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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 208-764-9 | CAS number: 541-02-6
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Gene mutation (Bacterial reverse mutation assay / Ames test): Negative
with and without activation in all strains tested (OECD TG 471) (RCC
Cytotest cell research, 2003).
Cytogenicity in mammalian cells: Negative in Chinese hamster V79 cells
(OECD TG 473) (Dow Corning Corporation, 2003).
Mutagenicity in mammalian cells: Negative in L5178Y mouse lymphoma cells
(similar to OECD TG 476) (Litton Bionetics, 1978).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital beta-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 33, 100, 333, 1000, 2500 and 5000 μg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: the solvent was chosen because of its solubility properties and relative non-toxicity to bacteria, and on request of the sponsor. - Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- All strains (with activation)
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine
- Remarks:
- TA 98, TA 1537 (without activation)
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 100, TA 1535 (without activation)
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- WP2uvrA (without activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 minutes
- Expression time (cells in growth medium): 48 hours
NUMBER OF REPLICATIONS: 3 plates for each test concentration
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; background lawn - Evaluation criteria:
- The test article is considered a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA-98, TA-100 and WP2 uvrA) or thrice (strains TA-1535, TA-1537) the colony count of the corresponding solvent control is observed. An increase exceeding the threshold at only one concentration is judged as biologically relevant if produced in an independent second experiment. A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration. A dose dependent increase in the number of revertant colonies below the threshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment. However, whenever the colony counts remain within the historical range of the negative and solvent controls such an increase is not considered biologically relevant.
- Statistics:
- No statistical evaluation is required. Responses (number of revertants) to the test article were compared to concurrent
negative and positive controls. - Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No substantial increase in revertants colony numbers of any the five tester strains was observed following treatment with D5 at any dose level, either in the presence or absence of metabolic activation. Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies. The controls were within historical values with the following exceptions: Strain TA 1535 without activation: number of revertants greater than historical values; small deviations were observed in the negative controls of two strains in the second experiment. These deviations do not affect the validity of the experiment.
- Conclusions:
- Decamethylcyclopentasiloxane has been tested according to OECD 471 and in compliance with GLP using Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and Escherichia coli WP2 uvrA. No test-substance related increase in the number of revertants was detected in the presence or absence of metabolic activation in either the initial (RCC Cytotest cell research, 2003) plate incorporation assay or the repeat experiment using pre-incubation, up to limit concentrations. Appropriate positive, solvent and untreated controls were included and gave expected results. The test substance is therefore considered to be negative for mutagenicity to bacteria under the conditions of the test.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9
- Test concentrations with justification for top dose:
- Expt. I: up to 0.2 ul/ml (without S9 mix) and up to 5 ul/ml (with S9 mix)
Expt II: up to 0.025 ul/ml (without S9 mix) and up to 5 ul/ml (with S9 mix) continuous exposure - Vehicle / solvent:
- Ethanol
- Untreated negative controls:
- yes
- Remarks:
- Growth medium
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- (without activation)
- Untreated negative controls:
- yes
- Remarks:
- Growth medium
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- (with activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: (without activation) 4 hours exp 1; 18, 28 hours exp 2. (with activation) 4 hours exp 1 and 2
- Expression time (cells in growth medium): (without activation) 18,18, 28 hours exp 1; (with activation) 18, 28 hours exp 2
NUMBER OF REPLICATIONS: 2 plates for each test concentration
NUMBER OF CELLS EVALUATED: 100 metaphase cells scored per plate
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; relative total growth
OTHER EXAMINATIONS:
- Determination of polyploidy: determined as % of control - Evaluation criteria:
- Chromosomes analysed for aberrations and statistical significance calculated.
- Statistics:
- Statistical significance was determined by means of the Fischer exact test (p<0.05).
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 4 hrs at 0.039 to 0.6 ul/ml and for 24 hrs at 0.039 ul/ml and above in the absence of S9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Other confounding effects: In experiment 1, in the absence of S9 mix, oily drops were observed on the surface of the culture medium 4 hours after the start of treatment at 0.1 and 0.2 ul/ml. - Conclusions:
- Decamethylcyclopentasiloxane has been tested according to OECD 473 and in compliance with GLP in Chinese hamster lung fibroblasts (V79 cells). No test-substance related increase in the number of cells with structural or numerical aberrations was detected in the presence or absence of metabolic activation in either the initial or the repeat exposure when tested up to cytotoxic concentrations. Appropriate positive, solvent and untreated controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations (i.e. is not clastogenic) under the conditions of the test.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- yes
- Remarks:
- no duplicates
- Principles of method if other than guideline:
- The procedure used is a modification of that reported by Clive and Spector (Mutation Research, 31 17-29, 1975).
- GLP compliance:
- no
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- Mouse liver S9
- Test concentrations with justification for top dose:
- 0.8-12.5 µl/ml (-S9); 0.8-6.4 µl/ml (+S9)
- Vehicle / solvent:
- Ethanol
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-dimethylnitrosamine
- Remarks:
- (with activation)
- Evaluation criteria:
- A compound is considered mutagenic if the minimum increase is at least 2.5 times greater than the solvent control value.
- Statistics:
- A mutation index was derived by dividing the number of clones found in the BUdR-containing selection medium by the number found in the same medium without BUdR. The ratio was then compared to that obtained from other dose levels and from positive and negative controls.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- COMPARISON WITH HISTORICAL CONTROL DATA: Responses were within the excepted ranges.
- Conclusions:
- Decamethylcyclopentasiloxane has been tested in a study conducted according to a protocol that is similar to OECD TG 476. No significant mutagenic activity was noted for the test substance with or without metabolic activation when tested in L5178Y TK+/- mouse lymphoma cells up to cytotoxic concentrations. Appropriate positive, solvent and untreated controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.
Referenceopen allclose all
Table 1 Experiment 1 plate incorporation: Number of revertants per plate (mean of 3 plates)
|
TA 1535 |
TA 1537 |
TA 98 |
||||||
Conc. |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
Untreated |
16 |
17 |
no |
6 |
21 |
no |
27 |
32 |
no |
0* |
13 |
27 |
no |
8 |
15 |
no |
28 |
44 |
no |
33 |
13 |
14 |
no |
5 |
13 |
no |
30 |
41 |
no |
100 |
14 |
17 |
no |
5 |
11 |
no |
32 |
42 |
no |
333 |
10 |
18 |
no |
7 |
16 |
no |
34 |
42 |
no |
1000 |
15 |
14 |
no |
9 |
15 |
no |
30 |
40 |
no |
2500 |
14 |
16 |
no |
7 |
11 |
no |
33 |
39 |
no |
5000 |
16 |
13 |
no |
8 |
13 |
no |
36 |
33 |
no |
Positive control |
884 |
161 |
- |
58 |
67 |
- |
273 |
658 |
- |
*solvent control with ethanol
Table 2 Experiment 1 plate incorporation: Number of revertants per plate (mean of 3 plates)
|
TA 100 |
E coli WP2 uvrA |
||||
Conc. |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
Untreated |
162 |
178 |
no |
35 |
42 |
no |
0* |
152 |
164 |
no |
40 |
47 |
no |
33 |
166 |
194 |
no |
38 |
36 |
no |
100 |
156 |
190 |
no |
45 |
39 |
no |
333 |
151 |
215 |
no |
35 |
43 |
no |
1000 |
148 |
207 |
no |
35 |
47 |
no |
2500 |
164 |
206 |
no |
26 |
46 |
no |
5000 |
144 |
190 |
no |
31 |
47 |
no |
Positive control |
773 |
970 |
- |
768 |
180 |
- |
*solvent control with ethanol
Table 3 Experiment 2 preincubation: Number of revertants per plate (mean of 3 plates)
|
TA 1535 |
TA 1537 |
TA 98 |
||||||
Conc. |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
Untreated |
18 |
16 |
no |
8 |
15 |
no |
33 |
40 |
no |
0* |
15 |
21 |
no |
9 |
12 |
no |
38 |
48 |
no |
33 |
11 |
17 |
no |
11 |
14 |
no |
32 |
39 |
no |
100 |
16 |
20 |
no |
10 |
9 |
no |
34 |
46 |
no |
333 |
21 |
19 |
no |
8 |
15 |
no |
40 |
48 |
no |
1000 |
18 |
17 |
no |
11 |
13 |
no |
41 |
47 |
no |
2500 |
15 |
15 |
no |
9 |
10 |
no |
40 |
48 |
no |
5000 |
16 |
14 |
no |
8 |
11 |
no |
43 |
55 |
no |
Positive control |
1319 |
147 |
- |
72 |
64 |
no |
229 |
507 |
- |
*solvent control with ethanol
Table 4 Experiment 2 preincubation: Number of revertants per plate (mean of 3 plates)
|
TA 100 |
E coli WP2 uvrA |
||||
Conc. |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
Untreated |
178 |
248 |
no |
38 |
31 |
no |
0* |
206 |
287 |
no |
44 |
37 |
no |
33 |
191 |
265 |
no |
32 |
49 |
no |
100 |
187 |
251 |
no |
38 |
51 |
no |
333 |
213 |
244 |
no |
41 |
46 |
no |
1000 |
185 |
239 |
no |
36 |
38 |
no |
2500 |
217 |
269 |
no |
39 |
35 |
no |
5000 |
229 |
318 |
no |
47 |
43 |
no |
Positive control |
581 |
624 |
- |
284 |
166 |
- |
*solvent
control with ethanol
Summary of results: mean of duplicate cultures, 100 cells per culture counted
Concentration μl/ml |
Polyploid cells (% of control) |
Cell numbers (% of control) |
Mitotic indices (% of control) |
Cells with aberrations (%) |
||
inc gaps |
exc gaps |
with exchanges |
||||
Experiment 1 without metabolic activation; 4 h exposure |
||||||
0* |
2.4 |
n.t. |
100 |
1.5 |
0.5 |
0.0 |
0** |
2.9 |
100 |
100 |
0.5 |
0.5 |
0.0 |
Positive control |
2.7 |
n.t. |
132 |
18.0 |
15.5 |
7.5 |
0.003 |
2.6 |
102 |
136 |
3.0 |
0.5 |
0.0 |
0.013 |
2.9 |
54 |
81 |
2.5 |
1.5 |
1.0 |
0.025 |
2.5 |
40 |
93 |
1.0 |
0.5 |
0.0 |
Experiment 2 without metabolic activation; 18 h exposure |
||||||
0* |
1.3 |
n.t |
100 |
2.0 |
1.5 |
0.0 |
0** |
1.9 |
100 |
100 |
0.5 |
0.0 |
0.0 |
Positive control |
1.4 |
n.t. |
140 |
11.5 |
9.0 |
3.0 |
0.003 |
1.4 |
90 |
112 |
1.5 |
0.5 |
0.0 |
0.006 |
1.7 |
96 |
75 |
1.5 |
0.5 |
0.0 |
0.013 |
2.1 |
31 |
39 |
0.0 |
0.0 |
0.0 |
Experiment 2 without metabolic activation; 28 h exposure |
||||||
0* |
1.8 |
n.t |
100 |
1.0 |
0.5 |
0.0 |
0** |
2.1 |
100 |
100 |
2.5 |
2.0 |
0.0 |
Positive control |
1.7 |
n.t. |
86 |
30.0 |
28.0 |
13.0 |
0.003 |
1.8 |
85 |
116 |
1.0 |
0.5 |
0.0 |
0.006 |
1.9 |
36 |
57 |
0.0 |
0.0 |
0.0 |
Experiment 1 with metabolic activation; 4 h exposure |
||||||
0* |
2.2 |
n.t |
100 |
2.0 |
1.5 |
0.0 |
0** |
2.6 |
100 |
100 |
3.0 |
2.0 |
0.5 |
Positive control |
1.9 |
n.t. |
98 |
14.0 |
13.0 |
5.5 |
3.0 |
2.1 |
77 |
93 |
4.0 |
3.0 |
0.5 |
4.0 |
1.9 |
95 |
87 |
3.0 |
2.0 |
1.0 |
5.0 |
2.0 |
99 |
92 |
2.5 |
1.5 |
0.5 |
Experiment 2 with metabolic activation; 4 h exposure |
||||||
0* |
1.1 |
n.t |
100 |
0.0 |
0.0 |
0.0 |
0** |
0.9 |
100 |
100 |
1.0 |
0.5 |
0.0 |
Positive control |
1.0 |
n.t. |
93 |
11.0 |
10.0 |
0.5 |
3.0 |
0.7 |
95 |
122 |
0.5 |
0.5 |
0.0 |
4.0 |
1.2 |
116 |
103 |
1.0 |
0.0 |
0.0 |
5.0 |
1.5 |
87 |
96 |
0.0 |
0.0 |
0.0 |
* negative control (untreated)
** solvent control (ethanol)
Table 2: Results of Mammalian Mutagenicity assay with L5178Y/TK+/- Mouse Lymphoma cells
Concentration µl/ml |
Mutant* Frequency |
Mutant* Frequency |
%Relative Growth. |
%Relative Growth. |
Cytotoxicity |
|
— MA |
+ MA |
— MA |
+ MA |
- |
Solvent Control |
11.5 |
74.7 |
100 |
100 |
No |
Negative Control |
- |
- |
78 |
221.2 |
No |
Positive Control |
400 |
247.9 |
8.1 |
5.0 |
No |
0.8 |
24.2 |
13.1 |
83.6 |
112.1 |
No |
1.6 |
16.6 |
6.5 |
99.5 |
242.3 |
No |
3.2 |
14.3 |
17 |
82.4 |
183.1 |
No |
6.4 |
14.7 |
140 |
103.6 |
14.9 |
yes (+MA) |
12.5 |
21.5 |
- |
79.7 |
- |
no |
*Per 106surviving cells
Solvent control with Ethanol
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Micronucleus assay inhalation study in rat: Negative (OECD TG 474) (RCC
Cytotest cell research, 2004).
Unscheduled DNA synthesis inhalation study in rat: Negative (OECD 486)
(RCC Cytotest cell research, 2004).
Link to relevant study records
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- unscheduled DNA synthesis
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Males 8 weeks / Females 9 - 12 weeks
TEST ANIMALS
- Source: Chales River
- Age at study initiation: Males 8 weeks / Females 9 - 12 weeks
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: 2 same sex animals in stainless steel cages in sealed chambers
- Diet: ad libitum, except during exposure periods
- Water: ad libitum, except during exposure periods
- Acclimation period: 5days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 - Route of administration:
- inhalation
- Vehicle:
- - Vehicle(s)/solvent(s) used: air
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: whole body
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2200 L, stainless steel chambers equipped with glass doors
- Source and rate of air: Compressed air (40l/min)
- System of generating particulates/aerosols: Vapours generated by heating round-bottom flask containing test article
- Air flow rate: 380 l/min
- Duration of treatment / exposure:
- 6 hours/day for 7 days
- Frequency of treatment:
- daily for 7 consecutive treatments
- Dose / conc.:
- 160 ppm (nominal)
- Remarks:
- highest that can be prepared consistently based on vapour pressure
- No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- 2-acetylaminofluorene
- Route of administration: Oral gavage
- Doses / concentrations: 100 mg/kg b.w. - Tissues and cell types examined:
- hepatocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): All animals were observed for mortality/moribundity twice daily during the 7 day exposure period, prior to and following exposure. Body weights were taken on the first day of the acclimatization period and on exposure days 1, 4 and 7.
DETAILS OF SLIDE PREPARATION: Primary hepatocytes were obtained by liver perfusion and cultures were established and exposed for 4 hours to 3HTdR, which is incorporated if UDS occurs. Cells were fixed to coverslips, which were contained in the culture dishes, and prepared for silver grain counting (autoradiography)
METHOD OF ANALYSIS: At least two slides/animal and 50 cells/slide were evaluated. The nuclear and cytoplasmic grain counts, as well as, the net grain counts (nuclear minus cytoplasmic grains) were reported separately. - Evaluation criteria:
- A test item is classified as positive if the mean number of net grains is higher than five per nucleus at one of the test points. A group average between 0 and 5 net grains is considered a marginal response.
- Statistics:
- Student's t-test for body weights; Mann-Whitney test for analysis of micronucleated polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE).
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- The mean nominal concentration for the groups exposed to D5 (Groups 2, 5, 8 and 11) was 164.1 ± 3.2 ppm. The mean
analytical concentration for the same groups was 156.4 ± 3.1 ppm, thus, 4.7% lower than the mean nominal concentration.
There were no unscheduled deaths or clinical signs observed during the course of the study. There were no statistically
significant differences in body weight between the treatment and the control groups.
The viability of the hepatocytes was not substantially affected by the in vivo treatment with the test item at any
of the treatment periods. The interindividual variations obtained for the numbers and the viabilities of the isolated
hepatocytes were in the range of the laboratory's historical control.
The test item did not induce any UDS in the hepatocytes of the treated animals as compared to the current vehicle
controls. Neither the nuclear grains nor the resulting net grains were distinctly enhanced due to the in vivo treatment
of the animals with the test item. Therefore, the net grain values obtained after treatment with the test item were
consistently negative. In addition, no substantial shift to higher values was obtained in the percentage distributions
of the nuclear grain counts.
In vivo treatment with 2-AAF revealed distinct increases in the number of nuclear and net grain counts. - Conclusions:
- Decamethylcyclopentasiloxane has been tested according to OECD 486 and in compliance with GLP in an inhalation study in rat. No test substance related induction of unscheduled DNA synthesis in the hepatocytes of treated rats relative to the vehicle was observed. Appropriate positive control substance was used and gave expected results. it is concluded that the test substance is negative for the induction of unscheduled DNA synthesis in rat hepatocytes under the conditions of the test.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Qualifier:
- according to guideline
- Guideline:
- other: Commission Directive 2000/32/EC, Annex 4C
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Males 8 weeks / Females 9 - 12 weeks - Route of administration:
- inhalation: vapour
- Vehicle:
- - Vehicle(s)/solvent(s) used: air
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: whole body
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2200 L stainless steel chambers equipped with glass doors
- Source and rate of air: Compressed air
- Method of conditioning air: Compressed air (40l/min) was used to carry vapours from the heated round-bottom flask (containing the test article) to the chamber inlet where it was mixed with filtered dilution air (380 l/min).
- Air flow rate: 380 l/min - Duration of treatment / exposure:
- 6 hours
- Frequency of treatment:
- Daily for 7 consecutive days
- Post exposure period:
- 24 hours
- Dose / conc.:
- 160 ppm (nominal)
- No. of animals per sex per dose:
- Groups 1 - 9 each consisted of twelve animals/group (six animals/sex) while groups 10 - 11 consisted of only six
animals/group (females only). - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- One positive control group treated the same as the air control groups except dosed by oral gavage with
cyclophosphamide (CPA at 40 mg/kg b.w.) after the final exposure (group 9). - Tissues and cell types examined:
- For the analysis of micronucleated erythrocytes, animals were sacrificed 24 hours following the last exposure and the marrow from the femora was harvested.
- Details of tissue and slide preparation:
- The erythrocytes were separated from the nucleated cells and smears were air-dried, stained and coverslipped. At least one slide was made from each bone marrow sample. At least 2000 polychromatic erythrocytes (PCE) were analysed/animal for micronuclei (chromosomal fragments or whole chromosomes induced by clastogens).
- Evaluation criteria:
- The ratio between polychromatic and normochromatic erythrocytes (NCE) was determined to assess cytotoxicity. For an acceptable test, the polychromatic/normochromatic erythrocyte ratio (PCE/NCE) should be within 20% of the negative control.
- Statistics:
- Statistical analysis was performed to determine if the mean number of micronucleated PCEs or NCEs in the test group
was significantly increased (p<0.05) compared to the control group.
Student's t-test for body weights; Mann-Whitney test for analysis of micronucleated polychromatic erythrocytes (PCE)
and normochromatic erythrocytes (NCE). - Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- The mean nominal concentration for the groups exposed to D5 (Groups 2, 5, 8 and 11) was 164.1 ± 3.2 ppm. The mean
analytical concentration for the same groups was 156.4 ± 3.1 ppm, thus, 4.7% lower than the mean nominal concentration.
There were no unscheduled deaths or clinical signs observed during the course of the study. There were no statistically
significant differences in body weight between the treatment and the control groups.
The mean number of PCEs was not decreased after treatment with the test item as compared to the mean values of the
vehicle control, indicating that decamethylcyclo-pentasiloxane (D5) had no cytotoxic properties in the bone marrow.
In comparison to the corresponding vehicle controls there was no statistically significant or biologically relevant
enhancement in the frequency of the detected micronuclei in both NCEs and PCEs after administration of the test item.
The mean values of micronuclei observed after treatment with decamethylcyclopentasiloxane (D5) were below or near to the
value of the vehicle control group.
CPA administered orally was used as a positive control which showed a statistically significant increase of induced micronucleus
frequency. - Conclusions:
- Decamethylcyclopentasiloxane has been tested according to OECD 474 and in compliance with GLP in an inhalation study in rat. No increase levels of
micronucleated cells relative to control was observed in the bone marrow cells of the treated rats. Appropriate vehicle and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.
Referenceopen allclose all
Table 1 Mean net grains per nucleus
Treatment |
Net grains per nucleus (males) |
Net grains per nucleus (females) |
||
Period |
5/6 hours |
16 hours |
5/6 hours |
16 hours |
Air control |
-9.57 |
-14.80 |
-6.51 |
-12.85 |
160 ppm D5 |
-9.72 |
-13.16 |
-7.26 |
-11.83 |
Positive control |
45.65 |
17.99 |
34.27 |
13.41 |
Table 1 Micronucleus results: males
Test group |
NCEs with micronuclei (%) |
PCEs with micronuclei (%) |
PCE/NCE |
Air control |
0.030 |
0.190 |
2000/2226 |
160 ppm D5 |
0.040 |
0.100 |
2000/2435 |
40 mg/kg bw CPA* |
0.020 |
0.775 |
2000/3263 |
*CPA Cyclophosphamide (positive control)
Table 2 Micronucleus results: females
Test group |
NCEs with micronuclei (%) |
PCEs with micronuclei (%) |
PCE/NCE |
Air control |
0.025 |
0.125 |
2000/2493 |
160 ppm D5 |
0.060 |
0.100 |
2000/2214 |
40 mg/kg bw CPA* |
0.045 |
0.380 |
2000/3086 |
*CPA
Cyclophosphamide (positive control)
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Information is available from reliable studies for all the required in vitro endpoints. Where there was more than one result for an endpoint the most reliable study available was chosen as key study. Where there was more than one reliable study, the most recent study was selected. In addition to the standard assays, there are results available from an in vitro sister chromatid exchange assay in L5178Y cells, and DNA damage in bacterial and L5178Y cells. The results of all the studies were in agreement.
D5 has been tested according to OECD 471 and in compliance with GLP using Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and Escherichia coli WP2 uvrA (RCC Cytotest cell research, 2003). No test-substance related increase in the number of revertants was detected in the presence or absence of metabolic activation in either the initial plate incorporation assay or the repeat experiment using pre-incubation up to limit concentrations. Appropriate positive, solvent and untreated controls were included and gave expected results. The test substance is therefore considered to be negative for mutagenicity to bacteria under the conditions of the test.
D5 has been tested according to OECD 473 and in compliance with GLP in Chinese hamster lung fibroblasts (V79 cells) (Dow Corning Corporation, 2003). No test-substance related increase in the number of cells with structural or numerical aberrations was detected in the presence or absence of metabolic activation in either the initial or the repeat exposure when tested up to cytotoxic concentrations. Appropriate positive, solvent and untreated controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations (i.e. is not clastogenic) under the conditions of the test.
D5 has been tested in a study conducted according to a protocol that is similar to OECD TG 476 (Litton Bionetics, 1978). No significant mutagenic activity was noted for the test substance with or without metabolic activation when tested in L5178Y TK+/- mouse lymphoma cells up to cytotoxic concentrations. Appropriate positive, solvent and untreated controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.
D5 has been tested according to OECD 474 and in compliance with GLP in an inhalation study in rat (RCC Cytotest cell research, 2004). No increase levels of micronucleated cells relative to control was observed in the bone marrow cells of the treated rats. Appropriate vehicle and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.
D5 has been tested according to OECD 486 and in compliance with GLP in an inhalation study in rat (RCC Cytotest cell research, 2004). No test substance related induction of unscheduled DNA synthesis in the hepatocytes of treated rats relative to the vehicle was observed. Appropriate positive control substance was used and gave expected results. it is concluded that the test substance is negative for the induction of unscheduled DNA synthesis in rat hepatocytes under the conditions of the test.
Overall, the mutagenicity of D5 was
investigated for the above endpoints. D5 neither induced gene mutations
in bacteria in vitro, nor caused an increase in cells with chromosome
aberrations. These negative results were confirmed under in vivo
conditions. Treatment with D5 also neither led to an increase in cells
with micronuclei in the bone marrow cells of mice, nor caused
unscheduled DNA synthesis in rats. Consequently, D5 can be considered to
have no genotoxic potential and additional tests are not required.
Justification for classification or non-classification
Based on the available data decamethylcyclopentasiloxane does not require classification for mutagenicity according to Regulation (EC) No. 1272/2008.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)