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EC number: 208-765-4 | CAS number: 541-05-9
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2002-03-25 to 200211-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 422
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Hexamethylcyclotrisiloxane
- EC Number:
- 208-765-4
- EC Name:
- Hexamethylcyclotrisiloxane
- Cas Number:
- 541-05-9
- Molecular formula:
- C6H18O3Si3
- IUPAC Name:
- hexamethyl-1,3,5,2,4,6-trioxatrisilinane
- Test material form:
- other: white solid (no further information)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Canada, 188 LaSalle, St. Constant, Canada
- Age at study initiation: >=8 wk
- Weight at study initiation: 187-238 g (f); 250-313 g (m)
- Housing: 1/suspended wire cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 h/12 h
IN-LIFE DATES: From: 2002-03-25 To: 2002-11-07
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 450 l steel and glass Rochester-style inhalation chambers with stainless steel exposure caging.
- Method of holding animals in test chamber: individual stainless steel caged compartments
- Method of conditioning air: air passed through series of purification filters
- System of generating particulates/aerosols: TS placed in warming chamber (75 deg C). The liquid TS was then metered into a heated metal J-tube for vapourization.
- Air change rate: at 10 exchanges of chamber volume per h
TEST ATMOSPHERE
- Brief description of analytical method used: GC
- Samples taken from breathing zone: automatic sampling from chamber
Acclimatization for 3 h on 2 days - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis of test atmosphere was conducted by gas chromatography with flame ionisation detection (GC/FID) and each chamber was evaluated at least once per hour during the exposure period. For each day of exposure the mean test atmosphere D3 concentration (actual) as determined from the GC/FID analysis, was compared with the theoretical concentration (nominal), derived from the estimated chamber air flow rate and test substance consumption, as a quality control measure to evaluate exposure system performance.
- Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: continuously until evidence of copulation
- Proof of pregnancy: vaginal plug or sperm in vaginal smear (day 0) - Duration of treatment / exposure:
- Exposure period: 28 days for males and 46 days for females.
Premating exposure period (males): 2 weeks.
Premating exposure period (females): 2 weeks.
Mated femaes were exposed up to Day 19 of gestation.
Dams were not exposed during the lactation period. - Frequency of treatment:
- 6 hours/day; 7 days/week
- Duration of test:
- 46 days
- No. of animals per sex per dose:
- 10
- Control animals:
- other: yes, control group was exposed to filtered air
- Details on study design:
- - Dose selection rationale: based on the results of a previous 90-day inhalation study (DCC, 2001)
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily or twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes (see Table 1)
- Time schedule for collection of blood: at sacrifice
- Anaesthetic used for blood collection: Ketamine, HCL/Xylazine
- How many animals: all toxicity groups
CLINICAL CHEMISTRY: Yes (see Table 1)
- Time schedule for collection of blood: at sacrifice
- How many animals: all toxicity groups
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to exposure and during wk 4
- Dose groups that were examined: all toxicity groups
- Battery of functions tested: FOB and motor activity examinations. These included: cage-side, hand-held, open field and categorical observations, rectal temperature, hindlimb/forelimb grip strength and landing foot splay. Motor activity was also determined using a Cage Rack Activity System.
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: No
- Number of late resorptions: No - Fetal examinations:
- Examination for gross external malformations only.
- Statistics:
- Statistical methods: Bartlett's test and Kolmogorov-Smirnov test. Parametric data was tested using one-way Analysis of Variance (ANOVA) followed by Dunnett's Test (if significant); nonparametric data was tested by Kruskal-Wallis Test followed by Wilcoxon. Categorical data and histomorphology findings were evaluated with Fisher's
Exact Test. Statistically significant probabilities are reported at either the p<0.05 or p<0.01 levels.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Observations recorded during the weekly detailed physical examinations were not different from those recorded during the daily clinical examinations. The clinical observations that were indicative of an adverse effect of the treatment were minimal and involved an increased incidence of anogenital staining and brown staining on the head. Anogenital staining was observed in 100% of reproductive group females in the 2500 ppm groups. A single occurrence was observed in one reproductive group female in the 100 ppm group. 100% of the reproductive group females in the 2500 ppm groups exhibited staining on the head at least once during the in-life phase of the study. There were no other clinical effects of toxicity.
- Mortality:
- no mortality observed
- Description (incidence):
- All adult animals survived to their scheduled necropsy.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Group mean body weight for 500 and 2500 ppm -exposed reproductive group females were consistently lower (≤ 8%) than the control group. However, the decreases were not statistically significant except for the 2500 ppm exposure group on gestation day 20 (8% lower relative to Control). Similarly, group mean body weight gain for the exposed reproductive group females in the 500 and 2500 ppm exposure groups were typically lower (S 30%), though not statistically significant, than controls prior to week 3 of gestation. Females in the 2500 ppm exposure group demonstrated a statistically significant 21% decrease in body weight gain at gestation week 3. These changes in body weight and body weight gain are consistent with those observed for the toxicity group females (pre-mating) and with the effects on litter size (gestation and post-partum periods).
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There were no statistically significant differences in mean weekly food consumption values for the exposed reproductive group females relative to control. However, values were generally lower than control (2-12%). The one exception being a greater consumption of food (21%) during the parturition period (gestation day 20 - postpartum day 0/1) that likely represents differences in parturition (litter size and care).
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Description (incidence and severity):
- Not examined for reproductive toxicity group females.
- Clinical biochemistry findings:
- not examined
- Description (incidence and severity):
- Not examined for reproductive toxicity group females.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Description (incidence and severity):
- Not examined for reproductive toxicity group females.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were noted on ovary and uterine weights for toxicity group females.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No effects seen in female reproductive organs and tissues.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No effects seen in female reproductive organs and tissues.
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant decreases in the number of uterine implantation sites (33% decrease) when compared to the control in the 2500 ppm group.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- There were no effects on pup viability.
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- There were no effects on gestation length.
- Changes in number of pregnant:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All of the reproductive group females presented with positive evidence of mating on or before the seventh day of pairing and all but one of the reproductive group females became pregnant. The exception was a female from the 2500 ppm exposure D (Animal D0033). The uterus from this female was negative for implantation sites.
- Other effects:
- no effects observed
- Description (incidence and severity):
- There were no effects on number of corpora lutea.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 500 ppm
- Based on:
- test mat.
- Basis for effect level:
- pre and post implantation loss
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant decreases were noted for litter size (number of pups per litter on PND 0 and 4) and litter weight (27% decreases relative to control on PND 0 and 4) at 2500 ppm.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant decreases were noted for litter size (number of pups per litter on PND 0 and 4) and litter weight (27% decreases relative to control on PND 0 and 4) at 2500 ppm.
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 500 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- changes in litter size and weights
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 2 500 ppm
- Treatment related:
- yes
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In the combined repeated dose/reproductive and developmental inhalation toxicity screening test, conducted according to OECD Test Guideline 422 and in compliance with GLP, exposure to 2500 ppm (22.8 mg/L) of the test substance was associated with decreased implantation sites and litter size at 2500 ppm dose group. Therefore, the NOAEC for reproductive and developmental toxicity was concluded to be 500 ppm (4.55 mg/L).
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