Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro and in vivo, the following genotoxic endpoints were assessed:

- Gene mutation potential: one reverse bacterial gene mutation test (Thompson #1, 1992) was selected as a key study, (OECD 471, Kr: 1). In this study, ITC 288/S is not mutagenic in S. typhimurium strains TA1535, TA1537, TA98 and TA100 and E. coli strain WP2uvrA- with and without metabolic activation, up to a limit concentration.These results are confirmed by a supporting study (Thompson #2, 1992), (OECD 471, Kr: 2) providing negative results with or without metabolic activation. Therefore, ITC 288/S showed no mutagenic action in Bacteria.

- Chromosomal aberration potential: In vitro, one cytogenetic study in CHO cells (OECD 473, Kr: 1) was available and was selected as the key study (Wright, 1993). The results were negative with metabolic activation, up to limit concentration. Weak clastogenic effects were observed at the maximum concentration used without metabolic activation, together with a high level of cytotoxicity (cell survival reduced by 80%) and at the medium concentration (7.5% of cells with aberrations), but based on "Evaluation criteria" of this test , these results were considered as ambiguous. In vivo, ITC 288/S was also evaluated for its ability to induce chromosomal aberrations in a mouse micronucleus test (Durward R, 1993), (key study, OECD 474, Kr:1). No increase in micronucleated polychromatic erythrocytes (micronuclei) and no significant change in the NCE/PCE ratio was observed in male or female mice 24,48 or 72 hours following i.p. injection of 1000 mg/kg. Therefore, ITC 288/S is considered as not genotoxic.

- DNA repair potential:

In the in vivo liver unscheduled DNA synthesis (UDS) assay,(Durward, 1997), (key study, OECD 486, Kr:1), male rats were treated by gavage with ITC 288/S at 700 and 2000 mg/kg body weight. Primary hepatocytes cultures were prepared 2 and 16 hours later, incubated with3H-thymidine and assessed for induction of UDS. No DNA repair activity was seen, therefore ITC 288/S is considered as not genotoxic.

In conclusion: based on all these studies, ITC 288/S is considered as not genotoxic.

Short description of key information:

- Mutagenicity: negative in Bacteria (OECD 471, Kr:1).

- Clastogenicity/Aneugenicity: ambiguous in vitro and negative in vivo (OECD 473 and OECD 474, Krs:1).

- DNA damage and/or repair: negative in vivo (OECD 486, Kr:1).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo data, ITC 288/S is considered as not genotoxic, therefore no classification is required according to the EU legislation (Directive 67/548/EEC and CLP regulation (1272/2008).