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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
Type of information:
other: read across from analogue substance
Adequacy of study:
key study
Study period:
Since July 31, 1989 to August 28, 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant with international guideline

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EEC Directive 87/302, L 133, p. 61 - 63
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
mammalian cell gene mutation assay

Test material

Constituent 1
Reference substance name:
Similar substance 1
IUPAC Name:
Similar substance 1
Details on test material:
- Name of test material : FAT 40'3171B
- Substance type: organic dye for food
- Physical state: powder, dark-brown
- Composition of test material, percentage of components: about 70%, water: 9,4%
- Lot/batch No.: Op 1/88

Method

Target gene:
no data
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
without S9 mix: 5.0; 10.0; 25.0 and 50.0 µg/ml
with S9 mix: 5.0; 10.0; 25.0 and 50.0 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: 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
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
7,12-dimethylbenzanthracene
Remarks:
with S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: MEM medium supplemented with 10 % fetal calf serum

NUMBER OF REPLICATIONS:2

NUMBER OF CELLS EVALUATED: 8 x 10^5
Evaluation criteria:
A test article is classified as positive if it induces either a significant dose-related increase in the mutant frequency or a reproducible and significant positive response for at least one of the test points.
A test article producing neither a significant dose related increase in the mutant frequency nor a significant and reproducible positive response at any one of the test points is considered non-mutagenic in this system.
A significant response is described as follows:
The test article is classified as mutagenic if it induces reproducibly with at least one of the concentrations a mutation frequency that is three times higher than the spontaneous mutation frequency in the experiment.
The test article is classified as mutagenic if there is a reproducible concentration - related increase in the mutation frequency. Such evaluation may be considered independently of an enhancement factor for induced mutants.

Results and discussion

Test results
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS

- Precipitation:
higher concentrations precipitated in the culture medium. Therefore, in the main experiments 50.0 µg/ml was chosen as highest concentration.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

In conclusion it can be stated that during the described mutagenicity test and under the experimental conditions reported the test article did not induce point mutations at the HGPRT locus in V79 cells. Therefore, the substance is considered to be non-mutagenic in this HGPRT assay.
Executive summary:

The study was performed to investigate the potential of the substance to induce gene mutations at the HGPRT locus in V79 cells of the Chinese hamster in vitro. The assay was performed in two independent experiments, using identical procedures, both with and without liver microsomal activation. The test article was tested with the following concentrations:

without S9 mix:               5,0; 10,0; 25.0 and 50.0 µg/ml

with       S9 mix: 5.0; 10.0; 25.0 and 50.0 µg/ml

According to the pre-experiment for toxicity the concentration range was selected to yield concentration related toxic effects. The highest concentration applied produced no distinct decrease of the plating efficiency. However, higher concentrations than 50.0 µg/ml precipitated in the culture medium. Up to the highest investigated dose no relevant increase in mutant colony numbers was obtained in two independent experiments. Appropriate reference mutagens were used as positive controls and showed a distinct increase in induced mutant colonies.

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