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Description of key information

No repeated dose toxicity study with strontium oxide is available. Since strontium oxide completely dissolves upon contact and during the reaction with water andbased on the assumption that strontium is the moiety of concern,the repeated dose toxicity will be addressed only with existing data on the moiety strontium. 

In a relevant and reliable repeated dose toxicity study conducted with strontium dichloride, no toxicological findings were reported that would justify a classification for specific target organ toxicity with repeated exposure. Thus, strontium oxide does not have to be classified.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL

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

Strontium

A sub-chronic study was conducted with strontium chloride hexahydrate using groups of 10 male and 10 female Wistar rats. The rats were given the test substance via diet at dose levels of 0, 75, 300, 1200 or 4800 ppm (0, 7.5, 30, 120, or 480 mg/kg/day, respectively) for a duration of 90 days. The following parameters were investigated: clinical signs/mortality, body weight, food consumption/food efficiency, haematology, clinical chemistry, urinalysis, organ weights, and histopathology. Additional 10 males were included as satellite animals for the determination of the strontium levels in blood, bone and muscle, which were examined in weeks 0, 4, 8 and 12.

In a range-finding experiment, rats with an initial body weight of 130-170 g were divided into 5 groups each consisting of 3 females and 3 males, receiving 0, 3, 30, 300 and 3000 ppm strontium chloride hexahydrate in the diets respectively during two weeks. The animals were weighed at the beginning of the experiment and after 1 and 2 weeks. Food intake was recorded during the experimental period and was measured per cage (two rats) and expressed as the average intake per day per rat. Food conversion was calculated, blood samples were taken at the end of the experiment and haematological investigation was restricted to haemoglobin, haematocrit and the number of erythrocytes and leucocytes. The mean cell volume, mean cell haemoglobin concentration, and mean cell haemoglobin were calculated. At the end of the 2 weeks X-ray photographs were made of all animals. Strontium concentration was measured in blood, bone and muscle. Liver and kidneys were weighed and examined histopathologically by preparing paraffin sections (5 µm) stained with hematoxylin and eosin. Behaviour, growth, food intake and food efficiency were not affected in the range-finding experiment. Haematological investigation revealed only a slight elevation of the total number of erythrocytes in males and females and a slight increase of the white cell count in the males at the highest dose level. No differences were found in liver and kidney weights and histopathological examination revealed no abnormalities. Strontium in blood and muscle were only noted at the highest dose level whereas from 300 ppm onwards increased concentrations were found in bone.

In the main study, growth, behaviour, food intake and food efficiency were not affected by the treatment. Apart from a slight increase in the ALP activity in the highest dose group, no differences in clinical chemistry were noted. Levels of Ca, Mg and P in blood were similar for all animals and the Ca/P ratio was unaffected. Significant increase of the relative thyroid weights was found for the males at the 1200 ppm (control group: 0.0054 %; treatment group: 0.0072 %; P < 0.01) and 4800 ppm dose levels (control group: 0.0054 %; treatment group: 0.0068 %; P < 0.001). Although, no reasoning for this finding was be given, it was regarded as treatment-related. Relative pituitary weights of the females at 300 ppm dose level (control group: 0.0074 %; treatment group: 0.0062 %; P < 0.05) and at 4800 ppm dose level (control group: 0.0074 %; treatment group: 0.0056 %; P < 0.01) were significantly decreased, but not in the 1200 ppm group. Due to the lack of a dose-response relationship, this finding is not considered biologically relevant. 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. Increased strontium concentrations in blood and muscle were solely measured in animals at 4800 ppm. The strontium content in bone was increased at all dose levels with a plateau on week 4 and onwards (steady state). No treatment-related changes were observed in the X-ray photographs or during microscopical examination. Slight changes in the liver (glycogen depletion) and thyroid (activation). Thus, up to the highest dose of 4800 ppm no rachitic changes occurred.

The NOAEL (males) of 300 ppm strontium chloride hexahydrate (equivalent to 30 mg/kg/day, nominal) was derived, based on the significant increase of the relative thyroid weights, found for the males at the 1200 ppm and 4800 ppm dose levels. The substance NOAEL corresponds to NOAEL (males) of 9.9 mg strontium/kg/day (nominal).

 

Strontium oxide

Based on data reported in a highly reliable repeated dose toxicity study conducted with strontium dichloride and the fact that strontium is the moiety of concern, strontium oxide in all probability has also no potential to induce adverse effects after repeated exposure.

For the purpose of hazard assessment of strontium oxide, the point of departure for the most sensitive endpoint of strontium, as moiety of concern, will be used for the DNEL derivation. Thus, the NOAEL of 9.9 mg Sr/kg bw/day for the repeated dose toxicity will be used.

Justification for classification or non-classification

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, strontium oxide does neither have to be classified and has no obligatory labelling requirement for repeated oral toxicity nor for specific target organ toxicity after repeated exposure (STOT RE).