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Endpoint summary

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Key value for chemical safety assessment

Genetic toxicity in vitro

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

Genetic toxicity in vivo

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

Additional information

The available data on genetic toxicity allow a conclusive statement on this endpoint for divalent tin salts. Irrespective of the reporting quality of the publications, both positive and negative findings are reported in in vitro as well as in vivo test systems.

Following a rigorous relevance and reliability screening, it can be concluded that divalent tin salts do not show any clastogenic potential. The references discussed under in vitro clastogenicity do not show a consistent pattern on the induction of chromosome and the overall conclusion was equivocal. However, high-quality in vivo cytogenicity studies with divalent tin salts via intraperitoneal injection and oral administration in mice and rats did not show an increase of micronuclei formation or chromosome aberration up to the maximum tolerated dose. This finding is supported by a negative dominant lethal test in rats after single and repeated oral administration in rats. Also, there was no evidence for any mutagenic activity in bacterial reverse mutation or mammalian gene mutation assays. Consequently, divalent tin salts are considered not to induce gene mutations.

Overall, there is no consistent evidence of induction of genetic toxicity with relevance to humans for divalent tin salts.

Both positive and negative results have been reported for fluoride in in vitro genotoxicity studies, but the in vivo studies indicate no genotoxicity when evaluated in reliable studies conducted following administration by an appropriate route of exposure.  Fluoride salts are therefore not expected to be genotoxic.

Justification for classification or non-classification

The in vivo data for divalent tin(II) salts present a consistent pattern. In reliable and guideline compliant studies as discussed above, combining chromosome aberration and micronucleus endpoints up to toxic doses in mice and rats, divalent tin(II) salts did not show any test item induced genetic toxicity.

None of the in vitro genotoxicity studies rated as reliable showed any effect in bacterial reverse mutation assays, in mammalian cell gene mutation test (TK assay). Mammalian cell chromosome aberration or micronucleus tests returned an equivocal outcome. Since higher-tier in vivo data should take precedence over in vitro data, these equivocal findings were sufficiently addressed by in vivo data and shown not to occur.

While both positive and negative results have been reported for fluoride in vitro, the reliable in-vivo studies indicate that fluoride salts do not interact directly with DNA and are not genotoxic when administered by an appropriate route of exposure. No classification is proposed.

The classification criteria acc. to regulation (EC) 1272/2008 as germ cell mutagen are not met, thus no is classification applicable.