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Toxicological information

Carcinogenicity

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Description of key information

Fluoride salts are not likely to present a risk of carcinogenicity based on the results of carcinogenicity studies in rodents.  The key study, as identified in the dossier on potassium fluoride reports a NOAEL of 25 mg NaF/kg bw/day for carcinogenicity. This corresponds to 23.8 mg K2TiF6/kg bw/day, based on the fluoride content.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
23.8 mg/kg bw/day
Study duration:
chronic
Species:
rat

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a reported carcinogenicity study (Maurer, et al.,1990) in which sodium fluoride was added to the diet of Sprague-Dawley male and female rats at a dose of 4, 10 or 25 mg/kg/day for up to 99 weeks, sodium fluoride did not alter the incidence of preneoplastic and neoplastic lesions at any site in rats of either sex despite clear evidence of toxicity in male and female rats. Fluoride toxicity included a 30% decrement in weight gain at 25 mg NaF/kg/day and macroscopic and microscopic changes in teeth, bone and stomach of male and female rats. The incidence of dental changes in rats dosed at 4 mg NaF/kg bw/day was increased slightly compared to the prominent incidence in rats dosed at 10 and 25 mg NaF/kg bw/day. At 10 and 25 mg NaF/kg bw/day toxic effects in the bones and stomach were also observed. The incidence and severity of the changes in teeth, bones and stomach were related to increased dose of sodium fluoride and increased duration of exposure.

The U.S. National Toxicology Program conducted 2 -year toxicity and carcinogenicity studies (NTP, 1990; Bucher, et al., 1991) with sodium fluoride administered in the drinking water of F344/N rats and B6C3F1 mice at concentrations of 0, 25, 100 or 175 ppm (equivalent to 0, 11, 45 or 79 ppm fluoride). There was equivocal evidence of carcinogenic activity of sodium fluoride based on the occurrence of a small number of osteosarcomas in male rats dosed at concentrations of 100 and 175 ppm. No evidence of carcinogenic activity was found in male rats receiving 25 ppm sodium fluoride or in female rats receiving up to 175 ppm sodium fluoride in drinking water. Additionally, there was no evidence of carcinogenic activity of sodium fluoride at concentrations up to 175 ppm in male and female B6C3F1 mice. The results in male rats are weakly supportive of an association between sodium fluoride administration in drinking water and carcinogenicity, and are considered inconclusive.


Justification for selection of carcinogenicity via oral route endpoint:
Key study, as identified in the dossier on potassium fluoride. A NOAEL of 25 mg NaF/kg bw/day for carcinogenicity is reported in this study. This corresponds to 23.8 mg K2TiF6/kg bw/day, based on the fluoride content.

Justification for classification or non-classification

As noted in several reviews including the EU risk assessment report (RAR), the data from carcinogenicity studies are predominately negative with the slight increased incidence of osteosarcomas observed in male rats in the NTP study considered to be inconclusive and not sufficient to suggest fluoride salts would be carcinogenic. No classification is proposed.