Valeric anhydride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

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, 1538 and TA 1537 and E. Coli in the presence and absence of S9 mix according to OECD TG 471. Evaluation of the data does not indicate that the test substance possesses a mutagenic potential in the bacterial reverse mutation test (direct plate incorporation procedure), when tested up to the maximum recommended or up to the clearly cytotoxic dose level in the absence and presence of a metabolic activation system.

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:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

- Justification why the confirmation of the negative result is not considered necessary is not provided.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: no data
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: The solutions and further dilutions were prepared immediately before addition to the test bacteria. Thus, no remarkable instability is expected which could influence the outcome of the study.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no data

Target gene:

Histidine gene locus

Species / strain / cell type:

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

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 Sprague-Dawley rat liver S9 mix

Test concentrations with justification for top dose:

without metabolic activation:
TA98; TA100; TA1535: 0.001 to 5.0 µL/plate ; TA1537; TA1538 and E. Coli: 0.001 to 0.25 µL/plate
Due to the cytotoxicity of the test substance the experiments on strains TA98, TA 1 00 and TA 1535 were repeated using a lower dose range
(0.001 to 0.25 µL/plate).

with metabolic activation:
TA98; TA100; TA1535; TA1537; TA1538 and E. coli: 0.1, 0.25, 0.5, 1.0, 2.5 and 5.0 µL/plate

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

sodium azide

benzo(a)pyrene

cyclophosphamide

ethylmethanesulphonate

other: anthracen-2-amine, 4-Nitro-o-phenylenediamine, N-Methyl-N¿-nitro-N-nitrosoguanidine

Evaluation criteria:

The arithmetic means of the number of mutant colonies of the 3 parallel plates in the negative control groups were compared with those of the compound groups. However, in the tables the given mean values are rounded to the nearest integer. A positive response was considered if the number of revertants of the compound groups compared to the number of revertants of the negative group was reproducibly higher than 2-fold. A dose-dependent increase in the number of revertants was also considered to indicate a mutagenic effect.

Species / strain:

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

Metabolic activation:

with

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:

valid

Positive controls validity:

valid

Species / strain:

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

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with

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:

valid

Positive controls validity:

valid

Additional information on results:

Precipitates in the agar could not be found at any dose level.
In the experiments without metabolic activation growth inhibition of the background lawn was observed starting from 0.05 µL/plate with all tester strains. In the experiments with S9 mix growth inhibition of the background lawn started at 0.1 µL/plate (TA100. TA 1537), 0.25 µL/plate (TA1538) or 0.5 µL/plate (TA98, TA1535, E. coli WP2uvrA).

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

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 the test substance at the doses tested.

Appropriate positive control chemicals induced marked increases in revertant colony numbers with all strains.

Conclusions:

negative

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, 1538 and TA 1537 and E. Coli in the presence and absence of S9 mix according to OECD TG 471. Evaluation of the data does not indicate that the test substance possesses a mutagenic potential in the bacterial reverse mutation test (direct plate incorporation procedure), when tested up to the maximum recommended or up to the clearly cytotoxic dose level in the absence and presence of a metabolic activation system.

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 available information classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.