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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Stability under test conditions: A stability test in the solvent (10 mg/ml and 50 mg/ml) did not reveal significant degradation of the active ingredient.

Method

Target gene:
histidine locus
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 98, TA 102
Metabolic activation:
with and without
Metabolic activation system:
S9-Mix from the liver of Aroclor 1254 induced male rats
Test concentrations with justification for top dose:
0, 50, 158, 500, 1581, 5000 µg/plate (with and without S9-mix)
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, cumene hydroperoxide, 2-aminoanthracene.
Remarks:
2-aminoanthracene (promutangen) only used with S9-mix, the other positive controls only used without S9-mix.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation), for an independent repeat the preincubation method was used.

DETERMINATION OF CYTOTOXICITY
- gross appraisal of background growth
- a toxic effect was assumed when there was a marked and dose-dependent reduction in the mutant-count per plate, copared to the negative controls
- total bacterial counts
Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas for TA 1537, at least a threefold increase should be reached. For TA 102 an increase of about 100 mutants should be reached. Otherwise, the result is evaluated as negative. However, these guidelines may be overruled by good scientific judgment. In case of questionable results, investigations should continue, possibly with modifications, until a final evaluation is possible.
Statistics:
Not specified.

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 98, TA 102
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
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

The test item showed no mutagenic activity in the Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 in the absence and in the presence of a metabolic activation system.