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Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro:

In the available reverse mutation assays (according to method similar to OECD Guideline 471) using Salmonella typhimurium or Escherichia coli strains, the substance showed different results.

In the Salmonella strains TA100 and TA1535, the substance was positive with and without metabolic activation. The strain TA98 was tested ambiguous (negative, positive and ambiguous) in the absence of S9 and negative in the presence of S9 (Silhankova et al. 1982, Zeiger et al. 1988, Stolzenberg and Hine 1979). In the E. coli strains WP2, TM930 and TM1080, the substance was negative both with and without metabolic activation (Silhankova et al. 1982).

In a yeast assay with Schizosaccharomyces pombe, the substance was positive (Rossi et al., 1983). In a mouse lymphoma assay (similar to OECD TG 476) the substance was positive both in the absence and presence of metabolic activation. It can be concluded that the substance has mutagenic activity in vitro. Clastogenicity has not been tested in vitro, but this was assessed in vivo. Genetic toxicity in vivo: The available rat in vivo bone marrow micronucleus test (Robjohns et al. 2003) according to OECD TG 474 showed no increase in the number of micronucleated polychromatic erythrocytes at any dose level. The rat liver UDS assay (Robjohns et al. 2003) according to OECD TG 486 did not show any evidence of an increase in unscheduled DNA synthesis. It can be concluded that the substance does not show genetic toxicity in vivo. This is supported by the in vivo comet assay in two rat strains which did not show any genotoxicity either (El Ramy et al., 2007)

Short description of key information:
Genetic toxicity in vitro:
Bacterial reverse mutation tests are available (Zeiger et al., 1988; Stolzenberg and Hine 1979; Silhankova et al., 1982), a mouse lymphoma study (Henderson et al., 1987) and an in vitro comet assay (El Ramy, 2007). These studies have been reviewed and summarized. The studies mainly showed positive results in vitro.
Other in vitro genotoxicity studies appearing in the IUCLID4 file found on the ESIS website have just been copied as these were either not relevant or support the existing studies. The studies taken from IUCLID4 include: Rossi et al. (1983), Piasecki et al. (1990), Painter and Howard (1982), May (1991) and Gorlitz (1991).

Genetic toxicity in vivo:
Two studies have been entered: Robjohns et al. (2003) and El Ramy et al. (2007). Robjohns described the in vivo rat bone marrow micronucleus test (OECD474) and the unscheduled DNA synthesis test in rat (OECD486). El Ramy conducted an in vivo comet assay using two rat strains. All tests were negative in vivo.
Other in vivo genotoxicity studies appearing in the IUCLID4 file found on the ESIS website have just been copied as these were either not relevant or support the existing studies. The studies taken from IUCLID4 include: Epstein et al. (1972), Jones et al. (1976) and Jaccaud and Aeschbacher (1989).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Although the substance shows mutagenic effects in vitro, it does not show such effects in three reliable in vivo assays. Therefore, it can be concluded that the substance has no significant genotoxic potential in vivo, and consequently classification is not necessary according to CLP criteria.

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