Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
HPRT
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
permanent V79 cell line UI/109 from the Chinese hamster.
Forward mutation assay using the HPRT gene; cells deficient in HPRT (due to mutation) are selected by medium containing 6-thioguanine.
Metabolic activation:
with and without
Test concentrations with justification for top dose:
Without MA: 2, 5, 10, 15, 20, 25 µg/ml (3 h exposure); 2, 5, 10, 15, 20, 25 µg/ml (6 h exposure); 1, 2, 5, 7.5, 10, 12.5, 15 µg/ml (repetition 6 h exposure).
With MA: 1, 2, 5, 10, 20, 40 µg/ml (3 h exposure); 0.25, 0.5, 1, 2, 5, 10, 20, 40 µg/ml (6 h exposure)
Vehicle / solvent:
nutrient medium (DMEM)
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9,10-dimethylbenzanthracene
ethylmethanesulphonate
Details on test system and experimental conditions:
Positive control:
1 µl/ml ethylmethane sulfonate without metabolic activation (MA)
10 µg/ml dimethylbenz(a)anthracene with MA
Evaluation criteria:
as described in OECD guideline 476

Results and discussion

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

Applicant's summary and conclusion

Conclusions:
Weak mutagenic activity with and without metabolic activation at concentrations near the cytotoxic range.
Executive summary:

Study performed according to the OECD guideline 476. V79 cells were exposed without metabolic activation (MA) to: 2, 5, 10, 15, 20, 25 µg/ml (3 h exposure); 2, 5, 10, 15, 20, 25 µg/ml (6 h exposure); 1, 2, 5, 7.5, 10, 12.5, 15 µg/ml (repetition 6 h exposure). With MA the following concentrations were used: 1, 2, 5, 10, 20, 40 µg/ml (3 h exposure); 0.25, 0.5, 1, 2, 5, 10, 20, 40 µg/ml (6 h exposure) The test substance induced an increased number of mutant cells with and without metabolic activation. The test substance was considered to be mutagenic under the condition of this study. Although study results might be discussed critically due to the fact that mutagenic effects occurred at concentrations near cytotoxic concentrations. Results are presumably also due to the hydrolysis product formaldehyde. Weak mutagenic activity with and without metabolic activation at concentrations near the cytotoxic range.