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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

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from 2005-04-26 to 2005-10-24
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
- Reference Type:
- other: letter
- Title:
- Re: TSCA Section 8(e) Notification of Substance Risk: Dodecamethylcyclohexasiloxane.
- Author:
- SEHSC
- Year:
- 2 009
- Bibliographic source:
- Letter from SEHSC
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
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
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Labs, Raleigh, NC, USA
- Age at study initiation: 9 wk
- Weight at study initiation: 173-254 (f); 285-386 (m)
- Housing: 1/suspended wire mesh cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 67.7-72.5 deg F (approximately 20 degrees celsius)
- Humidity (%): 35-59
- Air changes (per hr): 15.6
- Photoperiod (hrs dark / hrs light): 12 h/12 h
IN-LIFE DATES: From 2005-05-12 for 28 or 29 days in the toxicity portion of this study.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Prepared for the whole study. Analysed (GC) 4 times to ensure homogeneity, stability and concentration.
VEHICLE
Corn oil
- Lot/batch no.: 015K0115 - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- GC analysis on 4 occasions to ensure homogeneity, stability and concentration.
- Duration of treatment / exposure:
- males 28d
toxicity females 29d
reproductive females 46d - Frequency of treatment:
- daily, 7 days/wk
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 330 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10 males
10 toxicity and 10 reproductive females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
- Rationale for animal assignment (if not random): weight stratified randomization
- Rationale for selecting satellite groups: none
- Post-exposure recovery period in satellite groups: none - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at sacrifice
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: yes
- How many animals: all toxicity groups
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at sacrifice
- Animals fasted: Yes / No / No data
- How many animals: all toxicity groups
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: FOB at start and completion
- Dose groups that were examined: males and toxicity group females
- Battery of functions tested: cage-side observations, hand-held observations, open field observations, categorical observations, hind and forelimb grip strength, landing foot splay, motor activity. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
all toxicity groups
HISTOPATHOLOGY: Yes
Microscopic examination of a relatively large range of tissues of all control and hi-dose group animals, and the lungs and thyroid of both sexes and liver of females at the low and mid doses.
ORGAN WEIGHTS
weights of a relatively large range of organs determined - Other examinations:
- Examination for reproductive parameters (reported in the relevant IUCLID section).
- Statistics:
- ANOVA (analysis of variance): body weights, organ weight, haematology, clinical chemistry etc
ANCOVA (analysis of covariance): FOB
Cochran-Armitage: microscopic findings
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Prothrombin time prolonged in males at >=300 mg/kg bw/day with no clinical indication of clotting abnormalities.
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased absolute and/or relative liver weight in both sexes at all doses (>=100 mg/kg bw/day; statistically significant), with a modest dose-relation in females. It was said that only the relative liver weight in high-dose females exceeded historical control values.
Relative absolute and/or adrenal weights in females were increased at all doses (>=100 mg/kg bw/day; statistically significant) without any dose relationship.
Kidney weights were increased in both sexes at all doses, but only for the low and mid dose groups was the change statistically significant. There was no dose relationship. - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Microscopic examination identified a dose related increase in periportal lipidosis in the liver of females (controls: 4/10 minimal severity; treated groups 100, 330, 1000 mg/kg bw/day: 10/10, 10/10, 9/10 minimal to moderate severity). There was no other evidence of hepatotoxicity and the report considers this effect to be of “minimal toxicologic significance”. A subsequent re-evaluation of these data (TSCA 8(e), 2009) note that in the light of a dose-response in liver weight in females in the presence of hepatic histopathological changes in this sex, “it cannot be ruled out that the findings may be test article related”. In the context of this view, the LOAEL would be 100 mg/kg bw/day (in females).
Lung effects were considered an artefact due to the treatment route (further justification not given in study report, but presumably due to accidental dosing into the trachea). - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Microscopic examination identified a dose related increase in periportal lipidosis in the liver of females (controls: 4/10 minimal severity; treated groups 100, 330, 1000 mg/kg bw/day: 10/10, 10/10, 9/10 minimal to moderate severity). There was no other evidence of hepatotoxicity and the report considers this effect to be of “minimal toxicologic significance”. A subsequent re-evaluation of these data (TSCA 8(e), 2009) note that in the light of a dose-response in liver weight in females in the presence of hepatic histopathological changes in this sex, “it cannot be ruled out that the findings may be test article related”. In the context of this view, the LOAEL would be 100 mg/kg bw/day (in females).
Lung effects were considered an artefact due to the treatment route (further justification not given in study report, but presumably due to accidental dosing into the trachea).
The incidence of animals with follicular cell hypertrophy in the thyroid appeared possibly related to treatment (incidence in groups 0, 100, 330, 1000 mg/kg bw/day: 0, 5, 2, 6 in males and 1, 2, 1, 5 in females). Severity was not affected by dose in either sex. This effect was considered to be secondary and adaptive, and typical of a xenobiotic which induces hepatic microsomal enzymes with increased degradation of thyroxin and triiodothyronine as a side effect. - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No adverse effect observed.
Target system / organ toxicity
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In the oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with dodecamethylcyclohexasiloxane (D6), conducted according to OECD Test Guideline 422 and in compliance with GLP (Dow Corning Corporation, 2005), the NOAEL for systemic toxicity was concluded to be at least 1000 mg/kg bw/day, the highest dose tested. The observed liver effects (increased absolute and/or relative liver weight in all treated groups and periportal lipidosis at all doses in females) were described as “of minimal toxicologic significance” and the thyroid effects (follicular cell hypertrophy, incidence possibly treatment-related in both sexes) were referred to as secondary and adaptive to the liver changes.
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