Registration Dossier

Administrative data

Description of key information

Comprehensive repeated dose oral toxicity data are available for sodium fluoride; read-across is therefore proposed.

Key value for chemical safety assessment

Additional information

Repeated dose oral toxicity

No studies have been performed with HFS acid, however comprehensive data are available for sodium fluoride. The repeated dose oral toxicity of HFS acid and NaF are considered to be essentially identical, with the exception of likely irritant/corrosive effects of HFS acid at high dose levels. The repeated dose oral toxicity of HFS acid will be due to fluoride, therefore read-across from the comprehensive NTP dataset with the soluble salt NaF is appropriate.

In a 14 -day range-finding study with NaF in the rat, mortality was seen at drinking water concentrations of 400 and 800 ppm. Signs of toxicity (reduced weight gain, reduced water consumption, lethargy and dehydration) were noted in surviving animals in these groups. The NOAEL for this study was 200 ppm.

In a 14-day range-finding study in the mouse, mortality was seen at the highest dose level of 800 ppm; signs of toxicity (reduced weight gain, abnormal gait and posture, reduced water consumption) were also apparent at this dose level. A NOAEL of 400 ppm is determined for this study.

In a 6 -month rat study, the effects of exposure to NaF were limited to reduced weight gain, dental fluorosis, thickening and ulceration of the gastric mucosa at the highest dose level of 300 ppm; gastric effects were also seen at 100 ppm. The fluoride content of plasma, bone and teeth increased with dose levels. The NOEL for this study was 30 ppm, however these local effects are not considered to be relevant for the risk assessment therefore a NOAEL of 100 ppm can be determined.

In a 6 -month nouse study, mortality attributable to acute nephrosis was seen at the highest dose level of 600 ppm. Skeletal effects were seen in males at the lowest dose level of 50 ppm.

Repeated dose dermal toxicity

No studies are available. The effects of dermal exposure will be dominated by local irritation / corrosion. There is no evidence of significant dermal absorption of HFS acid under exposure conditions where the integrity of the skin barrier is maintained. Testing for repeated dose dermal toxicity can therefore be waived on scientific grounds and for reasons of animal welfare. The effects of repeated inhalation exposure to HFS acid have been adequately characterised; the effects of repeated exposure to fluoride are also well characterised.

Repeated exposure inhalation toxicity

Read-across data are available for HF. In a published study (Sadilova et al, 1974), female rats were exposed to 1 mg/m3 HF 6 hours/day for 1 month. Effects were noted on the teeth, bones and respiratory tract. Two proprietary studies (Placke et al;1990, 1991) show an over-all NOAEL for repeated inhalatory exposure in male and female rats as 0.72 mg/m3(actual HF concentration) for a 6 hours per 5 days per week for 91 days exposure regimen. No adverse effects were noted at this concentration. At higher concentrations death, tissue irritation, dental malformations, haematological and biological changes and changes in several organ weights were observed.

Summary

Effects of repeated fluoride exposure in experimental animals were seen on the teeth, bones, respiratory tract and kidney. Evidence from epidemiological studies in humans also indicate that prolonged exposure to fluoride causes dental and skeletal effects.

Justification for classification or non-classification

Hexafluorosilicic acid is listed on Annex I of Directive 67/548/EEC with no classification for repeated dose toxicity. No classification is proposed in the absence of any relevant data; no GHS classification is proposed.