Strontium carbonate

Endpoint summary

Description of key information

Strontium carbonate is not expected to show effects at 12.4 mg SrCO3/kg bw/d (equivalent to 7.4 mg Sr/kg bw/d) based on the 90-day repeated dose toxicity study conducted with strontium chloride.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment in Section 13.

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

NOAEL

Effect level:

7.4 mg/kg bw/day (nominal)

Based on:

element

Remarks:

Sr

Sex:

male

Basis for effect level:

organ weights and organ / body weight ratios

Remarks on result:

other: The increased concentrations of strontium in the bone are considered a non-toxic effect.

Dose descriptor:

LOAEL

Effect level:

29.6 mg/kg bw/day (nominal)

Based on:

element

Remarks:

Sr

Sex:

male

Basis for effect level:

organ weights and organ / body weight ratios

Remarks on result:

other: The increased concentrations of strontium in the bone are considered a non-toxic effect.

Critical effects observed:

not specified

Conclusions:

If the increased concentrations of strontium in the bone can be considered a non-toxic effect, a NOAEL of 7.4 mg Sr/kg/day (corresponding to 12.4 mg SrCO3/kg/day) can be derived from this study, which is based on the weight changes of thyroids at the doses of 29.6 mg Sr/kg/day (LOAEL, corresponding to 49.6 mg SrCO3/kg/day) and 118.4 mg Sr/kg/day (corresponding to 198.4 mg SrCO3/kg/day).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

12.4 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Organ:

thyroid gland

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Critical effects observed:

not specified

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

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Critical effects observed:

not specified

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 carbonate itself. However, an analogue approach is used for the read-across of toxicological properties of strontium carbonate 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 21 mg SrCO3/kg bw/d. This study is defined as key study.

Repeated dose toxicity, inhalation:

In accordance with Annex XI of the regulation (EC) 1907/2006, the initiation of a second route for long term toxicity study is scientifically not justified due to the fact that for risk assessment purposes a DNEL for determination of long term inhalation toxicity for systemic effects could be derived by route-to-route extrapolation from a 90-day oral toxicity study performed with SrCl2. Furthermore, a worst case DNEL for long term inhalation local effects is available by taking the IOEL value of 0.5 mg Ba2+/m3 into consideration for poorly soluble strontium substances. In conclusion, it is neither scientifically nor justified due to animal welfare to initiate testing.

 

Repeated dose toxicity, dermal:

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

- A 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.

- In accordance with ECHA guidance on information requirements and chemical safety assessment-chapter R.8: characterisation of dose [concentration]-response for human health, May 2008, a DNEL for systemic effects could be derived by route-to-route extrapolation from a 90-day oral toxicity study in rats with SrCl₂.

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 Sr 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 Cat2 (> 100 mg/kg bw/d rat oral, 90-day).