Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Hexafluorosilic acid

No evidence of mutagenicity was seen in a guideline-comparable Ames test (Shimizu et al, 1985).

Sodium hexafluorosilicate

No evidence of mutagenicity is reported in an Ames test (Gocke et al, 1981) or in a screening assay in S. typhimurium and E. coli

(Kanematsu et al, 1980).

A negative Rec assay is also reported (Kanematsu et al, 1980; Kada et al, 1980). In studies in vivo, no evidence of genotoxicity is reported in a Drosophila assay or in a mouse bone marrow micronucleus assay (Gocke et al, 1981). Read-across is appropriate as this substance is water souble and will dissociate to hexafluorilicate (with subsequent hydrolysis to fluoride) under aqueous conditions.

Hydrogen fluoride and sodium fluoride

Hexafluorosilicic acid will rapidly dissociate in aqueous conditions to the hydronium and fluorosilicate ions, with subsequent hydrolysis of the fluorosilicate to silicate and fluoride. Read-across from water-soluble fluorides such as hydrogen fluoride and sodium fluoride is therefore justified.

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.

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.

The EU RAR 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:
Hexafluorosilicic acid was negative in a guideline-comparable Ames test. With the read-across compound, sodium hexafluorosilicate, no evidence of mutagenicity was seen in an Ames test, a bacterial mutation screening assaya or a Rec assay. In vivo, no evidence of genotoxicity was seen in a Drosophila assay or a mouse bone marrow micronucleus assay with sodium hexafluorosilicate.

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). HFS acid is not predcited to be genotoxic.