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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test: negative: OECD Guideline 471, GLP

Chromosome aberration in CHO cells: negative: OECD Guideline 473, GLP

HPRT-Assay in CHO-cells: negative, OECD guideline 476, GLP 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In-vitro:

- Gene mutation in bacteria:

The substance was tested for mutagenic activity in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and Escherichia coli WP2uvrA at concentrations ranging from 312.5 to 5000 µg per plate (OECD 471, GLP) (Ciba-Geigy 1992c). The tests were conducted, using the preincubation method, on agar plates in the presence and absence of an Aroclor 1254 induced rat liver preparation and co-factors (S9 mix) required for mixed-function oxidase activity. Positive control compounds demonstrated the sensitivity of the assay and the metabolising, potential of the S9 mix. The test was performed without detection of any toxic and/or mutagenic effects. The values of the negative controls were found to be within the acceptable range and the values of the positive controls met the criteria for a positive response. These results confirm the correct performance of the test.

 

- Clastogenicity in mammalian cells:

The test substance was tested for clastogenic effects on Chinese hamster ovary cells in vitro (OECD 473, GLP) (Ciba-Geigy 1992d). The highest concentration of the test material in the experiments without and with metabolic activation was 750 µg/ml in DMSO.

The highest concentration of 93.75 µg/ml selected for analysis in the first experiment of the original study caused 60.89 % suppression of mitotic activity. The highest concentration of 187.5 µg/ml selected for analysis in the second experiment of the original study caused 64.29 % suppression of mitotic activity. In the third experiment of the confirmatory study with a 42 hours treatment period the highest concentration of 93.75 µg/ml selected for analysis caused 33.67 % suppression of mitotic activity. At the next higher concentration, mitotic activity was suppressed by 95.02%. In the fourth experiment (3 hours treatment / 39 hours recovery) the highest concentration of 93.75 µg/ml selected for analysis caused no suppression of mitotic activity. At the next higher concentration, mitotic activity was suppressed by 97.66% and was therefore not scorable. No indication of a clastogenic effect was observed in any of the experiments.

 

The test item was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro. Two independent experiments were carried out, both with and without the addition of liver S9 mix from phenobarbital- and β-naphthoflavone induced rats (exogenous metabolic activation). The test substance was poorly soluble in culture medium. Precipitates were observed from about 100 μg/mL onward under all experimental conditions. In this study, in the 1st Experiment in the absence and presence of metabolic activation cytotoxicity was observed at an intermediate concentration of 1 250 μg/mL, each. Besides, in the 2nd Experiment in the absence of metabolic activation the highest applied concentration tested for gene mutations was cytotoxic. Based on the results of the present study, the test substance did not cause any relevant increase in the mutant frequencies either without S9 mix or after the addition of a metabolizing system in two experiments performed independently of each other. Thus, under the experimental conditions of this study, the test substance is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and the presence of metabolic activation.

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genetic toxicity under Regulation (EC) No. 1272/2008.