Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 208-762-8 | CAS number: 540-97-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2008-09-18 to 2009-02-06
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- (1998)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ICH S2A (1996) and ICH S2B (1997)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Dodecamethylcyclohexasiloxane
- EC Number:
- 208-762-8
- EC Name:
- Dodecamethylcyclohexasiloxane
- Cas Number:
- 540-97-6
- Molecular formula:
- C12H36O6Si6
- IUPAC Name:
- dodecamethylcyclohexasiloxane
- Test material form:
- other: liquid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan, Frederick MD
- Age at study initiation: 6-8 weeks
- Weight at study initiation: range finding: males 30.1-33.5 g, females 24.8-26.7 g); definitive micronucleus study: males 28.6-33.4 g, females 23.8-26.3 g.
- Assigned to test groups randomly: under following basis: according to a computer-generated program, which is based on distribution according to body weight.
- Fasting period before study: no
- Housing: up to five per rodent Micro-Barrier cage
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50 ± 20%
- Air changes (per hr): at least 10 changes of fresh HEPA-filtered air every hour.
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark
IN-LIFE DATES: no information
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Justification for choice of solvent/vehicle: based on good solubility/workability of the test article in the vehicle and compatibility with the test system and route of administration.
- Concentration of test material in vehicle: Stock solution 100 mg/ml diluted to appropriate doses: 25, 50, 100 mg/ml for definitive assay
- Lot/batch no. (if required): 3783J - Frequency of treatment:
- Single treatment
- Post exposure period:
- 24 and 78 hours
Doses / concentrationsopen allclose all
- Dose / conc.:
- 25 other: mg/ml (nominal)
- Remarks:
- analysis of dosing solutions showed 85-115% of target solution
- Dose / conc.:
- 50 other: mg/ml (nominal)
- Remarks:
- analysis of dosing solutions showed 85-115% of target solution
- Dose / conc.:
- 100 other: mg/ml (nominal)
- Remarks:
- analysis of dosing solutions showed 85-115% of target solution
- No. of animals per sex per dose:
- 5 (low and mid dose, and positive control); 10 (vehicle control); 15 (high dose)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - cyclophosphamide
- Justification for choice of positive control(s): none given in report - standard positive control substance
- Route of administration: intraperitoneal
- Doses / concentrations: concentration 2.5 mg/ml, dose 50 mg/kg bw
Examinations
- Tissues and cell types examined:
- Femoral bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Based on preliminary toxicity study.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): no additional information
DETAILS OF SLIDE PREPARATION: (slides) were prepared and stained with May-Gruenwald-Giemsa stain
METHOD OF ANALYSIS: Using a light microscope and a medium magnification (400X), an area of acceptable quality was selected such that the cells were well spread and stained. Using oil immersion (1000X), the following cell populations and cellular components were evaluated and enumerated:
Polychromatic erythrocytes (PCEs)
PCEs stain bluish. PCEs are young erythrocytes (early stage of erythropoiesis) and are the target cells for evaluation of the test article clastogenicity. Two-thousand PCEs per mouse were scored for the presence of micronuclei resulting in evaluation of a total of 10,000 PCEs per each treatment group.
Normochromatic erythrocytes (NCEs)
NCEs stain pink (reddish). NCEs are mature erythrocytes (red blood cells) and are the final cell population formed during erythropoiesis. The number of NCEs and micronucleated NCEs (MNCEs) in the field of 1000 total erythrocytes (ECs) was determined for each animal in order to determine the proportion of polychromatic erythrocytes to total erythrocytes (PCEs/ECs). The incidence of MNCEs per 2000 PCEs was enumerated for each animal, but the results were not presented in the report
Micronuclei (M)
Micronuclei are round, darkly-staining nuclear (chromosome) fragments with a sharp contour and diameters usually from 1/20 to 1/5 of an erythrocyte. Micronuclei may occur in PCEs (MPCEs) or NCEs (MNCEs).
The proportion of polychromatic erythrocytes to total erythrocytes was also recorded per 1000 erythrocytes per each animal (PCEs/ECs ratio).
- Evaluation criteria:
- A dose-dependent increase in the incidence of micronucleated polychromatic erythrocytes and one or more doses statistically elevated relative to the vehicle control would be considered a positive result.
- Statistics:
- Kastenbaum-Bowman Tables (binomial distribution, p ≤ 0.05)
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- piloerection (1000 and 2000 mg/kg), lethargy (2000 mg/kg); reductions in PCE/EC ratio (up to 11%) were observed in some test article groups relative to the vehicle control group.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 1, 10, 100, 1000 and 2000 mg/kg bw
- Solubility: no information
- Clinical signs of toxicity in test animals: lethargy and piloerection at top and top two doses respectively
- Evidence of cytotoxicity in tissue analyzed: none
- Rationale for exposure: up to limit dose
- Harvest times: 3 days
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): none
- Ratio of PCE/CE (for Micronucleus assay): reductions of up to 22% observed in some test article groups. Reduction of this magnitude without a dose response suggests that the test article did not inhibit erythropoiesis.
- Appropriateness of dose levels and route: appropriate dose levels and route
- Statistical evaluation: appropriate statistical evaluation of results
- The number of micronucleated PCEs in the vehicle control groups did not exceed the historical vehicle control range.
Any other information on results incl. tables
Table 1: Summary of Bone Marrow Micronucleus Analysis Following a Single Intraperitoneal Administration of Dodecamethylcyclohexasiloxane (D6) in ICR Mice
Treatment (20 ml/kg) |
Sex |
Time (hr) |
Number of Animals |
PCE/Total Erythrocytes (Mean +/- SD) |
Change from Control (%) |
Number of MPCE/1000 PCE (Mean +/- SD) |
Number of MPCE/PCE Scored |
||
Corn Oil
|
M |
24 |
5 |
0.426 ±0.05 |
- |
0.1 ± 0.22 |
1/10000 |
||
F |
24 |
5 |
0.396 ± 0.08 |
- |
0.1 ± 0.22 |
1/10000 |
|||
Dodecamethylcyclohexasiloxane (D6) |
|
||||||||
500 mg/kg bw |
M |
24 |
5 |
0.387 ± 0.04 |
-9 |
0.2 ± 0.27 |
2/10000 |
||
F |
24 |
5 |
0.370 ± 0.09 |
-7 |
0.2 ± 0.27 |
2/10000 |
|||
1000 mg/kg bw |
M |
24 |
5 |
0.380 ± 0.03 |
-11 |
0.01 ± 0.22 |
1/10000 |
||
F |
24 |
5 |
0.393 ± 0.07 |
-1 |
0.01 ± 0.22 |
1/10000 |
|||
2000 mg/kg bw |
M |
24 |
5 |
0.462 ± 0.02 |
8 |
0.04 ± 0.22 |
4/10000 |
||
F |
24 |
5 |
0.449 ± 0.07 |
13 |
0.02 ± 0.27 |
2/10000 |
|||
M |
48 |
5 |
0.484 ± 0.03 |
-9 |
0.2 ± 0.27 |
2/10000 |
|||
F |
48 |
5 |
0.489 ± 0.15 |
-11 |
0.2 ± 0.27 |
2/10000 |
|||
Cyclophosphamide 50 mg/kg |
M |
24 |
5 |
0.336 ± 0.04 |
-21 |
11.9 ± 1.43 |
*119/10000 |
||
F |
24 |
5 |
0.348 ± 0.04 |
-12 |
10.9 ± 1.29 |
*109/10000 |
|||
|
M |
24 |
5 |
0.530 ± 0.03 |
- |
0.2 ± 0.27 |
2/10000 |
||
Corn Oil |
F |
24 |
5 |
0.550 ± 0.03 |
- |
0.2 ± 0.27 |
2/10000 |
*Statistically significant increase, p </= to 0.05 (Kastenbaum-Bowman Tables)
Applicant's summary and conclusion
- Conclusions:
- Dodecamethylcyclohexasiloxane (D6) has been tested in a reliable in vivo micronucleus assay in ICR mice conducted according to OECD Test Guideline 474 and in compliance with GLP. No statistically significant increase in the incidence of micronucleated polychromatic erythrocytes relative to control was observed in any test substance group up to limit concentrations at 24 and 48 hours after intraperitoneal administration of the test substance. Reductions in PCE/EC ratio (up to 11%) were observed in some test article groups, indicating that the test article had reached the target tissue. Administration of cyclophosphamide (the positive control) induced marked increases in micronucleated polychromatic erythrocytes. It is concluded that the test substance is negative for the induction of micronuclei in vivo under the conditions of the test.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.