Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Qualifier:
according to
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Qualifier:
according to
Guideline:
EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): Polyether V 531
- Molecular weight: 356
- Physical state: liquid
- Content: 100 %
- Stability under test conditions: the stability in the vehicle was approved analytically

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
S9: isolated from Arochlor 1254 male Sprague Dawley rat liver microsomal fraction
Test concentrations with justification for top dose:
900, 1800, 3600 µg/ml
Vehicle / solvent:
deionized water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: see below
Details on test system and experimental conditions:
Positive controls:
without S9 mix: Mitomycin C, 0.1 µg/ml (for 4 hour treatment) and 0.03 µg/ml (for 18 hour treatment)
with S9 mix: Cyclophosphamide, 2 µg/ml
Chromosomes were prepared 18 and 30 hours (for 4 hour treatment) or 18 hours (for 18 hour treatment) after start of treatment with test substances. The treatment interval was 4 hours with and without metabolic activation and 18 hours without metabolic activation. In each experimental group two paralell cultures were set up. Per culture 100 metaphases were scored for structural chromosomal aberrations. Polyploid metaphases were recorded.
Evaluation criteria:
An increased incidence of gaps of both types without concomitant increase of other aberration types was not considered as indication of a clastogenic effect.
A test was considered positive, if there was a relevant and statistically significant increasein the aberration rate.
A test was considered negative, if there was no such increase at any time interval.
A test was also considered negative, if there were statistical significant values, which were, however, within the range of historical negative controls.
In addition, a test was considered equivocal if there was an increase of aberrant metaphases above the range of attached historical negative controls, provided the increase was not significant and the result of the negative control was not closely related to the data of the respective treatment group. A test was also considered equivocal, if its result was implausible.
Statistics:
Statistical significance at the 5% level (p<0.05) was evaluated by means of the chi-square test. Evaluation was performed only for cells carrying aberrations exclusive gaps.

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:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
- Effects on pH: none
- Effects of osmolality: no effects
- Water solubility: soluble up to at least 360 mg/ml
- Precipitation: none



Applicant's summary and conclusion

Conclusions:
No evidnece of clastogenicity was seen under the conditions of this study.
Executive summary:

The clastogenic potential of the test substance was evaluated in a chromosome aberration test on Chinese hamster V79 cells in the presence and absence of S9 mix according to OECD TG 473.

None of the cultures treated with the test substance in the absence and in the presence of S9 mix showed biologically relevant or statistically significant increased numbers of aberrant metaphases.

Based on this test, the test substance is considered not to be clastogenic for mammalian cells in vitro.