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Toxicological information

Carcinogenicity

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Description of key information

High quality NTP studies in the rat and mouse are available for sodium fluoride  The EU RAR for HF concludes that the data are sufficient to suggest that fluoride is not carcinogenic in animals.

Key value for chemical safety assessment

Additional information

There are no carcinogenicity studies available for calcium difluoride, however studies are available for the water soluble salt sodium fluoride. The much greater water solubility of sodium fluoride (41300 mg/L) compared to calcium fluoride (15 mg/L) means that the bioavailability of fluoride from NaF is likely to be much greater than that of fluoride from CaF2 and therefore represents a worst case.

Studies in the rat

The NTP rat study showed evidence of an effect of sodium fluoride administration on the bones and teeth, consistent with the findings of other studies. There was no effect on survival in this study; bodyweights, food and water consumption, haematological and clinical chemistry parameters and organ weights were unaffected by treatment. Serum, urine and bone fluoride concentrations were increased in all treated groups; the urine calcium concentration was also marginally higher in females at the highest dose level. Osteosclerosis was seen in females at the highest dose level. The incidence of osteosarcoma was increased in males at the intermediate dose level (2%) and the high dose level (4%) but was within the historical range (0 -6%; mean 0.5%). The NTP concluded that the study provides 'equivocal evidence' for carcinogenicity in male rats.

An additional carcinogenicity study with NaF in the rat is available (Maurer et al, 1990). No evidence of carcinogenicity was seen in this study, at dose levels sufficient to cause toxicity.

Studies in the mouse

The NTP mouse study showed evidence of an effect of sodium fluoride administration on the teeth, consistent with the findings of other studies. There was no effect on survival in this study; bodyweights, food and water consumption, haematological parameters and organ weights were unaffected by treatment. Clinical chemistry revealed elevated ALP activity in females at the highest dose level. Microscopic findings were limited to dentine dysplasia in male mice at 175 ppm. There was no evidence of carcinogencity in either sex.

An additional carcinogenicity study with NaF is available (Maurer et al, 1993). A high level of osteosarcomas was seen in all (control and treated) groups in this study, a finding which was attributed to infection with a retrovirus. No conclusion on the carcinogenicity of sodium fluoride can be drawn from this study.

Justification for classification or non-classification

No classification is proposed according to the CLP Regulation (1272/2008/EC). The EU RAR for HF concludes that the data are sufficient to suggest that fluoride is not carcinogenic in animals.