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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 469-070-1 | CAS number: 17861-60-8
- 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: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13 March 2008 to 13 April 2008
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)
- Deviations:
- yes
- Remarks:
- refer to "Overall Remarks"
- Principles of method if other than guideline:
- Current guideline requirements require 150 cells to be scored/animal and that the historical control ranges presented should use C-charts, C-bar charts to identify the variability in the data set. This has not been undertaken.
- GLP compliance:
- yes
- Type of assay:
- mammalian comet assay
Test material
- Reference substance name:
- -
- EC Number:
- 469-070-1
- EC Name:
- -
- Cas Number:
- 17861-60-8
- Molecular formula:
- C9H26O2Si3
- IUPAC Name:
- 4-ethyl-2,2,4,6,6-pentamethyl-3,5-dioxa-2,4,6-trisilaheptane
- Test material form:
- liquid
- Details on test material:
- Appearance: Clear colorless liquid
Constituent 1
- Specific details on test material used for the study:
- Stability of test compound: Confirmed stable for the duration of the study
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Commonly used strain that has been used for many years
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Test animals:
Species: rat
Strain: Wistar
Age: 7-9 wks at dosing
Weight at dosing: 218-236g
Source: Harlan, Frederick
Acclimation period: 5 days
Diet: Harlan 2018C Certified Global Rodent Diet, ad libitum
Water: Municipal water, ad libitum
Housing: Five animals of the same sex/cage
Environmental conditions:
Temperature: 19-25°C
Humidity: 30-70%
Air changes: not stated
Photoperiod: 12h light/dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Corn oil (dose volume 10 mL/kg bw)
- Details on exposure:
- Preparation of dosing solutions:
The test article was prepared and diluted in corn oil before treatment. - Duration of treatment / exposure:
- Single oral dose
- Frequency of treatment:
- single
- Post exposure period:
- sampling of liver and stomach 4 and 24 h post a single oral dose
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- Sacrifice time: 4 hours: 0, 1000, 15000, 2000 mg/kg bw, MMS: 50 mg/kg bw; No. of animals: 5/gp
Sacrifice time: 24 hours: 0, 1000, 1500, 2000 mg/kg bw; No. of animals: 5/gp - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Methylmethanesulphonate (MMS) a widely used postive control for comet induction was used. A single oral dose, via gavage at 50 mg/kg bw (employing a dose volume of 10 mL/kg bw) was used
Examinations
- Tissues and cell types examined:
- Hepatocytes and stomach epithelial cells were isolated and a single cell preparation was prepared.
- Details of tissue and slide preparation:
- Details of tissue preparation:
- Liver:
The hepatocytes were isolated from the liver and the cell suspension was strained using a cell strainer and then kept on ice until slide preparation. The number of isolated living cells was determined by the trypan blue dye exclusion test.
- Stomach:
Stomachs were removed and cut open and washed free from food using mincing buffer. The forestomach was cut, removed and discarded. The surface epithelia of the glandular portion of the stomach was gently scraped using a scrapper. This layer was discarded and the gastric mucosa was rinsed with the cold mincing buffer. Then the stomach epithelium was carefully scraped 4-5 times with a scrapper. The cell suspension was then strained using a cell strainer and kept on ice until preparation of slides. The number of isolated living cells was determined by the trypan blue dye exclusion test.
Slide preparation:
From each liver and stomach cell suspension an aliquot of 5 uL and 10 uL, respectively were mixed with low melting agar and the cell/agarose suspension was applied to glass microscope slides previously coated with normal melting agarose.
Lyses:
After the agarose gel has solidified, the slides were placed overnight at 2-8 °C, in a lysis solution consisting of high salts and detergents. The Iysing solution was chilled prior to use, primarily to maintain the stability of the agarose gel.
Unwinding:
After cell lysis two slides for each organ/animal were washed with neutralisation buffer and place in the electrophoresis chamber. The chamber was filled with alkaline buffer and the slides remained in the buffer for 20 minutes to allow DNA to unwind.
Electrophoresis:
After alkali unwinding, the single-stranded DNA in the gels was electrophoresed under alkaline conditions to produce comets. The electrophoretic conditions were 0.7 V/cm for 30 minutes at room temperature (15-30°).
Neutralization and dehydration of slides:
After electrophoresis, the alkali in the gels were neutralized by rinsing the slides with neutralisation buffer and then dehydrated with 100% ethanol, air dried and stored at room temperature.
Staining:
Slides were stained with Sybr-gold prior to scoring.
Scoring:
Fifty randomly selected, non-overlapping cells/slide were scored for DNA damage using the Comet Assay IV v.4.11 Perceptive Instruments software.
DNA damage was assessed by the software system by measuring:
- Comet migration: distance from the perimeter of the comet head to the last visible point in the tail
- %Tail DNA: % tail intensity, the % of DNA present in the tail
- Olive tail moment: product of tail length and %DNA in tail
Each slide was also assessed for possible indications of cytotoxicity, i.e. presence of clouds (termed hedgehogs). The rough estimate of the %clouds was recorded for each slide.
DNA damage evaluation:
Median of 100 counts of %tail DNA, Olive tail moment and tail migration were determined and presented for each animal in each treatment group for each organ. The mean and standard deviation of the median values for %tail DNA and Olive tail moment were presented for each treatment group for each organ. - Evaluation criteria:
- The test article was considered to induce DNA damage if:
- A least one of the test doses exhibited a statistically significant increase in tail intensity, compared with the concurrent vehicle control
- The increase was dose related
The test article was considered negative in this assay if neither of the above criteria were met and target tissue was confirmed. - Statistics:
- Levene's test was performed to determine heterogenous group variances (p<0.05). Where evidence of heterogeneity was present, the data were rank transformed prior to analysis. Linear regression was used to determine the dose response relationship for the significance level (p<0.01).
Results and discussion
Test resultsopen allclose all
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Liver
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- not determinable because of methodological limitations
- Remarks:
- No evidence of target organ exposure demonstrated
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Stomach
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- Analytical determinations:
Analysis of Y-14877 in the dosing formulations met the acceptance criteria of 85-115% of target concentration and an RSD of <5%. No test article was detected in the vehicle control.
Comet assay:
1. Clinical observations: No test article related clinical signs of toxicity were observed.
2. Body weight: No test article related effects on body weight were observed.
3. Toxicity: No test article related toxicity, as evident by hedgehog occurrence on comet slides were observed.
4. Clinical chemistry: not undertaken
5. Necropsy and pathology: Both macroscopic and microscopic observations were deemed to be unremarkable.
6. Target tissue exposure: Concurrent target organ (liver) exposure was not demonstrated. Whilst target exposure to the stomach was not demonstrated, it was not considered necessary as the stomach was the first site of contact following oral gavage dosing directly into the stomach.
7. Comet analysis:
- Liver: The presence of hedgehogs was <3% and <4% for the liver at 4 and 24 hour time points, respectively. Group mean %tail intensity and tail moment values for all groups of animals treated with Y-14877 were similar to the group mean vehicle control data. There were no statistically significant differences in %tail intensity (or tail moment values) between treated and the control group at either time point. All individual animal data at all dose levels were consistent with the vehicle control animals and were generally comparable with the laboratory’s historical control observed range (refer to Table CA 7.6.2/03-1).
-Stomach: The presence of hedgehogs was <27% for the stomach at both time points. The increase in hedgehog values is typical for the stomach due to the mechanical harvesting of stomach epithelium cells required (i.e. scraping of the stomach mucosal epithelia, prior to epithelium cell harvesting).. Group mean %tail intensity values for all groups of animals treated with Y-14877 were similar to the group mean vehicle control data. There were no statistically significant differences in %tail between treated and the control group at either time point. All individual animal data at all dose levels were consistent with the vehicle control animals and were generally comparable with the laboratory’s historical control observed range.
Group mean tail moment values of animals treated with Y-14877 showed a statistically significant decrease at the 4 h sample time point. Typically, decreases in comet parameters are deemed indicative of a cross-linking effects, however the standard comet assay needs to be modified to detect such effects, with such effects not being robustly determined in a standard assay. The statistically significant decrease in tail moment values were limited to the 4 h sample time point, were not replicated at the 24 h nor replicated in the %tail intensity values and were not dose related. Therefore, it can be concluded that the decrease in tail moment values were deemed not biologically relevant (refer to Table CA 7.6.2/03-2).
Cell viability (assessed by trypan blue exclusion) for the test article-treated liver and stomach cells was <97% for both time points.
The positive controls induced an acceptable increase in %tail intensity in both liver and stomach, thereby demonstrating the sensitivity and specificity of the test system.
Any other information on results incl. tables
Table CA 7.6.2/03-1:
Group mean and individual animal liver data
Dose level (mg/kg bw) |
No. of animals |
No .of cells scored |
Mean tail intensitya |
Mean tail momenta |
Mean % hedgehogs |
||
4 hour sample time |
|||||||
0 |
5 |
500 |
1.89 ±1.18 |
0.42 ±0.23 |
---b |
||
500 |
5 |
500 |
1.71 ±0.89 |
0.39 ±0.20 |
---b |
||
1000 |
5 |
500 |
3.42 ±1.84 |
0.62 ±0.32 |
---b |
||
2000 |
5 |
500 |
1.90 ±1.18 |
0.40 ±0.22 |
---b |
||
MMS, 50 |
5 |
500 |
60.74 ±4.46* |
23.13 ±4.30* |
---b |
||
24 hour sample time |
|||||||
0 |
5 |
500 |
0.70 ±0.41 |
0.15 ±0.08 |
---b |
||
500 |
5 |
500 |
1.07 ±0.82 |
0.23 ±0.13 |
---b |
||
1000 |
5 |
500 |
0.7 ±0.25 |
0.17 ±0.04 |
---b |
||
2000 |
5 |
500 |
1.38 ±0.42 |
0.30 ±0.10 |
---b |
||
|
|||||||
Historical control data ranges for rat liver comet assay |
|||||||
Vehicle |
Mean tail intensity(% ±SD) |
Olive tail moment (±SD) |
|||||
Mean: |
4.40 ±4.23 |
Mean: |
1.03 ±1.07 |
||||
Observed range: |
0.14 – 10.49 |
Observed range: |
0.02 – 3.33 |
||||
Positive |
Mean tail intensity(% ±SD) |
Olive tail moment (±SD) |
|||||
Mean: |
50.13 ±22.18 |
Mean: |
18.94 ±13.01 |
||||
Observed range: |
16.86 – 78.68 |
Observed range: |
3.08 – 38.82 |
||||
*: p<0.05, statistically significant increase +ve control: EMS – ethyl methylsulphonate a median values of each slide calculated. The mean of the slide medians were calculated to give the individual mean animal value. The individual mean animal values were averaged to provide group means b no numerical values presented for each animal / group |
|||||||
Table CA 7.6.2/03-2:
Group mean and individual animal stomach data
Dose level (mg/kg bw) |
No. of animals |
No .of cells scored |
Mean tail intensitya |
Mean tail momenta |
Mean % hedgehogs |
||
4 hour sample time |
|||||||
0 |
5 |
500 |
24.37 ±3.90 |
7.54 ±1.41 |
---b |
||
500 |
5 |
500 |
17.55 ±3.62 |
4.89 ±1.14** |
---b |
||
1000 |
5 |
500 |
15.44 ±1.63 |
3.94 ±0.61** |
---b |
||
2000 |
5 |
500 |
17.47 ±6.02 |
4.42 ±1.69** |
---b |
||
MMS, 50 |
5 |
500 |
77.59 ±4.47* |
40.80 ±5.26* |
---b |
||
24 hour sample time |
|||||||
0 |
5 |
500 |
5.83 ±2.18 |
1.39 ±0.51 |
---b |
||
500 |
5 |
500 |
12.45 ±12.39 |
3.57 ±4.06 |
---b |
||
1000 |
5 |
500 |
10.00 ±5.03 |
2.32 ±1.09 |
---b |
||
2000 |
5 |
500 |
6.48 ±1.75 |
1.61 ±0.35 |
---b |
||
|
|||||||
Historical control data ranges for rat liver comet assay |
|||||||
Vehicle |
Mean tail intensity(% ±SD) |
Olive tail moment (±SD) |
|||||
Mean: |
14.11 ±7.65 |
Mean: |
4.63 ±3.48 |
||||
Observed range: |
7.41 – 26.90 |
Observed range: |
1.75 – 11.40 |
||||
Positive |
Mean tail intensity(% ±SD) |
Olive tail moment (±SD) |
|||||
Mean: |
50.15 ±22.99 |
Mean: |
20.06 ±16.86 |
||||
Observed range: |
30.61 – 75.53 |
Observed range: |
7.22 – 43.24 |
||||
*: p<0.05, statistically significant increase, **: p<0.05, statistically significant decrease a median values of each slide calculated. The mean of the slide medians were calculated to give the individual mean animal value. The individual mean animal values were averaged to provide group means b no numerical values presented for each animal / group |
Applicant's summary and conclusion
- Conclusions:
- Based on the results of a reliable Comet assay it is concluded that 3-ethylheptamethyltrisiloxane does not induce DNA damage in stomach and liver cells of male rats following a single oral gavage dose of 2000 mg/kg bw/day, the regulatory maximum recommended dose in accordance with currently regulatory guidelines for short-term in vivo toxicity testing. Although systemic exposure was not demonstrated in this study. based on the full data-set it is reasonable to assume that systemic exposure took place.
- Executive summary:
In a liver and stomach comet assay, Sprague Dawley rats (5/group) received a single oral dose of Y-14877 suspended in corn oil (employing a dose volume of 10 mL/kg bw). Doses selected for the comet assay were 0, 1000, 1500 and 2000 mg/kg bw. Liver and stomach were sampled at 4 and 24 hours post dose. A further group of animals (5/sex/group) received a single oral dose of methyl methane sulphonate, with liver and stomach sampled at 4 hour post dosing.
The presence of hedgehogs was <3% and <4% for the liver at 4 and 24 hour time points, respectively. Group mean %tail intensity and tail moment values for all groups of animals treated with Y-14877 were similar to the group mean vehicle control data. There were no statistically significant differences in %tail intensity (or tail moment values) between treated and the control group at either time point. All individual animal data at all dose levels were consistent with the vehicle control animals and were generally comparable with the laboratory’s historical control observed range
The presence of hedgehogs was <27% for the stomach at both time points. The increase in hedgehog values is typical for the stomach due to the mechanical harvesting of stomach epithelium cells required (i.e. scraping of the stomach mucosal epithelia, prior to epithelium cell harvesting).. Group mean %tail intensity values for all groups of animals treated with Y-14877 were similar to the group mean vehicle control data. There were no statistically significant differences in %tail between treated and the control group at either time point. All individual animal data at all dose levels were consistent with the vehicle control animals and were generally comparable with the laboratory’s historical control observed range.
Group mean tail moment values of animals treated with Y-14877 showed a statistically significant decrease at the 4 h sample time point. Typically, decreases in comet parameters are deemed indicative of a cross-linking effects, however the standard comet assay needs to be modified to detect such effects, with such effects not being robustly determined in a standard assay. The statistically significant decrease in tail moment values were limited to the 4 h sample time point, were not replicated at the 24 h nor replicated in the %tail intensity values and were not dose related. Therefore, it can be concluded that the decrease in tail moment values were deemed not biologically relevant (refer to Table CA 7.6.2/03-2).
Cell viability (assessed by trypan blue exclusion) for the test article-treated liver and stomach cells was <97% for both time points.
The positive controls induced an acceptable increase in %tail intensity in both liver and stomach, thereby demonstrating the sensitivity and specificity of the test system.
It is concluded that Y-14877 did not induce DNA damage in the stomach of male rats following a single oral gavage dose, with harvesting of stomach tissue at 4 and 24 hours later. The maximum dose administered was 2000 mg/kg bw/day, the regulatory maximum recommended dose in accordance with currently regulatory guidelines for short-termi n vivo toxicity testing.
Although systemic exposure was not demonstrated in this study. based on the full data-set it is reasonable to assume that systemic exposure took place.
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.