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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
25 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Repeated dose toxicity has been tested for sodium fluoride. No studies are available for disodium hexafluorosilicate. Due to the presence of hydrolysable groups on its chemical structure, fluorosilicate anions are not expected to remain in solution long under environmental conditions. Instead, fluoride anions will be formed. Thus, the performance of such tests is unjustified, since there are reliable studies on sodium fluoride or hydrogen fluoride. Read-across to sodium fluoride is appropriate.

In a 28 day study on male and female rats which were feed by gavage with 0.0%, 0.0025%, 0.025% or 0.25% aqueous NaF (w/w), several effects, such as depression in mean cell haemoglobin, depression in total protein, increase of fluoride in urine, were observed.

Male and female rats suffered a continuous exposure for a period of 6 months to NaF. This fact caused weight loss at dose =300ppm, fluorosis of the teeth and hyperplastia of the gastric mucosa of the stomach at 100 and 300 ppm. Bone and urine also increased their level of fluoride when fluoride concentration in drinking water increased.

Male and female mice were feed NaF for 6 month in a continuous exposure in drinking water. During this period some animals died after ingesting the highest dose, 600 ppm. Weight loss, fluorosis and effects on liver were observed. Increasing fluoride concentration in drinking water, fluoride content of bones and urine increased.

A study carried out for 2 years on rats and mices which were feed with NaF in drinking water showed that bones and teeth tend to accumulate fluoride. In addition, fluorosis in teeth was observed. However, these effects occurred using a much higher concentration of NaF than normally used in human drinking water. The presence of osteosarcomas was observed in some animals. However, this fact is not directly attributable to the presence of fluoride in drinking water.

EURAR HF 2001 reported that for the repeated dose toxicity via inhalation studies the available animal data set for HF permit the derivation of a NOAEL for repeated subchronic inhalatory exposure. The over-all NOAEL is taken form 91 day GLP study with female and male rats and amounts 0.72 mg HF/m3for 6 h per day 5 days per week exposure regimen with no adverse effects. At the next exposure level death, tissue irritation, dental malformations, haematological and biological changes and changes in several organ weights were observed. In humans prolonged intake of fluoride results in skeletal fluorosis. Exposure to 1.16 mg HF/m3for 6 hr/d may result in some discomfort, slight stinging sensation in eyes and facial skin and slight irritation of the nasal mucosa. This concentration can be considered as a LOAEL for inhalatory exposure. Beneficial effects like prevention of dental carries after low fluoride intake have been observed. On the other hand, excessive fluoride intake can cause dental fluorosis (dental lesions) and osteofluorosis (bone structural changes).


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: blood coagulation; digestive: liver; digestive: stomach; other: bone

Justification for classification or non-classification