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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Test material form:
liquid

Method

Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9-Mix from Aroclor 1254 induced rat liver
Test concentrations with justification for top dose:
0.08, 0.4, 2, 10 and 50 mg/ml of treatment solutions
Final concentration (µg/plate) 8, 40, 200, 1000, and 5000
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-nitrofluorene, sodium azide, 9-aminoacridine, 2-aminoanthracene

Results and discussion

Test results
Key result
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested

Any other information on results incl. tables

Negative (solvent) and positive control treatments were included for all strains in both experiments. The mean numbers of revertant colonies on negative control plates all fell within acceptable ranges, and were significantly elevated by positive control treatments. No Benzonitrile treatment of any tester strain, either in the absence or presence of S-9, resulted in the two-fold (strains TA98 and TA100) or three-fold (strains TA 1535, TA1537 and TA 1538) increases in revertant numbers sufficient to indicate that an induction of mutation had occurred. It is concluded that Benzonitrile was unable to induce mutation in five strains of Salmonella typhimurium when tested up to 5000 µg/plate, either in the absence or presence of a rat liver metabolic activation system.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Benzonitrile was unable to induce mutation in five strains of Salmonella typhimurium when tested up to 5000 µg/plate, either in the absence or presence of a rat liver metabolic activation system.
Executive summary:

In a reverse gene mutation assay in bacteria, with five strains (TA98, TA100, TA1535, TA1537 and TA1538) of S. typhimurium were exposed to Benzonitrile (98.56%) in sterile analytical grade anhydrous dimetyl sulphoxide (DMSO) at concentrations of 0.08, 0.4, 2, 10 and 50 µg/plate in the presence and absence of mammalian metabolic activation of a rat liver post-mitochondrial fraction (S-9).

Benzonitril was tested up to limit concentration of 5000 µg/plate. No evidence of toxicity was observed in a range-finder experiments, and the same series of concentrations was therefore retained for treatment of the remaining strains in both experiments. The mean numbers of revertant colonies on negative control plates all fell within acceptable ranges, and were significantly elevated by positive control treatments.

No Benzonitrile treatment of any strain, either in the absence or presence of S-9, resulted in the two-fold (strains TA98 and TA100) or three-fold (strains TA 1535, TA1537 and TA 1538) increases in revertant numbers sufficient to indicate that an induction of mutation had occurred.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.