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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to internationally accepted testing guidelines and performed according to GLP. The assessment of Escherichia Coli strain is missing.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
E. coli or TA102 is not tested and only one positive control for tests with S9 mix
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced S9 mix from rat liver
Test concentrations with justification for top dose:
Exp.I: 10.0; 100.0; 333.3; 1000.0; and 5000.0 µg/plate
Exp.II: 100.0; 333.3; 1000.0; 2500.0; and 5000.0 µg/plate
Vehicle / solvent:
- Vehicle used: water.
- Justification for choice of vehicle: test substance is soluble in water.
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
other: 4-nitro-o-phenylene-diamine and 2-aminoanthracene
Remarks:
Without S9: TA1535 and TA100 sodium azide (in water dest.); TA98, TA1537 and TA1538 4-nitro-o-phenylene-diamine (in DMSO). With S9: 2-aminoanthracene (in DMSO) for all strains.
Details on test system and experimental conditions:
Each concentration, including the controls, was tested in triplicates.

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
only in strain TA 98 without metabolic activation at 5000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES:
To evaluate the toxicity of the test article a pre-study was performed with strains TA 98 and TA 100. The plates with the test article showed normal background growth up to 5000 µg/plate in strain TA 98 and TA 100, respectively.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Up to the highest investigated dose, neither a significant and reproducible increase of the number of revertants was found in any strain as compared to the solvent control nor a concentration dependent enhancement of the revertant number exists. The presence of liver microsomal activation did not influence these findings.

In strain TA 98 a slight increase in revertant colony numbers was observed at 5000.0 µg/plate in the presence of metabolic activation in experiment II. This effect is considered being irrelevant since it could not be reproduced in the independent experiment. Appropriate reference mutagens were used as positive controls and showed a distinct increase in induced revertant colonies.

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 by base pair changes or frameshifts in the genome of the strains used.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

The test substance did not induce point mutations by base pair changes or frameshifts in the genome of the strains used.
Executive summary:

Method

The test substance matgenic potential was evaluated following the procedures outlined into the OECD guideline 471. The test substance was assessed for its potential to induce point mutations, i.e. base pair changes or frameshifts in the genome, according to the plate incorporation test using Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100. The assay was performed in two independent experiments, using identical procedures, both with and without activation with liver microsomal preparations from Aroclor induced rats. The test item was tested at 10, 100, 333.3, 1000 and 5000 micrograms/plate in the first experiment and at 100, 333.3, 1000, 2500 and 5000 micrograms/plate in the second experiment. Each concentration, including the controls, was tested in triplicates.

Results

Up to the highest investigated dose, neither a significant and reproducible increase of the number of revertants was found. In strain TA 98 a slight increase in revertant colony numbers was observed at 5000.0 µg/plate in the presence of metabolic activation in experiment II. This effect is considered being irrelevant since it could not be reproduced in the independent experiment.

It can be stated that during the described mutagenicity test and under the experimental conditions reported, the test article did not induce point mutations by base pair changes or frameshifts in the genome of the strains used.