| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
<226 |
ppm |
mouse |
- |
- |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=<226; DOSE=There were dose-dependent ultrastructural changes in hepatocytes in all treated groups.; EFFECT=seen. There were dose-dependent ultrastructural changes in hepatocytes in all treated groups. An increase in the smooth endoplasmic reticulum was seen at the 2 highest exposure doses. There were decreases in relative mitochondria volume at all exposure doses and a reduction in rough endoplasmic reticulum at most higher doses. Vacuolation of the zona fasciculata of the adrenal cortex was evident in most of the animals. Thymic atrophy was seen in all animals but was most pronounced at the highest concentration. The NOAEL was considered to be <226 ppm (2.8 mg/l air). Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; Guinea pig, Hartley; Hamster, Golden Syrian; and Rabbit, New Zealand White Group size: 10 males and 10 females per dose except rabbit 5 male/female Test substance: Dow Corning 244 fluid Batch: D4 lot LL107568 Purity: ≥97% octamethylcyclotretrasiloxane (impurities were D5 and D3, i.e. decamethylcyclopentasiloxane, hexamethylcyclotrisiloxane) Dose levels: 0 and 700 ppm (0 and 8.4 mg/l) Vehicle: air Exposure: 6 h whole; CITATION=Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; CITATION_NUMBERS=[10,1]; REFERENCE=Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 10 Guideline: / Species/strain: Mouse, CD-1","dose":"There were dose-dependent ultrastructural changes in hepatocytes in all treated groups.","duration":"","effect":"seen. There were dose-dependent ultrastructural changes in hepatocytes in all treated groups. An increase in the smooth endoplasmic reticulum was seen at the 2 highest exposure doses. There were decreases in relative mitochondria volume at all exposure doses and a reduction in rough endoplasmic reticulum at most higher doses. Vacuolation of the zona fasciculata of the adrenal cortex was evident in most of the animals. Thymic atrophy was seen in all animals but was most pronounced at the highest concentration. The NOAEL was considered to be <226 ppm (2.8 mg/l air). Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; Guinea pig, Hartley; Hamster, Golden Syrian; and Rabbit, New Zealand White Group size: 10 males and 10 females per dose except rabbit 5 male/female Test substance: Dow Corning 244 fluid Batch: D4 lot LL107568 Purity: ≥97% octamethylcyclotretrasiloxane (impurities were D5 and D3, i.e. decamethylcyclopentasiloxane, hexamethylcyclotrisiloxane) Dose levels: 0 and 700 ppm (0 and 8.4 mg/l) Vehicle: air Exposure: 6 h whole","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"<226","page":20,"route":"","species":"mouse","study_id":"sccp_o_035_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
10 |
ppm |
rat |
- |
13 week |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=10; DOSE=It was concluded that the NOEL was 10 ppm.; EFFECT=ht (~28%) at the end of the 13 week exposure period, but it was comparable to controls after the 4 week recovery period. There were no other exposure-related abnormalities in clinical signs, food consumption, body weights, haematology, serum biochemistry, urinalysis, ophthalmology, or macroscopic or microscopic tissue evalua- tions. No exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. There was no pathological evidence of hepatomegaly. It was concluded that the NOEL was 10 ppm. Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley) Group size: Control and high dose 20 male/female, low and mid dose 10 male/female Test substance: Dow Corning 244 fluid; CITATION=Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley) Group size: Control and high dose 20 male/female, low and mid dose 10 male/female Test substance: Dow Corning 244 fluid; CITATION_NUMBERS=[13,20,10,244]; REFERENCE=Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley) Group size: Control and high dose 20 male/female, low and mid dose 10 male/female Test substance: Dow Corning 244 fluid; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley) Group size: Control and high dose 20 male/female, low and mid dose 10 male/female Test substance: Dow Corning 244 fluid","dose":"It was concluded that the NOEL was 10 ppm.","duration":"13 week","effect":"ht (~28%) at the end of the 13 week exposure period, but it was comparable to controls after the 4 week recovery period. There were no other exposure-related abnormalities in clinical signs, food consumption, body weights, haematology, serum biochemistry, urinalysis, ophthalmology, or macroscopic or microscopic tissue evalua- tions. No exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. There was no pathological evidence of hepatomegaly. It was concluded that the NOEL was 10 ppm. Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley) Group size: Control and high dose 20 male/female, low and mid dose 10 male/female Test substance: Dow Corning 244 fluid","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"10","page":22,"route":"","species":"rat","study_id":"sccp_o_035_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
50 |
ppm |
rat |
inhalation |
13 weeks |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=50; DOSE=A decreased ovary weight at the high exposure dose was noted in the recovery group only.; EFFECT=ure females. There were no other exposure-related abnormalities in haematology, serum biochemistry, urinalysis, ophthalmology. Liver weights increased in all male exposed groups and in the mid and high exposure females. This liver weight increase was reversible in males but not in females. A decreased ovary weight at the high exposure dose was noted in the recovery group only. No other exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. It was concluded that the NOEL was 50 ppm in females and less than 50 ppm in males based on liver weights. Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344). Group size: Control and high dose 30 males/females, low and mid dose 20 males/females Test substance: Dow Corning 244 fluid Batch: D4 lot LL023S10 Purity: >99.42% Dose levels: 0, 35, 122, 488 or 898 ppm (0.42, 1.48, 5.91 and 10.87 mg/l) Vehicle: air Exposure: 6 h nose only inhalation 5 days/week for 13 weeks Recovery: 4 weeks Co; CITATION=Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344); CITATION_NUMBERS=[14,3,412,1991,344]; REFERENCE=Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344); DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344)","dose":"A decreased ovary weight at the high exposure dose was noted in the recovery group only.","duration":"13 weeks","effect":"ure females. There were no other exposure-related abnormalities in haematology, serum biochemistry, urinalysis, ophthalmology. Liver weights increased in all male exposed groups and in the mid and high exposure females. This liver weight increase was reversible in males but not in females. A decreased ovary weight at the high exposure dose was noted in the recovery group only. No other exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. It was concluded that the NOEL was 50 ppm in females and less than 50 ppm in males based on liver weights. Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344). Group size: Control and high dose 30 males/females, low and mid dose 20 males/females Test substance: Dow Corning 244 fluid Batch: D4 lot LL023S10 Purity: >99.42% Dose levels: 0, 35, 122, 488 or 898 ppm (0.42, 1.48, 5.91 and 10.87 mg/l) Vehicle: air Exposure: 6 h nose only inhalation 5 days/week for 13 weeks Recovery: 4 weeks Co","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"50","page":23,"route":"inhalation","species":"rat","study_id":"sccp_o_035_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
35 |
ppm |
rat |
- |
chronic |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=35; DOSE=Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest exposure • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atroph...; EFFECT=d of the recovery period. Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest exposure • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atrophy at the highest exposure All these effects were reversible or showed a clear tendency for reversibility. The increased liver weights suggest a NOEL of 35 ppm. Moreover, it was concluded that the LOEL was 35 ppm based on the presence of lung lesions at all exposure levels. The lung effects are not considered relevant in relation to the use of cosmetics. Ref.: 15, AR 3 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Rats (F344) Group size: 10 rats/sex/dose group (sacrificed after 12 months of exposure; see below: Subgroup B) 20 rats/sex/dose group (exposed to D4 for 12 month and sacrificed after a 12 month recovery period; see below: Sub; CITATION=Ref.: 15, AR 3 3; CITATION_NUMBERS=[15,3]; REFERENCE=Ref.: 15, AR 3 3; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 15, AR 3 3","dose":"Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest exposure • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atroph...","duration":"chronic","effect":"d of the recovery period. Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest exposure • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atrophy at the highest exposure All these effects were reversible or showed a clear tendency for reversibility. The increased liver weights suggest a NOEL of 35 ppm. Moreover, it was concluded that the LOEL was 35 ppm based on the presence of lung lesions at all exposure levels. The lung effects are not considered relevant in relation to the use of cosmetics. Ref.: 15, AR 3 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Rats (F344) Group size: 10 rats/sex/dose group (sacrificed after 12 months of exposure; see below: Subgroup B) 20 rats/sex/dose group (exposed to D4 for 12 month and sacrificed after a 12 month recovery period; see below: Sub","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"35","page":24,"route":"","species":"rat","study_id":"sccp_o_035_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
10 |
ppm |
- |
- |
12 months |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=10; DOSE=The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.; EFFECT=ared to controls for both sexes and the relative liver weights (normalized either to body or brain weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Based on the study a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months, and a NOAEL of 150 ppm based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males after 12 months. Ref.: 37 (submission II), AR 4; CITATION=Ref.: 37 (submission II), AR 4; CITATION_NUMBERS=[37,4]; REFERENCE=Ref.: 37 (submission II), AR 4; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 37 (submission II), AR 4","dose":"The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.","duration":"12 months","effect":"ared to controls for both sexes and the relative liver weights (normalized either to body or brain weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Based on the study a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months, and a NOAEL of 150 ppm based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males after 12 months. Ref.: 37 (submission II), AR 4","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"10","page":25,"route":"","species":"","study_id":"sccp_o_035_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
- |
- |
12 months |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=150; DOSE=The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.; EFFECT=rain weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Based on the study a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months, and a NOAEL of 150 ppm based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males after 12 months. Ref.: 37 (submission II), AR 4; CITATION=Ref.: 37 (submission II), AR 4; CITATION_NUMBERS=[37,4]; REFERENCE=Ref.: 37 (submission II), AR 4; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 37 (submission II), AR 4","dose":"The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.","duration":"12 months","effect":"rain weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Based on the study a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months, and a NOAEL of 150 ppm based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males after 12 months. Ref.: 37 (submission II), AR 4","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"150","page":25,"route":"","species":"","study_id":"sccp_o_035_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
rat |
- |
- |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=150; DOSE=It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls.; EFFECT=tatistically significant (p < 0.05) using the Peto analysis. It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls. If the MNCL in the 700 ppm group is compared to the 10 ppm group, the increase in the 700 ppm group is significant (p<0.0094). No increase in MNCL was found among the exposed female rats. It is likely that a threshold exists in the induction of MNCL. If it is considered that the very high frequency in the control group may be erroneous, the NOAEL for MNCL induction is 150 ppm (320 mg/kg bw/d). Ref.: 37 (submission II), AR 4, AR 5; CITATION=Ref.: 37 (submission II), AR 4, AR 5; CITATION_NUMBERS=[37,4,5]; REFERENCE=Ref.: 37 (submission II), AR 4, AR 5; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 37 (submission II), AR 4, AR 5","dose":"It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls.","duration":"","effect":"tatistically significant (p < 0.05) using the Peto analysis. It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls. If the MNCL in the 700 ppm group is compared to the 10 ppm group, the increase in the 700 ppm group is significant (p<0.0094). No increase in MNCL was found among the exposed female rats. It is likely that a threshold exists in the induction of MNCL. If it is considered that the very high frequency in the control group may be erroneous, the NOAEL for MNCL induction is 150 ppm (320 mg/kg bw/d). Ref.: 37 (submission II), AR 4, AR 5","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"150","page":30,"route":"","species":"rat","study_id":"sccp_o_035_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
70 |
ppm |
rat |
oral |
- |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=70; DOSE=liver-to-plasma D4 ratio remained constant over the dose range.; EFFECT=liver-to-plasma D4 ratio remained constant over the dose range. The lowest dose level to induce significant hepatomegaly was 150 ppm. D4 content in fat, liver and plasma increased proportionately with increasing exposure concentrations. A dose-depen- dent increase occurred in PROD activity and in CYP2B1/2 proteins with a maximum response at 500 ppm D4. These findings are consistent with those reported for phenobarbital and confirm that D4 is a “phenobarbital-like” inducer of rat hepatic cytochrome P450 enzymes. A NOEL of 70 ppm D4 is based on enzyme induction in female rats. Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx. 98% Test formulation: D4 in 0.5% aqueous methylcellulose Dose level: Two groups received 1600 mg/kg/day D4 oral gavage for 14 consecutive days Vehicle/Control: Negative controls (two groups of 10 males) vehicle only at 4 ml/kg GLP statement: in compliance This was a morphometric study and DNA analysis desi; CITATION=Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx; CITATION_NUMBERS=[60,10,4,1088,31]; REFERENCE=Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx","dose":"liver-to-plasma D4 ratio remained constant over the dose range.","duration":"","effect":"liver-to-plasma D4 ratio remained constant over the dose range. The lowest dose level to induce significant hepatomegaly was 150 ppm. D4 content in fat, liver and plasma increased proportionately with increasing exposure concentrations. A dose-depen- dent increase occurred in PROD activity and in CYP2B1/2 proteins with a maximum response at 500 ppm D4. These findings are consistent with those reported for phenobarbital and confirm that D4 is a “phenobarbital-like” inducer of rat hepatic cytochrome P450 enzymes. A NOEL of 70 ppm D4 is based on enzyme induction in female rats. Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx. 98% Test formulation: D4 in 0.5% aqueous methylcellulose Dose level: Two groups received 1600 mg/kg/day D4 oral gavage for 14 consecutive days Vehicle/Control: Negative controls (two groups of 10 males) vehicle only at 4 ml/kg GLP statement: in compliance This was a morphometric study and DNA analysis desi","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"70","page":55,"route":"oral","species":"rat","study_id":"sccp_o_035_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
rat |
- |
chronic |
- |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=150; DOSE=Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas [37, submission II].; EFFECT=halation of D4 in Fischer 344 rats. Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas [37, submission II]. An earlier onset and increased incidence of mononuclear cell leukemia (MNCL) was observed in male rats, not in exposed female rats. A NOAEL of 150 ppm was identified in this study based on either MNCL or endometrial adenomas. D4 is not genotoxic; therefore, an epigenetic mode-of-action was considered to be responsible for its neoplastic effect. Special studies (section 3.3.12) conducted to understand its mode-of- action in the chronic study support a secondary effect rather than a direct effect of D4 on the uterus: It is unlikely that D4’s very weak estrogenic activity can account for the effects seen in this study. Rather, the data support the conclu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas [37, submission II].","duration":"chronic","effect":"halation of D4 in Fischer 344 rats. Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas [37, submission II]. An earlier onset and increased incidence of mononuclear cell leukemia (MNCL) was observed in male rats, not in exposed female rats. A NOAEL of 150 ppm was identified in this study based on either MNCL or endometrial adenomas. D4 is not genotoxic; therefore, an epigenetic mode-of-action was considered to be responsible for its neoplastic effect. Special studies (section 3.3.12) conducted to understand its mode-of- action in the chronic study support a secondary effect rather than a direct effect of D4 on the uterus: It is unlikely that D4’s very weak estrogenic activity can account for the effects seen in this study. Rather, the data support the conclu","endpoint":"","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"150","page":62,"route":"","species":"rat","study_id":"sccp_o_035_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
<226 |
ppm |
mouse |
inhalation |
28 days |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=<226; DOSE=There were dose- dependent ultrastructural changes in hepatocytes in all treated groups.; EFFECT=een. There were dose- dependent ultrastructural changes in hepatocytes in all treated groups. An increase in the smooth endoplasmic reticulum was seen at the 2 highest exposure doses. There were decreases in relative mitochondria volume at all exposure doses and a reduction in rough endoplasmic reticulum at most higher doses. Vacuolation of the zona fasciculata of the adrenal cortex was evident in most of the animals. Thymic atrophy was seen in all animals but was most pronounced at the highest concentration. The NOAEL was considered to be <226 ppm (2.8 mg/l air). Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; Guinea pig, Hartley; Hamster, Golden Syrian; and Rabbit, New Zealand White Group size: 10 males and 10 females per dose except rabbit 5 male/female Test substance: Dow Corning 244 fluid Batch: D4 lot LL107568 Purity: ≥97% octamethylcyclotretrasiloxane (impurities were D5 and D3) Dose levels: 0 and 700 ppm (0 and 8.4 mg/l) Vehicle: air Exposure: 6 h whole body inhalation for 28 days GLP: in compliance This was a mul; CITATION=Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; CITATION_NUMBERS=[10,1]; REFERENCE=Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 10 Guideline: / Species/strain: Mouse, CD-1","dose":"There were dose- dependent ultrastructural changes in hepatocytes in all treated groups.","duration":"28 days","effect":"een. There were dose- dependent ultrastructural changes in hepatocytes in all treated groups. An increase in the smooth endoplasmic reticulum was seen at the 2 highest exposure doses. There were decreases in relative mitochondria volume at all exposure doses and a reduction in rough endoplasmic reticulum at most higher doses. Vacuolation of the zona fasciculata of the adrenal cortex was evident in most of the animals. Thymic atrophy was seen in all animals but was most pronounced at the highest concentration. The NOAEL was considered to be <226 ppm (2.8 mg/l air). Ref.: 10 Guideline: / Species/strain: Mouse, CD-1; Guinea pig, Hartley; Hamster, Golden Syrian; and Rabbit, New Zealand White Group size: 10 males and 10 females per dose except rabbit 5 male/female Test substance: Dow Corning 244 fluid Batch: D4 lot LL107568 Purity: ≥97% octamethylcyclotretrasiloxane (impurities were D5 and D3) Dose levels: 0 and 700 ppm (0 and 8.4 mg/l) Vehicle: air Exposure: 6 h whole body inhalation for 28 days GLP: in compliance This was a mul","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"<226","page":23,"route":"inhalation","species":"mouse","study_id":"sccs_o_029_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
10 |
ppm |
rat |
- |
13 week |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=10; DOSE=It was concluded that the NOEL was 10 ppm.; EFFECT=ight (~28%) at the end of the 13 week exposure period, but it was comparable to controls after the 4 week recovery period. There were no other exposure-related abnormalities in clinical signs, food consumption, body weights, haematology, serum biochemistry, urinalysis, ophthalmology, or macroscopic or microscopic tissue evaluations. No exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. There was no pathological evidence of hepatomegaly. It was concluded that the NOEL was 10 ppm. Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley); CITATION=Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley); CITATION_NUMBERS=[13]; REFERENCE=Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley); DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley)","dose":"It was concluded that the NOEL was 10 ppm.","duration":"13 week","effect":"ight (~28%) at the end of the 13 week exposure period, but it was comparable to controls after the 4 week recovery period. There were no other exposure-related abnormalities in clinical signs, food consumption, body weights, haematology, serum biochemistry, urinalysis, ophthalmology, or macroscopic or microscopic tissue evaluations. No exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. There was no pathological evidence of hepatomegaly. It was concluded that the NOEL was 10 ppm. Ref.: 13 Guideline: / Species/strain: Rats (Sprague Dawley)","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"10","page":25,"route":"","species":"rat","study_id":"sccs_o_029_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
50 |
ppm |
rat |
inhalation |
13 weeks |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=50; DOSE=A decreased ovary weight at the high exposure dose was noted in the recovery group only.; EFFECT=ure females. There were no other exposure-related abnormalities in haematology, serum biochemistry, urinalysis, ophthalmology. Liver weights increased in all male exposed groups and in the mid and high exposure females. This liver weight increase was reversible in males but not in females. A decreased ovary weight at the high exposure dose was noted in the recovery group only. No other exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. It was concluded that the NOEL was 50 ppm in females and less than 50 ppm in males based on liver weights. Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344). Group size: Control and high dose 30 males/females, low and mid dose 20 males/females Test substance: Dow Corning 244 fluid Batch: D4 lot LL023S10 Purity: >99.42% Dose levels: 0, 35, 122, 488 or 898 ppm (0.42, 1.48, 5.91 and 10.87 mg/l) Vehicle: air Exposure: 6 h nose only inhalation 5 days/week for 13 weeks Recovery: 4 weeks Co; CITATION=Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344); CITATION_NUMBERS=[14,3,412,1991,344]; REFERENCE=Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344); DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344)","dose":"A decreased ovary weight at the high exposure dose was noted in the recovery group only.","duration":"13 weeks","effect":"ure females. There were no other exposure-related abnormalities in haematology, serum biochemistry, urinalysis, ophthalmology. Liver weights increased in all male exposed groups and in the mid and high exposure females. This liver weight increase was reversible in males but not in females. A decreased ovary weight at the high exposure dose was noted in the recovery group only. No other exposure related histopathological findings were found at 13 weeks or after the 4 week recovery period. It was concluded that the NOEL was 50 ppm in females and less than 50 ppm in males based on liver weights. Ref.: 14 Nose only inhalation study (3 months) Guideline: OECD 412 (1991) Species/strain: Rats (Fischer 344). Group size: Control and high dose 30 males/females, low and mid dose 20 males/females Test substance: Dow Corning 244 fluid Batch: D4 lot LL023S10 Purity: >99.42% Dose levels: 0, 35, 122, 488 or 898 ppm (0.42, 1.48, 5.91 and 10.87 mg/l) Vehicle: air Exposure: 6 h nose only inhalation 5 days/week for 13 weeks Recovery: 4 weeks Co","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"50","page":26,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
35 |
ppm |
rat |
- |
chronic |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=35; DOSE=Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest dose • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atrophy at...; EFFECT=iod. Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest dose • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atrophy at the highest exposure All these effects were reversible or showed a clear tendency for reversibility. Ref.: 15, AR 3 Comment The increased liver weights suggest a NOEL of 35 ppm. Moreover, it was concluded that the LOEL was 35 ppm based on the presence of lung lesions at all exposure levels. The lung effects are not considered relevant in relation to the use of cosmetics. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Rats (F344) Group size: 10 rats/sex/dose group (sacrificed after 12 months of exposure; see below: Subgroup B) 20 rats/sex/dose group (exposed to D4 for 12 month and sacrificed after a 12 month recovery period; see below: Subgroup C,) Test; CITATION=Ref.: 15, AR 3 Comment The increased liver weights suggest a NOEL of 35 ppm; CITATION_NUMBERS=[15,3,35]; REFERENCE=Ref.: 15, AR 3 Comment The increased liver weights suggest a NOEL of 35 ppm; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 15, AR 3 Comment The increased liver weights suggest a NOEL of 35 ppm","dose":"Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest dose • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atrophy at...","duration":"chronic","effect":"iod. Histopathological changes were: • increased incidence and severity of goblet cell proliferation in the nasal cavity at the highest dose • increased alveolar macrophage foci in the lungs in all treated groups • chronic interstitial inflammation of the lungs in all treated groups • vaginal mucification and increased incidence of ovarian atrophy at the highest exposure All these effects were reversible or showed a clear tendency for reversibility. Ref.: 15, AR 3 Comment The increased liver weights suggest a NOEL of 35 ppm. Moreover, it was concluded that the LOEL was 35 ppm based on the presence of lung lesions at all exposure levels. The lung effects are not considered relevant in relation to the use of cosmetics. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Rats (F344) Group size: 10 rats/sex/dose group (sacrificed after 12 months of exposure; see below: Subgroup B) 20 rats/sex/dose group (exposed to D4 for 12 month and sacrificed after a 12 month recovery period; see below: Subgroup C,) Test","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"35","page":27,"route":"","species":"rat","study_id":"sccs_o_029_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
700 |
ppm |
rat |
- |
chronic |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=700; DOSE=From the chronic toxicity study, a NOAEL of 150 ppm was derived, based on non-neoplastic changes (increased liver weights and centrilobular hypertrophy of hepatocytes in male rats receiving 700 ppm D4 for 12 months).; EFFECT=hanges observed were reversible. A reversible liver enlargement (hypertrophy) and phenobarbital-like increases in xenobiotic metabolising enzyme activities are considered to be an adaptive response to xenobiotics, reversible upon cessation of exposure and not associated with overt hepatotoxicity. From the chronic toxicity study, a NOAEL of 150 ppm was derived, based on non-neoplastic changes (increased liver weights and centrilobular hypertrophy of hepatocytes in male rats receiving 700 ppm D4 for 12 months). This NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"From the chronic toxicity study, a NOAEL of 150 ppm was derived, based on non-neoplastic changes (increased liver weights and centrilobular hypertrophy of hepatocytes in male rats receiving 700 ppm D4 for 12 months).","duration":"chronic","effect":"hanges observed were reversible. A reversible liver enlargement (hypertrophy) and phenobarbital-like increases in xenobiotic metabolising enzyme activities are considered to be an adaptive response to xenobiotics, reversible upon cessation of exposure and not associated with overt hepatotoxicity. From the chronic toxicity study, a NOAEL of 150 ppm was derived, based on non-neoplastic changes (increased liver weights and centrilobular hypertrophy of hepatocytes in male rats receiving 700 ppm D4 for 12 months). This NOAEL","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"700","page":28,"route":"","species":"rat","study_id":"sccs_o_029_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
rat |
- |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls.; EFFECT=tatistically significant (p < 0.05) using the Peto analysis. It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls. If the MNCL in the 700 ppm group is compared to the 10 ppm group, the increase in the 700 ppm group is significant (p<0.0094). No increase in MNCL was found among the exposed female rats. It is likely that a threshold exists in the induction of MNCL. If it is considered that the very high frequency in the control group may be erroneous, the NOAEL for MNCL induction is 150 ppm (320 mg/kg bw/d). Ref.: 79, AR 4 Comment In the lifetime study with D4, uterine (endometrial) adenomas and hyperplasia were observed at the highest dose level of 700 ppm. The lack of a genotoxic potential supports the view that tumour formation by D4 is due to threshold effects. The applicant has proposed that the endometrial adenomas and hyperplasia are due to dopamine-agonist like activity of D4 and thus not relevant to humans. But, this position is not supported to date; CITATION=Ref.: 79, AR 4 Comment In the lifetime study with D4, uterine (endometrial) adenomas and hyperplasia were observed at the highest dose level of 700 ppm; CITATION_NUMBERS=[79,4,700]; REFERENCE=Ref.: 79, AR 4 Comment In the lifetime study with D4, uterine (endometrial) adenomas and hyperplasia were observed at the highest dose level of 700 ppm; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 79, AR 4 Comment In the lifetime study with D4, uterine (endometrial) adenomas and hyperplasia were observed at the highest dose level of 700 ppm","dose":"It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls.","duration":"","effect":"tatistically significant (p < 0.05) using the Peto analysis. It is apparent that the frequencies of MNCL in the 10 ppm and 30 ppm groups are similar to the historical controls. If the MNCL in the 700 ppm group is compared to the 10 ppm group, the increase in the 700 ppm group is significant (p<0.0094). No increase in MNCL was found among the exposed female rats. It is likely that a threshold exists in the induction of MNCL. If it is considered that the very high frequency in the control group may be erroneous, the NOAEL for MNCL induction is 150 ppm (320 mg/kg bw/d). Ref.: 79, AR 4 Comment In the lifetime study with D4, uterine (endometrial) adenomas and hyperplasia were observed at the highest dose level of 700 ppm. The lack of a genotoxic potential supports the view that tumour formation by D4 is due to threshold effects. The applicant has proposed that the endometrial adenomas and hyperplasia are due to dopamine-agonist like activity of D4 and thus not relevant to humans. But, this position is not supported to date","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":33,"route":"","species":"rat","study_id":"sccs_o_029_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
70 |
ppm |
rat |
oral |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=70; DOSE=plasma D4 ratio remained constant over the dose range.; EFFECT=plasma D4 ratio remained constant over the dose range. The lowest dose level to induce significant hepatomegaly was 150 ppm. D4 content in fat, liver and plasma increased proportionally with increasing exposure concentrations. A dose- dependent increase occurred in PROD activity and in CYP2B1/2 proteins with a maximum response at 500 ppm D4. These findings are consistent with those reported for phenobarbital and confirm that D4 is a qualitative “phenobarbital-like” inducer of rat hepatic cytochrome P450 enzymes. A NOEL of 70 ppm D4 is based on enzyme induction in female rats. Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx. 98% Test formulation: D4 in 0.5% aqueous methylcellulose Dose level: Two groups received 1600 mg/kg/day D4 oral gavage for 14 consecutive days Vehicle/Control: Negative controls (two groups of 10 males) vehicle only at 4 ml/kg GLP statement: in compliance This was a morphometric study and DNA analysis desi; CITATION=Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx; CITATION_NUMBERS=[60,10,4,1088,31]; REFERENCE=Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx","dose":"plasma D4 ratio remained constant over the dose range.","duration":"","effect":"plasma D4 ratio remained constant over the dose range. The lowest dose level to induce significant hepatomegaly was 150 ppm. D4 content in fat, liver and plasma increased proportionally with increasing exposure concentrations. A dose- dependent increase occurred in PROD activity and in CYP2B1/2 proteins with a maximum response at 500 ppm D4. These findings are consistent with those reported for phenobarbital and confirm that D4 is a qualitative “phenobarbital-like” inducer of rat hepatic cytochrome P450 enzymes. A NOEL of 70 ppm D4 is based on enzyme induction in female rats. Ref.: 60 Guideline: / Species/strain: Rat, Sprague-Dawley, male Group size: 10 per group Test substance: D4 Batch: Lot number LL108831, purity approx. 98% Test formulation: D4 in 0.5% aqueous methylcellulose Dose level: Two groups received 1600 mg/kg/day D4 oral gavage for 14 consecutive days Vehicle/Control: Negative controls (two groups of 10 males) vehicle only at 4 ml/kg GLP statement: in compliance This was a morphometric study and DNA analysis desi","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"70","page":56,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
100 |
mg/kg |
rat |
oral |
13-week |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=100; DOSE=Five groups of 8 male and 8 female Sprague-Dawley rats received oral doses (via gavage) of 0, 25, 100, 400, and 1600 mg/kg bw, five days/week for two weeks.; EFFECT=1990) was cited in a recent report of the US Cosmetic Ingredient Review Expert Panel, 2009 (Ref. AR14). Five groups of 8 male and 8 female Sprague-Dawley rats received oral doses (via gavage) of 0, 25, 100, 400, and 1600 mg/kg bw, five days/week for two weeks. Neither treatment-related deaths, overt signs of toxicity, nor changes in behaviour were observed in any of the groups. Treatment-related increases in liver weights were observed at doses as low as 100 mg/kg in female rats (LOEL). A no-observed-effect-level (NOEL) for liver weight of 100 mg/kg was reported for male rats. No significant changes were observed at gross pathological examination. Ref.: AR3 Comment Similar observations were made in a 13-week oral gavage study (see section 3.4.5.2) that derived a LOEL of 100 mg/kg bw/day. A four week study was conducted in which 6 male and 6 female rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duration of the study. Animals were observed for signs of local or systemic toxicity, g; CITATION=Ref.: AR3 Comment Similar observations were made in a 13-week oral gavage study (see section 3; CITATION_NUMBERS=[3,13]; REFERENCE=Ref.: AR3 Comment Similar observations were made in a 13-week oral gavage study (see section 3; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: AR3 Comment Similar observations were made in a 13-week oral gavage study (see section 3","dose":"Five groups of 8 male and 8 female Sprague-Dawley rats received oral doses (via gavage) of 0, 25, 100, 400, and 1600 mg/kg bw, five days/week for two weeks.","duration":"13-week","effect":"1990) was cited in a recent report of the US Cosmetic Ingredient Review Expert Panel, 2009 (Ref. AR14). Five groups of 8 male and 8 female Sprague-Dawley rats received oral doses (via gavage) of 0, 25, 100, 400, and 1600 mg/kg bw, five days/week for two weeks. Neither treatment-related deaths, overt signs of toxicity, nor changes in behaviour were observed in any of the groups. Treatment-related increases in liver weights were observed at doses as low as 100 mg/kg in female rats (LOEL). A no-observed-effect-level (NOEL) for liver weight of 100 mg/kg was reported for male rats. No significant changes were observed at gross pathological examination. Ref.: AR3 Comment Similar observations were made in a 13-week oral gavage study (see section 3.4.5.2) that derived a LOEL of 100 mg/kg bw/day. A four week study was conducted in which 6 male and 6 female rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duration of the study. Animals were observed for signs of local or systemic toxicity, g","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"mg/kg","noael_value":"100","page":70,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
5 |
ppm |
rat |
inhalation |
14- day |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=5; DOSE=At 0.432 mg D5/l (28 ppm) and above, there was an increase in white blood cell and neutrophil counts (males only) a decreased number of red blood cells and mean corpuscular haemoglobin concentration.; EFFECT=e seen on body weight, body weight gain, food consumption, or clinical condition. There were no gross findings. At 0.432 mg D5/l (28 ppm) and above, there was an increase in white blood cell and neutrophil counts (males only) a decreased number of red blood cells and mean corpuscular haemoglobin concentration. An increase in relative liver weight (percentage not stated) was also observed in male and female rats at 0.432 mg D5/l (28 ppm) and above. All effects were reversible during the 14- day recovery period. The NOAEL reported in this study was 0.081 mg D5/L air (5 ppm). Ref.: 8 Comment A LOEL of 28 ppm D5 was reported based on changes of some haematological parameters and reversible effects on liver (an increase in relative weight, percentage not stated) in this study of 1984. However, neither two more recent rat studies with 4-week inhalation nor studies with longer exposure did observe such changes at similar concentrations. Thus, SCCS as well as the Canadian authorities (Ref. AR13) have not further considered this study of; CITATION=Ref.: 8 Comment A LOEL of 28 ppm D5 was reported based on changes of some haematological parameters and reversible effects on liver (an increase in relative weight, percentage not stated; CITATION_NUMBERS=[8,28,5]; REFERENCE=Ref.: 8 Comment A LOEL of 28 ppm D5 was reported based on changes of some haematological parameters and reversible effects on liver (an increase in relative weight, percentage not stated; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 8 Comment A LOEL of 28 ppm D5 was reported based on changes of some haematological parameters and reversible effects on liver (an increase in relative weight, percentage not stated","dose":"At 0.432 mg D5/l (28 ppm) and above, there was an increase in white blood cell and neutrophil counts (males only) a decreased number of red blood cells and mean corpuscular haemoglobin concentration.","duration":"14- day","effect":"e seen on body weight, body weight gain, food consumption, or clinical condition. There were no gross findings. At 0.432 mg D5/l (28 ppm) and above, there was an increase in white blood cell and neutrophil counts (males only) a decreased number of red blood cells and mean corpuscular haemoglobin concentration. An increase in relative liver weight (percentage not stated) was also observed in male and female rats at 0.432 mg D5/l (28 ppm) and above. All effects were reversible during the 14- day recovery period. The NOAEL reported in this study was 0.081 mg D5/L air (5 ppm). Ref.: 8 Comment A LOEL of 28 ppm D5 was reported based on changes of some haematological parameters and reversible effects on liver (an increase in relative weight, percentage not stated) in this study of 1984. However, neither two more recent rat studies with 4-week inhalation nor studies with longer exposure did observe such changes at similar concentrations. Thus, SCCS as well as the Canadian authorities (Ref. AR13) have not further considered this study of","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"5","page":72,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
>132 |
ppm |
- |
- |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=> 132; DOSE=live litter size were not adversely affected by test material exposure at exposure levels of 26 or 132 ppm.; EFFECT=live litter size were not adversely affected by test material exposure at exposure levels of 26 or 132 ppm. No exposure-related effects on pup viability throughout lactation and no exposure-related clinical signs were noted in the pups in either the 26 or 132-ppm groups. Pup sex ratios and mean pup weights were unaffected by exposure to the test material at any exposure level. No internal findings related to the test material were noted at either exposure level in females necropsied on post-mating day 25 (10). The NOAEL for this study was > 132 ppm. Ref.: 25; CITATION=Ref.: 25; CITATION_NUMBERS=[25]; REFERENCE=Ref.: 25; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 25","dose":"live litter size were not adversely affected by test material exposure at exposure levels of 26 or 132 ppm.","duration":"","effect":"live litter size were not adversely affected by test material exposure at exposure levels of 26 or 132 ppm. No exposure-related effects on pup viability throughout lactation and no exposure-related clinical signs were noted in the pups in either the 26 or 132-ppm groups. Pup sex ratios and mean pup weights were unaffected by exposure to the test material at any exposure level. No internal findings related to the test material were noted at either exposure level in females necropsied on post-mating day 25 (10). The NOAEL for this study was > 132 ppm. Ref.: 25","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"> 132","page":78,"route":"","species":"","study_id":"sccs_o_029_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
300 |
ppm |
rat |
- |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 93 liver and kidney weights were also noted at 300 ppm in the latter study.; EFFECT=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 93 liver and kidney weights were also noted at 300 ppm in the latter study. Thus, 300 ppm could be considered a LOEC rather than a NOAEL. The main toxicities are viewed differently in terms of their importance in safety assessment and in setting NOAELs as discussed below. The liver weight increase with centrilobular hepatocyte hypertrophy has been attributed to a “phenobarbital-like” induction of rat hepatic CYP enzymes (Ref. 57, 58). This change was reversible (Ref. 13, 14, 15) and was not associated with overt hepatotoxicity, i.e. morphological evidence of necrosis/degeneration or increases in hepatic serum enzymes. Mild enzyme induction is cons; CITATION=(Ref. 57, 58); CITATION_NUMBERS=[57,58]; REFERENCE=(Ref. 57, 58); DETAILS_JSON={"cas_number":"556-67-2","citation":"(Ref. 57, 58)","dose":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 93 liver and kidney weights were also noted at 300 ppm in the latter study.","duration":"","effect":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 93 liver and kidney weights were also noted at 300 ppm in the latter study. Thus, 300 ppm could be considered a LOEC rather than a NOAEL. The main toxicities are viewed differently in terms of their importance in safety assessment and in setting NOAELs as discussed below. The liver weight increase with centrilobular hepatocyte hypertrophy has been attributed to a “phenobarbital-like” induction of rat hepatic CYP enzymes (Ref. 57, 58). This change was reversible (Ref. 13, 14, 15) and was not associated with overt hepatotoxicity, i.e. morphological evidence of necrosis/degeneration or increases in hepatic serum enzymes. Mild enzyme induction is cons","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":93,"route":"","species":"rat","study_id":"sccs_o_029_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
rat |
- |
chronic |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=ion (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas (Ref.; EFFECT=ion (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas (Ref. 37, submission II). An earlier onset and increased incidence of mononuclear cell leukaemia (MNCL) was observed in male rats, not in exposed female rats. Since this tumour type is unique to F344 rats, its relevance to humans is questionable. A NOAEL of 150 ppm was identified in this study based on endometrial adenomas. Since D4 is not genotoxic, an epigenetic mode-of-action was considered to be responsible for its neoplastic effect. Special studies (section 3.3.12) conducted to understand the mode-of- action in the chronic study support a secondary effect rather than a direct effect of D4 on the uterus: It is unlikely that D4’s very weak estrogenic activity can account for the effects seen in this study. Rather, the data support the conclusion that D4 can act; CITATION=(Ref. 37, submission II); CITATION_NUMBERS=[37]; REFERENCE=(Ref. 37, submission II); DETAILS_JSON={"cas_number":"556-67-2","citation":"(Ref. 37, submission II)","dose":"ion (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas (Ref.","duration":"chronic","effect":"ion (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endometrial adenomas (Ref. 37, submission II). An earlier onset and increased incidence of mononuclear cell leukaemia (MNCL) was observed in male rats, not in exposed female rats. Since this tumour type is unique to F344 rats, its relevance to humans is questionable. A NOAEL of 150 ppm was identified in this study based on endometrial adenomas. Since D4 is not genotoxic, an epigenetic mode-of-action was considered to be responsible for its neoplastic effect. Special studies (section 3.3.12) conducted to understand the mode-of- action in the chronic study support a secondary effect rather than a direct effect of D4 on the uterus: It is unlikely that D4’s very weak estrogenic activity can account for the effects seen in this study. Rather, the data support the conclusion that D4 can act","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":94,"route":"","species":"rat","study_id":"sccs_o_029_noael_032"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
rat |
inhalation |
5 days |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE== 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed.; EFFECT== 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight female rat: 0.35 kg Exposure by inhalation, female rat [(2.0 x 15.7 x 6) x 5/7]/0.35 389 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL female rats (389 x 0.05) 19.5 mg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"= 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed.","duration":"5 days","effect":"= 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight female rat: 0.35 kg Exposure by inhalation, female rat [(2.0 x 15.7 x 6) x 5/7]/0.35 389 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL female rats (389 x 0.05) 19.5 mg","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":99,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_041"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
5 |
% |
rat |
inhalation |
5 days |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=5; DOSE=posure requires the respiratory minute volume and the % of the inhaled dose absorbed.; EFFECT=posure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight female rat: 0.35 kg Exposure by inhalation, female rat [(2.0 x 15.7 x 6) x 5/7]/0.35 389 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL female rats (389 x 0.05) 19.5 mg/kg bw/d 1 Default inhalation values for rat from REACH (chapter R.8 – Dose p. 70); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"posure requires the respiratory minute volume and the % of the inhaled dose absorbed.","duration":"5 days","effect":"posure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight female rat: 0.35 kg Exposure by inhalation, female rat [(2.0 x 15.7 x 6) x 5/7]/0.35 389 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL female rats (389 x 0.05) 19.5 mg/kg bw/d 1 Default inhalation values for rat from REACH (chapter R.8 – Dose p. 70)","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"%","noael_value":"5","page":99,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_042"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
5 |
% |
rat |
inhalation |
5 days |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=5; DOSE=1 ppm = 0.0135 mg/l Converted NOAEL:; EFFECT=r: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight female rat: 0.35 kg Exposure by inhalation, female rat [(2.0 x 15.7 x 6) x 5/7]/0.35 389 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL female rats (389 x 0.05) 19.5 mg/kg bw/d 1 Default inhalation values for rat from REACH (chapter R.8 – Dose p. 70); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"1 ppm = 0.0135 mg/l Converted NOAEL:","duration":"5 days","effect":"r: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight female rat: 0.35 kg Exposure by inhalation, female rat [(2.0 x 15.7 x 6) x 5/7]/0.35 389 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL female rats (389 x 0.05) 19.5 mg/kg bw/d 1 Default inhalation values for rat from REACH (chapter R.8 – Dose p. 70)","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"%","noael_value":"5","page":99,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_043"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
=0.1 |
mg/kg bw/day |
rat |
oral |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT== 0.1; DOSE=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (i...; LOAEL_VALUE=100 mg/kg bw/day; EFFECT=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (i...","duration":"","effect":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"100 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 0.1","page":100,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_044"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
=17.8 |
mg/kg bw/day |
rat |
oral |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT== 17.8; DOSE=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (i...; LOAEL_VALUE=100 mg/kg bw/day; EFFECT=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (e; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (i...","duration":"","effect":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (e","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"100 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 17.8","page":100,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_045"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
=0.2 |
mg/kg bw/day |
rat |
oral |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT== 0.2; DOSE=_________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety...; LOAEL_VALUE=100 mg/kg bw/day; EFFECT=_________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"_________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety...","duration":"","effect":"_________________________ 100 Calculation of the Margin of Safety (MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculat","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"100 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 0.2","page":100,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_046"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
=17.8 |
mg/kg bw/day |
rat |
oral |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT== 17.8; DOSE=MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun prot...; LOAEL_VALUE=100 mg/kg bw/day; EFFECT=MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculated on the basis of a NOAEL of 150 ppm from inhalation studies. In thi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun prot...","duration":"","effect":"MoS) from cosmetic products excluding sun protection products and oral products, based on inhalation studies Systemic exposure dose (SED) = 0.1 mg/kg bw/day NOAEL (inhalation, male rats):= = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculated on the basis of a NOAEL of 150 ppm from inhalation studies. In thi","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"100 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"= 17.8","page":100,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_047"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
52 |
% |
rat |
oral |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=52; DOSE== 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comme...; LOAEL_VALUE=100 mg/kg bw/day; EFFECT== 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculated on the basis of a NOAEL of 150 ppm from inhalation studies. In this particular case SCCS considers calculated MoS values <100 for an exposure scenario that includes also sun protection products with cyclomethicone acceptable for the following reasons: (i); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"= 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comme...","duration":"","effect":"= 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 178 Calculation of the Margin of Safety (MoS) from cosmetic products (excluding oral products) and sun protection products, based on inhalation studies Systemic exposure dose (SED) human = 0.2 mg/kg bw/day NOAEL (inhalation, male rats): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculated on the basis of a NOAEL of 150 ppm from inhalation studies. In this particular case SCCS considers calculated MoS values <100 for an exposure scenario that includes also sun protection products with cyclomethicone acceptable for the following reasons: (i)","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"100 mg/kg bw/day","noael_unit":"%","noael_value":"52","page":100,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_048"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
- |
oral |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=ts): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for...; LOAEL_VALUE=100 mg/kg bw/day; EFFECT=ts): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculated on the basis of a NOAEL of 150 ppm from inhalation studies. In this particular case SCCS considers calculated MoS values <100 for an exposure scenario that includes also sun protection products with cyclomethicone acceptable for the following reasons: (i) sun protection products are not regularly used. (ii) Recent surveys on product uses and cyclomethicone concentrations show that D5 is now used in a higher proportion of products than D4 (Talberg 2006; CIR 2009; Hori & Kannan 2008). (iii) The SED calculation is based on a value for derma; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"ts): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for...","duration":"","effect":"ts): = 17.8 mg/kg bw/day Margin of Safety NOAEL / SED = 89 Comment If MoS calculations were based on the LOAEL of 100 mg/kg bw/day from oral studies, adjusted for 52% oral absorption and a factor of 3 for converting the LOAEL to a NOAEL, the MoS for all cosmetic products (excluding sun protection and oral care products) would be 173; the MoS for cosmetic products including sun protection products (excluding oral care products) would be 87. These values are very similar to the figures calculated on the basis of a NOAEL of 150 ppm from inhalation studies. In this particular case SCCS considers calculated MoS values <100 for an exposure scenario that includes also sun protection products with cyclomethicone acceptable for the following reasons: (i) sun protection products are not regularly used. (ii) Recent surveys on product uses and cyclomethicone concentrations show that D5 is now used in a higher proportion of products than D4 (Talberg 2006; CIR 2009; Hori & Kannan 2008). (iii) The SED calculation is based on a value for derma","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"100 mg/kg bw/day","noael_unit":"ppm","noael_value":"150","page":100,"route":"oral","species":"","study_id":"sccs_o_029_noael_049"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
150 |
ppm |
rat |
inhalation |
3-month |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm).; EFFECT=SCCS-rejected applicant NOAEL: on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 102 4. CONCLUSION The SCCS is of the opinion that cyclomethicone (D4, D5) does not pose a risk for human health when used in cosmetic products. Other uses were not considered in this risk assessment. This conclusion is based on the currently available in-use concentrations as cited in this opinion. It should be noted that D4 is classified as a reprotoxic substance, category 3 [ECB 2006]. The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm). The Commission Services should consider whether an environmental risk assessment associated with the use of cyclomethicone (D4/D5) in cosmetic products is required. 5. MINORITY OPINION Not applicable 6. REFERENCES Burns-Naas LA, Mast RW, Meeks RG, Mann PC, Thevenaz P. (1998) Inhalation toxicology of decamethylcyclopentasiloxane (D5) following a 3-month nose-only exposure in Fischer 344 rats. Toxic; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm).","duration":"3-month","effect":"SCCS-rejected applicant NOAEL: on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 102 4. CONCLUSION The SCCS is of the opinion that cyclomethicone (D4, D5) does not pose a risk for human health when used in cosmetic products. Other uses were not considered in this risk assessment. This conclusion is based on the currently available in-use concentrations as cited in this opinion. It should be noted that D4 is classified as a reprotoxic substance, category 3 [ECB 2006]. The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm). The Commission Services should consider whether an environmental risk assessment associated with the use of cyclomethicone (D4/D5) in cosmetic products is required. 5. MINORITY OPINION Not applicable 6. REFERENCES Burns-Naas LA, Mast RW, Meeks RG, Mann PC, Thevenaz P. (1998) Inhalation toxicology of decamethylcyclopentasiloxane (D5) following a 3-month nose-only exposure in Fischer 344 rats. Toxic","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":102,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_053"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
=300 |
ppm |
rat |
inhalation |
3-month |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT== 300; DOSE=The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm).; EFFECT=SCCS-rejected applicant NOAEL: ___________________ 102 4. CONCLUSION The SCCS is of the opinion that cyclomethicone (D4, D5) does not pose a risk for human health when used in cosmetic products. Other uses were not considered in this risk assessment. This conclusion is based on the currently available in-use concentrations as cited in this opinion. It should be noted that D4 is classified as a reprotoxic substance, category 3 [ECB 2006]. The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm). The Commission Services should consider whether an environmental risk assessment associated with the use of cyclomethicone (D4/D5) in cosmetic products is required. 5. MINORITY OPINION Not applicable 6. REFERENCES Burns-Naas LA, Mast RW, Meeks RG, Mann PC, Thevenaz P. (1998) Inhalation toxicology of decamethylcyclopentasiloxane (D5) following a 3-month nose-only exposure in Fischer 344 rats. Toxicol Sci. 43(2): 230-240 .. Burns-Naas LA, Meeks RG, Kolesar GB, Mast RW, Elwell MR, Hardisty JF, Thev; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm).","duration":"3-month","effect":"SCCS-rejected applicant NOAEL: ___________________ 102 4. CONCLUSION The SCCS is of the opinion that cyclomethicone (D4, D5) does not pose a risk for human health when used in cosmetic products. Other uses were not considered in this risk assessment. This conclusion is based on the currently available in-use concentrations as cited in this opinion. It should be noted that D4 is classified as a reprotoxic substance, category 3 [ECB 2006]. The NOAEL for systemic toxicity (150 ppm) used for this risk assessment also covers reprotoxic effects (NOAEL = 300 ppm). The Commission Services should consider whether an environmental risk assessment associated with the use of cyclomethicone (D4/D5) in cosmetic products is required. 5. MINORITY OPINION Not applicable 6. REFERENCES Burns-Naas LA, Mast RW, Meeks RG, Mann PC, Thevenaz P. (1998) Inhalation toxicology of decamethylcyclopentasiloxane (D5) following a 3-month nose-only exposure in Fischer 344 rats. Toxicol Sci. 43(2): 230-240 .. Burns-Naas LA, Meeks RG, Kolesar GB, Mast RW, Elwell MR, Hardisty JF, Thev","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"= 300","page":102,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_054"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
- |
11 |
- |
- |
- |
- |
- |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=unclear:Table 11: Concentration of D4 + D5 in different types of cosmetic products: In conclusion, a NOAEL of 150 | ppm is chosen | with regard to | the most cr | itical effects of; DOSE=In conclusion, a NOAEL of 150 | ppm is chosen | with regard to | the most cr | itical effects of; EFFECT=Table 11: Concentration of D4 + D5 in different types of cosmetic products: In conclusion, a NOAEL of 150 | ppm is chosen | with regard to | the most cr | itical effects of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"In conclusion, a NOAEL of 150 | ppm is chosen | with regard to | the most cr | itical effects of","duration":"","effect":"Table 11: Concentration of D4 + D5 in different types of cosmetic products: In conclusion, a NOAEL of 150 | ppm is chosen | with regard to | the most cr | itical effects of","endpoint":"","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"","noael_value":"unclear:Table 11: Concentration of D4 + D5 in different types of cosmetic products: In conclusion, a NOAEL of 150 | ppm is chosen | with regard to | the most cr | itical effects of","page":97,"route":"","species":"","study_id":"sccs_o_029_noael_056"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
dermal absorption |
=0.1 |
mg/kg bw/day |
rat |
dermal |
5 days |
dermal absorption |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT== 0.1; DOSE=orption = 0.5 % Cyclomethicone absorbed = 6 mg/day Typical human body weight: = 60 kg SED (14.3*103 mg/day * 8.3/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyc...; EFFECT=orption = 0.5 % Cyclomethicone absorbed = 6 mg/day Typical human body weight: = 60 kg SED (14.3*103 mg/day * 8.3/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"orption = 0.5 % Cyclomethicone absorbed = 6 mg/day Typical human body weight: = 60 kg SED (14.3*103 mg/day * 8.3/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyc...","duration":"5 days","effect":"orption = 0.5 % Cyclomethicone absorbed = 6 mg/day Typical human body weight: = 60 kg SED (14.3*103 mg/day * 8.3/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0","endpoint":"dermal absorption","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 0.1","page":99,"route":"dermal","species":"rat","study_id":"sccs_o_029_noael_039"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
dermal absorption |
150 |
ppm |
rat |
dermal |
5 days |
dermal absorption |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=on of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at...; EFFECT=on of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight f; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"on of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at...","duration":"5 days","effect":"on of systemic exposure dose (SED) from sun protection products Applied amount = 18.0 g/day Average concentration = 7.2 % Dose cyclomethicone = 1.3 g/day Dermal absorption = 0.5 % Cyclomethicone absorbed = 6.5 mg/day Typical human body weight: = 60 kg SED (18*103 mg/day * 7.2/100 * 0.5/100) / 60 kg = 0.1 mg/kg bw/day Calculation of SED (rat) at the NOAEL Converting ppm concentrations to a systemic dose following inhalation exposure requires the respiratory minute volume and the % of the inhaled dose absorbed. NOAEL: 150 ppm (exposure 6 hours, 5 days per week) Conversion factor: 1 ppm = 0.012 mg/l (D4) and 0.015 mg/l (D5) Combined conversion factor: 1 ppm = 0.0135 mg/l Converted NOAEL: 150 ppm = 0.0135 mg/l x 150 = 2.0 mg/l (exposure 6 hours, 5 days per week) Inhalation volume1, male rat 20.5 l/h; Weight male rat: 0.5 kg; Exposure by inhalation, male rat: [(2.0 x 20.5 x 6) x 5/7]/0.5 356 mg/kg bw/day Absorption by inhalation, rat 5% NOAEL male rats (356 x 0.05) 17.8 mg/kg bw/d Inhalation volume female rat 15.7 l/h Weight f","endpoint":"dermal absorption","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":99,"route":"dermal","species":"rat","study_id":"sccs_o_029_noael_040"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
960 |
mg/kg |
rat |
inhalation |
14-day |
repeated dose toxicity |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=960; DOSE=Histology of the control and high dose group was carried out.; EFFECT=and at term. Clinical signs were observed at least twice daily. Skin changes scored after Draize. Haematology and blood chemistry were examined prior to termination. Post-mortems were performed on all animals and major organs weighed. Histology of the control and high dose group was carried out. Results There were no clinical signs of toxicity. There were no effects on survival, body weight gain, food consumption, haematology, clinical chemistry, urinalysis, macro and micro pathology. A No Observed Effect Level (NOEL) was 1 ml/kg (equivalent to 960 mg/kg body weight) in this study. Ref.: 7 3.3.5.1.3 Repeated Dose inhalation toxicity 14-day Guideline: / Species/strain: Rat (Charles River CD) Group size: 5 males and 5 females Test substance: Technical grade Dow Corning 244 fluid (TX-88-1824-01 Octamethylcyclotetrasiloxane) Purity: ~ 98% Batch: Technical grade D4, lot 107568 Dose levels: 0, 100, 200 and 400 ppm (0, 1.2, 2.4, 4.8 mg/l) Vehicle: air at 22 ±20C and 30-70% relative humidity Exposure: 6 h whole body inhalation GLP:; CITATION=Ref.: 7 3; CITATION_NUMBERS=[7,3]; REFERENCE=Ref.: 7 3; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 7 3","dose":"Histology of the control and high dose group was carried out.","duration":"14-day","effect":"and at term. Clinical signs were observed at least twice daily. Skin changes scored after Draize. Haematology and blood chemistry were examined prior to termination. Post-mortems were performed on all animals and major organs weighed. Histology of the control and high dose group was carried out. Results There were no clinical signs of toxicity. There were no effects on survival, body weight gain, food consumption, haematology, clinical chemistry, urinalysis, macro and micro pathology. A No Observed Effect Level (NOEL) was 1 ml/kg (equivalent to 960 mg/kg body weight) in this study. Ref.: 7 3.3.5.1.3 Repeated Dose inhalation toxicity 14-day Guideline: / Species/strain: Rat (Charles River CD) Group size: 5 males and 5 females Test substance: Technical grade Dow Corning 244 fluid (TX-88-1824-01 Octamethylcyclotetrasiloxane) Purity: ~ 98% Batch: Technical grade D4, lot 107568 Dose levels: 0, 100, 200 and 400 ppm (0, 1.2, 2.4, 4.8 mg/l) Vehicle: air at 22 ±20C and 30-70% relative humidity Exposure: 6 h whole body inhalation GLP:","endpoint":"repeated dose toxicity","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"mg/kg","noael_value":"960","page":17,"route":"inhalation","species":"rat","study_id":"sccp_o_035_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
960 |
mg/kg |
rat |
inhalation |
14-day |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=960; DOSE=Histology of the control and high dose group was carried out.; EFFECT=and at term. Clinical signs were observed at least twice daily. Skin changes scored after Draize. Haematology and blood chemistry were examined prior to termination. Post-mortems were performed on all animals and major organs weighed. Histology of the control and high dose group was carried out. Results There were no clinical signs of toxicity. There were no effects on survival, body weight gain, food consumption, haematology, clinical chemistry, urinalysis, macro and micro pathology. A No Observed Effect Level (NOEL) of 1 ml/kg (equivalent to 960 mg/kg body weight) was established for this study. Ref.: 7 3.3.5.1.3 Repeated Dose inhalation toxicity 14-day Guideline: / Species/strain: Rat (Charles River CD) Group size: 5 males and 5 females Test substance: Technical grade Dow Corning 244 fluid Octamethylcyclotetrasiloxane) Purity: ~ 98% Batch: Technical grade D4, lot 107568 Dose levels: 0, 100, 200 and 400 ppm (0, 1.2, 2.4, 4.8 mg/l) Vehicle: air at 22 ±20C and 30-70% relative humidity Exposure: 6 h whole body inhalation GLP; CITATION=Ref.: 7 3; CITATION_NUMBERS=[7,3]; REFERENCE=Ref.: 7 3; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 7 3","dose":"Histology of the control and high dose group was carried out.","duration":"14-day","effect":"and at term. Clinical signs were observed at least twice daily. Skin changes scored after Draize. Haematology and blood chemistry were examined prior to termination. Post-mortems were performed on all animals and major organs weighed. Histology of the control and high dose group was carried out. Results There were no clinical signs of toxicity. There were no effects on survival, body weight gain, food consumption, haematology, clinical chemistry, urinalysis, macro and micro pathology. A No Observed Effect Level (NOEL) of 1 ml/kg (equivalent to 960 mg/kg body weight) was established for this study. Ref.: 7 3.3.5.1.3 Repeated Dose inhalation toxicity 14-day Guideline: / Species/strain: Rat (Charles River CD) Group size: 5 males and 5 females Test substance: Technical grade Dow Corning 244 fluid Octamethylcyclotetrasiloxane) Purity: ~ 98% Batch: Technical grade D4, lot 107568 Dose levels: 0, 100, 200 and 400 ppm (0, 1.2, 2.4, 4.8 mg/l) Vehicle: air at 22 ±20C and 30-70% relative humidity Exposure: 6 h whole body inhalation GLP","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"mg/kg","noael_value":"960","page":21,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
10 |
ppm |
rabbit |
dermal |
12 months |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=10; DOSE=The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.; EFFECT=controls for both sexes and the relative liver weights (normalized either to body or brain weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Conclusion In this study, a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months. A NOAEL of 150 ppm was set based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed after 12 months in males receiving 700 ppm. Ref.: 79; AR 4 Conclusion on repeated dose toxicity D4 has been evaluated for its safety in a range of toxicity studies by different routes of exposure. A NOAEL of 960 mg/kg bw was found in a study in rabbits with dermal application of D4 for 28 days. Repeated dose studie; CITATION=Ref.: 79; CITATION_NUMBERS=[79]; REFERENCE=Ref.: 79; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 79","dose":"The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.","duration":"12 months","effect":"controls for both sexes and the relative liver weights (normalized either to body or brain weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Conclusion In this study, a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months. A NOAEL of 150 ppm was set based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed after 12 months in males receiving 700 ppm. Ref.: 79; AR 4 Conclusion on repeated dose toxicity D4 has been evaluated for its safety in a range of toxicity studies by different routes of exposure. A NOAEL of 960 mg/kg bw was found in a study in rabbits with dermal application of D4 for 28 days. Repeated dose studie","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"10","page":28,"route":"dermal","species":"rabbit","study_id":"sccs_o_029_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
150 |
ppm |
rabbit |
oral |
12 months |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.; EFFECT=weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Conclusion In this study, a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months. A NOAEL of 150 ppm was set based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed after 12 months in males receiving 700 ppm. Ref.: 79; AR 4 Conclusion on repeated dose toxicity D4 has been evaluated for its safety in a range of toxicity studies by different routes of exposure. A NOAEL of 960 mg/kg bw was found in a study in rabbits with dermal application of D4 for 28 days. Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects. Clinical sign; CITATION=Ref.: 79; CITATION_NUMBERS=[79]; REFERENCE=Ref.: 79; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 79","dose":"The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B.","duration":"12 months","effect":"weight) generally increased with increasing exposure concentrations. The liver weight increase might be associated with centrilobular hypertrophy of hepatocytes diagnosed in 700-ppm males in Subgroup B. The absolute and/or relative kidney weights increased in some exposed males and females at 12 months, but the differences were statistically significant at 700 ppm when compared with the controls. Conclusion In this study, a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months. A NOAEL of 150 ppm was set based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed after 12 months in males receiving 700 ppm. Ref.: 79; AR 4 Conclusion on repeated dose toxicity D4 has been evaluated for its safety in a range of toxicity studies by different routes of exposure. A NOAEL of 960 mg/kg bw was found in a study in rabbits with dermal application of D4 for 28 days. Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects. Clinical sign","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":28,"route":"oral","species":"rabbit","study_id":"sccs_o_029_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
960 |
mg/kg bw |
rabbit |
oral |
6 months |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=960; DOSE=ferences were statistically significant at 700 ppm when compared with the controls.; EFFECT=ferences were statistically significant at 700 ppm when compared with the controls. Conclusion In this study, a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months. A NOAEL of 150 ppm was set based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed after 12 months in males receiving 700 ppm. Ref.: 79; AR 4 Conclusion on repeated dose toxicity D4 has been evaluated for its safety in a range of toxicity studies by different routes of exposure. A NOAEL of 960 mg/kg bw was found in a study in rabbits with dermal application of D4 for 28 days. Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects. Clinical signs of toxicity were minimal and the histological changes observed were reversible. A reversible liver enlargement (hypertrophy) and phenobarbital-like increases in xenobiotic metabolising enzyme activities are considered to be an adaptive response to xenobiotics, reversible upon cessation of exposure and not associat; CITATION=Ref.: 79; CITATION_NUMBERS=[79]; REFERENCE=Ref.: 79; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 79","dose":"ferences were statistically significant at 700 ppm when compared with the controls.","duration":"6 months","effect":"ferences were statistically significant at 700 ppm when compared with the controls. Conclusion In this study, a NOEL of 10 ppm was identified based on increased liver weights in males after 6 months. A NOAEL of 150 ppm was set based on increased liver weights and on centrilobular hypertrophy of hepatocytes diagnosed after 12 months in males receiving 700 ppm. Ref.: 79; AR 4 Conclusion on repeated dose toxicity D4 has been evaluated for its safety in a range of toxicity studies by different routes of exposure. A NOAEL of 960 mg/kg bw was found in a study in rabbits with dermal application of D4 for 28 days. Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects. Clinical signs of toxicity were minimal and the histological changes observed were reversible. A reversible liver enlargement (hypertrophy) and phenobarbital-like increases in xenobiotic metabolising enzyme activities are considered to be an adaptive response to xenobiotics, reversible upon cessation of exposure and not associat","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"mg/kg bw","noael_value":"960","page":28,"route":"oral","species":"rabbit","study_id":"sccs_o_029_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
150 |
ppm |
rat |
oral |
28 days |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects.; EFFECT=ication of D4 for 28 days. Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects. Clinical signs of toxicity were minimal and the histological changes observed were reversible. A reversible liver enlargement (hypertrophy) and phenobarbital-like increases in xenobiotic metabolising enzyme activities are considered to be an adaptive response to xenobiotics, reversible upon cessation of exposure and not associated with overt hepatotoxicity. From the chronic toxicity study, a NOAEL of 150 ppm was derived, based on non-neoplastic changes (increased liver weights and centrilobular hypertrophy of hepatocytes in male rats receiving 700 ppm D4 for 12 months). This NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects.","duration":"28 days","effect":"ication of D4 for 28 days. Repeated dose studies at relatively high oral and inhalation doses revealed few systemic effects. Clinical signs of toxicity were minimal and the histological changes observed were reversible. A reversible liver enlargement (hypertrophy) and phenobarbital-like increases in xenobiotic metabolising enzyme activities are considered to be an adaptive response to xenobiotics, reversible upon cessation of exposure and not associated with overt hepatotoxicity. From the chronic toxicity study, a NOAEL of 150 ppm was derived, based on non-neoplastic changes (increased liver weights and centrilobular hypertrophy of hepatocytes in male rats receiving 700 ppm D4 for 12 months). This NOAEL","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":28,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
150 |
ppm |
- |
- |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation.; EFFECT=SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation. The respiratory tract changes in the nose and lungs are local effects in line with exposure to a mild, non-specific irritant. This change was reversible and not relevant for D4 exposure from cosmetics. In the combined chronic toxicity and carcinogenicity study, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (see section 3.3.7). Other non- neoplastic effects (liver weight increases) in th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation.","duration":"chronic","effect":"SCCS/1241/10 Opinion on cyclomethicone (D4 / D5) ___________________________________________________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation. The respiratory tract changes in the nose and lungs are local effects in line with exposure to a mild, non-specific irritant. This change was reversible and not relevant for D4 exposure from cosmetics. In the combined chronic toxicity and carcinogenicity study, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (see section 3.3.7). Other non- neoplastic effects (liver weight increases) in th","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":29,"route":"","species":"","study_id":"sccs_o_029_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
150 |
ppm |
rat |
oral |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=___________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation.; EFFECT=___________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation. The respiratory tract changes in the nose and lungs are local effects in line with exposure to a mild, non-specific irritant. This change was reversible and not relevant for D4 exposure from cosmetics. In the combined chronic toxicity and carcinogenicity study, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (see section 3.3.7). Other non- neoplastic effects (liver weight increases) in this study were observed at 150 ppm D4 in female rats. Effects on liver were also observed in subchronic toxicity studies with D4, with either inhalation exposure or oral administration: The oral LOEL for liver weight increase with D4 in rats and rabbits was 500 mg/kg bw/d. Liver weight increases after subchronic inhalation of D4 (≥ 35 ppm) were reversible upon cessation of exposure. Other studies evaluating changes in live; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"___________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation.","duration":"chronic","effect":"___________________________________________________ 29 for repeated dose toxicity equals the NOAEL of 150 ppm in the carcinogenicity study (see below and section 3.7) and was used in the MOS calculation. The respiratory tract changes in the nose and lungs are local effects in line with exposure to a mild, non-specific irritant. This change was reversible and not relevant for D4 exposure from cosmetics. In the combined chronic toxicity and carcinogenicity study, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (see section 3.3.7). Other non- neoplastic effects (liver weight increases) in this study were observed at 150 ppm D4 in female rats. Effects on liver were also observed in subchronic toxicity studies with D4, with either inhalation exposure or oral administration: The oral LOEL for liver weight increase with D4 in rats and rabbits was 500 mg/kg bw/d. Liver weight increases after subchronic inhalation of D4 (≥ 35 ppm) were reversible upon cessation of exposure. Other studies evaluating changes in live","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":29,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
100 |
mg/kg bw |
rat |
oral |
5 day |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=100; DOSE=17 Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref.; EFFECT=ite rabbits were exposed dermally to 0, 96, 288, or 960 mg D5/kg bw for 5 day/wk, for three weeks. The treatment period was followed by a two-week recovery period. Animals were observed for clinical signs of toxicity, mortality, and body weight changes. Haematology, clinical biochemistry, gross examination, and histopathology were performed. No effects were seen on clinical condition, survival, or body weight. No substance related findings were seen on gross examination or histopathology. Ref.: 17 Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref. 4) revealed a LOEL of about 100 mg/kg bw. The treatment related increases in absolute and relative liver weight in rats at 100 mg D5/kg bw can be considered as an adaptive response. In studies on repeated dose toxicity with inhalation exposure a LOEL of 160 ppm was found for systemic effects of D5 on rat liver (increase in absolute and relative weights). The effect was reversible upon cessation of exposure. A NOAEL of 1600 mg/kg bw; CITATION=Ref.: 17 Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref; CITATION_NUMBERS=[17,5]; REFERENCE=Ref.: 17 Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 17 Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref","dose":"17 Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref.","duration":"5 day","effect":"ite rabbits were exposed dermally to 0, 96, 288, or 960 mg D5/kg bw for 5 day/wk, for three weeks. The treatment period was followed by a two-week recovery period. Animals were observed for clinical signs of toxicity, mortality, and body weight changes. Haematology, clinical biochemistry, gross examination, and histopathology were performed. No effects were seen on clinical condition, survival, or body weight. No substance related findings were seen on gross examination or histopathology. Ref.: 17 Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref. 4) revealed a LOEL of about 100 mg/kg bw. The treatment related increases in absolute and relative liver weight in rats at 100 mg D5/kg bw can be considered as an adaptive response. In studies on repeated dose toxicity with inhalation exposure a LOEL of 160 ppm was found for systemic effects of D5 on rat liver (increase in absolute and relative weights). The effect was reversible upon cessation of exposure. A NOAEL of 1600 mg/kg bw","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"mg/kg bw","noael_value":"100","page":73,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
1600 |
mg/kg bw |
rat |
oral |
4 weeks |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=1600; DOSE=Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref.; EFFECT=Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref. 4) revealed a LOEL of about 100 mg/kg bw. The treatment related increases in absolute and relative liver weight in rats at 100 mg D5/kg bw can be considered as an adaptive response. In studies on repeated dose toxicity with inhalation exposure a LOEL of 160 ppm was found for systemic effects of D5 on rat liver (increase in absolute and relative weights). The effect was reversible upon cessation of exposure. A NOAEL of 1600 mg/kg bw was found in studies conducted in rats with dermal application of D5 up to 4 weeks. 3.4.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Oral Male and female Wistar rats were administered 100, 330, or 1000 mg neat D5/kg bw daily for 13 weeks by gavage. Animals were observed for clinical signs, effects on body weight, food consumption and ophthalmologic effects. Complete necropsies were performed, selected organs weighed and selected tissues grossly and microscopically examined. No; CITATION=(Ref. 4); CITATION_NUMBERS=[4]; REFERENCE=(Ref. 4); DETAILS_JSON={"cas_number":"556-67-2","citation":"(Ref. 4)","dose":"Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref.","duration":"4 weeks","effect":"Conclusion LOEL/NOEL for D5 Studies on repeated dose toxicity with two week oral application of D5 (Ref. 4) revealed a LOEL of about 100 mg/kg bw. The treatment related increases in absolute and relative liver weight in rats at 100 mg D5/kg bw can be considered as an adaptive response. In studies on repeated dose toxicity with inhalation exposure a LOEL of 160 ppm was found for systemic effects of D5 on rat liver (increase in absolute and relative weights). The effect was reversible upon cessation of exposure. A NOAEL of 1600 mg/kg bw was found in studies conducted in rats with dermal application of D5 up to 4 weeks. 3.4.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Oral Male and female Wistar rats were administered 100, 330, or 1000 mg neat D5/kg bw daily for 13 weeks by gavage. Animals were observed for clinical signs, effects on body weight, food consumption and ophthalmologic effects. Complete necropsies were performed, selected organs weighed and selected tissues grossly and microscopically examined. No","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"mg/kg bw","noael_value":"1600","page":73,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
150 |
ppm |
rat |
oral |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure.; EFFECT=(3.6), effect levels were selected/chosen that cover the most relevant toxicities observed for both D4 and D5. 3.6. Safety assessment of D4 and D5 Toxicities D4 and D5 exert a rather similar profile of toxicities. Since the two compounds are apparently used together in cosmetic products in varying proportions, the SCCS has decided to perform a combined risk assessment for the two compounds. For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chron; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure.","duration":"chronic","effect":"(3.6), effect levels were selected/chosen that cover the most relevant toxicities observed for both D4 and D5. 3.6. Safety assessment of D4 and D5 Toxicities D4 and D5 exert a rather similar profile of toxicities. Since the two compounds are apparently used together in cosmetic products in varying proportions, the SCCS has decided to perform a combined risk assessment for the two compounds. For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chron","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":96,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_034"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
300 |
ppm |
rat |
oral |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure.; EFFECT=unds are apparently used together in cosmetic products in varying proportions, the SCCS has decided to perform a combined risk assessment for the two compounds. For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chronic toxicity studies, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (Dow Corning 2004). D5 induced endometrial adenocarcinomas only at 160 ppm (Dow Corning 2005). Other non-neoplastic effects (e.g. liver weight in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure.","duration":"chronic","effect":"unds are apparently used together in cosmetic products in varying proportions, the SCCS has decided to perform a combined risk assessment for the two compounds. For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chronic toxicity studies, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (Dow Corning 2004). D5 induced endometrial adenocarcinomas only at 160 ppm (Dow Corning 2005). Other non-neoplastic effects (e.g. liver weight in","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":96,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_035"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
300 |
ppm |
rat |
oral |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure.; EFFECT=sk assessment for the two compounds. For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chronic toxicity studies, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (Dow Corning 2004). D5 induced endometrial adenocarcinomas only at 160 ppm (Dow Corning 2005). Other non-neoplastic effects (e.g. liver weight increases) were observed at 150 ppm D4 and 160 ppm D5 in these studies.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure.","duration":"chronic","effect":"sk assessment for the two compounds. For the safety evaluation, SCCS has considered the available database, and derived the following critical effect levels: a NOAEL of 150 ppm from chronic studies with inhalation exposure and a LOEL of 100 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chronic toxicity studies, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (Dow Corning 2004). D5 induced endometrial adenocarcinomas only at 160 ppm (Dow Corning 2005). Other non-neoplastic effects (e.g. liver weight increases) were observed at 150 ppm D4 and 160 ppm D5 in these studies.","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":96,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_036"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
700 |
ppm |
rat |
oral |
subchronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=700; DOSE=00 mg/kg bw/d from subchronic toxicity studies with oral exposure.; EFFECT=00 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chronic toxicity studies, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (Dow Corning 2004). D5 induced endometrial adenocarcinomas only at 160 ppm (Dow Corning 2005). Other non-neoplastic effects (e.g. liver weight increases) were observed at 150 ppm D4 and 160 ppm D5 in these studies.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"00 mg/kg bw/d from subchronic toxicity studies with oral exposure.","duration":"subchronic","effect":"00 mg/kg bw/d from subchronic toxicity studies with oral exposure. These values should also cover some possible differences in potency between D4 and D5. The NOAEL for reproductive toxicity of D4 in rats in the 2-generation study was defined as 300 ppm (Siddiqui et al. 2007a). The NOAEL for D5 in the 2-generation rat study was 160 ppm, i.e. the highest concentration that can be applied without aerosol formation (Siddiqui et al 2007b). In chronic toxicity studies, D4 caused endometrial adenomas only at 700 ppm; the NOAEL was 150 ppm (Dow Corning 2004). D5 induced endometrial adenocarcinomas only at 160 ppm (Dow Corning 2005). Other non-neoplastic effects (e.g. liver weight increases) were observed at 150 ppm D4 and 160 ppm D5 in these studies.","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"700","page":96,"route":"oral","species":"rat","study_id":"sccs_o_029_noael_037"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
150 |
ppm |
human |
oral |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2).; EFFECT=se (SED) is eliminated in exhaled air as the venous blood passes through the lungs. Moreover, the SED for combined human exposures to D4 and D5 is based on the average value of 0.5% dermal absorption for D4 as conservative approach, since information on the proportion of D4/D5 in various product categories was not available. The margin of safety calculation for cyclomethicone further depends upon the critical effect level derived from animal studies with D4 and/or D5. As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2). Critical effects of the compounds covered by the NOAEL of 150 ppm include carcinogenicity as well as reproductive toxicities. It is recognized that both are; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2).","duration":"chronic","effect":"se (SED) is eliminated in exhaled air as the venous blood passes through the lungs. Moreover, the SED for combined human exposures to D4 and D5 is based on the average value of 0.5% dermal absorption for D4 as conservative approach, since information on the proportion of D4/D5 in various product categories was not available. The margin of safety calculation for cyclomethicone further depends upon the critical effect level derived from animal studies with D4 and/or D5. As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2). Critical effects of the compounds covered by the NOAEL of 150 ppm include carcinogenicity as well as reproductive toxicities. It is recognized that both are","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":100,"route":"oral","species":"human","study_id":"sccs_o_029_noael_050"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
150 |
ppm |
- |
oral |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2).; EFFECT=n of safety calculation for cyclomethicone further depends upon the critical effect level derived from animal studies with D4 and/or D5. As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2). Critical effects of the compounds covered by the NOAEL of 150 ppm include carcinogenicity as well as reproductive toxicities. It is recognized that both are; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2).","duration":"chronic","effect":"n of safety calculation for cyclomethicone further depends upon the critical effect level derived from animal studies with D4 and/or D5. As explained in section 3.6, SCCS has chosen a NOAEL of 150 ppm based on chronic inhalation studies with D4 and D5, and a LOEL of 100 mg/kg bw/day from subchronic oral studies with D5, taking into account similar uses and function of D4 and D5, and their similar profile of toxicities in the animal studies (section 3.5.1 and 3.5.2). Critical effects of the compounds covered by the NOAEL of 150 ppm include carcinogenicity as well as reproductive toxicities. It is recognized that both are","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":100,"route":"oral","species":"","study_id":"sccs_o_029_noael_051"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
repeated dose toxicity |
300 |
ppm |
human |
inhalation |
chronic |
repeated dose toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=Non-neoplastic changes in chronic inhalation and reprotoxicity studies with D4 included increases in liver and kidney weights >150 ppm, and a decreased number of corpora lutea at 300 ppm.; EFFECT=____________________________________________________________________ 101 due to a mode of action that is thresholded. On the other hand, there is at present insufficient (published) data to dismiss altogether the proposed mode of action in rodents as not relevant for humans. Non-neoplastic changes in chronic inhalation and reprotoxicity studies with D4 included increases in liver and kidney weights >150 ppm, and a decreased number of corpora lutea at 300 ppm. Thus, 300 ppm could be considered a LOEC rather than a NOAEL. Other systemic effects observed at lower exposure levels of D4 and D5, namely increases in hepatic CYP enzymes, are considered as adaptive responses. Liver weight increases after subchronic inhalation of D4 and D5 (≥ 35 or 46 ppm) were reversible upon cessation of exposure. Local effects, such as goblet cell proliferation in the nasal cavity and minimal alveolar histiocytosis (pulmonary vascular mineralization) can be related to a mild irritant effect of D4/D5 and were not considered for safety calculations. The; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"Non-neoplastic changes in chronic inhalation and reprotoxicity studies with D4 included increases in liver and kidney weights >150 ppm, and a decreased number of corpora lutea at 300 ppm.","duration":"chronic","effect":"____________________________________________________________________ 101 due to a mode of action that is thresholded. On the other hand, there is at present insufficient (published) data to dismiss altogether the proposed mode of action in rodents as not relevant for humans. Non-neoplastic changes in chronic inhalation and reprotoxicity studies with D4 included increases in liver and kidney weights >150 ppm, and a decreased number of corpora lutea at 300 ppm. Thus, 300 ppm could be considered a LOEC rather than a NOAEL. Other systemic effects observed at lower exposure levels of D4 and D5, namely increases in hepatic CYP enzymes, are considered as adaptive responses. Liver weight increases after subchronic inhalation of D4 and D5 (≥ 35 or 46 ppm) were reversible upon cessation of exposure. Local effects, such as goblet cell proliferation in the nasal cavity and minimal alveolar histiocytosis (pulmonary vascular mineralization) can be related to a mild irritant effect of D4/D5 and were not considered for safety calculations. The","endpoint":"repeated dose toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":101,"route":"inhalation","species":"human","study_id":"sccs_o_029_noael_052"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
rat |
inhalation |
developmental |
reproductive toxicity |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=300; DOSE=Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats.; EFFECT=sed for 6 hours/day on gestation days 6 through 15 (rats) or gestation days 6 through 18 (rabbits). All animals survived the treatment period with no overt signs of toxicity. Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats. Reproduction and Caesarean parameters were not affected by treatment. Morphological evaluation of the foetuses did not demonstrate any test article-related malforma- tions or developmental variations. The NOAEL for maternal toxicity was 300 ppm for rats and rabbits. D4 was not teratogenic at the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Conclusion Embryofoetal inhalation studies in Sprague Dawley rats and New Zealand White rabbits revealed no evidence of developmental toxicity (teratogenicity) up to the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Ref.: 22, 23, 24, 25, 26 3.3.8.2. One-generation studies (general reproduction and fertility) A series of one-; CITATION=Ref.: 22, 23, 24, 25, 26 3; CITATION_NUMBERS=[22,23,24,25,26,3]; REFERENCE=Ref.: 22, 23, 24, 25, 26 3; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 22, 23, 24, 25, 26 3","dose":"Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats.","duration":"developmental","effect":"sed for 6 hours/day on gestation days 6 through 15 (rats) or gestation days 6 through 18 (rabbits). All animals survived the treatment period with no overt signs of toxicity. Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats. Reproduction and Caesarean parameters were not affected by treatment. Morphological evaluation of the foetuses did not demonstrate any test article-related malforma- tions or developmental variations. The NOAEL for maternal toxicity was 300 ppm for rats and rabbits. D4 was not teratogenic at the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Conclusion Embryofoetal inhalation studies in Sprague Dawley rats and New Zealand White rabbits revealed no evidence of developmental toxicity (teratogenicity) up to the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Ref.: 22, 23, 24, 25, 26 3.3.8.2. One-generation studies (general reproduction and fertility) A series of one-","endpoint":"reproductive toxicity","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"300","page":32,"route":"inhalation","species":"rat","study_id":"sccp_o_035_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
- |
- |
- |
reproductive toxicity |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=300; DOSE=reductions in reproductive parameters were recorded only at 700 ppm, while in the other study [32], reduced implantation sites and viable foetuses and increased pre-implantation losses were noted at 500 and 700 ppm.; EFFECT=reductions in reproductive parameters were recorded only at 700 ppm, while in the other study [32], reduced implantation sites and viable foetuses and increased pre-implantation losses were noted at 500 and 700 ppm. In addition, reduced numbers of corpora lutea were found at ≥ 300 ppm. However, as the reduction in corpora lutea was marginal at 300 ppm (14.6/dam vs. 16.2/dam in controls) without a clear exposure-related response and within the range of values in historical control database, (14.2/dam-20.5/dam), the NOAEL is considered to be 300 ppm. - similar reproductive changes were recorded in the two-generation study at 500 and 700 ppm, but, in addition increased oestrous cycle length in F1 females at 700 ppm as well as increased pituitary gland weights were noted. Also in F1 females there were histopatho- logical changes in ovaries and mammary gland at all exposure levels. However, when one considers that the histopathological changes were: 1) minor, and not clearly treatment-related except at 700 ppm,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"reductions in reproductive parameters were recorded only at 700 ppm, while in the other study [32], reduced implantation sites and viable foetuses and increased pre-implantation losses were noted at 500 and 700 ppm.","duration":"","effect":"reductions in reproductive parameters were recorded only at 700 ppm, while in the other study [32], reduced implantation sites and viable foetuses and increased pre-implantation losses were noted at 500 and 700 ppm. In addition, reduced numbers of corpora lutea were found at ≥ 300 ppm. However, as the reduction in corpora lutea was marginal at 300 ppm (14.6/dam vs. 16.2/dam in controls) without a clear exposure-related response and within the range of values in historical control database, (14.2/dam-20.5/dam), the NOAEL is considered to be 300 ppm. - similar reproductive changes were recorded in the two-generation study at 500 and 700 ppm, but, in addition increased oestrous cycle length in F1 females at 700 ppm as well as increased pituitary gland weights were noted. Also in F1 females there were histopatho- logical changes in ovaries and mammary gland at all exposure levels. However, when one considers that the histopathological changes were: 1) minor, and not clearly treatment-related except at 700 ppm,","endpoint":"reproductive toxicity","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"300","page":38,"route":"","species":"","study_id":"sccp_o_035_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
rat |
- |
274 days |
reproductive toxicity |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=300; DOSE=F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL.; EFFECT=_________________________________________________________________________________ 39 2) reported only in the F1 and not in the F0 generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL. Overall in the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting the effect of D4 on reproduction in females is due to delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consistent with a long-term suppression of LH rele; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL.","duration":"274 days","effect":"_________________________________________________________________________________ 39 2) reported only in the F1 and not in the F0 generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL. Overall in the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting the effect of D4 on reproduction in females is due to delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consistent with a long-term suppression of LH rele","endpoint":"reproductive toxicity","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"300","page":39,"route":"","species":"rat","study_id":"sccp_o_035_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
rat |
- |
274 days |
reproductive toxicity |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=300; DOSE=F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL.; EFFECT=generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL. Overall in the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting the effect of D4 on reproduction in females is due to delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consistent with a long-term suppression of LH release. 3.3.9. Toxicokinetics Octamethylcyclotetrasiloxane (D4), randomly labelled with carbon-14, was used in a number of studies t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL.","duration":"274 days","effect":"generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), then it is reasonable to consider 300 ppm as the NOAEL. Overall in the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting the effect of D4 on reproduction in females is due to delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consistent with a long-term suppression of LH release. 3.3.9. Toxicokinetics Octamethylcyclotetrasiloxane (D4), randomly labelled with carbon-14, was used in a number of studies t","endpoint":"reproductive toxicity","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"ppm","noael_value":"300","page":39,"route":"","species":"rat","study_id":"sccp_o_035_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
4 |
- |
rat |
inhalation |
90-day |
reproductive toxicity |
SOURCE_SUBDIR=sccp_o_035; REPORT_TITLE=Opinion on Octamethylcyclotetrasiloxane (D4) Cyclomethicone (INCI name); OPINION_NUMBER=SCCP/0893/05; COMMITTEE=Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP); REPORT_DATE=13 December 2005; VALUE_TEXT=unclear:d irritant to the respiratory tract when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. The mechanistic research completed on these effects supports the view that they are specific for the rat and not of concern for human health. In the case of D4 appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats [13, 14, 15] together with the two-generation repro- duction toxicity study in rats [34] and a combined chronic/carcinogenicity study [AR 4; #37, submission no.2]. These inhalation studies were conducted with the 90-day study in Sprague Dawley rats [14] and the two-generation study in rats [34] using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study [AR 4; #37, submission no.2]. Data from other animal species (mice, gui; DOSE=In the case of D4 appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats [13, 14, 15] together with the two-generation repro- duction toxicity study in rats [34] and a combined chronic/carcinogenicity study [AR 4; #37, submission no.2].; EFFECT=d irritant to the respiratory tract when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. The mechanistic research completed on these effects supports the view that they are specific for the rat and not of concern for human health. In the case of D4 appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats [13, 14, 15] together with the two-generation repro- duction toxicity study in rats [34] and a combined chronic/carcinogenicity study [AR 4; #37, submission no.2]. These inhalation studies were conducted with the 90-day study in Sprague Dawley rats [14] and the two-generation study in rats [34] using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study [AR 4; #37, submission no.2]. Data from other animal species (mice, gui; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"In the case of D4 appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats [13, 14, 15] together with the two-generation repro- duction toxicity study in rats [34] and a combined chronic/carcinogenicity study [AR 4; #37, submission no.2].","duration":"90-day","effect":"d irritant to the respiratory tract when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. The mechanistic research completed on these effects supports the view that they are specific for the rat and not of concern for human health. In the case of D4 appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats [13, 14, 15] together with the two-generation repro- duction toxicity study in rats [34] and a combined chronic/carcinogenicity study [AR 4; #37, submission no.2]. These inhalation studies were conducted with the 90-day study in Sprague Dawley rats [14] and the two-generation study in rats [34] using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study [AR 4; #37, submission no.2]. Data from other animal species (mice, gui","endpoint":"reproductive toxicity","ingredient":"Cyclomethicone (INCI); Cyclotetrasiloxane (INCI)","loael_value":"","noael_unit":"","noael_value":"unclear:d irritant to the respiratory tract when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. The mechanistic research completed on these effects supports the view that they are specific for the rat and not of concern for human health. In the case of D4 appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats [13, 14, 15] together with the two-generation repro- duction toxicity study in rats [34] and a combined chronic/carcinogenicity study [AR 4; #37, submission no.2]. These inhalation studies were conducted with the 90-day study in Sprague Dawley rats [14] and the two-generation study in rats [34] using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study [AR 4; #37, submission no.2]. Data from other animal species (mice, gui","page":60,"route":"inhalation","species":"rat","study_id":"sccp_o_035_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
rat |
inhalation |
developmental |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats.; EFFECT=posed for 6 hours/day on gestation days 6 through 15 (rats) or gestation days 6 through 18 (rabbits). All animals survived the treatment period with no overt signs of toxicity. Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats. Reproduction and Caesarean parameters were not affected by treatment. Morphological evaluation of the foetuses did not demonstrate any test article-related malformations or developmental variations. The NOAEL for maternal toxicity was 300 ppm for rats and rabbits. D4 was not teratogenic at the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Conclusion Embryofoetal inhalation studies in Sprague Dawley rats and New Zealand White rabbits revealed no evidence of developmental toxicity (teratogenicity) up to the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Ref.: 22, 23, 24, 25, 26 3.3.8.2. One-generation studies (general reproduction and fertility) A series of one-; CITATION=Ref.: 22, 23, 24, 25, 26 3; CITATION_NUMBERS=[22,23,24,25,26,3]; REFERENCE=Ref.: 22, 23, 24, 25, 26 3; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 22, 23, 24, 25, 26 3","dose":"Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats.","duration":"developmental","effect":"posed for 6 hours/day on gestation days 6 through 15 (rats) or gestation days 6 through 18 (rabbits). All animals survived the treatment period with no overt signs of toxicity. Food consumption was reduced in rabbits at 500 ppm and in rats at 700 ppm although a reduction in body weight gain was only noted for rats. Reproduction and Caesarean parameters were not affected by treatment. Morphological evaluation of the foetuses did not demonstrate any test article-related malformations or developmental variations. The NOAEL for maternal toxicity was 300 ppm for rats and rabbits. D4 was not teratogenic at the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Conclusion Embryofoetal inhalation studies in Sprague Dawley rats and New Zealand White rabbits revealed no evidence of developmental toxicity (teratogenicity) up to the highest dose levels tested, i.e. 700 ppm for rats and 500 ppm for rabbits. Ref.: 22, 23, 24, 25, 26 3.3.8.2. One-generation studies (general reproduction and fertility) A series of one-","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":35,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
- |
- |
- |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=s in reproductive parameters were recorded only at 700 ppm, while in the other study (Ref.; EFFECT=s in reproductive parameters were recorded only at 700 ppm, while in the other study (Ref. 32), reduced implantation sites and viable foetuses and increased pre-implantation losses were noted at 500 and 700 ppm. In addition, reduced numbers of corpora lutea were found at ≥ 300 ppm. However, as the reduction in corpora lutea was marginal at 300 ppm (14.6/dam vs. 16.2/dam in controls) without a clear exposure-related response and within the range of values in the historical control database, (14.2/dam-20.5/dam), the NOAEL is considered to be 300 ppm. - Similar reproductive changes were recorded in the two-generation study at 500 and 700 ppm, but, in addition increased oestrous cycle length in F1 females at 700 ppm as well as increased pituitary gland weights were noted. Also in F1 females there were histopathological changes in ovaries and mammary glands at all exposure levels. These histopathological changes were: 1) minor, and not clearly treatment-related except at 700 ppm, 2) reported only in the F1 and not in the F0 generatio; CITATION=(Ref. 32); CITATION_NUMBERS=[32]; REFERENCE=(Ref. 32); DETAILS_JSON={"cas_number":"556-67-2","citation":"(Ref. 32)","dose":"s in reproductive parameters were recorded only at 700 ppm, while in the other study (Ref.","duration":"","effect":"s in reproductive parameters were recorded only at 700 ppm, while in the other study (Ref. 32), reduced implantation sites and viable foetuses and increased pre-implantation losses were noted at 500 and 700 ppm. In addition, reduced numbers of corpora lutea were found at ≥ 300 ppm. However, as the reduction in corpora lutea was marginal at 300 ppm (14.6/dam vs. 16.2/dam in controls) without a clear exposure-related response and within the range of values in the historical control database, (14.2/dam-20.5/dam), the NOAEL is considered to be 300 ppm. - Similar reproductive changes were recorded in the two-generation study at 500 and 700 ppm, but, in addition increased oestrous cycle length in F1 females at 700 ppm as well as increased pituitary gland weights were noted. Also in F1 females there were histopathological changes in ovaries and mammary glands at all exposure levels. These histopathological changes were: 1) minor, and not clearly treatment-related except at 700 ppm, 2) reported only in the F1 and not in the F0 generatio","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":41,"route":"","species":"","study_id":"sccs_o_029_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
rat |
- |
274 days |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=1) minor, and not clearly treatment-related except at 700 ppm, 2) reported only in the F1 and not in the F0 generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproduc...; EFFECT=1) minor, and not clearly treatment-related except at 700 ppm, 2) reported only in the F1 and not in the F0 generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), Considering these points, it appears justified to set 300 ppm as the NOAEL. General comment on reproductive toxicity From the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting that the effect of D4 on reproduction in females is due to a delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consist; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"1) minor, and not clearly treatment-related except at 700 ppm, 2) reported only in the F1 and not in the F0 generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproduc...","duration":"274 days","effect":"1) minor, and not clearly treatment-related except at 700 ppm, 2) reported only in the F1 and not in the F0 generation, 3) similar in nature to those found in concurrent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), Considering these points, it appears justified to set 300 ppm as the NOAEL. General comment on reproductive toxicity From the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting that the effect of D4 on reproduction in females is due to a delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consist","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":41,"route":"","species":"rat","study_id":"sccs_o_029_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
rat |
- |
274 days |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=F1 female Sprague Dawley rats were about 274 days of age at sacrifice), Considering these points, it appears justified to set 300 ppm as the NOAEL.; EFFECT=rent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), Considering these points, it appears justified to set 300 ppm as the NOAEL. General comment on reproductive toxicity From the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting that the effect of D4 on reproduction in females is due to a delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consistent with a long-term suppression of LH release. 3.3.9. Toxicokinetics Octamethylcyclotetrasiloxane (D4), randomly labelled with carbon-14, was used in a number of st; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"F1 female Sprague Dawley rats were about 274 days of age at sacrifice), Considering these points, it appears justified to set 300 ppm as the NOAEL.","duration":"274 days","effect":"rent controls and, 4) considered to be probably a combination of D4’s effect on the LH surge, as well as a manifestation of the spontaneous, age-related waning of the female reproductive system in the rat (i.e. F1 female Sprague Dawley rats were about 274 days of age at sacrifice), Considering these points, it appears justified to set 300 ppm as the NOAEL. General comment on reproductive toxicity From the reproductive toxicology studies and taking the weight of evidence approach for reproduction parameters, the NOAEL is considered to be 300 ppm. There is evidence (see Special studies, section 3.3.12.) suggesting that the effect of D4 on reproduction in females is due to a delayed ovulation caused by a treatment-related delay in or blockage of the luteinising hormone surge on the day of pro-oestrus. The reproduction findings in the two-generation study are consistent with a long-term suppression of LH release. 3.3.9. Toxicokinetics Octamethylcyclotetrasiloxane (D4), randomly labelled with carbon-14, was used in a number of st","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":41,"route":"","species":"rat","study_id":"sccs_o_029_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
160 |
ppm |
rat |
- |
developmental |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=160; DOSE=In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm.; EFFECT=of F2 rats not selected for neuropathological evaluation. In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm. F0 and F1 reproductive performance was not affected at any concentration. No test-article-related total litter losses occurred. No neonatal toxicity was evident in the F1 and F2 generations at concentrations of 30, 70 or 160 ppm. No F2 developmental neurotoxicity was evident at any concentration. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm. Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref.: AR4). In line with the above description, the authors found no treatment-related gross findings or organ weight effects at the F0 and F1 necropsies, except for a 10% increase in liver weight at 160 ppm in F0 females, and minim; CITATION=Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref; CITATION_NUMBERS=[26,2]; REFERENCE=Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref","dose":"In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm.","duration":"developmental","effect":"of F2 rats not selected for neuropathological evaluation. In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm. F0 and F1 reproductive performance was not affected at any concentration. No test-article-related total litter losses occurred. No neonatal toxicity was evident in the F1 and F2 generations at concentrations of 30, 70 or 160 ppm. No F2 developmental neurotoxicity was evident at any concentration. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm. Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref.: AR4). In line with the above description, the authors found no treatment-related gross findings or organ weight effects at the F0 and F1 necropsies, except for a 10% increase in liver weight at 160 ppm in F0 females, and minim","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"160","page":80,"route":"","species":"rat","study_id":"sccs_o_029_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
160 |
ppm |
- |
- |
developmental |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=160; DOSE=In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm.; EFFECT=ats not selected for neuropathological evaluation. In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm. F0 and F1 reproductive performance was not affected at any concentration. No test-article-related total litter losses occurred. No neonatal toxicity was evident in the F1 and F2 generations at concentrations of 30, 70 or 160 ppm. No F2 developmental neurotoxicity was evident at any concentration. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm. Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref.: AR4). In line with the above description, the authors found no treatment-related gross findings or organ weight effects at the F0 and F1 necropsies, except for a 10% increase in liver weight at 160 ppm in F0 females, and minimal alveolar histiocytosis in all e; CITATION=Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref; CITATION_NUMBERS=[26,2]; REFERENCE=Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref","dose":"In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm.","duration":"developmental","effect":"ats not selected for neuropathological evaluation. In conclusion, no parental toxicity in the F0 and F1 generations was seen at exposure concentrations of 30, 70 or 160 ppm. F0 and F1 reproductive performance was not affected at any concentration. No test-article-related total litter losses occurred. No neonatal toxicity was evident in the F1 and F2 generations at concentrations of 30, 70 or 160 ppm. No F2 developmental neurotoxicity was evident at any concentration. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm. Ref.: 26 Comment Results of the 2-generation reproductive toxicity study were published recently in a peer reviewed journal (Ref.: AR4). In line with the above description, the authors found no treatment-related gross findings or organ weight effects at the F0 and F1 necropsies, except for a 10% increase in liver weight at 160 ppm in F0 females, and minimal alveolar histiocytosis in all e","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"160","page":80,"route":"","species":"","study_id":"sccs_o_029_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
160 |
ppm |
- |
- |
developmental |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=160; DOSE=There was a slight, but statistically significant, increase in the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5).; EFFECT=ion of offspring in each generation were not affected. There was a slight, but statistically significant, increase in the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5). An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies (see section 3.3.12) failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. The authors suggested a NOAEL of 160 ppm D5 for parental and reproductive toxicity. Conclusion For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from the two-generation study. 3.4.8.3. Teratogenicity Prenatal developmental study See above section 3.4.8.2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"There was a slight, but statistically significant, increase in the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5).","duration":"developmental","effect":"ion of offspring in each generation were not affected. There was a slight, but statistically significant, increase in the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5). An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies (see section 3.3.12) failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. The authors suggested a NOAEL of 160 ppm D5 for parental and reproductive toxicity. Conclusion For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from the two-generation study. 3.4.8.3. Teratogenicity Prenatal developmental study See above section 3.4.8.2","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"160","page":80,"route":"","species":"","study_id":"sccs_o_029_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
160 |
ppm |
- |
- |
developmental |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=160; DOSE=the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5).; EFFECT=the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5). An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies (see section 3.3.12) failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. The authors suggested a NOAEL of 160 ppm D5 for parental and reproductive toxicity. Conclusion For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from the two-generation study. 3.4.8.3. Teratogenicity Prenatal developmental study See above section 3.4.8.2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5).","duration":"developmental","effect":"the mean F1 male pup anogenital distance (AGD; was not measured in F1 male pups exposed to 30 and 70 ppm D5). An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies (see section 3.3.12) failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. The authors suggested a NOAEL of 160 ppm D5 for parental and reproductive toxicity. Conclusion For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from the two-generation study. 3.4.8.3. Teratogenicity Prenatal developmental study See above section 3.4.8.2","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"160","page":80,"route":"","species":"","study_id":"sccs_o_029_noael_027"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
4 |
- |
rat |
inhalation |
90-day |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=unclear:act when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. Mechanistic research in female rats indicates that suppression of the preovulatory luteinizing hormone surge could cause the delayed ovulation stage and reduced fertility (see below). For D4, appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats (Ref. 13, 14, 15) together with the reproduction toxicity studies in rats (Ref. 34; AR 14) and a combined chronic/carcinogenicity study (Ref.: 37; AR 4). These inhalation studies were conducted with the 90-day study in Sprague Dawley rats (Ref. 14) and the two-generation study in SD rats (Ref. 34) using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study (Ref.: 37; AR 4). Data from other animal species (mice, guinea pig,; DOSE=For D4, appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats (Ref.; EFFECT=act when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. Mechanistic research in female rats indicates that suppression of the preovulatory luteinizing hormone surge could cause the delayed ovulation stage and reduced fertility (see below). For D4, appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats (Ref. 13, 14, 15) together with the reproduction toxicity studies in rats (Ref. 34; AR 14) and a combined chronic/carcinogenicity study (Ref.: 37; AR 4). These inhalation studies were conducted with the 90-day study in Sprague Dawley rats (Ref. 14) and the two-generation study in SD rats (Ref. 34) using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study (Ref.: 37; AR 4). Data from other animal species (mice, guinea pig,; CITATION=Ref.: 37; CITATION_NUMBERS=[37]; REFERENCE=Ref.: 37; DETAILS_JSON={"cas_number":"556-67-2","citation":"Ref.: 37","dose":"For D4, appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats (Ref.","duration":"90-day","effect":"act when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. Mechanistic research in female rats indicates that suppression of the preovulatory luteinizing hormone surge could cause the delayed ovulation stage and reduced fertility (see below). For D4, appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats (Ref. 13, 14, 15) together with the reproduction toxicity studies in rats (Ref. 34; AR 14) and a combined chronic/carcinogenicity study (Ref.: 37; AR 4). These inhalation studies were conducted with the 90-day study in Sprague Dawley rats (Ref. 14) and the two-generation study in SD rats (Ref. 34) using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study (Ref.: 37; AR 4). Data from other animal species (mice, guinea pig,","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"","noael_value":"unclear:act when inhaled. A major adverse effect seen with D4 has been evidence of reproductive toxicity in rats. These effects consist of reductions in corpora lutea, implantation sites and number of pups born to dams exposed to high concentrations of D4, and are all inter-related. Mechanistic research in female rats indicates that suppression of the preovulatory luteinizing hormone surge could cause the delayed ovulation stage and reduced fertility (see below). For D4, appropriate pivotal studies to define a meaningful NOAEL are considered to be the three 90-day repeat-dose studies in rats (Ref. 13, 14, 15) together with the reproduction toxicity studies in rats (Ref. 34; AR 14) and a combined chronic/carcinogenicity study (Ref.: 37; AR 4). These inhalation studies were conducted with the 90-day study in Sprague Dawley rats (Ref. 14) and the two-generation study in SD rats (Ref. 34) using 7 days per week exposure to D4, and 5 days per week in the chronic 2 year study (Ref.: 37; AR 4). Data from other animal species (mice, guinea pig,","page":92,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
300 |
ppm |
rat |
inhalation |
3 days |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=300; DOSE=upport of the role of LH was obtained from a study of estrous cycle staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus.; EFFECT=upport of the role of LH was obtained from a study of estrous cycle staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus. Measurement of LH on the day of pro-estrus at 2, 4, 6, 8 and 10 p.m. showed a significant reduction of LH levels at 4, 6 and 8 p.m. which correlated with blocked ovulation (Ref. 75). The majority of reproduction findings in the two-generation study are also consistent with a long-term suppression of LH release. The NOAEL of 300 ppm for reproductive toxicity of D4 is higher than the NOAEL of 150 ppm derived from the chronic/carcinogenicity studies (below). Carcinogenicity A 2-year combined chronic/carcinogenicity study was conducted by whole body vapor inhalation of D4 in Fischer 344 rats. Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic; CITATION=(Ref. 75); CITATION_NUMBERS=[75]; REFERENCE=(Ref. 75); DETAILS_JSON={"cas_number":"556-67-2","citation":"(Ref. 75)","dose":"upport of the role of LH was obtained from a study of estrous cycle staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus.","duration":"3 days","effect":"upport of the role of LH was obtained from a study of estrous cycle staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus. Measurement of LH on the day of pro-estrus at 2, 4, 6, 8 and 10 p.m. showed a significant reduction of LH levels at 4, 6 and 8 p.m. which correlated with blocked ovulation (Ref. 75). The majority of reproduction findings in the two-generation study are also consistent with a long-term suppression of LH release. The NOAEL of 300 ppm for reproductive toxicity of D4 is higher than the NOAEL of 150 ppm derived from the chronic/carcinogenicity studies (below). Carcinogenicity A 2-year combined chronic/carcinogenicity study was conducted by whole body vapor inhalation of D4 in Fischer 344 rats. Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"300","page":94,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_030"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
150 |
ppm |
rat |
inhalation |
3 days |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus.; EFFECT=staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus. Measurement of LH on the day of pro-estrus at 2, 4, 6, 8 and 10 p.m. showed a significant reduction of LH levels at 4, 6 and 8 p.m. which correlated with blocked ovulation (Ref. 75). The majority of reproduction findings in the two-generation study are also consistent with a long-term suppression of LH release. The NOAEL of 300 ppm for reproductive toxicity of D4 is higher than the NOAEL of 150 ppm derived from the chronic/carcinogenicity studies (below). Carcinogenicity A 2-year combined chronic/carcinogenicity study was conducted by whole body vapor inhalation of D4 in Fischer 344 rats. Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endom; CITATION=(Ref. 75); CITATION_NUMBERS=[75]; REFERENCE=(Ref. 75); DETAILS_JSON={"cas_number":"556-67-2","citation":"(Ref. 75)","dose":"staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus.","duration":"3 days","effect":"staged female Sprague Dawley rats exposed to 700 or 900 ppm D4 for 6h/day for 3 days, i.e. on diestrus 1, diestrus 2, and pro-oestrus. Measurement of LH on the day of pro-estrus at 2, 4, 6, 8 and 10 p.m. showed a significant reduction of LH levels at 4, 6 and 8 p.m. which correlated with blocked ovulation (Ref. 75). The majority of reproduction findings in the two-generation study are also consistent with a long-term suppression of LH release. The NOAEL of 300 ppm for reproductive toxicity of D4 is higher than the NOAEL of 150 ppm derived from the chronic/carcinogenicity studies (below). Carcinogenicity A 2-year combined chronic/carcinogenicity study was conducted by whole body vapor inhalation of D4 in Fischer 344 rats. Changes were identified at the highest exposure concentration (700 ppm) only, and included increases in kidney weights associated with chronic nephropathy, increases in mean uterine weight and uterus-to-body weight ratios, an increase in cystic endometrial hyperplasia, and an increased incidence of uterine endom","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"150","page":94,"route":"inhalation","species":"rat","study_id":"sccs_o_029_noael_031"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
160 |
ppm |
rat |
dermal |
90 days |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=160; DOSE=On the other hand, in a nose-only inhalation study of 90 days duration in Fischer 344 rats, treatment-related histopathological findings included an increased incidence of ovarian interstitial gland hyperplasia and vaginal mucosal mucification and atrophy in the female rats exposed to 233 ppm, and a slight, not statistically significant, decreas...; EFFECT=n estrogen receptors α and β or progesterone receptors and was negative in ERα and ERβ reporter gene assays. On the other hand, in a nose-only inhalation study of 90 days duration in Fischer 344 rats, treatment-related histopathological findings included an increased incidence of ovarian interstitial gland hyperplasia and vaginal mucosal mucification and atrophy in the female rats exposed to 233 ppm, and a slight, not statistically significant, decrease in ovaries and testes weight of the animals. In conclusion, a NOAEL of 160 ppm for reproductive toxicity of D5 is appropriate. In the two-generation study, a statistically significant increase in the incidence of pulmonary vascular mineralization was observed in all F0 and F1 animals at 30 ppm and above. Also, increased incidences of minimal alveolar histiocytosis were observed at the high concentration (160 ppm) in F0 and F1 females, consistent with exposure to a mild irritant. When one further considers that the application for cosmetics is primarily dermal, then rat respiratory; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"On the other hand, in a nose-only inhalation study of 90 days duration in Fischer 344 rats, treatment-related histopathological findings included an increased incidence of ovarian interstitial gland hyperplasia and vaginal mucosal mucification and atrophy in the female rats exposed to 233 ppm, and a slight, not statistically significant, decreas...","duration":"90 days","effect":"n estrogen receptors α and β or progesterone receptors and was negative in ERα and ERβ reporter gene assays. On the other hand, in a nose-only inhalation study of 90 days duration in Fischer 344 rats, treatment-related histopathological findings included an increased incidence of ovarian interstitial gland hyperplasia and vaginal mucosal mucification and atrophy in the female rats exposed to 233 ppm, and a slight, not statistically significant, decrease in ovaries and testes weight of the animals. In conclusion, a NOAEL of 160 ppm for reproductive toxicity of D5 is appropriate. In the two-generation study, a statistically significant increase in the incidence of pulmonary vascular mineralization was observed in all F0 and F1 animals at 30 ppm and above. Also, increased incidences of minimal alveolar histiocytosis were observed at the high concentration (160 ppm) in F0 and F1 females, consistent with exposure to a mild irritant. When one further considers that the application for cosmetics is primarily dermal, then rat respiratory","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"ppm","noael_value":"160","page":96,"route":"dermal","species":"rat","study_id":"sccs_o_029_noael_033"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
150 |
ppm |
rat |
- |
- |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=150; DOSE=Other systemic effects, such as increases in hepatic CYP enzymes have been reported at relatively low concentrations of D4 or D5 (≥ 30 ppm), but are considered as adaptive responses.; LOAEL_VALUE=100 mg/kg; EFFECT=ble upon cessation of exposure (Burns-Naas et al. 2002, Burns-Naas et al. 1998). Other systemic effects, such as increases in hepatic CYP enzymes have been reported at relatively low concentrations of D4 or D5 (≥ 30 ppm), but are considered as adaptive responses. Local effects, such as goblet cell proliferation in the nasal cavity and minimal alveolar histiocytosis (pulmonary vascular mineralization) can be related to a mild irritant effect of D4/D5 and were not considered for safety calculations. In conclusion, a NOAEL of 150 ppm is chosen with regard to the most critical effects of cyclomethicone in rats, namely reproductive toxicity and potential carcinogenicity, and a LOAEL of 100 mg/kg body weight to cover organ weight changes in liver, kidney and thymus. Exposure Use levels of Cyclomethicone in cosmetic products Cyclomethicone is used in various cosmetic products as an antistatic / emollient / humectant / solvent / viscosity controlling / hair conditioning ingredient and for the good spreadability of the products. The appl; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"Other systemic effects, such as increases in hepatic CYP enzymes have been reported at relatively low concentrations of D4 or D5 (≥ 30 ppm), but are considered as adaptive responses.","duration":"","effect":"ble upon cessation of exposure (Burns-Naas et al. 2002, Burns-Naas et al. 1998). Other systemic effects, such as increases in hepatic CYP enzymes have been reported at relatively low concentrations of D4 or D5 (≥ 30 ppm), but are considered as adaptive responses. Local effects, such as goblet cell proliferation in the nasal cavity and minimal alveolar histiocytosis (pulmonary vascular mineralization) can be related to a mild irritant effect of D4/D5 and were not considered for safety calculations. In conclusion, a NOAEL of 150 ppm is chosen with regard to the most critical effects of cyclomethicone in rats, namely reproductive toxicity and potential carcinogenicity, and a LOAEL of 100 mg/kg body weight to cover organ weight changes in liver, kidney and thymus. Exposure Use levels of Cyclomethicone in cosmetic products Cyclomethicone is used in various cosmetic products as an antistatic / emollient / humectant / solvent / viscosity controlling / hair conditioning ingredient and for the good spreadability of the products. The appl","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"100 mg/kg","noael_unit":"ppm","noael_value":"150","page":97,"route":"","species":"rat","study_id":"sccs_o_029_noael_038"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies |
reproductive toxicity |
80 |
- |
- |
- |
- |
reproductive toxicity |
SOURCE_SUBDIR=sccs_o_029; REPORT_TITLE=OPINION ON Cyclomethicone Octamethylcyclotetrasiloxane (Cyclotetrasiloxane, D4) and Decamethylcyclopentasiloxane (Cyclopentasiloxane, D5); OPINION_NUMBER=SCCS/1241/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 June 2010; VALUE_TEXT=unclear:Unlabeled table on page 80: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive; EFFECT=Unlabeled table on page 80: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"556-67-2","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 80: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","endpoint":"reproductive toxicity","ingredient":"Octamethylcyclotetrasiloxane has","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 80: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","page":80,"route":"","species":"","study_id":"sccs_o_029_noael_055"} |