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Administrative data

Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro:

No bacteriotoxicity and no mutagenicity was observed in an Ames test with TA1535, 1537, 98, 100 (BASF AG, 1988). This standard plate and preincubation test was performed according to the current OECD-guideline 471 with test concentrations up to 5000 µg/plate, lacking the E. coli or TA 102 strains (detection of oxidizing or cross-linking mutagens).

Trioxane was also negative in a chromosomal aberration test in V79 Chinese Hamster Cells (in vitro cytogenicity study in mammalian cells, Hoechst AG, 1992), and in a HGPRT assay with V79 cells (in vitro gene mutation study in mammalian cells, Hoechst AG, 1992). Both assays were performed according to the current OECD-guidelines (473 or 476) with and without metabolic activation.

No contradictory results were reported in further Ames assays (e.g. Kowalski et al., 1984; Zeiger et al., 1988) which were not performed according to current guidelines. Though, in a Mouse Lymphoma Assay (Celanese, 1980) an increase of mutation frequencies was observed in presence of S-9 mix. This effect was clearly related to an increase in cytotoxicity at concentrations far beyond the limit concentration. Due to this high level of cytotoxicity the dose dependency could not be clarified. No increase in mutation frequencies was observed in absence of S-9 mix.

 

Genetic toxicity in vivo:

Trioxane caused no increase in unscheduled DNA synthesis in an in vivo UDS assay. 

The assay was performed according to OECD Guideline 486 and male rats were gavaged with dose levels up to 2000 mg/kg bw (BASF AG, 1997).

In an intraperitoneal Mouse Micronucleus Test trioxane did not induce an increase in micronucleated polychromatic erythrocytes (Pryzyboljewska et al., 1984). The assay was performed according to OECD Guideline 474 with test concentrations up to 4250 mg/kg bw.

Summarized sufficient and reliable evidence was found in in vitro and in vivo assays, to proof that no classification for genotoxicity is warranted.


Short description of key information:
No mutagenicity in bacteria (Ames Assay).
No mutagenicity in a HGPRT assay in V79 cells.
No cytogenicity in a chromosomal aberration assay in V79 cells.
Negative in a mouse micronucleus assay following i.p. application (OECD 474) and an unsheduled DNA assay in male rats gavaged with the test substance (OECD 486).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification for genetic toxicity indicated according to Directive 67/548/EEC and Directive 1272/2008.