Benzonitrile

Genetic toxicity: in vitro

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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Benzonitrile

EC Number:

202-855-7

EC Name:

Benzonitrile

Cas Number:

100-47-0

Molecular formula:

C7H5N

IUPAC Name:

benzonitrile

impurity 1

Reference substance name:

Toluene

EC Number:

203-625-9

EC Name:

Toluene

Cas Number:

108-88-3

Molecular formula:

C7H8

IUPAC Name:

toluene

impurity 2

Reference substance name:

Benzaldehyde

EC Number:

202-860-4

EC Name:

Benzaldehyde

Cas Number:

100-52-7

Molecular formula:

C7H6O

IUPAC Name:

benzaldehyde

impurity 3

Reference substance name:

Terephthalonitrile

EC Number:

210-783-2

EC Name:

Terephthalonitrile

Cas Number:

623-26-7

Molecular formula:

C8H4N2

IUPAC Name:

terephthalonitrile

impurity 4

Reference substance name:

Benzene-1,3-dicarbonitrile

EC Number:

210-933-7

EC Name:

Benzene-1,3-dicarbonitrile

Cas Number:

626-17-5

Molecular formula:

C8H4N2

IUPAC Name:

isophthalonitrile

impurity 5

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

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.