Potassium hydrogendifluoride

Endpoint summary

Additional information

Overview

Under physiological conditions, the substance will dissociate to form its constituent ions (i.e. potassium, hydrogen and fluoride). The hydrogen and potassium ions exist in the body at high levels and are therefore unlikely to be genotoxic. Genotoxicity data for fluoride substances are available and are referenced.

Genetic toxicity in vitro (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 lynmphoma assay (NTP, 1990). Sister chromatid exchange and chromosomal aberrations are reported in an additonal NTP study. Caspary et al (1987) report positive results for sodium fluoride and sodium hydrogen fluoride at cytotoxic concentrations in a mouse lymphoma assay.

Genetic toxicity in vivo (fluoride)

Gerdes (1971) reports a marginally (but not statistically significant) positive response in a study in Drosophila melanogaster; positive effects in Drosophila are also reported by Mohamed et al (1971). The significance of these results is unclear; the EU RAR for HF considers the findings of these two Drosophila studies to be inconclusive. 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 on the genotoxicity of fluoride

The EU RAR for HF concludes that, while the dataset on the genotoxicity of HF is limited, studies with sodium fluoride are also informative as for both substances target tissues will exposed to fluoride (either free or bound to organic molecules). The EU RAR therefore 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:
Studies with HF and NaF are available.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is proposed. 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). Data therefore indicate that the substance is unlikley to be genotoxic.