Valeronitrile

Genetic toxicity: in vitro

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

Study period:

May-June 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study performed in accordance with the corresponding OECD-/EU-testing guidelines

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1995

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 reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methyl acetoacetate

EC Number:

203-299-8

EC Name:

Methyl acetoacetate

Cas Number:

105-45-3

IUPAC Name:

methyl 3-oxobutanoate

Details on test material:

- Physical state: Clear colourless liquid
- Storage condition of test material: Room temperature, protected from light

Method

Target gene:

not applicable

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9-liver fractions of Sprague-Dawley rats, induced with Aroclor 1254

Test concentrations with justification for top dose:

Test substance concentrations of 50, 150, 500, 1500 and 5000 microg/plate were used in the main test.

Vehicle / solvent:

- Vehicle: Acetone
- Justification for choice of solvent/vehicle: high solubility, better than others

Controls

Untreated negative controls:

yes

Remarks:

each strain alone or in presence of the solvent

Negative solvent / vehicle controls:

yes

Remarks:

acetone

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

further positive control substances were used: 9-Aminoacridine, 2-Nitroquinoline-oxide, 2-Aminoanthracene

Details on test system and experimental conditions:

The study was performed by the direct plate incorporation method with and without metabolic activation.

Evaluation criteria:

For a substance to be considered positive in this test system, it should have induced a dose-related and statistically significant increase in mutation rate (of at least twice the spontaneous reversion rate) in one or more strains of bacteria in the presence and/or absence of the S9 microsomal enzymes in both experiments at sub-toxic dose levels. If the two experiments give conflicting results or equivocal results are obtained, then a third experiment may be used to confirm the correct response.
To be considered negative the number of induced revertants compared to spontaneous revertants should be less than twofold at each dose level employed, the intervals of which should be between 2 and 5 fold and extend to the limits imposed by toxicity, solubility or up to the maximum recommended dose of 5000 ug/plate. In this case the limiting factor was the maximum recommended dose.

Statistics:

According to the OECD guideline 471, a statistical analysis of the data is not mandatory.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No precipitation observed.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

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

It can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations in the five strains tested.

Executive summary:

The assay was performed 1995 in compliance with GLP. The test was performed with and without liver microsomal activation and used strains TA 1535, TA 1537, TA 98, TA 100 and E.coli WP2uvrA. Each concentration and the controls, were tested in triplicate.

The test item was tested at the following concentrations: 50; 150; 500; 1500 and 5000 µg/plate (pre-experiment and main test). The plates incubated with the test item showed normal back­ground growth up to 5000 µg/plate with and without S9 mix in all strains used. No toxic effects, evident as a reduction in the number of revertants occurred in the test groups with and without metabolic activation. Precipitation was not observed.

Valeronitrile was found to be non-mutagenic in this test system.