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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance is considered to be not mutagenic based on the negative results in bacteria (OECD 471) (Huntington Life Sciences Ltd 1995) and in cultivated CHO cells (BASF 2011). It is not clastogenic based on the negative result in Chinese Hamster Lung Fibroblasts (OECD 473) (CCR 1997).

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 - Bacteria Cells

Using a test procedure that complies with the requirements of OECD TG 471, the test article was tested in a Bacterial Reverse Mutation Test using the plate incorporation method. Following strains were used: Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 as well as Escherichia coli (WP2 uvr A). In each of two runs, the test article was tested in triplicates at concentrations of 0, 312.5, 625, 1250, 2500 and 5000 µg/plate in the presence and absence of Aroclor-induced rat liver S-9 mix. The vehicle was dimethyl sulfoxide. Cytotoxicity was absent up to 5000 µg/plate.The concurrent positive control compounds demonstrated the sensitivity of the assay and the metabolising activity of the liver preparations. There was no evidence of induced mutant colonies over background up to the maximum dose of 5000 μg/ plate both in the presence and absence of metabolic activation (Huntingdon Life Sciences Ltd. 1995).

In vitro Gene Mutation - Mammalian Cells

The substance 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 (BASF 2011). The study followed OECD testing guideline 476 and the principles of GLP. Two independent experiments were carried out, both with and without the addition of liver S9 mix from induced rats (exogenous metabolic activation). According to an initial range-finding cytotoxicity test for the determination of the experimental doses and taking into account the cytotoxicity actually found in the main experiments, the following doses were tested and the doses in bold type were evaluated in this study:

1st Experiment:

without S9 mix (4-hour exposure period): 0; 19.5; 39.1; 78.1; 156.3; 1 250.0; 2 500.0; 5 000.0 μg/mL

with S9 mix (4-hour exposure period): 0; 19.5; 39.1; 78.1; 156.3; 312.5; 625.0; 1 250.0 μg/mL

2nd Experiment:

without S9 mix (24-hour exposure period): 0; 25; 50; 100; 625; 1 250; 2 500; 5 000 μg/mL

with S9 mix (4-hour exposure period): 0; 25; 50; 100; 200; 400; 600; 800 μg/mL

After an attachment period of 20 - 24 hours and a treatment period of 4 hours both with and without metabolic activation and 24 hours without metabolic activation, an expression phase of about 6 - 8 days and a selection period of about 1 week followed. The colonies of each test group were fixed with methanol, stained with Giemsa and counted. The vehicle controls gave mutant frequencies within the range expected for the CHO cell line. Both positive control substances, EMS and MCA, led to the expected increase in the frequencies of forward mutations. Cytotoxicity indicated by reduced survival (CE1) of below 20% of control was observed in both experiments in the presence of metabolic activation only. On the basis from 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 adding a metabolizing system in two experiments performed independently of each other.

In Vitro Cytogenetics

In a mammalian in-vitro cytogenetic assay (chromosome aberration) that complies with the test requirements of OECD TG 473, Chinese hamster lung fibroblasts (V79) were exposed to the test article in dimethyl sulfoxide (1% final concentration) at concentrations of 10, 30, 50, 100, 300, and 1000 µg/mL for 4 hours (fixation interval of 18 hours) with metabolic activation and 18 hours without metabolic activation. Another set of cultures were exposed to concentrations of 50, 100, 300, and 1000 µg/mL for 4 hours (fixation interval of 28 hours) with metabolic activation and 28 hours without metabolic activation. Cytotoxic effects were evident from 100 µg/mL and above. However, toxicity was observed only in the presence of test article precipitation (> 100 µg/mL). Positive controls induced the appropriate response. Per culture, 100 metaphase were scored for structural chromosome aberrations. There was no evidence of chromosome aberration induced over background. Both in the absence and presence of S9-mix, the test article did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations or the number of polyploid cells (CCR, 1997).

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 the purpose of classification under Regulation 1272/2008. Based on the criteria laid down in Regulation (EC) No.1272/2008, classification for genetic toxicity is not warranted.