Strontium hydroxide

Endpoint summary

Description of key information

Strontium hydroxide is not expected to show systemic effects up to 10.3 mg Sr(OH)2/kg bw/d based on read-across from a 90-day repeated dose toxicity study conducted with strontium chloride (NOAEL: 22.5 mg SrCl2.6H2O/kg bw/d; equal to 7.4 mg Sr/kg bw/d)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

10.3 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Please refer to the discussion for "repeated dose toxicity, oral" below.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity, oral:

No repeated dose toxicity study by oral route is available on Strontium hydroxide itself. However, an analogue approach is used for the read-across of toxicological properties of strontium hydroxide from strontium chloride, based on the hypothesis that properties are likely to be similar as a result of the presence of a common metal ion Sr2+. Further information on the read-across justification is included as attachment in Section 13.

 

In a sub-chronic feeding study by Kroes et al. (1977) SPF Wistar rats (40-60 g of body weight, 10 males and 10 females per group) received strontium chloride hexahydrate in a semi-purified diet at dose levels of 0, 75, 300, 1200, and 4800 ppm for 90 days. The diet contained adequate levels of Ca, Mg, P and vitamin D3. Growth, behaviour, food intake and food efficiency were not affected in the 90-day study. No differences in clinical chemistry were noted, except of an indication of increased alkaline phosphatase activity in the highest dose group. Urinalysis showed no differences in the groups. The levels of Ca, Mg and P in blood were similar for all dose levels and the Ca/P ratio was constant. In males, thyroid weights were significantly increased in the 1200 and 4800 ppm groups. Although, no clear explanation of this finding could be given it was regarded as treatment-related. In females, pituitary weights were significantly decreased in the 300 and 4800 ppm group, but not in the 1200 ppm group, and this finding was regarded as difficult to interpret. Glycogen depletion of the liver was noted in the highest dose group. However, this was may be caused by stress, starvation or diurnal rhythm and not by treatment with the test substance. Detectable amounts of strontium in blood and muscle were only noticed at the dose of 4800 ppm. The strontium content in bone was increased at all dose levels having a constant level from 4 weeks onwards (steady-state level). No treatment-related changes were observed in the X-ray photographs and on histopathological examination except, slight changes in the liver (glycogen depletion) and thyroid (activation). Thus, upto the highest dose of 4800 ppm no rachitic changes occurred. The dose of 4800 ppm corresponds to a dose of 360 mg/kg bw/d strontium chloride (equal to 199 mg Sr/kg bw/d) assuming an average rat body weight of 200 g and a daily food intake of 15 g.

Considering the increased concentrations of strontium in the bone as a non-toxic effect, a NOAEL of 300 ppm SrCl2 can be derived from this study based on the weight changes of thyroids at the doses of 1200 ppm (LOAEL) and 4800 ppm, and thyroid activation at 4800 ppm. No data on daily food intake are available in order to calculate daily dose levels. The NOAEL of 300 ppm strontium chloride corresponds to a dose of 22.5 mg/kg bw/d (equal to 12.4 mg Sr/kg bw/d). This value refers to approximately 17.3 mg Sr(OH)₂/kg bw/d. This study is defined as key study.

Repeated dose toxicity, inhalation

According to the Regulation (EC) 1907/2006, testing on long term inhalation toxicity is considered not being scientifically justified. Strontium hydroxide is classified as corrosive by worst case. Therefore, the assumption has to be made that the substance is also corrosive to the respiratory tract. Due to animal welfare testing is not foreseen.

Considering that an official indicative occupational exposure limit value exist for soluble barium compounds (e.g. Ba(OH)₂); published in the Official Journal of the European Union (Commission Directive 2006/15/EC, 7 February 2006), this value was used for the derivation of a DNEL for long-term inhalation, local effects for Ba(OH)₂ as worst case due to the corrosivity of the substance. Reflected that the pH of Ba(OH)₂ and Sr(OH)₂ results in identical values of 13.6 which based on saturated solutions (water solubility of both substances: 37.1 g/L for Ba(OH)₂ and 22.5 g/L for Sr(OH)₂) and the corrosive effect is based on the OH^- concentration which is the same for both substances, the IOEL could be regarded as worst case DNEL for Sr(OH)₂ as well. Thus, for risk assessment purposes a DNEL for long-term inhalation toxicity, local effects is used based on the available IOEL of 0.5 mg Sr²⁺/m³ for Sr compounds. In conclusion, there is no need to initiate testing on long term inhalation toxicity and derogation is considered to be justified.

Repeated dose toxicity, dermal

According to Annex VIII, column 2, and Annex XI (weight of evidence) of Regulation (EC) 1907/2006, testing for sub-chronic dermal toxicity is not considered to be required, for the following reasons:

- Repeated dose toxicity study via dermal route does not need to be performed since the physico-chemical and toxicological properties do not suggest potential for a significant rate of absorption through the skin.

- The substance is classified as corrosive to skin. Thus, due to animal welfare reasons testing is not allowed. A qualitative approach for hazard assessment was chosen.

Justification for classification or non-classification

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – repeated exposure, oral are not met, and thus no classification for specific target organ toxicant (STOT-RE) is required. However, some evidence of an effect of strontium on thyroid function is observed in the 90-day oral toxicity study in rats, but the incidence is very slight and seen only in males, but not in females, of the highest dose group tested, which is clearly above the cut-off levels for STOT-RE classification Cat.2 (> 100 mg/kg bw/d rat oral, 90-day).