NOAEL Studies
Cosmetic Ingredient
Cyclomethicone NOAEL Studies
INCI: CYCLOPENTASILOXANE
CAS: 541-02-6
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
NTP_ICE_acute_inhalation 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_acute_inhalation | LC50 | >8.2595 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=1080; Record_ID=acute_inhalation_737; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID1027184; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response_Modifier=>; Response=8.2595; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/3/3/?documentUUID=68f583cf-b552-49f8-bd36-0499bb1fcf6d; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184 |
| NTP_ICE_acute_inhalation | LC50 | 8.67 | mg/L | - | Inhalation | Duration=4 hr | In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity | sheet=Data; excel_row=1081; Record_ID=acute_inhalation_777; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID1027184; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response=8.67; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/3/3/?documentUUID=d60ea98d-93ea-4930-ab1e-35238e818ff4; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184 |
NTP_ICE_acute_oral 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_acute_oral | LD50 | >5000 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | record_id=acute_oral_7438; row=2792; data_type=In Vivo; mixture=Chemical; chemical_name=Decamethylcyclopentasiloxane; preferred_name=Decamethylcyclopentasiloxane; dtxsid=DTXSID1027184; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184; source_file=acute_oral.xlsx |
| NTP_ICE_acute_oral | LD50 | >20000 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | record_id=acute_oral_7440; row=2793; data_type=In Vivo; mixture=Chemical; chemical_name=Decamethylcyclopentasiloxane; preferred_name=Decamethylcyclopentasiloxane; dtxsid=DTXSID1027184; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184; source_file=acute_oral.xlsx |
| NTP_ICE_acute_oral | LD50 | >61440 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | record_id=acute_oral_7444; row=2794; data_type=In Vivo; mixture=Chemical; chemical_name=Decamethylcyclopentasiloxane; preferred_name=Decamethylcyclopentasiloxane; dtxsid=DTXSID1027184; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184; source_file=acute_oral.xlsx |
| NTP_ICE_acute_oral | LD50 | >24134 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | record_id=acute_oral_7442; row=2795; data_type=In Vivo; mixture=Chemical; chemical_name=Decamethylcyclopentasiloxane; preferred_name=Decamethylcyclopentasiloxane; dtxsid=DTXSID1027184; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184; source_file=acute_oral.xlsx |
NTP_ICE_adme_parameters 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_adme_parameters | Clint | 0 | uL/min/10^6 cells | Human | - | - | Measured; httk, Human Hepatic Intrinsic Clearance | sheet=Data; excel_row=590; Record_ID=adme_parameters_963; Data_Type=Measured; DTXSID=DTXSID1027184; Assay=httk, Human Hepatic Intrinsic Clearance; Endpoint=Clint; Response=0.0; Response_Unit=ul/min/10^6 cells; Species=Human; Reference=httk2.3.1, Wambaugh 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184 |
NTP_ICE_endocrine 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_endocrine | Model Score | 0 | unitless | - | - | - | ARPathway2016; AR Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=7408; RecordID=ARPathway2016_1303; DatasetName=ARPathway2016; DTXSID=DTXSID1027184; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184 |
NTP_ICE_eye_irritation 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_eye_irritation | Intensity | 0.02 | %/sec | - | Ocular | - | In Vitro; Vitrigel | sheet=Data; excel_row=598; Record_ID=eye_irritation_1328; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID1027184; Assay=Vitrigel; Endpoint=Intensity; Response=0.02; Response_Unit=%/sec; PMID=26472347.0; Reference=Yamaguchi et al. 2016; URL=10.1002/jat.3254; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184 |
| NTP_ICE_eye_irritation | Lag time | >180 | s | - | Ocular | - | In Vitro; Vitrigel | sheet=Data; excel_row=597; Record_ID=eye_irritation_1328; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID1027184; Assay=Vitrigel; Endpoint=Lag time; Response_Modifier=>; Response=180; Response_Unit=sec; PMID=26472347.0; Reference=Yamaguchi et al. 2016; URL=10.1002/jat.3254; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184 |
| NTP_ICE_eye_irritation | Plateau level | 0 | % | - | Ocular | - | In Vitro; Vitrigel | sheet=Data; excel_row=599; Record_ID=eye_irritation_1328; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID1027184; Assay=Vitrigel; Endpoint=Plateau level; Response=0; Response_Unit=%; PMID=26472347.0; Reference=Yamaguchi et al. 2016; URL=10.1002/jat.3254; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID1027184 |
SCCS_vision_codex 56 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =48 | % | rat | oral | 5 days | NOAEL study | {"citation":"Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duratio","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":"study was conducted to evaluate the potential effects of D5 in rats. 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 (absolute and relative weights) were observed at 100 (31%), 400 (36%) and 1600 mg/kg bw/day (48%) in female rats. A LOAEL and a NOAEL for increased liver weight of 100 and 25 mg/kg bw/day, respectively, were reported for female rats. No significant changes were observed at gross pathological examination. Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley 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, general appearance, behavioural abnormalities and mortality. Body weight and food","page":21,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | ppm | rat | inhalation | 5 days | NOAEL study | {"citation":"Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation","dose":"The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy.","effect":"ng increased incidence and severity of submucosal inflammation in the lung, which were reversible after the recovery period. The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy. No histopathological changes were noted. At the week 6-recovery necropsy, no effects on liver weights were observed. Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation. A NOAEL of 25 ppm based on the treatment-related changes observed in lung and nasal cavity of rats may be derived from this study. These effects were reversible after the recovery period. In another study (OECD guideline 412), 5 groups of 10 male and female Fischer 344 rats were exposed by nose-only inhalation for 6 hrs/day, 5 days/week for 4 weeks to 0, 0.45, 0.66, 1.34, or 2.29/3.71 mg D5/l (0, 28, 42, 96, 151/197 ppm, respectively). Animals were exposed to the highest exposure concentration of 2.29 mg/l (151 ppm) fo","page":22,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_002"} |
| SCCS_vision_codex | NOAEL | =96 | ppm | rat | inhalation | 28 days | irritation | {"dose":"Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study.","effect":"SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 23 lungs) are consistent with changes due to inhalation of a mild irritant. Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study. In another non guideline study performed in Fischer 344 rats, effects of repeated whole- body vapour inhalation exposure of rats to D5 on liver and thyroid cell proliferation and liver hypertrophy was assessed. Female rats (30 per dose group) were exposed to D5 at nominal vapour concentrations of 0 or 160 ppm daily for 28 days with 5 days of exposure followed by 2 days of non exposure; On days 0, 7, and 21, 10 rats per dose were sacrificed and examined. Histopathological","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | ppm | rat | inhalation | 14-day | NOAEL study | {"citation":"Ref.: 42 SCCS 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","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.: 42 SCCS 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, the SCCS as well as the Canadian authorities (Ref. AR13) have not further considered thi","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_004"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d.","effect":"SCCS-rejected applicant NOAEL: s. Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d. Histologically this was accompanied by hypertrophy of goblet cells and pneumonias with granuloma. Several animals receiving 1000 mg/kg bw/d had hepatocytic cytoplasmic changes that were interpreted to be morphological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: hological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all doses. This increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. It should be noticed that gamma-glutamyl transferase activity was not reported in this study. Inhalation Taken from SCCS/1241/10 Two groups of ten male and ten female Sprague-Da","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | - | oral | subchronic | repeated dose toxicity | {"citation":"(ref 45)","dose":"Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","effect":"ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCS/1241/10, slightly modified","page":27,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_007"} |
| SCCS_vision_codex | NOAEL | =160 | ppm | - | - | developmental | reproductive toxicity | {"citation":"Ref.: 51, Siddiqui et al","dose":"ot measured in F1 male pups exposed to 30 and 70 ppm D5).","effect":"ot measured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 pp","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | - | NOAEL study | {"citation":"(ref 45)","dose":"73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.","effect":"iles, C02 carcass and tissues. In addition, this study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabol","page":40,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_011"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg | rat | oral | 3-month | carcinogenicity | {"dose":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref.","effect":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref. 58). In contrast, data on changes in levels of these liver enzymes following oral administration were not located. Liver weights were increased at 100, 330 and 1000 mg/kg bw/day of D5 in a 3-month oral rat study (Jager and Hartmann 1991, ref. 45). As no adverse effects were observed, 100 mg/kg-bw/day is considered to be the NOAEL for D5. Studies to investigate relevance and potential modes of action for uterine effects Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 months exposure plus 12 months recovery in air and after 24 months exposure but were only significant at the dose of 160 ppm (see section 3.3.7). There is uncertainty whether the uterine tumours are relevant or not to humans. The applicant performed additional studies to further investigate the mode of action by which endometrial adenocarcin","page":50,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_013"} |
| SCCS_vision_codex | NOAEL | =17.8 | mg/kg bw/day | - | inhalation | - | NOAEL study | {"citation":"(Ref 3)","dose":"The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010).","effect":"ries of cosmetic products defined by the SCCS in the note of guidance and a skin penetration value of 0.5% has been taken, as used by the SCCS in the opinion on cyclomethicone (SCCS/1241/10). Inhalation exposure has been determined using a methodology similar to that described by Rothe (Ref 3) and has been aggregated for air styling, foot care and deodorant aerosol products; The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010). The SCCS concurs with the negligible risk due to D4 as an impurity of D5 at the level of the batches used in the dossier submitted by the applicant (D5 purity > 95%) and therefore the SCCS recommends that the level of purity of D5 in the cosmetic products put on the market should be kept as high as possible.","page":68,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_020"} |
| SCCS_vision_codex | NOAEL | =25 | - | - | - | - | NOAEL study | {"dose":"A NOAEL could not be derived from this study as adverse effects were observed at all dose","effect":"Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_021"} |
| SCCS_vision_codex | NOAEL | =35 | - | - | - | - | reproductive toxicity | {"effect":"Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_022"} |
| SCCS_vision_codex | NOAEL | =12 | - | - | - | - | NOAEL study | {"effect":"Table 12: Systemi: POD = NOAEL (mg | /kg) | 100","page":61,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_023"} |
| SCCS_vision_codex | NOAEL | =48 | % | rat | oral | 5 days | NOAEL study | {"citation":"Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duratio","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":"study was conducted to evaluate the potential effects of D5 in rats. 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 (absolute and relative weights) were observed at 100 (31%), 400 (36%) and 1600 mg/kg bw/day (48%) in female rats. A LOAEL and a NOAEL for increased liver weight of 100 and 25 mg/kg bw/day, respectively, were reported for female rats. No significant changes were observed at gross pathological examination. Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley 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, general appearance, behavioural abnormalities and mortality. Body weight and food","page":21,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | ppm | rat | inhalation | 5 days | NOAEL study | {"citation":"Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation","dose":"The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy.","effect":"ng increased incidence and severity of submucosal inflammation in the lung, which were reversible after the recovery period. The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy. No histopathological changes were noted. At the week 6-recovery necropsy, no effects on liver weights were observed. Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation. A NOAEL of 25 ppm based on the treatment-related changes observed in lung and nasal cavity of rats may be derived from this study. These effects were reversible after the recovery period. In another study (OECD guideline 412), 5 groups of 10 male and female Fischer 344 rats were exposed by nose-only inhalation for 6 hrs/day, 5 days/week for 4 weeks to 0, 0.45, 0.66, 1.34, or 2.29/3.71 mg D5/l (0, 28, 42, 96, 151/197 ppm, respectively). Animals were exposed to the highest exposure concentration of 2.29 mg/l (151 ppm) fo","page":22,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_002"} |
| SCCS_vision_codex | NOAEL | =96 | ppm | rat | inhalation | 28 days | irritation | {"dose":"Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study.","effect":"SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 23 lungs) are consistent with changes due to inhalation of a mild irritant. Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study. In another non guideline study performed in Fischer 344 rats, effects of repeated whole- body vapour inhalation exposure of rats to D5 on liver and thyroid cell proliferation and liver hypertrophy was assessed. Female rats (30 per dose group) were exposed to D5 at nominal vapour concentrations of 0 or 160 ppm daily for 28 days with 5 days of exposure followed by 2 days of non exposure; On days 0, 7, and 21, 10 rats per dose were sacrificed and examined. Histopathological","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | ppm | rat | inhalation | 14-day | NOAEL study | {"citation":"Ref.: 42 SCCS 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","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.: 42 SCCS 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, the SCCS as well as the Canadian authorities (Ref. AR13) have not further considered thi","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_004"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d.","effect":"SCCS-rejected applicant NOAEL: s. Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d. Histologically this was accompanied by hypertrophy of goblet cells and pneumonias with granuloma. Several animals receiving 1000 mg/kg bw/d had hepatocytic cytoplasmic changes that were interpreted to be morphological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: hological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all doses. This increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. It should be noticed that gamma-glutamyl transferase activity was not reported in this study. Inhalation Taken from SCCS/1241/10 Two groups of ten male and ten female Sprague-Da","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | - | oral | subchronic | repeated dose toxicity | {"citation":"(ref 45)","dose":"Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","effect":"ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCS/1241/10, slightly modified","page":27,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_007"} |
| SCCS_vision_codex | NOAEL | =160 | ppm | - | - | developmental | reproductive toxicity | {"citation":"Ref.: 51, Siddiqui et al","dose":"ot measured in F1 male pups exposed to 30 and 70 ppm D5).","effect":"ot measured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 pp","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | - | NOAEL study | {"citation":"(ref 45)","dose":"73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.","effect":"iles, C02 carcass and tissues. In addition, this study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabol","page":40,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_011"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg | rat | oral | 3-month | carcinogenicity | {"dose":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref.","effect":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref. 58). In contrast, data on changes in levels of these liver enzymes following oral administration were not located. Liver weights were increased at 100, 330 and 1000 mg/kg bw/day of D5 in a 3-month oral rat study (Jager and Hartmann 1991, ref. 45). As no adverse effects were observed, 100 mg/kg-bw/day is considered to be the NOAEL for D5. Studies to investigate relevance and potential modes of action for uterine effects Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 months exposure plus 12 months recovery in air and after 24 months exposure but were only significant at the dose of 160 ppm (see section 3.3.7). There is uncertainty whether the uterine tumours are relevant or not to humans. The applicant performed additional studies to further investigate the mode of action by which endometrial adenocarcin","page":50,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_013"} |
| SCCS_vision_codex | NOAEL | =17.8 | mg/kg bw/day | - | inhalation | - | NOAEL study | {"citation":"(Ref 3)","dose":"The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010).","effect":"ries of cosmetic products defined by the SCCS in the note of guidance and a skin penetration value of 0.5% has been taken, as used by the SCCS in the opinion on cyclomethicone (SCCS/1241/10). Inhalation exposure has been determined using a methodology similar to that described by Rothe (Ref 3) and has been aggregated for air styling, foot care and deodorant aerosol products; The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010). The SCCS concurs with the negligible risk due to D4 as an impurity of D5 at the level of the batches used in the dossier submitted by the applicant (D5 purity > 95%) and therefore the SCCS recommends that the level of purity of D5 in the cosmetic products put on the market should be kept as high as possible.","page":68,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_020"} |
| SCCS_vision_codex | NOAEL | =25 | - | - | - | - | NOAEL study | {"dose":"A NOAEL could not be derived from this study as adverse effects were observed at all dose","effect":"Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_021"} |
| SCCS_vision_codex | NOAEL | =35 | - | - | - | - | reproductive toxicity | {"effect":"Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_022"} |
| SCCS_vision_codex | NOAEL | =12 | - | - | - | - | NOAEL study | {"effect":"Table 12: Systemi: POD = NOAEL (mg | /kg) | 100","page":61,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_023"} |
| SCCS_vision_codex | NOAEL | =48 | % | rat | oral | 5 days | NOAEL study | {"citation":"Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duratio","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":"study was conducted to evaluate the potential effects of D5 in rats. 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 (absolute and relative weights) were observed at 100 (31%), 400 (36%) and 1600 mg/kg bw/day (48%) in female rats. A LOAEL and a NOAEL for increased liver weight of 100 and 25 mg/kg bw/day, respectively, were reported for female rats. No significant changes were observed at gross pathological examination. Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley 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, general appearance, behavioural abnormalities and mortality. Body weight and food","page":21,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | ppm | rat | inhalation | 5 days | NOAEL study | {"citation":"Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation","dose":"The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy.","effect":"ng increased incidence and severity of submucosal inflammation in the lung, which were reversible after the recovery period. The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy. No histopathological changes were noted. At the week 6-recovery necropsy, no effects on liver weights were observed. Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation. A NOAEL of 25 ppm based on the treatment-related changes observed in lung and nasal cavity of rats may be derived from this study. These effects were reversible after the recovery period. In another study (OECD guideline 412), 5 groups of 10 male and female Fischer 344 rats were exposed by nose-only inhalation for 6 hrs/day, 5 days/week for 4 weeks to 0, 0.45, 0.66, 1.34, or 2.29/3.71 mg D5/l (0, 28, 42, 96, 151/197 ppm, respectively). Animals were exposed to the highest exposure concentration of 2.29 mg/l (151 ppm) fo","page":22,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_002"} |
| SCCS_vision_codex | NOAEL | =96 | ppm | rat | inhalation | 28 days | irritation | {"dose":"Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study.","effect":"SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 23 lungs) are consistent with changes due to inhalation of a mild irritant. Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study. In another non guideline study performed in Fischer 344 rats, effects of repeated whole- body vapour inhalation exposure of rats to D5 on liver and thyroid cell proliferation and liver hypertrophy was assessed. Female rats (30 per dose group) were exposed to D5 at nominal vapour concentrations of 0 or 160 ppm daily for 28 days with 5 days of exposure followed by 2 days of non exposure; On days 0, 7, and 21, 10 rats per dose were sacrificed and examined. Histopathological","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | ppm | rat | inhalation | 14-day | NOAEL study | {"citation":"Ref.: 42 SCCS 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","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.: 42 SCCS 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, the SCCS as well as the Canadian authorities (Ref. AR13) have not further considered thi","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_004"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d.","effect":"SCCS-rejected applicant NOAEL: s. Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d. Histologically this was accompanied by hypertrophy of goblet cells and pneumonias with granuloma. Several animals receiving 1000 mg/kg bw/d had hepatocytic cytoplasmic changes that were interpreted to be morphological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: hological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all doses. This increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. It should be noticed that gamma-glutamyl transferase activity was not reported in this study. Inhalation Taken from SCCS/1241/10 Two groups of ten male and ten female Sprague-Da","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | - | oral | subchronic | repeated dose toxicity | {"citation":"(ref 45)","dose":"Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","effect":"ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCS/1241/10, slightly modified","page":27,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_007"} |
| SCCS_vision_codex | NOAEL | =160 | ppm | - | - | developmental | reproductive toxicity | {"citation":"Ref.: 51, Siddiqui et al","dose":"ot measured in F1 male pups exposed to 30 and 70 ppm D5).","effect":"ot measured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 pp","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | - | NOAEL study | {"citation":"(ref 45)","dose":"73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.","effect":"iles, C02 carcass and tissues. In addition, this study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabol","page":40,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_011"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg | rat | oral | 3-month | carcinogenicity | {"dose":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref.","effect":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref. 58). In contrast, data on changes in levels of these liver enzymes following oral administration were not located. Liver weights were increased at 100, 330 and 1000 mg/kg bw/day of D5 in a 3-month oral rat study (Jager and Hartmann 1991, ref. 45). As no adverse effects were observed, 100 mg/kg-bw/day is considered to be the NOAEL for D5. Studies to investigate relevance and potential modes of action for uterine effects Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 months exposure plus 12 months recovery in air and after 24 months exposure but were only significant at the dose of 160 ppm (see section 3.3.7). There is uncertainty whether the uterine tumours are relevant or not to humans. The applicant performed additional studies to further investigate the mode of action by which endometrial adenocarcin","page":50,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_013"} |
| SCCS_vision_codex | NOAEL | =17.8 | mg/kg bw/day | - | inhalation | - | NOAEL study | {"citation":"(Ref 3)","dose":"The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010).","effect":"ries of cosmetic products defined by the SCCS in the note of guidance and a skin penetration value of 0.5% has been taken, as used by the SCCS in the opinion on cyclomethicone (SCCS/1241/10). Inhalation exposure has been determined using a methodology similar to that described by Rothe (Ref 3) and has been aggregated for air styling, foot care and deodorant aerosol products; The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010). The SCCS concurs with the negligible risk due to D4 as an impurity of D5 at the level of the batches used in the dossier submitted by the applicant (D5 purity > 95%) and therefore the SCCS recommends that the level of purity of D5 in the cosmetic products put on the market should be kept as high as possible.","page":68,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_020"} |
| SCCS_vision_codex | NOAEL | =25 | - | - | - | - | NOAEL study | {"dose":"A NOAEL could not be derived from this study as adverse effects were observed at all dose","effect":"Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_021"} |
| SCCS_vision_codex | NOAEL | =35 | - | - | - | - | reproductive toxicity | {"effect":"Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_022"} |
| SCCS_vision_codex | NOAEL | =12 | - | - | - | - | NOAEL study | {"effect":"Table 12: Systemi: POD = NOAEL (mg | /kg) | 100","page":61,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_023"} |
| SCCS_vision_codex | NOAEL | =48 | % | rat | oral | 5 days | NOAEL study | {"citation":"Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duratio","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":"study was conducted to evaluate the potential effects of D5 in rats. 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 (absolute and relative weights) were observed at 100 (31%), 400 (36%) and 1600 mg/kg bw/day (48%) in female rats. A LOAEL and a NOAEL for increased liver weight of 100 and 25 mg/kg bw/day, respectively, were reported for female rats. No significant changes were observed at gross pathological examination. Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley 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, general appearance, behavioural abnormalities and mortality. Body weight and food","page":21,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | ppm | rat | inhalation | 5 days | NOAEL study | {"citation":"Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation","dose":"The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy.","effect":"ng increased incidence and severity of submucosal inflammation in the lung, which were reversible after the recovery period. The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy. No histopathological changes were noted. At the week 6-recovery necropsy, no effects on liver weights were observed. Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation. A NOAEL of 25 ppm based on the treatment-related changes observed in lung and nasal cavity of rats may be derived from this study. These effects were reversible after the recovery period. In another study (OECD guideline 412), 5 groups of 10 male and female Fischer 344 rats were exposed by nose-only inhalation for 6 hrs/day, 5 days/week for 4 weeks to 0, 0.45, 0.66, 1.34, or 2.29/3.71 mg D5/l (0, 28, 42, 96, 151/197 ppm, respectively). Animals were exposed to the highest exposure concentration of 2.29 mg/l (151 ppm) fo","page":22,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_002"} |
| SCCS_vision_codex | NOAEL | =96 | ppm | rat | inhalation | 28 days | irritation | {"dose":"Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study.","effect":"SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 23 lungs) are consistent with changes due to inhalation of a mild irritant. Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study. In another non guideline study performed in Fischer 344 rats, effects of repeated whole- body vapour inhalation exposure of rats to D5 on liver and thyroid cell proliferation and liver hypertrophy was assessed. Female rats (30 per dose group) were exposed to D5 at nominal vapour concentrations of 0 or 160 ppm daily for 28 days with 5 days of exposure followed by 2 days of non exposure; On days 0, 7, and 21, 10 rats per dose were sacrificed and examined. Histopathological","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | ppm | rat | inhalation | 14-day | NOAEL study | {"citation":"Ref.: 42 SCCS 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","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.: 42 SCCS 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, the SCCS as well as the Canadian authorities (Ref. AR13) have not further considered thi","page":23,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_004"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d.","effect":"SCCS-rejected applicant NOAEL: s. Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d. Histologically this was accompanied by hypertrophy of goblet cells and pneumonias with granuloma. Several animals receiving 1000 mg/kg bw/d had hepatocytic cytoplasmic changes that were interpreted to be morphological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | - | oral | - | irritation | {"citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: hological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all doses. This increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. It should be noticed that gamma-glutamyl transferase activity was not reported in this study. Inhalation Taken from SCCS/1241/10 Two groups of ten male and ten female Sprague-Da","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | - | oral | subchronic | repeated dose toxicity | {"citation":"(ref 45)","dose":"Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","effect":"ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCS/1241/10, slightly modified","page":27,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_007"} |
| SCCS_vision_codex | NOAEL | =160 | ppm | - | - | developmental | reproductive toxicity | {"citation":"Ref.: 51, Siddiqui et al","dose":"ot measured in F1 male pups exposed to 30 and 70 ppm D5).","effect":"ot measured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 pp","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_008"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | oral | - | NOAEL study | {"citation":"(ref 45)","dose":"73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.","effect":"iles, C02 carcass and tissues. In addition, this study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabol","page":40,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_011"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg | rat | oral | 3-month | carcinogenicity | {"dose":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref.","effect":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref. 58). In contrast, data on changes in levels of these liver enzymes following oral administration were not located. Liver weights were increased at 100, 330 and 1000 mg/kg bw/day of D5 in a 3-month oral rat study (Jager and Hartmann 1991, ref. 45). As no adverse effects were observed, 100 mg/kg-bw/day is considered to be the NOAEL for D5. Studies to investigate relevance and potential modes of action for uterine effects Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 months exposure plus 12 months recovery in air and after 24 months exposure but were only significant at the dose of 160 ppm (see section 3.3.7). There is uncertainty whether the uterine tumours are relevant or not to humans. The applicant performed additional studies to further investigate the mode of action by which endometrial adenocarcin","page":50,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_013"} |
| SCCS_vision_codex | NOAEL | =17.8 | mg/kg bw/day | - | inhalation | - | NOAEL study | {"citation":"(Ref 3)","dose":"The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010).","effect":"ries of cosmetic products defined by the SCCS in the note of guidance and a skin penetration value of 0.5% has been taken, as used by the SCCS in the opinion on cyclomethicone (SCCS/1241/10). Inhalation exposure has been determined using a methodology similar to that described by Rothe (Ref 3) and has been aggregated for air styling, foot care and deodorant aerosol products; The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010). The SCCS concurs with the negligible risk due to D4 as an impurity of D5 at the level of the batches used in the dossier submitted by the applicant (D5 purity > 95%) and therefore the SCCS recommends that the level of purity of D5 in the cosmetic products put on the market should be kept as high as possible.","page":68,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_020"} |
| SCCS_vision_codex | NOAEL | =25 | - | - | - | - | NOAEL study | {"dose":"A NOAEL could not be derived from this study as adverse effects were observed at all dose","effect":"Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose","page":25,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_021"} |
| SCCS_vision_codex | NOAEL | =35 | - | - | - | - | reproductive toxicity | {"effect":"Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","page":35,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_022"} |
| SCCS_vision_codex | NOAEL | =12 | - | - | - | - | NOAEL study | {"effect":"Table 12: Systemi: POD = NOAEL (mg | /kg) | 100","page":61,"pdf":"sccs_o_174.pdf","row_type":"noael_study","study_id":"sccs_o_174_noael_023"} |
ToxValDB_ECHA_IUCLID 14 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_ECHA_IUCLID | NOAEC | >=2426.32 | mg/m3 | Rat | inhalation | - | chronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c823e4b0a7c65d216e7d; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/8?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15816749:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d1b1a4f9dd166c37bd7184779f65f402 |
| ToxValDB_ECHA_IUCLID | NOAEC | >=2441.48 | mg/m3 | Rat | inhalation | - | developmental | GUIDELINE=OECD Guideline 414 (Prenatal Developmental Toxicity Study); QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d1ebe4b0a7c65d230aad; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/9/3?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15821002:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_00b7a8e494f59cb9c4ed7d5366057bed |
| ToxValDB_ECHA_IUCLID | NOAEC | >=3396.85 | mg/m3 | Rat | inhalation | subchronic; 3 months | subchronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61fa0e4b096bca877e2a6; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/3?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15826912:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_2784f40136b95a8634c1d515a6e0bc5c |
| ToxValDB_ECHA_IUCLID | NOAEC | =81 | mg/m3 | Rat | inhalation | short-term; 4 weeks | short-term | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/3?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15827217:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_cefab6728a42780358957f208a76061a |
| ToxValDB_ECHA_IUCLID | NOAEC | >=2350 | mg/m3 | Rat | inhalation | short-term; 4 weeks | short-term | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/3?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15827644:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_bd06ee632a67737b80cc8e5603e6a5f6 |
| ToxValDB_ECHA_IUCLID | NOAEC | >=1819.74 | mg/m3 | Rat | inhalation | short-term; 28 days | short-term | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/3?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15828132:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_844d5d23c463430cba0b6512089091f0 |
| ToxValDB_ECHA_IUCLID | NOAEC | =606.58 | mg/m3 | Rat | inhalation | chronic; 6 months | chronic | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/3?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15829384:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_82ad1e93a48bed08813b28bc6709cf85 |
| ToxValDB_ECHA_IUCLID | NOAEL | >=960 | mg/kg bw/day | Rabbit | dermal | short-term; 3 weeks | short-term | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61d4be4b096bca877537f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/4?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15826119:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_c87647551bf9847bd6d2259a259c1988 |
| ToxValDB_ECHA_IUCLID | NOAEL | >=1600 | mg/kg bw/day | Rat | dermal | short-term; 28 days | short-term | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61d82e4b096bca8775fd6; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/4?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15826187:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_20136e6ae53bf578601a4d8cceaf99a3 |
| ToxValDB_ECHA_IUCLID | NOAEL | >=1000 | mg/kg bw/day | Rabbit | dermal | short-term; 3 weeks | short-term | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61de7e4b096bca8777898; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/4?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15826335:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ce99b5a1ce74b3e09fecb7d6e4f01abb |
| ToxValDB_ECHA_IUCLID | NOAEL | >=1500 | mg/kg bw/day | Rat | oral | short-term; 28 days | short-term | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eae65e4b0a7c65d1c8f9e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/6/2?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15834878:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_b40d2796f0cc60be6c3dc53cf6dfd2b0 |
| ToxValDB_ECHA_IUCLID | NOAEL | >=2426.32 | mg/m3 | Rat | inhalation | - | reproduction developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c904e4b0a7c65d21b228; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/9/2?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15857585_15857697:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_49bc74fc906e021e94a2c92d1cbb4967 |
| ToxValDB_ECHA_IUCLID | NOAEL | >=2001.71 | mg/m3 | Rat | inhalation | - | reproduction developmental | QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c904e4b0a7c65d21b25c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/9/2?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15857585_15857697:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_83d1ce5c1280e261105bcce235404e26 |
| ToxValDB_ECHA_IUCLID | NOEC | >2426.32 | mg/m3 | Rabbit | inhalation | - | developmental | GUIDELINE=OECD Guideline 414 (Prenatal Developmental Toxicity Study); QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d1ebe4b0a7c65d230ab7; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14807/7/9/3?documentUUID=3f067151-9a94-44e1-b90d-29fd842b1c00; YEAR=1999; ORIGINAL_YEAR=1999; STUDY_GROUP=ECHA IUCLID:15821857:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_a12a16d2b995deadc14490f51fa1e4b1 |
ToxValDB_GESTIS_DNEL 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_GESTIS_DNEL | DNEL local | =24.2 | mg/m3 | Human | inhalation | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15630925_15630926:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_43c0e689e9432fc5126c612e38214211 |
| ToxValDB_GESTIS_DNEL | DNEL systemic | =97.3 | mg/m3 | Human | inhalation | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15630925_15630926:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_de0f4995b16cbbce7b54dc6ea89b1739 |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 25 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 48 | % | rat | oral | 5 days | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=48; 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.; LOAEL_VALUE=25 mg/kg bw/day; EFFECT=study was conducted to evaluate the potential effects of D5 in rats. 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 (absolute and relative weights) were observed at 100 (31%), 400 (36%) and 1600 mg/kg bw/day (48%) in female rats. A LOAEL and a NOAEL for increased liver weight of 100 and 25 mg/kg bw/day, respectively, were reported for female rats. No significant changes were observed at gross pathological examination. Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley 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, general appearance, behavioural abnormalities and mortality. Body weight and food; CITATION=Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duratio; CITATION_NUMBERS=[35,6,1500,5]; REFERENCE=Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duratio; DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley rats were given 1500 mg/kg bw/day of the test substance via oral gavage 5 days a week for the duratio","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":"5 days","effect":"study was conducted to evaluate the potential effects of D5 in rats. 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 (absolute and relative weights) were observed at 100 (31%), 400 (36%) and 1600 mg/kg bw/day (48%) in female rats. A LOAEL and a NOAEL for increased liver weight of 100 and 25 mg/kg bw/day, respectively, were reported for female rats. No significant changes were observed at gross pathological examination. Ref.: 35 A four week study was conducted in which 6 male and 6 female Sprague-Dawley 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, general appearance, behavioural abnormalities and mortality. Body weight and food","endpoint":"","ingredient":"codes.................................... 7","loael_value":"25 mg/kg bw/day","noael_unit":"%","noael_value":"48","page":21,"route":"oral","species":"rat","study_id":"sccs_o_174_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | ppm | rat | inhalation | 5 days | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=25; DOSE=The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy.; EFFECT=ng increased incidence and severity of submucosal inflammation in the lung, which were reversible after the recovery period. The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy. No histopathological changes were noted. At the week 6-recovery necropsy, no effects on liver weights were observed. Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation. A NOAEL of 25 ppm based on the treatment-related changes observed in lung and nasal cavity of rats may be derived from this study. These effects were reversible after the recovery period. In another study (OECD guideline 412), 5 groups of 10 male and female Fischer 344 rats were exposed by nose-only inhalation for 6 hrs/day, 5 days/week for 4 weeks to 0, 0.45, 0.66, 1.34, or 2.29/3.71 mg D5/l (0, 28, 42, 96, 151/197 ppm, respectively). Animals were exposed to the highest exposure concentration of 2.29 mg/l (151 ppm) fo; CITATION=Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation; CITATION_NUMBERS=[37]; REFERENCE=Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation; DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation","dose":"The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy.","duration":"5 days","effect":"ng increased incidence and severity of submucosal inflammation in the lung, which were reversible after the recovery period. The mean (absolute and relative) liver weights in the 160 ppm group, especially the females, were increased at the week 4 primary necropsy. No histopathological changes were noted. At the week 6-recovery necropsy, no effects on liver weights were observed. Ref.: 37 SCCS comment This study is only reported as a published paper and the original study report was not available for evaluation. A NOAEL of 25 ppm based on the treatment-related changes observed in lung and nasal cavity of rats may be derived from this study. These effects were reversible after the recovery period. In another study (OECD guideline 412), 5 groups of 10 male and female Fischer 344 rats were exposed by nose-only inhalation for 6 hrs/day, 5 days/week for 4 weeks to 0, 0.45, 0.66, 1.34, or 2.29/3.71 mg D5/l (0, 28, 42, 96, 151/197 ppm, respectively). Animals were exposed to the highest exposure concentration of 2.29 mg/l (151 ppm) fo","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"25","page":22,"route":"inhalation","species":"rat","study_id":"sccs_o_174_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 5 | ppm | rat | inhalation | 14-day | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; 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.: 42 SCCS 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, the SCCS as well as the Canadian authorities (Ref. AR13) have not further considered thi; CITATION=Ref.: 42 SCCS 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; CITATION_NUMBERS=[42,28,5]; REFERENCE=Ref.: 42 SCCS 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; DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 42 SCCS 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","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.: 42 SCCS 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, the SCCS as well as the Canadian authorities (Ref. AR13) have not further considered thi","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"5","page":23,"route":"inhalation","species":"rat","study_id":"sccs_o_174_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 10 | % | rat | oral | - | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=10; DOSE=73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.; EFFECT=iles, C02 carcass and tissues. In addition, this study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabol; CITATION=(ref 45); CITATION_NUMBERS=[45]; REFERENCE=(ref 45); DETAILS_JSON={"cas_number":"541-02-6","citation":"(ref 45)","dose":"73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.","duration":"","effect":"iles, C02 carcass and tissues. In addition, this study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabol","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_174_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 10 | % | rat | oral | - | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=10; DOSE=73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.; EFFECT=his study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabolites and five minor metabolites have been ide; CITATION=(ref 45); CITATION_NUMBERS=[45]; REFERENCE=(ref 45); DETAILS_JSON={"cas_number":"541-02-6","citation":"(ref 45)","dose":"73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure.","duration":"","effect":"his study indicated that the oral absorption of D5 could be influenced by the carrier used to deliver 14C-D5. With neat D5, absorption was approximately 10%. Ref. 73 SCCS comments In the oral study rats were exposed to very high dose of D5 (1000 mg/kg bw/day) and then it is difficult to extrapolate the pharmacokinetic profile to much lower doses that are more relevant to the human exposure. For oral absorption, 10% bioavailability will be used to calculate the internal NOAEL as in the key study used to derive the NOAEL for risk assessment (ref 45), neat D5 was administered. 3.3.9.3. Dermal route See section 3.3.4 3.3.9.4. Metabolism Metabolism of D5 (and D4) occurs in the liver by methyl-group-oxidation, rearrangement of the subsequent Si-CH2OH to SiOCH3 followed by hydrolysis with ring opening to produce a series of linear silanols that are excreted in urine. Unlike D4, D5 is metabolized to a stable, lipophilic cyclic metabolite, possibly hydroxyl-D5 (ref 81). Two major metabolites and five minor metabolites have been ide","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"10","page":40,"route":"oral","species":"rat","study_id":"sccs_o_174_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 17.8 | mg/kg bw/day | - | inhalation | - | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=17.8; DOSE=The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010).; EFFECT=ries of cosmetic products defined by the SCCS in the note of guidance and a skin penetration value of 0.5% has been taken, as used by the SCCS in the opinion on cyclomethicone (SCCS/1241/10). Inhalation exposure has been determined using a methodology similar to that described by Rothe (Ref 3) and has been aggregated for air styling, foot care and deodorant aerosol products; The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010). The SCCS concurs with the negligible risk due to D4 as an impurity of D5 at the level of the batches used in the dossier submitted by the applicant (D5 purity > 95%) and therefore the SCCS recommends that the level of purity of D5 in the cosmetic products put on the market should be kept as high as possible.; CITATION=(Ref 3); CITATION_NUMBERS=[3]; REFERENCE=(Ref 3); DETAILS_JSON={"cas_number":"541-02-6","citation":"(Ref 3)","dose":"The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010).","duration":"","effect":"ries of cosmetic products defined by the SCCS in the note of guidance and a skin penetration value of 0.5% has been taken, as used by the SCCS in the opinion on cyclomethicone (SCCS/1241/10). Inhalation exposure has been determined using a methodology similar to that described by Rothe (Ref 3) and has been aggregated for air styling, foot care and deodorant aerosol products; The overall aggregate exposure to D4 has been calculated to be < 5 µg/kg bw/day, which provides a margin of safety of > 3500 compared to the NOAEL of 17.8 mg/kg bw/day determined by the SCCS (2010). The SCCS concurs with the negligible risk due to D4 as an impurity of D5 at the level of the batches used in the dossier submitted by the applicant (D5 purity > 95%) and therefore the SCCS recommends that the level of purity of D5 in the cosmetic products put on the market should be kept as high as possible.","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"17.8","page":68,"route":"inhalation","species":"","study_id":"sccs_o_174_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=unclear:Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose; DOSE=A NOAEL could not be derived from this study as adverse effects were observed at all dose; EFFECT=Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"A NOAEL could not be derived from this study as adverse effects were observed at all dose","duration":"","effect":"Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 25: A NOAEL could not be derived from this study as adverse effects were observed at all dose","page":25,"route":"","species":"","study_id":"sccs_o_174_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 12 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=unclear:Table 12: Systemi: POD = NOAEL (mg | /kg) | 100; EFFECT=Table 12: Systemi: POD = NOAEL (mg | /kg) | 100; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"","duration":"","effect":"Table 12: Systemi: POD = NOAEL (mg | /kg) | 100","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Table 12: Systemi: POD = NOAEL (mg | /kg) | 100","page":61,"route":"","species":"","study_id":"sccs_o_174_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 10 | % | - | oral | - | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=10; EFFECT=Table 12: Systemi: Absorption by oral | route * | 10%; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"","duration":"","effect":"Table 12: Systemi: Absorption by oral | route * | 10%","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"10","page":61,"route":"oral","species":"","study_id":"sccs_o_174_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 10 | % | - | - | - | - | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=10; EFFECT=Table 12: Systemi: * 10% based on th | e toxicokine | tic data; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"","duration":"","effect":"Table 12: Systemi: * 10% based on th | e toxicokine | tic data","endpoint":"","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"10","page":61,"route":"","species":"","study_id":"sccs_o_174_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 100 | mg/kg | rat | oral | 3-month | carcinogenicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=100; DOSE=dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref.; EFFECT=dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref. 58). In contrast, data on changes in levels of these liver enzymes following oral administration were not located. Liver weights were increased at 100, 330 and 1000 mg/kg bw/day of D5 in a 3-month oral rat study (Jager and Hartmann 1991, ref. 45). As no adverse effects were observed, 100 mg/kg-bw/day is considered to be the NOAEL for D5. Studies to investigate relevance and potential modes of action for uterine effects Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 months exposure plus 12 months recovery in air and after 24 months exposure but were only significant at the dose of 160 ppm (see section 3.3.7). There is uncertainty whether the uterine tumours are relevant or not to humans. The applicant performed additional studies to further investigate the mode of action by which endometrial adenocarcin; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref.","duration":"3-month","effect":"dy, absolute and relative liver (liver/body and liver/brain) weights and gamma glutamyltransferase (γ-GT) were significantly increased in females at 2400 mg/m3 (160 ppm) (Dow Corning 2005, ref. 58). In contrast, data on changes in levels of these liver enzymes following oral administration were not located. Liver weights were increased at 100, 330 and 1000 mg/kg bw/day of D5 in a 3-month oral rat study (Jager and Hartmann 1991, ref. 45). As no adverse effects were observed, 100 mg/kg-bw/day is considered to be the NOAEL for D5. Studies to investigate relevance and potential modes of action for uterine effects Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 months exposure plus 12 months recovery in air and after 24 months exposure but were only significant at the dose of 160 ppm (see section 3.3.7). There is uncertainty whether the uterine tumours are relevant or not to humans. The applicant performed additional studies to further investigate the mode of action by which endometrial adenocarcin","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg","noael_value":"100","page":50,"route":"oral","species":"rat","study_id":"sccs_o_174_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 100 | mg/kg bw | - | oral | 2-year | carcinogenicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=100; DOSE=For lip cosmetics, the SCCS will used the NOAEL of 100 mg/kg bw as described above.; EFFECT=SCCS-rejected applicant NOAEL: dermal and oral exposure (see 3.3.9.4). Oral route is then not appropriate to represent systemic exposure of D5 after dermal exposure except for lip products for which ingestion is anticipated. Therefore, for cosmetic products other than lip cosmetics, the SCCS will rely on the studies by inhalation to derive PODs for the safety evaluation of D5. The kinetic of D5 after exposure by inhalation is comparable to the systemic distribution and elimination after dermal exposure. For lip cosmetics, the SCCS will used the NOAEL of 100 mg/kg bw as described above. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC for local effects. For systemic effects of D5 by inhalation, the SCCS will rely on the NOAEC of 40 ppm derived from the 2-year inhalation bioassay. Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was indeed observed after 12 months inhalation exposure plus 12 months recovery and after 24 months exposure and was significant only at the highest dose of 160 ppm. No; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"For lip cosmetics, the SCCS will used the NOAEL of 100 mg/kg bw as described above.","duration":"2-year","effect":"SCCS-rejected applicant NOAEL: dermal and oral exposure (see 3.3.9.4). Oral route is then not appropriate to represent systemic exposure of D5 after dermal exposure except for lip products for which ingestion is anticipated. Therefore, for cosmetic products other than lip cosmetics, the SCCS will rely on the studies by inhalation to derive PODs for the safety evaluation of D5. The kinetic of D5 after exposure by inhalation is comparable to the systemic distribution and elimination after dermal exposure. For lip cosmetics, the SCCS will used the NOAEL of 100 mg/kg bw as described above. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC for local effects. For systemic effects of D5 by inhalation, the SCCS will rely on the NOAEC of 40 ppm derived from the 2-year inhalation bioassay. Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was indeed observed after 12 months inhalation exposure plus 12 months recovery and after 24 months exposure and was significant only at the highest dose of 160 ppm. No","endpoint":"carcinogenicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"100","page":60,"route":"oral","species":"","study_id":"sccs_o_174_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 96 | ppm | rat | inhalation | 28 days | irritation | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=96; DOSE=Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study.; EFFECT=SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 23 lungs) are consistent with changes due to inhalation of a mild irritant. Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study. In another non guideline study performed in Fischer 344 rats, effects of repeated whole- body vapour inhalation exposure of rats to D5 on liver and thyroid cell proliferation and liver hypertrophy was assessed. Female rats (30 per dose group) were exposed to D5 at nominal vapour concentrations of 0 or 160 ppm daily for 28 days with 5 days of exposure followed by 2 days of non exposure; On days 0, 7, and 21, 10 rats per dose were sacrificed and examined. Histopathological; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study.","duration":"28 days","effect":"SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 23 lungs) are consistent with changes due to inhalation of a mild irritant. Based on the effects on the lung and the liver observed at the highest dose, a NOAEL of 96 ppm may be derived from this study. In another non guideline study performed in Fischer 344 rats, effects of repeated whole- body vapour inhalation exposure of rats to D5 on liver and thyroid cell proliferation and liver hypertrophy was assessed. Female rats (30 per dose group) were exposed to D5 at nominal vapour concentrations of 0 or 160 ppm daily for 28 days with 5 days of exposure followed by 2 days of non exposure; On days 0, 7, and 21, 10 rats per dose were sacrificed and examined. Histopathological","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"96","page":23,"route":"inhalation","species":"rat","study_id":"sccs_o_174_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 1000 | mg/kg bw/d | - | oral | - | irritation | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=1000; DOSE=Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d.; EFFECT=SCCS-rejected applicant NOAEL: s. Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d. Histologically this was accompanied by hypertrophy of goblet cells and pneumonias with granuloma. Several animals receiving 1000 mg/kg bw/d had hepatocytic cytoplasmic changes that were interpreted to be morphological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all; CITATION=Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation); CITATION_NUMBERS=[45]; REFERENCE=Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation); DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d.","duration":"","effect":"SCCS-rejected applicant NOAEL: s. Anatomically, changes in lung parenchyma were observed in males from 330 mg/kg/d and in females from 100 mg/kg/d. Histologically this was accompanied by hypertrophy of goblet cells and pneumonias with granuloma. Several animals receiving 1000 mg/kg bw/d had hepatocytic cytoplasmic changes that were interpreted to be morphological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":25,"route":"oral","species":"","study_id":"sccs_o_174_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 100 | mg/kg bw/d | - | oral | - | irritation | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=100; DOSE=Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d.; EFFECT=SCCS-rejected applicant NOAEL: hological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all doses. This increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. It should be noticed that gamma-glutamyl transferase activity was not reported in this study. Inhalation Taken from SCCS/1241/10 Two groups of ten male and ten female Sprague-Da; CITATION=Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation); CITATION_NUMBERS=[45]; REFERENCE=Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation); DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation)","dose":"Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d.","duration":"","effect":"SCCS-rejected applicant NOAEL: hological signs of an adaptation to increased metabolic activity and were not considered as adverse effect. Decrease in haemoglobin concentration was observed at the doses of 1000 mg/kg bw/d. A NOAEL could not be derived from this study as adverse effects were observed at all dose levels. Ref.: 45 SCCS comments Effects observed on the lungs could be considered as local toxic effects and not as systemic ones (due to gavage or regurgitation following stomach irritation). Based on the effects observed in the liver, a NOAEL of 100 mg/kg bw/d may be derived from this study. The effects observed in this study on the liver were mainly statistically significant increases in the liver weight in male and females at all doses. This increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. It should be noticed that gamma-glutamyl transferase activity was not reported in this study. Inhalation Taken from SCCS/1241/10 Two groups of ten male and ten female Sprague-Da","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"100","page":25,"route":"oral","species":"","study_id":"sccs_o_174_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | irritation | 10 | % | rat | oral | - | irritation | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=10; DOSE=Systemic POD derived from exposure by oral route POD = NOAEL (mg/kg) 100 Absorption by oral route * 10% Systemic POD mg/kg bw/day 10 * 10% based on the toxicokinetic data • For other products than lip product the POD by inhalation will be:; EFFECT=SCCS-rejected applicant NOAEL: SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 61 • For lip products the POD will be: Table 12: Systemic POD derived from exposure by oral route POD = NOAEL (mg/kg) 100 Absorption by oral route * 10% Systemic POD mg/kg bw/day 10 * 10% based on the toxicokinetic data • For other products than lip product the POD by inhalation will be: SCCS consider that the histopathological changes observed both in the lung and the nasal cavity of rats exposed to the high concentrations of D5 may be due to the localized irritation from aerosol deposition and were not considered as systemic toxicity of the test substance. Table 13: Local POD derived from exposure by inhalation POD =; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"Systemic POD derived from exposure by oral route POD = NOAEL (mg/kg) 100 Absorption by oral route * 10% Systemic POD mg/kg bw/day 10 * 10% based on the toxicokinetic data • For other products than lip product the POD by inhalation will be:","duration":"","effect":"SCCS-rejected applicant NOAEL: SCCS/1549/15 Final version of the Opinion on decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products ___________________________________________________________________________________________ 61 • For lip products the POD will be: Table 12: Systemic POD derived from exposure by oral route POD = NOAEL (mg/kg) 100 Absorption by oral route * 10% Systemic POD mg/kg bw/day 10 * 10% based on the toxicokinetic data • For other products than lip product the POD by inhalation will be: SCCS consider that the histopathological changes observed both in the lung and the nasal cavity of rats exposed to the high concentrations of D5 may be due to the localized irritation from aerosol deposition and were not considered as systemic toxicity of the test substance. Table 13: Local POD derived from exposure by inhalation POD =","endpoint":"irritation","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"%","noael_value":"10","page":61,"route":"oral","species":"rat","study_id":"sccs_o_174_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg bw | - | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=100; DOSE=Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.; EFFECT=ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCS/1241/10, slightly modified; CITATION=(ref 45); CITATION_NUMBERS=[45]; REFERENCE=(ref 45); DETAILS_JSON={"cas_number":"541-02-6","citation":"(ref 45)","dose":"Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","duration":"subchronic","effect":"ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. Concerning exposure to D5 by inhalation, the inhaled concentration of 49 ppm was considered as a NOAEC. 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCS/1241/10, slightly modified","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"100","page":27,"route":"oral","species":"","study_id":"sccs_o_174_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg bw | - | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=100; DOSE=Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.; EFFECT=SCCS-rejected applicant NOAEL: increase in liver weight. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. The kinetic behavior of D5 is similar for inhalation and dermal exposures, but dissimilar when comparing dermal and oral exposure (see 3.3.9.4). Oral route is then not appropriate to represent systemic exposure of D5 after dermal exposure except for lip products for which ingestion is anticipated. Therefore, for cosmetic products other than lip cosmetics, the SCCS will rely on the studies by inhalation to derive PODs for the safety evaluation of D5. The kinetic of D5 after exposure by inhalation is comparable to; CITATION=(ref 45); CITATION_NUMBERS=[45]; REFERENCE=(ref 45); DETAILS_JSON={"cas_number":"541-02-6","citation":"(ref 45)","dose":"Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","duration":"subchronic","effect":"SCCS-rejected applicant NOAEL: increase in liver weight. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL. The kinetic behavior of D5 is similar for inhalation and dermal exposures, but dissimilar when comparing dermal and oral exposure (see 3.3.9.4). Oral route is then not appropriate to represent systemic exposure of D5 after dermal exposure except for lip products for which ingestion is anticipated. Therefore, for cosmetic products other than lip cosmetics, the SCCS will rely on the studies by inhalation to derive PODs for the safety evaluation of D5. The kinetic of D5 after exposure by inhalation is comparable to","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"100","page":60,"route":"oral","species":"","study_id":"sccs_o_174_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg bw | human | oral | chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=100; DOSE=This NOAEC will then be converted to a human equivalent systemic exposure dose, to be used as a POD for the calculation of the MoS.; EFFECT=the lack of a thorough mode of action in rodents and also in human for this type of tumours, the SCCS cannot exclude that these effects could be relevant in humans. However, the limited negative genotoxicity results suggest that the tumours observed in the chronic toxicity/carcinogenicity study are due to threshold effects. This NOAEC will then be converted to a human equivalent systemic exposure dose, to be used as a POD for the calculation of the MoS. In summary: For the risk assessment, the SCCS considered a NOAEL of 100 mg/kg bw derived from the oral subchronic (13 weeks) toxicity study based on the effects observed in the liver (Ref. 45) and a NOAEC of 49 ppm for local effects, derived from the 3 months inhalation studies, based on effects on a local toxicity to the lungs (Ref. 47, 48) and a systemic NOAEC of 40 ppm based on the uterine tumors observed in the 2- year inhalation bioassay. These values are used as Points of Departure (POD) for the safety assessment of D5 in cosmetic products.; CITATION=(Ref. 45); CITATION_NUMBERS=[45]; REFERENCE=(Ref. 45); DETAILS_JSON={"cas_number":"541-02-6","citation":"(Ref. 45)","dose":"This NOAEC will then be converted to a human equivalent systemic exposure dose, to be used as a POD for the calculation of the MoS.","duration":"chronic","effect":"the lack of a thorough mode of action in rodents and also in human for this type of tumours, the SCCS cannot exclude that these effects could be relevant in humans. However, the limited negative genotoxicity results suggest that the tumours observed in the chronic toxicity/carcinogenicity study are due to threshold effects. This NOAEC will then be converted to a human equivalent systemic exposure dose, to be used as a POD for the calculation of the MoS. In summary: For the risk assessment, the SCCS considered a NOAEL of 100 mg/kg bw derived from the oral subchronic (13 weeks) toxicity study based on the effects observed in the liver (Ref. 45) and a NOAEC of 49 ppm for local effects, derived from the 3 months inhalation studies, based on effects on a local toxicity to the lungs (Ref. 47, 48) and a systemic NOAEC of 40 ppm based on the uterine tumors observed in the 2- year inhalation bioassay. These values are used as Points of Departure (POD) for the safety assessment of D5 in cosmetic products.","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"100","page":60,"route":"oral","species":"human","study_id":"sccs_o_174_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg bw | - | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=100; DOSE=Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.; EFFECT=ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.; CITATION=(ref 45); CITATION_NUMBERS=[45]; REFERENCE=(ref 45); DETAILS_JSON={"cas_number":"541-02-6","citation":"(ref 45)","dose":"Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","duration":"subchronic","effect":"ht. In the subchronic oral study (ref 45), this increase in liver weight was not accompanied by histopathological lesions and no biologically relevant alterations in enzymatic activities were observed. No liver effects were reported in the chronic inhalation toxicity/carcinogenicity study. Therefore, the SCCS followed the HED guidance document on how to interpret hepatocellular hypertrophy (2002) and concluded that these liver effects are not adverse. Therefore the oral dose of 100 mg/kg bw may be considered as a NOAEL.","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"mg/kg bw","noael_value":"100","page":66,"route":"oral","species":"","study_id":"sccs_o_174_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 160 | ppm | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=160; DOSE=ot measured in F1 male pups exposed to 30 and 70 ppm D5).; EFFECT=ot measured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 pp; CITATION=Ref.: 51, Siddiqui et al; CITATION_NUMBERS=[51]; REFERENCE=Ref.: 51, Siddiqui et al; DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 51, Siddiqui et al","dose":"ot measured in F1 male pups exposed to 30 and 70 ppm D5).","duration":"developmental","effect":"ot measured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 pp","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"160","page":35,"route":"","species":"","study_id":"sccs_o_174_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 160 | ppm | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=160; DOSE=ured in F1 male pups exposed to 30 and 70 ppm D5).; EFFECT=ured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from this two-; CITATION=Ref.: 51, Siddiqui et al; CITATION_NUMBERS=[51]; REFERENCE=Ref.: 51, Siddiqui et al; DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 51, Siddiqui et al","dose":"ured in F1 male pups exposed to 30 and 70 ppm D5).","duration":"developmental","effect":"ured in F1 male pups exposed to 30 and 70 ppm D5). 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.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from this two-","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"160","page":35,"route":"","species":"","study_id":"sccs_o_174_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 160 | ppm | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=160; DOSE=tudy, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm.; EFFECT=tudy, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm. Ref.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from this two-generation study. 3.3.8.2 Developmental Toxicity See above section 3.3.8.1; CITATION=Ref.: 51, Siddiqui et al; CITATION_NUMBERS=[51]; REFERENCE=Ref.: 51, Siddiqui et al; DETAILS_JSON={"cas_number":"541-02-6","citation":"Ref.: 51, Siddiqui et al","dose":"tudy, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm.","duration":"developmental","effect":"tudy, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive toxicity, neonatal toxicity, and developmental neurotoxicity is considered to be 160 ppm. Ref.: 51, Siddiqui et al. (2007b) SCCS comments An increase in male pup anogenital distance may indicate an anti-estrogenic or androgenic effect. Yet, other studies failed to show such hormonal activity for D5. Vaginal patency and balanopreputial separation were unchanged compared to controls. For developmental and reproductive toxicity a NOAEL of 160 ppm D5 can be derived from this two-generation study. 3.3.8.2 Developmental Toxicity See above section 3.3.8.1","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"160","page":35,"route":"","species":"","study_id":"sccs_o_174_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 160 | ppm | rat | inhalation | 90 days | reproductive toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; 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. Carcinogenicity Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 mont; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","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. Carcinogenicity Carcinogenicity of D5 (uterine endometrial adenocarcinomas) was observed after 12 mont","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"ppm","noael_value":"160","page":67,"route":"inhalation","species":"rat","study_id":"sccs_o_174_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 35 | - | - | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_174; REPORT_TITLE=OPINION ON decamethylcyclopentasiloxane (cyclopentasiloxane, D5) in cosmetic products; OPINION_NUMBER=SCCS/1549/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 29 July 2016; VALUE_TEXT=unclear:Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive; EFFECT=Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"541-02-6","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","endpoint":"reproductive toxicity","ingredient":"codes.................................... 7","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 35: study, the NOAEL (no-observed-adverse-effect level) for parental toxicity, reproductive","page":35,"route":"","species":"","study_id":"sccs_o_174_noael_022"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | 0THT5PCI0R | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H30O5Si5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"0THT5PCI0R"} |
| openFDA substances | FDA UNII substance identifier | 0THT5PCI0R | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H30O5Si5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"0THT5PCI0R"} |
| openFDA substances | FDA UNII substance identifier | 0THT5PCI0R | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H30O5Si5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"0THT5PCI0R"} |
| openFDA substances | FDA UNII substance identifier | 0THT5PCI0R | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H30O5Si5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"0THT5PCI0R"} |