Potassium hydrogendifluoride

Endpoint summary

Description of key information

The toxicity of potassium hydrogen difluoride will be dominated by local (site of contact) effects, as a consequence of its corrosive nature.  Systemic expousre is likely to be limited, but systemic toxicity is predicted to be due to fluoride and the critical effect will be skeletal fluorosis.  Comprehensive repeated dose oral toxicity data are available for sodium fluoride; read-across is therefore proposed. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Study duration:

subacute

Species:

rat

Additional information

The substance will form HF under physiological conditions, with subsequent dissociation to the constituent (hydrogen, potassium and fluoride) ions. The substance is corrosive and, therefore, repeated inhalation and dermal exposure will result in local effects at the site of contact. The toxicologically relevant component of the substance is considered to be fluoride, and systemic toxicity following repeated oral and inhalation exposure may result from fluoride. Read-across is therefore proposed to other soluble fluoride salts, which demonstrate the critical effect to be skeletal fluorosis. Dermal absorption of fluoride is not predicted under normal conditions of use.

Repeated dose oral toxicity

No studies have been performed with potassium bifluoride, however comprehensive data are available for sodium fluoride. The repeated dose oral toxicity of potassium bifluoride and NaF are considered to be essentially identical, with the exception of likely irritant/corrosive effects of potassium bifluoride at high dose levels. The repeated dose oral toxicity of potassium bifluoride 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 mouse 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 to potassium bifluoride will be dominated by local irritation / corrosion. There is unlikley to be significant dermal absorption of fluoride under normal 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.

Repeated exposure inhalation toxicity

The effects of repeated inhalation exposure to potassium bifluoride may be local (due to the generation of HF) or systemic (due to the absorption of fluoride. However the substance is a non-volatile solid and significant inhalation expousre is not predicted based on its physicochemical properties. 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.

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.

Repeated dose toxicity: via oral route - systemic effects (target organ) other: bone

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: other

Repeated dose toxicity: dermal - systemic effects (target organ) other: skin

Justification for classification or non-classification

No classification is required for repeated dose toxicity.