| UnifiedCodex:SCCNFP:beta.noael_studies |
- |
=10 |
mg/kg/d |
mouse |
- |
- |
- |
SOURCE_SUBDIR=out280_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING MUSK XYLENE AND MUSK KETONE; OPINION_NUMBER=SCCNFP/0817/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT== 10; DOSE=SCCNFP/0817/04 Evaluation and opinion on Musk xylene and Musk ketone ____________________________________________________________________________________________ 12 NOAEL = 10 mg/kg/d (see page 9) Exposure dose 223.9 µg/kg/d.; EFFECT=SCCNFP/0817/04 Evaluation and opinion on Musk xylene and Musk ketone ____________________________________________________________________________________________ 12 NOAEL = 10 mg/kg/d (see page 9) Exposure dose 223.9 µg/kg/d. Absorption 10% SED = 22 µg/kg/d. MOS = 10/0.022 = 455 Lifetime cancer risk (T25 method) The tumours induced in the mice may be caused by a non-genotoxic mechanism indicating the presence of a threshold dose below which no tumours are induced. However, it is not possible from the available data to identify NOAELs for tumour induction or for the underlying mechanisms. Quantitative risk characterisation has been carried out on the basis of the T25 method. R; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"81-15-2","citation":"","dose":"SCCNFP/0817/04 Evaluation and opinion on Musk xylene and Musk ketone ____________________________________________________________________________________________ 12 NOAEL = 10 mg/kg/d (see page 9) Exposure dose 223.9 µg/kg/d.","duration":"","effect":"SCCNFP/0817/04 Evaluation and opinion on Musk xylene and Musk ketone ____________________________________________________________________________________________ 12 NOAEL = 10 mg/kg/d (see page 9) Exposure dose 223.9 µg/kg/d. Absorption 10% SED = 22 µg/kg/d. MOS = 10/0.022 = 455 Lifetime cancer risk (T25 method) The tumours induced in the mice may be caused by a non-genotoxic mechanism indicating the presence of a threshold dose below which no tumours are induced. However, it is not possible from the available data to identify NOAELs for tumour induction or for the underlying mechanisms. Quantitative risk characterisation has been carried out on the basis of the T25 method. R","endpoint":"","ingredient":"Musk xylene","loael_value":"","noael_unit":"mg/kg/d","noael_value":"= 10","page":12,"route":"","species":"mouse","study_id":"out280_en_noael_002"} |
| UnifiedCodex:SCCNFP:beta.noael_studies |
- |
=10 |
mg/kg/d |
mouse |
- |
- |
- |
SOURCE_SUBDIR=out280_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING MUSK XYLENE AND MUSK KETONE; OPINION_NUMBER=SCCNFP/0817/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT== 10; DOSE=xposure to the fragrance ingredient is determined by adding figures for the different product types expressed as mg/kg body weight/day.; EFFECT=xposure to the fragrance ingredient is determined by adding figures for the different product types expressed as mg/kg body weight/day. In view of all the above assumptions, this figure has to be regarded as conservative; it is most unlikely that a consumer will consistently use a number of different cosmetic products which are all perfumed with the upper 97.5th percentile level of the fragrance ingredient. Risk assessment The risk assessment for Musk ketone is based on the same experiments as for Musk xylene. NOAEL = 10 mg/kg/d HT10-4 = 7.3 µg/kg/d MOS approach Exposure dose 217.5 µg/kg/d. Absorption 14% SED = 30 µg/kg/d. MOS = 10/0.030 = 333 Lifetime cancer risk (T25 method) HT10-4 = 7.3 µg/kg/d Lifetime exposure dose representing a lifetime cancer risk of 10-4 was about 7.3 µg/kg bw/d both when based on the liver carcinomas or the Harderian gland tumours in male mice exposed to Musk xylene. As the worst case daily intake of Musk ketone is about 30 µg/kg bw/day, it follows that this intake could represent a lifetim; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"81-15-2","citation":"","dose":"xposure to the fragrance ingredient is determined by adding figures for the different product types expressed as mg/kg body weight/day.","duration":"","effect":"xposure to the fragrance ingredient is determined by adding figures for the different product types expressed as mg/kg body weight/day. In view of all the above assumptions, this figure has to be regarded as conservative; it is most unlikely that a consumer will consistently use a number of different cosmetic products which are all perfumed with the upper 97.5th percentile level of the fragrance ingredient. Risk assessment The risk assessment for Musk ketone is based on the same experiments as for Musk xylene. NOAEL = 10 mg/kg/d HT10-4 = 7.3 µg/kg/d MOS approach Exposure dose 217.5 µg/kg/d. Absorption 14% SED = 30 µg/kg/d. MOS = 10/0.030 = 333 Lifetime cancer risk (T25 method) HT10-4 = 7.3 µg/kg/d Lifetime exposure dose representing a lifetime cancer risk of 10-4 was about 7.3 µg/kg bw/d both when based on the liver carcinomas or the Harderian gland tumours in male mice exposed to Musk xylene. As the worst case daily intake of Musk ketone is about 30 µg/kg bw/day, it follows that this intake could represent a lifetim","endpoint":"","ingredient":"Musk xylene","loael_value":"","noael_unit":"mg/kg/d","noael_value":"= 10","page":14,"route":"","species":"mouse","study_id":"out280_en_noael_003"} |
| UnifiedCodex:SCCNFP:beta.noael_studies |
carcinogenicity |
10 |
mg/kg/d |
mouse |
- |
- |
carcinogenicity |
SOURCE_SUBDIR=out280_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING MUSK XYLENE AND MUSK KETONE; OPINION_NUMBER=SCCNFP/0817/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=10; DOSE=g control group: malignant and benign liver cell tumours were clearly increased; in males the incidence of Harderian gland tumours was also significantly greater in both treated groups than in the controls.; EFFECT=g control group: malignant and benign liver cell tumours were clearly increased; in males the incidence of Harderian gland tumours was also significantly greater in both treated groups than in the controls. No carcinogenic effect was observed in other organs. In the absence of genotoxicity, the induction of CYP2B enzymes could possibly explain the increased formation of the liver tumours. No thresholds for tumour induction in mice have been identified. Biochemical in vivo studies on mice with Musk xylene suggest a NOAEL of 10 mg/kg/d. No carcinogenicity study is available for Musk ketone. It has been found, however, that Musk ketone like Musk xylene induced CYP2B enzymes. Consequently, Musk ketone might be a mice carcinogen. Absorption, distribution, and excretion of Musk xylene and Musk ketone have been investigated in vitro and in vivo, in animals and in human skin. Based on in vivo studies in human under simulated exposure conditions less than 0.3% and 0.5% was absorbed of Musk xylene and Musk ketone, repectively, but 10% of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"81-15-2","citation":"","dose":"g control group: malignant and benign liver cell tumours were clearly increased; in males the incidence of Harderian gland tumours was also significantly greater in both treated groups than in the controls.","duration":"","effect":"g control group: malignant and benign liver cell tumours were clearly increased; in males the incidence of Harderian gland tumours was also significantly greater in both treated groups than in the controls. No carcinogenic effect was observed in other organs. In the absence of genotoxicity, the induction of CYP2B enzymes could possibly explain the increased formation of the liver tumours. No thresholds for tumour induction in mice have been identified. Biochemical in vivo studies on mice with Musk xylene suggest a NOAEL of 10 mg/kg/d. No carcinogenicity study is available for Musk ketone. It has been found, however, that Musk ketone like Musk xylene induced CYP2B enzymes. Consequently, Musk ketone might be a mice carcinogen. Absorption, distribution, and excretion of Musk xylene and Musk ketone have been investigated in vitro and in vivo, in animals and in human skin. Based on in vivo studies in human under simulated exposure conditions less than 0.3% and 0.5% was absorbed of Musk xylene and Musk ketone, repectively, but 10% of","endpoint":"carcinogenicity","ingredient":"Musk xylene","loael_value":"","noael_unit":"mg/kg/d","noael_value":"10","page":15,"route":"","species":"mouse","study_id":"out280_en_noael_004"} |
| UnifiedCodex:SCCNFP:beta.noael_studies |
reproductive toxicity |
10 |
mg/kg/d |
- |
- |
- |
reproductive toxicity |
SOURCE_SUBDIR=out280_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING MUSK XYLENE AND MUSK KETONE; OPINION_NUMBER=SCCNFP/0817/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=10; DOSE=1 Liver weight versus dose.; EFFECT=Musk xylene and Musk ketone ____________________________________________________________________________________________ 9 Fig. 1 Liver weight versus dose. Fig. 2 Liver to body weight versus dose. Fig. 3 Microsomal protein versus dose. Fig. 4 Total cytochrome versus dose. In figs 1 – 4 the data in Table 2 have been plotted. It is seen that a threshold cannot be identified with certainty for any of the parameters. However, from the biochemical data in Table 2, 10 mg/kg/d may be considered as a NOAEL. Thus, the risk characterization in the present opinion will be based both on MOS considerations and on the assumption of non-threshold by the T25 method. 4.8. Reproductive toxicity No new data 4.9. Toxicokinetics No new data 4.10. Photo-induced toxicity Microsomal protein 0 50 100 150 200 10 15 20 Dose (mg/kg) Microsomal protein (mg/g liver) Total cytochrome 0 50 100 150 200 1 2 Dose (mg/kg) Total cytochrome P-450 (nmol/mg protein); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"81-15-2","citation":"","dose":"1 Liver weight versus dose.","duration":"","effect":"Musk xylene and Musk ketone ____________________________________________________________________________________________ 9 Fig. 1 Liver weight versus dose. Fig. 2 Liver to body weight versus dose. Fig. 3 Microsomal protein versus dose. Fig. 4 Total cytochrome versus dose. In figs 1 – 4 the data in Table 2 have been plotted. It is seen that a threshold cannot be identified with certainty for any of the parameters. However, from the biochemical data in Table 2, 10 mg/kg/d may be considered as a NOAEL. Thus, the risk characterization in the present opinion will be based both on MOS considerations and on the assumption of non-threshold by the T25 method. 4.8. Reproductive toxicity No new data 4.9. Toxicokinetics No new data 4.10. Photo-induced toxicity Microsomal protein 0 50 100 150 200 10 15 20 Dose (mg/kg) Microsomal protein (mg/g liver) Total cytochrome 0 50 100 150 200 1 2 Dose (mg/kg) Total cytochrome P-450 (nmol/mg protein)","endpoint":"reproductive toxicity","ingredient":"Musk xylene","loael_value":"","noael_unit":"mg/kg/d","noael_value":"10","page":9,"route":"","species":"","study_id":"out280_en_noael_001"} |