Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Toxicological relevance of the counterion “sulfate”

The registrant is of the opinion that the toxicity of strontium sulfate is driven by the strontium moiety and that the sulfate anion does not contribute to the overall toxicity of the substance strontium sulfate to any relevant extent, for the following reasons:

Sulfate anions are abundantly present in the human body in which they play an important role for the ionic balance in body fluids. Sulfate is required for the biosynthesis of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) which in turn is needed for the biosynthesis of many important sulfur-containing compounds, such as chondroitin sulfate and cerebroside sulfate. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) concludes that the few available studies in experimental animals do not raise any concern about the toxicity of the sulphate ion in sodium sulphate. Sodium sulphate is also used clinically as a laxative. In clinical trials in humans using 2-4 single oral doses of up to 4500 mg sodium sulphate decahydrate per person (9000 – 18000 mg per person), only occasional loose stools were reported. These doses correspond to 2700 - 5400 mg sulphate ion per person. High bolus dose intake of sulphate ion may lead to gastrointestinal discomfort in some individuals. No further adverse effects were reported (JECFA 2000, 2002). This position was adopted by the European Food Safety Authority (EFSA 2004) without alteration.

Based on the above information, one can therefore safely assume that the sulfate anion in strontium sulfate does not contribute to the overall toxicity of strontium, sulfate. It is concluded that only the effect of “strontium” is further considered in the human health hazard assessment of strontium sulfate.

Read across concept:

(i) from SrCl2to SrSO4

The toxicity of strontium substances such as strontium sulfate can reasonably assumed to be determined by the availability of strontium ions in solution. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Strontium chloride is highly water soluble with ~538 g/L at pH ~ 7, whereas strontium sulfate is moderately soluble (~125 mg/L at pH ~ 6.5). Hence, any read across from strontium chloride to strontium sulfate is inherently very conservative.

 

(ii) from Sr(NO3)2to SrSO4:

The toxicity of strontium substances such as strontium sulfate can reasonably assumed to be determined by the availability of strontium ions in solution. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Strontium nitrate is highly water soluble with ≤ 802 g/L at pH ~7, whereas strontium sulfate is moderately soluble (~125 mg/L at pH ~ 6.2). Hence, any read across from strontium nitrate to strontium sulfate is inherently very conservative.

Strontium chloride hexahydrate caused no visible reduction in the growth of the bacterial lawn at any of the dose levels to any of the strains of Salmonella tested. No significant increase in the frequency of revertant colonies was recorded for any of the bacterial strains with any of the concentrations tested, either with or without metabolic activation.

 

Strontium nitrate did not induce micronuclei in cultured human peripheral blood lymphocytes following treatments in the absence and presence of an Aroclor induced rat liver metabolic activation system (S-9 mix). Concentrations were tested and analysed up to 2116 µg/mL.

Furthermore, strontium nitrate did not induce mutation at the tk locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study.

These conditions included treatments up to precipitating concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system (S-9 mix).

 

Based on the test results and since read across is fully justified (see above), further testing of in vivo genetic toxicity tests with strontium sulfate is not considered necessary.


Short description of key information:
Strontium substances have been tested in bacterial reverse mutation assays, in vitro gene mutation and chromosome aberration test. The tests show a negative response, thus strontium sulfate is not to be classified as mutagenic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Strontium sulfate could be regarded to have no mutagenicity / genotoxicity effects, tested in vitro. Hence, no classification and labelling is required.