Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Studies of bacterial mutation (Ames test), cytogenicity and gene mutation in mammalian cells are available for calcium difluoride: additional data are available for other soluble fluoride salts.

Genetic toxicity in vitro

No evidence of mutagenicity was reported in a modern Ames test performed with calcium difluoride (Schulz & Landsiedel, 2010) in Salmonella typhimurium strains TA1535, TA100, TA98, TA1537 and in E. coli strain WP2 uvrA. No evidence of mutagenicity was observed in a recent mammalian cell gene mutation assay (V79/HPRT) performed with calcium difluoride (Wollny, 2010). Likewise, no evidence of cytogenicity was seen in V79 cells in a chromosome aberration test with calcium difluoride (Hall, 2010).

Additionally, a number of studies are available for the read-across source susbtance sodium fluoride. No evidence of mutagenicity was seen with sodium fluoride in an Ames test (NTP, 1990). No evidence of mutagenicity was seen in a mammalian cell mutation assay (V79/HPRT) with sodium fluoride. This study was performed only in the absence of metabolic activation, however this deviation is not considered to be critical as the test substance is not metabolised. A positive result with sodium fluoride is reported in a mouse lymphoma assay (NTP, 1990). Sister chromatid exchange and chromosomal aberrations are reported in an additional NTP study.

Genetic toxicity in vivo

Zeiger et al (1994) report no evidence of clastogenicity, even at dose levels causing severe toxicity, in a well-conducted mouse study performed with sodium fluoride in which chromosomal aberrations and micronucleus formation was assessed.

In contrast, a poorly reported inhalation exposure study performed with HF (Voroshilin et al, 1975) reports clastogenicity in the bone marrow of exposed rats but no dominant lethal effect in exposed mice.

Conclusion

The EU RAR for HF reviews the available data for NaF and HF and concludes that fluoride does not interact directly with DNA and is not genotoxic when administered via an appropriate route (i.e. by oral or inhalation exposure).


Short description of key information:
A negative Ames test, a negative study of cytogenicity in V79 cells in vitro and a negative study of gene mutation in V79 cells in vitro are available for calcium difluoride. Some positive studies in vitro are reported for the more soluble sodium fluoride salt, however reliable in vivo studies are negative. The available data indicate that fluoride does not interact directly with DNA and is not genotoxic when administered via an appropriate route (i.e. by oral or inhalation exposure).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is proposed for genetic toxicity according to the CLP Regulation (1272/2008/EC). The available data indicate that fluoride does not interact directly with DNA and is not genotoxic when administered via an appropriate route (i.e. by oral or inhalation exposure).