α-acetyl-γ-butyrolactone

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation study in bacteria:

The test substance was evaluated for mutagenic activity in the Ames test. A standard plate incorporation in absence and in presence of an exogenous metabolic activation system (S9) were performed. Five Salmonella typhimurium tester strains (TA1535, TA97a, TA98, TA100, and TA102) were employed. The activity of the S9 -mix and the responsiveness of the tester strains were verified by including appropriate controls into each experiment. The substance was dissolved in water. Concentration ranges between 0.1 to 5 mg/plate were chosen for the experiments. No cytotoxicity and precipitation were observed up to and including 5 mg/plate.

No significant increase in the number of revertant colonies was apparent in all five tester strains (TA1535, TA97a, TA98, TA100, and TA102) after treatment with the test substance.

Based on these data test substance can be considered as not mutagenic in the Ames test under the described experimental conditions.

Link to relevant study records

Reference

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:

28.02 - 07.08.2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

repeat restricted to two S. typhimurium strains

Principles of method if other than guideline:

-

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine gene locus

Species / strain / cell type:

S. typhimurium, other: TA97a, TA98, TA100, TA102, TA 1535

Metabolic activation:

with and without

Metabolic activation system:

phenobarbital/naphthoflavone induced male Wistar rat liver S9 mix

Test concentrations with justification for top dose:

Experiment I: 5000 µg/plate (+/-S9 mix, all strains)
Experiment II: 5000, 2500, 1250, 625, 100 µg/plate (+/-S9 mix, TA97a); 5000, 2500 µg/plate (+/-S9 mix, TA98)

Vehicle / solvent:

water (test substance)
DMSO (positive control)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

benzo(a)pyrene

other: 4-nitro-1,2-phenylenediamine

Species / strain:

S. typhimurium, other: TA98, TA100, TA102, TA 1535

Remarks:

Experiment I

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

-

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Remarks:

-

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA97a, TA98

Remarks:

Experiment I

Metabolic activation:

with and without

Genotoxicity:

ambiguous

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

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA97a, TA98

Remarks:

Experiment II

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

True negative controls validity:

not applicable

Positive controls validity:

valid

Conclusions:

negative

Executive summary:

The test substance was evaluated for mutagenic activity in the Ames test. A standard plate incorporation in absence and in presence of an exogenous metabolic activation system (S9) were performed. Five Salmonella typhimurium tester strains (TA1535, TA97a, TA98, TA100, and TA102) were employed. The activity of the S9 -mix and the responsiveness of the tester strains were verified by including appropriate controls into each experiment. The substance was dissolved in water. Concentration ranges between 0.1 to 5 mg/plate were chosen for the experiments. No cytotoxicity and precipitation were observed up to and including 5 mg/plate.

No significant increase in the number of revertant colonies was apparent in all five tester strains (TA1535, TA97a, TA98, TA100, and TA102) after treatment with the test substance.

Based on these data test substance can be considered as not mutagenic in the Ames test under the described experimental conditions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the study results for genetic toxicity no classification according to Regulation (EC) No. 1272/2008 (CLP), ANNEX I, is warranted.