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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-12-20 to 1989-01-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented GLP and guideline study according to prior OECD TG.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes
Remarks:
GLP compliance statement attached to full study report.
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Eucaryotic cells: Mutants at the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) locus.
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
S9-Mix
Test concentrations with justification for top dose:
80, 300, 600, 800 µg/ml
Vehicle / solvent:
DMSO
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 S9-mix

Migrated to IUCLID6: concentration: 1mg/ml
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9,10-dimethylbenzanthracene
Remarks:
with S9-Mix

Migrated to IUCLID6: 7.7 µg/ml dissolved in DMSO, final concentration: 0.5%
Details on test system and experimental conditions:
- Cell culture medium: MEM (Minimal essential medium) with Hanks salts and 25 mM Hepes-buffer
- Two days old exponentially growing cultures more than 50% confluent were trypsinated and a single cell suspension was prepared
- Subsequently, the cells were replated for mutagenicity testing and for determination of plating efficiency
- Treatment of the cells with the test substance in the presence or the absence of metabolic activation for 4 hrs
Evaluation criteria:
- The test substance is classified as mutagenic if it induces with one of the test substance concentrations reproducibly a mutation frequency that is three times higher than the spontaneous mutant frequency in this experiment.
- The test substance is classified as mutagenic if there is a reproducible concentration-related increase in the mutation frequency. Such evaluations may be considered independently from the enhancement factor for induced mutants.
However, in a case by case evaluation both decisions depend on the level of the corresponding negative control data.

Results and discussion

Test results
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
Remarks:
Tested up to the limit of solubility of 800 µg/ml.
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
- Highest concentration w/o precipitation was found to be 800µg/mL
- The test item was proven not to be cytotoxic to the cells up to the limit of solubility
- 800 µg/mL was the highest dose tested in the experiments on mutagenicity
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The results permit to draw the conclusion that the test compound is not mutagenic in the HGPRT-test with cells of the V79 Chinese hamster cell line.