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Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 August 2011 to 20 December 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Version / remarks:
(1997)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
Version / remarks:
(1998)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Version / remarks:
(2008)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Reference substance name:
Reference substance 001
Cas Number:
675-62-7
Constituent 2
Chemical structure
Reference substance name:
Dichloromethyl(3,3,3-trifluoropropyl)silane
EC Number:
211-623-4
EC Name:
Dichloromethyl(3,3,3-trifluoropropyl)silane
Cas Number:
675-62-7
Molecular formula:
C4H7Cl2F3Si
IUPAC Name:
dichloro(methyl)(3,3,3-trifluoropropyl)silane

Method

Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
- Type and identity of media: MEM
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
Metabolic activation:
with and without
Metabolic activation system:
Liver S9 of Wistar phenobarbital and ß-naphthoflavone-induced rat liver S9 mix
Test concentrations with justification for top dose:
Pre-experiment:
with and without metabolic activation: 0.020, 0.039, 0.078, 0.16, 0.31, 0.63, 1.25, 2.5, 5.0, and 10.0 mM

Experiment I:
without metabolic activation: 0.63, 1.25, and 2.5 mM
with metabolic activation: 1.25, 2.5, and 5.0 mM
Experiment II:
without metabolic activation: 0.16, 0.63, and 1.75 mM
with metabolic activation: 2.0, 4.0, and 6.0 mM
Vehicle / solvent:
-Vehicle (s)/solvent(s) used: cell culture medium (MEM)
-Justification for choice of solvent/vehicle: The test item was dissolved in medium. The solvent was compatible with the survival of the cells and the S9 activity.
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation: 400 and 900 µg/ml
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with metabolic activation: 0.83 µg/ml
Details on test system and experimental conditions:
TREATMENT TIME:
4 hours (Experiment I with and without metabolic activation, experiment II with metabolic activation)
20 hours (Experiment II without metabolic activation)

FIXATION INTERVAL: 20 hours (Experiment I and II with and without metabolic activation)
NUMBER OF REPLICATIONS: 2 independent experiments
NUMBER OF CELLS SEEDED: 1E4 - 5E4 cells
NUMBER OF CULTURES: two cultures per concentration
NUMBER OF CELLS SCORED: 200 cells per concentration (100 cells per culture), (except in experiment I at a concentration of 0.63 mM without metabolic activation: 250 cells and in experiment II at a concentration of 2 mM with metabolic activation: 300 cells).
DETERMINATION OF CYTOTOXICITY: Mitotic index, cell density
Evaluation criteria:
There are several criteria for determining a positive result:
- a clear and dose-related increase in the number of cells with aberrations,
- a biologically relevant response for at least one of the dose groups, which is higher than the laboratory negative control range (0.0% - 4.0% aberrant cells (with and without metabolic activation)).
Statistics:
According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary.

Results and discussion

Test results
Key result
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Results of chromosome analysis
without metabolic activation
     Cytotoxicity Chromatid aberrations         Isochromatid aberrations       rel. Mitotic index (%) rel. Cell density (%)  Poly- ploidy mean % aberrant cells
Scored cells  gaps breaks  inter- changes  other  gaps breaks  inter- changes  other incl. Gaps excl. Gaps
 Experiment I                              
solvent control 200 - 2 1 0 0 0 0 0 0 100 100 1 1.5 0.5
0.16 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 83 n.d. n.d. n.d. n.d.
0.31 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 98 n.d. n.d. n.d. n.d.
0.63 mM 250 no 5 4 1 0 0 0 2 0 93 93 3 4.8 2.8
1.25 mM 200 no 3 1 0 0 0 0 0 0 82 97 2 2.0 0.5
2.5 mM 200 yes   7 3 0 0 1 0 0 0 40 71 0 4.0 1.5
5.0 mM - yes   n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 18 n.d. n.d. n.d. n.d.
EMS 900 µg/mL 200 - 5 13 8 1 0 0 0 3 61 74 1 12.5 11.5
 Experiment II                                  
solvent control 200 - 1 0 0 0 0 0 2 0 100 100 0 1.5 1.0
0.08 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 80 n.d. n.d. n.d. n.d.
0.16 mM 200 no 3 0 0 0 1 0 0 0 85 92 2 2.0 0.0
0.31 mM 200 yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 56 n.d. n.d. n.d. n.d.
0.63 mM 200 yes 0 0 0 0 0 0 0 0 54 77 1 0.0 0.0
1.25 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 46 n.d. n.d. n.d. n.d.
1.75 mM 200 yes 5 2 1 1 0 0 1 0 48 56 0 4.5 2.5
2.5 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.
5.0 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.
EMS 400 µg/mL 200 - 0 12 5 0 1 0 1 1 54 98 1 8.5 8.0
Results of chromosome analysis
with metabolic activation
     Cytotoxicity Chromatid aberrations         Isochromatid aberrations       rel. Mitotic index (%) rel. Cell density (%)  Poly- ploidy mean % aberrant cells
Scored cells  gaps breaks  inter- changes  other  gaps breaks  inter- changes  other incl. Gaps excl. Gaps
 Experiment I                              
solvent control 200 - 8 5 0 0 0 0 0 0 100 100 2 5.5 2.5
0.63 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 98 n.d. n.d. n.d. n.d.
1.25 mM 200 no 4 1 0 0 0 0 0 0 77 72 2 2.5 0.5
2.5 mM 200 yes   1 1 0 1 0 0 0 0 62 93 0 1.5 1.0
5.0 mM 200 yes  3 1 0 0 0 0 0 0 40 76 2 2.0 0.5
7.5 mM - yes  n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 14 n.d. n.d. n.d. n.d.
10.0 mM - yes  n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.
CPA 0.83 µg/mL 200 - 3 9 6 1 1 1 0 1 74 81 1 10.0 8.5
 Experiment II                                  
solvent control 200 - 2 1 2 1 0 0 0 0 100 100 2 2.5 1.5
0.5 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 103 n.d. n.d. n.d. n.d.
1.0 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 80 n.d. n.d. n.d. n.d.
2.0 mM 300 no 3 6 0 1 0 0 2 0 87 98 2.5 3.7 3.0
4.0 mM 200 no 3 2 0 1 1 0 2 0 87 99 3 4.0 2.5
6.0 mM 200 yes 7 3 0 1 1 0 1 0 46 80 2 6.5 2.5
8.0 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 10 n.d. n.d. n.d. n.d.
10.0 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 3 n.d. n.d. n.d. n.d.
CPA 0.83 µg/mL 200 - 0 10 5 1 1 0 0 2 88 98 1 9.0 8.5

n.d. not determined

Applicant's summary and conclusion

Conclusions:
Dichloromethyl(3,3,3-trifluoropropyl)silane was tested for in vitro cytogenicity to mammalian cells according to the OECD TG 473 and in compliance with GLP. The test item did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line with and without metabolic activation up to cytotoxic concentrations. Appropriate positive and solvent controls were included into the study and gave the expected results. The test item is therefore considered to be non-clastogenic under the conditions of the test.