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Effects on fertility

Description of key information

Based on the information available from a 90-day repeated dose oral toxicity study (according OECD 408) conducted with strontium chloride hexahydrate using male and female Wistar rats, it was concluded using a read-across concept that strontium difluoride does not present a reproductive hazard to both sexes, since no histopathological findings were made in the gonads.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
226.1 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Key study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Selected endpoints for the human health hazard assessment are addressed by read-across, using a combination of data on the fluoride moiety and the strontium moiety (or one of its readily soluble salts). This way forward is acceptable, since strontium difluoride dissociates to the fluoride anion and the strontium cation upon dissolution in aqueous media.

Once the individual constituents of strontium difluoride become bioavailable (i.e. in the acidic environment in the gastric passage or after phagocytosis by pulmonary macrophages), the “overall” toxicity of the dissociated substance can be described by the toxicity of the “individual” constituents. Since synergistic effects are not expected, the human health hazard assessment consists of an individual assessment of the strontium cation and the fluoride anion.

For more detailed information on read-across justification please refer to the report attached on IUCLID section 13 "SrF2_Read Across Assessment Framework Report"

Strontium:

Kroes et al. (1977) investigated the effects of strontium chloride hexahydrate in a repeated dose oral toxicity study according to OECD 408. Groups of 10 male and 10 female Wistar rats were treated with 0, 75, 300, 1200 or 4800 ppm (0, 7.5, 30, 120, or 480 mg/kg/day) ad lbitium via feed for a duration of 90 days. According to the authors, no histological changes for uterus, ovaries, testes and prostate after the administration of up to and including 4800 ppm strontium chloride hexahydrate (equivalent to 480 mg Strontium chloride hexahydrate/kg/day) were observed.

 

Fluoride:

Collins, et al. (2001) reported that sodium fluoride in drinking water of Sprague-Dawley rats at levels up to 250 ppm the highest concentration tested. This concentration, equivalent to 28.4 mg sodium fluoride/kg body weight/day or 12.8 mg fluoride/kg body weight/day, had no adverse effects on reproduction throughout three generations. Mating, fertility and survival indices were not affected.

Toxicity to reproduction: other studies

Additional information

Read-across concept:

Strontium difluoride – general considerations

Strontium difluoride completely dissolves upon contact with water to Sr2+and 2*F-. The water solubility (CRC handbook, 2008) of strontium difluoride indicates a complete dissolution and a rapid formation of Sr2+and 2*F-(210 mg/L at 25°C; logK 8.4). The pH of a saturated aqueous solution of strontium difluoride is pH 4.9. Considering that systemic human health effects of strontium difluoride are due the dissolved concentrations of Sr2+and F-in physiological solutions, read-across to very soluble (i.e., > 10 g/L at room temperature) inorganic strontium compounds and very soluble (i.e., > 10 g/L at room temperature) inorganic fluoride compounds is performedand considered to be very conservative.

 

In sum, data are read-across for soluble inorganic strontium substances and for different fluoride salts (mainly sodium fluoride) and avid to assess the toxicity of strontium difluoride on a conservatively basis in view of the water solubility. All read-across substances used for the assessment of strontium difluoride are more soluble (≥ 41 g/L) than strontium difluoride (210 mg/L at 25°C).Since, the toxicity of strontium difluoride is based on the concentration of strontium cations and fluoride anions in solution, read-across is considered to be conservative and unrestricted read-across is fully justified with regard to systemic toxicity. For detailed information please refer to the report attached on IUCLID "0" Category.

Justification for classification or non-classification

Based on the overall evaluation of the available data for soluble inorganic strontium substances and fluorides (i.e., sodium) on reproduction and developmental toxicity, a classification and labelling for reproduction of strontium difluoride is not considered to be justified according to Regulation (EC) 1272/2008 and subsequent adaptations.

Additional information