","duration":"","effect":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,","endpoint":"","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.0281","page":48,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_016"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=50; DOSE=After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered.; EFFECT=Peak excretion for all metabolites occurred between 2 and 5 h after oral application, with the primary metabolites (lysmerol and lysmerylic acid) being excreted about 1 h earlier than the secondary metabolites (hydroxylated lysmerylic acid and TBBA). After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered. As there are no oral bioavailability data available, a default value of 50% is used to calculate systemic NOAEL. Human data /; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered.","duration":"","effect":"Peak excretion for all metabolites occurred between 2 and 5 h after oral application, with the primary metabolites (lysmerol and lysmerylic acid) being excreted about 1 h earlier than the secondary metabolites (hydroxylated lysmerylic acid and TBBA). After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered. As there are no oral bioavailability data available, a default value of 50% is used to calculate systemic NOAEL. Human data /","endpoint":"","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"%","noael_value":"50","page":52,"route":"oral","species":"human","study_id":"sccs_o_213_noael_025"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=50; DOSE=After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered.; EFFECT=Peak excretion for all metabolites occurred between 2 and 5 h after oral application, with the primary metabolites (lysmerol and lysmerylic acid) being excreted about 1 h earlier than the secondary metabolites (hydroxylated lysmerylic acid and TBBA). After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered. As there are no oral bioavailability data available, a default value of 50% is used to calculate systemic NOAEL. Human data /; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered.","duration":"","effect":"Peak excretion for all metabolites occurred between 2 and 5 h after oral application, with the primary metabolites (lysmerol and lysmerylic acid) being excreted about 1 h earlier than the secondary metabolites (hydroxylated lysmerylic acid and TBBA). After 48 h, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered. As there are no oral bioavailability data available, a default value of 50% is used to calculate systemic NOAEL. Human data /","endpoint":"","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"%","noael_value":"50","page":52,"route":"oral","species":"human","study_id":"sccs_o_213_0_noael_025"}

sccs_o_213_0.pdf

{"dose":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.","effect":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,","page":48,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_016"}

sccs_o_213.pdf

{"dose":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.","effect":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,","page":48,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_016"}

sccs_o_213.pdf

{"dose":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.","effect":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,","page":48,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_016"}

sccs_o_213.pdf

{"dose":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day.","effect":"SCCS/1591/17 Final version The use of a first-tier deterministic approach (adding all of the numbers derived above) leads to the total SED level of 0.0281 mg/kg bw/day. CALCULATION OF THE MARGIN OF SAFETY (aggregate exposure) Total systemic exposure dose (SED) = 0.0281 mg/kg bw No observed adverse effect level NOAELsys = 4.5 mg/kg bw/d (EOGRTS, oral, rat)Bioavailability 50% * NOAELsys = 2.25 mg/kg bw/d Margin of Safety (MOS) NOAELsys/SED = 80 * Standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 2018. Individual MoS calculations for the respective product groups: Product types Systemic Exposure Dose [µg/kg bw/day] Individual MoS calculations for the respective product groups Hydroalcoholic-based fragrances (e.g. Eau de Toilette, perfume,","page":48,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_016"}

sccs_o_213.pdf

{"dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","effect":"SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one","page":35,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_003"}

sccs_o_213.pdf

{"dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","effect":"SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one","page":35,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_003"}

sccs_o_213.pdf

{"dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","effect":"SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one","page":35,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_003"}

sccs_o_213.pdf

{"dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","effect":"SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one","page":35,"pdf":"sccs_o_213.pdf","row_type":"noael_study","study_id":"sccs_o_213_noael_003"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.; EFFECT=0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean ov; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean ov","endpoint":"developmental toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_007"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.; EFFECT=re only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b,; CITATION=Ref.: BASF SE, 2015, 2017b,; CITATION_NUMBERS=[2015,2017]; REFERENCE=Ref.: BASF SE, 2015, 2017b,; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b,","dose":"The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"re only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b,","endpoint":"developmental toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_008"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.; EFFECT=0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean ov; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean ov","endpoint":"developmental toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_007"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.; EFFECT=re only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b,; CITATION=Ref.: BASF SE, 2015, 2017b,; CITATION_NUMBERS=[2015,2017]; REFERENCE=Ref.: BASF SE, 2015, 2017b,; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b,","dose":"The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"re only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b,","endpoint":"developmental toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_008"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=40; DOSE=In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.; EFFECT=SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","duration":"2 weeks","effect":"SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one","endpoint":"developmental toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"40","page":35,"route":"","species":"rat","study_id":"sccs_o_213_noael_003"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=40; DOSE=In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.; EFFECT=SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","duration":"2 weeks","effect":"SCCS/1591/17 Final version Opinion on the safety Butylphenyl methylpropional (p- BMHCA) in cosmetic products - Submission II ___________________________________________________________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one","endpoint":"developmental toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"40","page":35,"route":"","species":"rat","study_id":"sccs_o_213_0_noael_003"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=4.5; DOSE=(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day.; EFFECT=(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinetics of p-BMHCA are available from rat, mouse, rabbit, guinea pig, dog and rhesus monkey and human studies. Given its physicochemical properties, p-BMHCA is likely to have high bioavailability via the oral route. After oral and dermal administration to experimental animals and humans, there is clear evidence of systemic absorption of p-BMHCA. Howev; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day.","duration":"developmental","effect":"(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinetics of p-BMHCA are available from rat, mouse, rabbit, guinea pig, dog and rhesus monkey and human studies. Given its physicochemical properties, p-BMHCA is likely to have high bioavailability via the oral route. After oral and dermal administration to experimental animals and humans, there is clear evidence of systemic absorption of p-BMHCA. Howev","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4.5","page":41,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_015"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=4.5; DOSE=(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day.; EFFECT=(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinetics of p-BMHCA are available from rat, mouse, rabbit, guinea pig, dog and rhesus monkey and human studies. Given its physicochemical properties, p-BMHCA is likely to have high bioavailability via the oral route. After oral and dermal administration to experimental animals and humans, there is clear evidence of systemic absorption of p-BMHCA. Howev; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day.","duration":"developmental","effect":"(SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinetics of p-BMHCA are available from rat, mouse, rabbit, guinea pig, dog and rhesus monkey and human studies. Given its physicochemical properties, p-BMHCA is likely to have high bioavailability via the oral route. After oral and dermal administration to experimental animals and humans, there is clear evidence of systemic absorption of p-BMHCA. Howev","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4.5","page":41,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_015"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=5; DOSE=Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days.; EFFECT=tive than dogs to this compound irrespective of the length of treatment. Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system. Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days. In addition, effects on adrenal glands in females were also observed at the same dose levels. From this most meaningful oral study, with respect to the doses administered, a NOAEL of 5 mg/kg bw/day can be derived for systemic effects. On the other hand, dermal administration in rats for 5 days led to adverse effects (including testicular toxicity) only at excessive dose levels (2000 mg/kg bw/day). No 90-day studies on dermal or inhalative administration were available. 3.3.5.1 Repeated dose short-term oral / dermal / inhalation toxicity Additional data from Applicant’s submission II dossier The results of screening studies provided (BASF SE, 2011b, SMI: 15, #59014 and Givaudan, 2009, SMI; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days.","duration":"90 days","effect":"tive than dogs to this compound irrespective of the length of treatment. Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system. Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days. In addition, effects on adrenal glands in females were also observed at the same dose levels. From this most meaningful oral study, with respect to the doses administered, a NOAEL of 5 mg/kg bw/day can be derived for systemic effects. On the other hand, dermal administration in rats for 5 days led to adverse effects (including testicular toxicity) only at excessive dose levels (2000 mg/kg bw/day). No 90-day studies on dermal or inhalative administration were available. 3.3.5.1 Repeated dose short-term oral / dermal / inhalation toxicity Additional data from Applicant’s submission II dossier The results of screening studies provided (BASF SE, 2011b, SMI: 15, #59014 and Givaudan, 2009, SMI","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":20,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_001"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=5; DOSE=In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.; EFFECT=_________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies. Since the onset of developmental toxicity was tightly accompanied by maternal toxicity, the malformations and tissue variations observed likely resulted from general fetotoxicity rather than from specific teratogenicity. 3.3.8.1 Two generation reproduction toxicity Additional data from Applicant’s submission II dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","duration":"2 weeks","effect":"_________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies. Since the onset of developmental toxicity was tightly accompanied by maternal toxicity, the malformations and tissue variations observed likely resulted from general fetotoxicity rather than from specific teratogenicity. 3.3.8.1 Two generation reproduction toxicity Additional data from Applicant’s submission II dossier","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":35,"route":"","species":"rat","study_id":"sccs_o_213_noael_004"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=5; DOSE=In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.; EFFECT=ystemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose toxicity studies. The data available point to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","duration":"2 weeks","effect":"ystemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose toxicity studies. The data available point to","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":49,"route":"","species":"rat","study_id":"sccs_o_213_noael_020"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=5; DOSE=Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days.; EFFECT=tive than dogs to this compound irrespective of the length of treatment. Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system. Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days. In addition, effects on adrenal glands in females were also observed at the same dose levels. From this most meaningful oral study, with respect to the doses administered, a NOAEL of 5 mg/kg bw/day can be derived for systemic effects. On the other hand, dermal administration in rats for 5 days led to adverse effects (including testicular toxicity) only at excessive dose levels (2000 mg/kg bw/day). No 90-day studies on dermal or inhalative administration were available. 3.3.5.1 Repeated dose short-term oral / dermal / inhalation toxicity Additional data from Applicant’s submission II dossier The results of screening studies provided (BASF SE, 2011b, SMI: 15, #59014 and Givaudan, 2009, SMI; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days.","duration":"90 days","effect":"tive than dogs to this compound irrespective of the length of treatment. Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system. Decreases in plasma cholinesterase activity levels in both sexes of rats were observed after oral exposure to ≥25 mg/kg bw/day for 90 days. In addition, effects on adrenal glands in females were also observed at the same dose levels. From this most meaningful oral study, with respect to the doses administered, a NOAEL of 5 mg/kg bw/day can be derived for systemic effects. On the other hand, dermal administration in rats for 5 days led to adverse effects (including testicular toxicity) only at excessive dose levels (2000 mg/kg bw/day). No 90-day studies on dermal or inhalative administration were available. 3.3.5.1 Repeated dose short-term oral / dermal / inhalation toxicity Additional data from Applicant’s submission II dossier The results of screening studies provided (BASF SE, 2011b, SMI: 15, #59014 and Givaudan, 2009, SMI","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":20,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_001"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=5; DOSE=In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.; EFFECT=_________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies. Since the onset of developmental toxicity was tightly accompanied by maternal toxicity, the malformations and tissue variations observed likely resulted from general fetotoxicity rather than from specific teratogenicity. 3.3.8.1 Two generation reproduction toxicity Additional data from Applicant’s submission II dossier; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","duration":"2 weeks","effect":"_________________________________________ 35 such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as most sensitive species with regard to p-BMHCA-mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and was already found at lower concentrations. Here, a NOAEL based on developmental toxicity is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies. Since the onset of developmental toxicity was tightly accompanied by maternal toxicity, the malformations and tissue variations observed likely resulted from general fetotoxicity rather than from specific teratogenicity. 3.3.8.1 Two generation reproduction toxicity Additional data from Applicant’s submission II dossier","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":35,"route":"","species":"rat","study_id":"sccs_o_213_0_noael_004"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=5; DOSE=In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.; EFFECT=ystemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose toxicity studies. The data available point to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months.","duration":"2 weeks","effect":"ystemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic toxicity in rats based on repeated dose toxicity studies. The data available point to","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":49,"route":"","species":"rat","study_id":"sccs_o_213_0_noael_020"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=25; DOSE=Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia.; EFFECT=S conclusion on carcinogenicity No carcinogenicity data are available for p-BMHCA. Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia. Additional data from Applicant’s submission II dossier No additional data. 3.3.8 Reproductive toxicity From submission I SCCS conclusion on reproductive toxicity Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. It is to be emphasised that reproductive toxicity already became occasionally visible after a single application of 50 mg/kg bw/day. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia.","duration":"5 days","effect":"S conclusion on carcinogenicity No carcinogenicity data are available for p-BMHCA. Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia. Additional data from Applicant’s submission II dossier No additional data. 3.3.8 Reproductive toxicity From submission I SCCS conclusion on reproductive toxicity Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. It is to be emphasised that reproductive toxicity already became occasionally visible after a single application of 50 mg/kg bw/day. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":34,"route":"","species":"rat","study_id":"sccs_o_213_noael_002"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=25; DOSE=se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day.; EFFECT=se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day.","duration":"5 days","effect":"se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":49,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_018"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=25; DOSE=Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia.; EFFECT=S conclusion on carcinogenicity No carcinogenicity data are available for p-BMHCA. Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia. Additional data from Applicant’s submission II dossier No additional data. 3.3.8 Reproductive toxicity From submission I SCCS conclusion on reproductive toxicity Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. It is to be emphasised that reproductive toxicity already became occasionally visible after a single application of 50 mg/kg bw/day. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia.","duration":"5 days","effect":"S conclusion on carcinogenicity No carcinogenicity data are available for p-BMHCA. Currently there is no evidence from repeated dose studies that p-BMHCA is able to induce hyperplasia or neoplasia. Additional data from Applicant’s submission II dossier No additional data. 3.3.8 Reproductive toxicity From submission I SCCS conclusion on reproductive toxicity Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. It is to be emphasised that reproductive toxicity already became occasionally visible after a single application of 50 mg/kg bw/day. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":34,"route":"","species":"rat","study_id":"sccs_o_213_0_noael_002"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=25; DOSE=se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day.; EFFECT=se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day.","duration":"5 days","effect":"se-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":49,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_018"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=40; DOSE=the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies.; EFFECT=the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies.","duration":"5 days","effect":"the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic to","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"40","page":49,"route":"","species":"rat","study_id":"sccs_o_213_noael_019"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=40; DOSE=the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies.; EFFECT=the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies.","duration":"5 days","effect":"the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame of a 1-generation study over 6 weeks prior to mating. In all investigations available, testicular toxicity in rats was accompanied by signs of systemic toxicity. By contrast, other species such as mice and dogs were less sensitive. In dogs, a NOAEL of 40 mg/kg bw/day has been established based on the onset of testicular toxicity after treatment periods of 2 weeks and 3 months. So, from the animal data available, male rats revealed as the most sensitive species with regard to p-BMHCA- mediated testicular toxicity. On the other hand, in female rats developmental toxicity was accompanied by systemic toxicity and found already at lower concentrations. Here, a NOAEL is to be set at 5 mg/kg bw/day. This value is identical to the one defined for general systemic to","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"40","page":49,"route":"","species":"rat","study_id":"sccs_o_213_0_noael_019"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=45; DOSE=SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/...; EFFECT=osmetic products - Submission II ___________________________________________________________________________________________ 41 3.3.8.3 Developmental Toxicity Additional data from Applicant’s submission II dossier No additional data. SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinet; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/...","duration":"Developmental","effect":"osmetic products - Submission II ___________________________________________________________________________________________ 41 3.3.8.3 Developmental Toxicity Additional data from Applicant’s submission II dossier No additional data. SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinet","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"45","page":41,"route":"","species":"rat","study_id":"sccs_o_213_noael_014"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=45; DOSE=SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/...; EFFECT=osmetic products - Submission II ___________________________________________________________________________________________ 41 3.3.8.3 Developmental Toxicity Additional data from Applicant’s submission II dossier No additional data. SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinet; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/...","duration":"Developmental","effect":"osmetic products - Submission II ___________________________________________________________________________________________ 41 3.3.8.3 Developmental Toxicity Additional data from Applicant’s submission II dossier No additional data. SCCS overall comment on reproductive toxicity based on studies from submission I and II In the previous Opinion (SCCS/1540/14) the SCCS concluded that based on the study in which pregnant female rats were exposed to p-BMHCA at 5, 15 or 45 mg/kg bw/d (BASF SE, 2004, RIFM# 52014), a NOAEL based on developmental toxicity could be set at 5 mg/kg bw/day. This value was identical to the one defined for general systemic toxicity in rats based on repeated dose (90-days) toxicity studies (Givaudan, 1990a, RIFM #12144, Givaudan, 1990i, RIFM #12143). However, based on the study provided with submission II, the SCCS considers that the NOAEL for developmental toxicity should be set 4.5 mg/kg bw/d. 3.3.9 Toxicokinetics From submission I SCCS conclusion on toxicokinetics Quantitative data on the toxicokinet","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"45","page":41,"route":"","species":"rat","study_id":"sccs_o_213_0_noael_014"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=50; DOSE=food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs).; EFFECT=food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs). Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system (testicular toxicity). In a 90-day GLP study in rats BMHCA dose-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame o; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs).","duration":"subacute","effect":"food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs). Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system (testicular toxicity). In a 90-day GLP study in rats BMHCA dose-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame o","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":49,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_017"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=50; DOSE=food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs).; EFFECT=food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs). Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system (testicular toxicity). In a 90-day GLP study in rats BMHCA dose-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame o; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs).","duration":"subacute","effect":"food consumption and/or clinical signs of toxicity were observed after subacute oral administration of p-BMHCA at doses of ≥50 mg/kg bw/day (rats) and ≥200 mg/kg bw/day (dogs). Clinical chemistry and histopathological examinations repeatedly revealed adverse effects on the liver and male reproductive system (testicular toxicity). In a 90-day GLP study in rats BMHCA dose-dependently induced systemic toxicity in both sexes at levels of ≥25 mg/kg bw/day and testicular toxicity in males at ≥50 mg/kg bw/day. Thus oral NOAEL values of 5 mg/kg bw/day and 25 mg/kg bw/day were derived for systemic effects and reproductive effects, respectively. Reproductive toxicity Based on the previous SCCS Opinion (SCCS/1540/14) and submission II: Adverse effects of p-BMHCA on the male reproductive system have been consistently observed in several repeated dose and reproduction toxicity studies. A NOAEL of 25 mg/kg bw/day in male rats with regard to this endpoint is substantiated by studies applying the compound for 5 days, 90 days or in the frame o","endpoint":"repeated dose toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":49,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_017"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=4.5; DOSE=meters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: meters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"meters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: meters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4.5","page":40,"route":"","species":"","study_id":"sccs_o_213_noael_013"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=4.5; DOSE=meters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: meters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"meters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: meters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4.5","page":40,"route":"","species":"","study_id":"sccs_o_213_0_noael_013"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.; EFFECT=cell counts in the spleen tissue (B-, T-lymphocytes, CD4-, CD8- T lymphocytes and natural killer (NK) cells) displayed any treatment-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an i; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"cell counts in the spleen tissue (B-, T-lymphocytes, CD4-, CD8- T lymphocytes and natural killer (NK) cells) displayed any treatment-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an i","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_005"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.; EFFECT=ent-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"ent-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_006"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.; EFFECT=t considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit; CITATION_NUMBERS=[2015,2017,4,8]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit","dose":"The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"t considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_009"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=F1 progeny is 10 mg/kg bw/d, the highest dose tested.; EFFECT=SCCS-rejected applicant NOAEL: F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"F1 progeny is 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"","study_id":"sccs_o_213_noael_010"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"","study_id":"sccs_o_213_noael_011"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"","species":"","study_id":"sccs_o_213_noael_012"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.; EFFECT=ia the oral route and suggesting that this metabolite may also exert testicular toxicity (along with systemic toxicity). However, the doses applied in these studies from the 1960s – 1980s were high and the quality of the studies generally low. The data available therefore do not support the conclusion that this metabolite would be mainly responsible for the testicular effects observed with p-BMHCA in rats. In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be establi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.","duration":"","effect":"ia the oral route and suggesting that this metabolite may also exert testicular toxicity (along with systemic toxicity). However, the doses applied in these studies from the 1960s – 1980s were high and the quality of the studies generally low. The data available therefore do not support the conclusion that this metabolite would be mainly responsible for the testicular effects observed with p-BMHCA in rats. In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be establi","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"rat","study_id":"sccs_o_213_noael_021"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.; EFFECT=ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lowe; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.","duration":"developmental","effect":"ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lowe","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"","study_id":"sccs_o_213_noael_022"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.; EFFECT=city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irr; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.","duration":"developmental","effect":"city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irr","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"","study_id":"sccs_o_213_noael_023"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irritation/sensitisation Based on the previous SCCS Opinion (SCCS/1540/14): Para-BMHCA as neat compound is irritating to the skin and eyes of rabbits. A solution of 2% p-BMHCA in propylene glycol led to mild skin erythema. In general the obse; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irritation/sensitisation Based on the previous SCCS Opinion (SCCS/1540/14): Para-BMHCA as neat compound is irritating to the skin and eyes of rabbits. A solution of 2% p-BMHCA in propylene glycol led to mild skin erythema. In general the obse","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"rabbit","study_id":"sccs_o_213_noael_024"}

sccs_o_213.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.; EFFECT=cell counts in the spleen tissue (B-, T-lymphocytes, CD4-, CD8- T lymphocytes and natural killer (NK) cells) displayed any treatment-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an i; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"cell counts in the spleen tissue (B-, T-lymphocytes, CD4-, CD8- T lymphocytes and natural killer (NK) cells) displayed any treatment-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an i","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_005"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.; EFFECT=ent-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"ent-related changes. Conclusion The extended one-generation reproduction toxicity study is predominantly designed to focus on reproductive and developmental effects that may occur as a result of pre- and postnatal exposure to a substance as well as an evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. Under the conditions of this study, the NOAEL for fertility and reproductive performance in the F0 and F1 parental rats was 10 mg/kg bw/d, the highest dose tested. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_006"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.; EFFECT=t considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit; CITATION_NUMBERS=[2015,2017,4,8]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit","dose":"The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"t considered as an indication for specific developmental toxicity. The NOAEL for developmental neurotoxicity (DNT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. Although an inhibitory effect at this dose on the peripheral AChE activity in pups and adolescent rats cannot be excluded, there were no corresponding effects evident in the neurobehavioral or neuropathological examinations. The NOAEL for developmental immunotoxicity (DIT) for the F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicit","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_009"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=F1 progeny is 10 mg/kg bw/d, the highest dose tested.; EFFECT=SCCS-rejected applicant NOAEL: F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"F1 progeny is 10 mg/kg bw/d, the highest dose tested.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: F1 progeny is 10 mg/kg bw/d, the highest dose tested. The NOAEL for general, systemic toxicity is 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"","study_id":"sccs_o_213_0_noael_010"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: valent to a mean overall oral dose of 4.5 mg/kg bw/d) for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"oral","species":"","study_id":"sccs_o_213_0_noael_011"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.; CITATION=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; CITATION_NUMBERS=[2015,2017,4,8,10]; REFERENCE=Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and; DETAILS_JSON={"cas_number":"80-54-6","citation":"Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and","dose":"evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: evidence for distinct liver toxicity, as well as corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. Ref.: BASF SE, 2015, 2017b, SMII, 4, 8 SCCS comment The SCCS agrees that NOAEL for fertility and reproductive as well as systemic toxicity of p- BMHCA in this study is 10 mg/kg bw/d and the NOAEL for developmental toxicity is 3 mg/kg bw/d. However, the SCCS does not agree with the developmental neurotoxicity NOAEL since inhibition of AChE in different tissues at 10 mg/kg bw/d should be considered adverse. Based on the overall assessment, the NOAEL value of 4.5 mg/kg bw/d could be applied for MoS calculation.","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":40,"route":"","species":"","study_id":"sccs_o_213_0_noael_012"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.; EFFECT=ia the oral route and suggesting that this metabolite may also exert testicular toxicity (along with systemic toxicity). However, the doses applied in these studies from the 1960s – 1980s were high and the quality of the studies generally low. The data available therefore do not support the conclusion that this metabolite would be mainly responsible for the testicular effects observed with p-BMHCA in rats. In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be establi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.","duration":"","effect":"ia the oral route and suggesting that this metabolite may also exert testicular toxicity (along with systemic toxicity). However, the doses applied in these studies from the 1960s – 1980s were high and the quality of the studies generally low. The data available therefore do not support the conclusion that this metabolite would be mainly responsible for the testicular effects observed with p-BMHCA in rats. In the extended one-generation reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be establi","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"rat","study_id":"sccs_o_213_0_noael_021"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.; EFFECT=ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lowe; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.","duration":"developmental","effect":"ion reproduction toxicity study which results were provided in submission II, the NOAEL for general, systemic toxicity of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lowe","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"","study_id":"sccs_o_213_0_noael_022"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.; EFFECT=city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irr; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity.","duration":"developmental","effect":"city of p-BMHCA applied in encapsulated form at 1, 3, or 10 mg/kg bw/d, was established at 3 mg/kg bw/d for the F0 and F1 parental as well as adolescent animals, based on evidence for distinct liver toxicity. This value was further supported by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irr","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"","study_id":"sccs_o_213_0_noael_023"}

sccs_o_213_0.pdf

SOURCE_SUBDIR=sccs_o_213_0; REPORT_TITLE=OPINION ON the safety of Butylphenyl methylpropional (p-BMHCA) in cosmetic products; OPINION_NUMBER=SCCS/1591/17; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 10 May 2019; VALUE_TEXT=10; DOSE=d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.; EFFECT=SCCS-rejected applicant NOAEL: d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irritation/sensitisation Based on the previous SCCS Opinion (SCCS/1540/14): Para-BMHCA as neat compound is irritating to the skin and eyes of rabbits. A solution of 2% p-BMHCA in propylene glycol led to mild skin erythema. In general the obse; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"80-54-6","citation":"","dose":"d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: d by corresponding effects on food consumption, body weights and clinical pathological parameters, which were observed at 10 mg/kg bw/d predominantly in females. The NOAEL for fertility and reproductive toxicity of p-BMHCA in this study could be established at 10 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 and F2 progeny was 3 mg/kg bw/d (equivalent to a mean overall oral dose of 4.5 mg/kg bw/d), based on reduced pup body weights in the F1 and F2 offspring, which were observed at 10 mg/kg bw/d. This NOAEL for developmental toxicity is used for the calculation of the MoS. As these weight reductions were only observed in the presence of maternal toxicity, including lower weight gain during pregnancy, they are not considered as an indication for specific developmental toxicity. Irritation/sensitisation Based on the previous SCCS Opinion (SCCS/1540/14): Para-BMHCA as neat compound is irritating to the skin and eyes of rabbits. A solution of 2% p-BMHCA in propylene glycol led to mild skin erythema. In general the obse","endpoint":"reproductive toxicity","ingredient":"by other scientific bodies (e.g. under REACH) should also be","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"10","page":50,"route":"oral","species":"rabbit","study_id":"sccs_o_213_0_noael_024"}

sccs_o_213_0.pdf