Methyl valerate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (bacterial reverse mutation assay / Ames test): negative with and without metabolic activation [Reimann and Jarzombek 2007]

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:

June 2006

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:

no confirmation of negative results

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Solubility and stability of the test substance in the solvent/vehicle: The solution and further dilutions were prepared immediately betore addition to the test bacteria.

Target gene:

Histidine gene locus

Species / strain / cell type:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538

Additional strain / cell type characteristics:

not applicable

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced male rat liver S9 mix

Test concentrations with justification for top dose:

0.1 - 5.0 µl/plate

Vehicle / solvent:

DMSO

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine, 2-nitrofluorene , sodium azide, benzo(a)pyrene, cyclophosphamide, ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, 2-aminoanthracene

Species / strain:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538

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 examined

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

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 examined

Positive controls validity:

valid

None of the six tester strains S. typhimurium TA1535, TA100, TA1537, TA1538, TA98 and E.coli WP2uvrA showed increased reversion to prototrophy in assays with ZK 56517 at the doses tested between 0.1 and 5.0 µl/plate, either in the absence or presence of metabolic activation. However, the experiment on strain TA98 was repeated in order to check the results.

Precipitates in the agar were not found .

Growth inhibition of the background lawn was observed in strains TA98, TA1537, TA1538 and TA100 at the maximum dose of 5 µL/plate ZK 56517 without and with metabolic activation, whereas in strain TA100 the growth inhibition already started at 2.5 µL/plate in the experiment with S9-mix. Growth inhibition of the background lawn was not observed in strains TA1535 and WP2uvrA.

The counts recorded on appropriate negative control plates confirmed the characteristically spontaneous reversion rates of the tester strains. Furthermore, appropriate positive controls with known mutagens (2-aminoanthracene, benzo[a]pyrene, cyclophosphamide, ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, 2-nitro-fluorene, 4-nitro-o-phenylenediamine, sodium azide) produced the expected distinct increase in the number of revertant colonies.

Executive summary:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538 and E. coli WP2uvrA in the presence and absence of S9 mix according to OECD TG 471. Evidence of mutagenic activity was not seen up to the maximum recommended dose level of 5.0 µl/plate. No substantial increases in revertant colony numbers of any of the six tester strains were observed at any dose level in the presence and absence of metabolic activation. Therefore, the test substance was considered to be non-mutagenic in the Salmonella typhimurium reverse mutation assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538 and E. coli WP2uvrA in the presence and absence of S9 mix according to OECD TG 471. Evidence of mutagenic activity was not seen up to the maximum recommended dose level of 5.0 µl/plate. No substantial increases in revertant colony numbers of any of the six tester strains were observed at any dose level in the presence and absence of metabolic activation. Therefore, the test substance was considered to be non-mutagenic in the Salmonella typhimurium reverse mutation assay.

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.