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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

Additional information

Justification for classification or non-classification

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