Registration Dossier

Administrative data

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

Additional information

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.