Strontium sulphide

Endpoint summary

Additional information

READ ACROSS CONCEPT

Valid toxicological data on mutagenicity specifically for strontium sulfide from animal studies are not available. Therefore, because of the lack of appropriate experimental data, read-across from studies with sulfides and strontium compoundsis proposed based on the following reasoning:

 

Read-across to H₂S:

The readily water-soluble compound strontium sulfide will initially dissociate upon dissolution in water and/or relevant physiological media into strontium and sulfide ions.

 

However, sulfide anions will react with water in a pH-dependant reverse dissociation to form hydrogensulfide anions (HS-) or H₂S, respectively, according to the following equation:

 

H₂S  ↔  H⁺  +  HS^-  ↔  2H⁺  +  S^2-

 

The dissociation behaviour is presented in the Hägg g raph reported under IUCLID section 5.1.2 Hydrolysis.

 

The pKa values for the first and second dissociation steps of H2S are 7.0 and 12.9 (for details, refer to the IUCLID section on dissociation constant), respectively. Therefore, at neutral physiological pH values, hydrogen sulfide in the non-dissociated form (H2S) and the hydrogen sulfide anion (HS-) will be present in almost equimolar proportion, whereas only very small amounts of the sulfide anion (S2-) will be present. Conversely, at gastric pH (pH 1-2), non-dissociated H2S will be the predominant species.

 

In conclusion, under physiological conditions, inorganic sulfides or hydrogensulfides as well as H2S will dissociate to the respective species relevant to the pH of the physiological medium, irrespective of the nature of the “sulfide”, which is why read-across between these substances and H2S is considered to be appropriate without any restrictions for the purpose of hazard and risk assessment of strontium sulfide.

Read-across to Sr(NO₃)₂and SrCl₂, respectively:

Upon dissolution in water and/or physiological media, dissociation of strontium sulfide to release Sr²⁺ions may initially be expected.

However, based on the established fact that strontium ions may form poorly soluble species for example with physiologically present carbonate ions, the bioaccessibility/bioavailability may vary between different physiological conditions. Notwithstanding this limitation, it is considered justified to read-across from available data either on strontium dinitrate and/or strontium dichloride. In this context, the water solubility of a substance is used as a first approximation of bioavailability:

-        strontium dichloride is highly water soluble with ca. 538 g/L at 20°C/pH ca. 7 (solubility at pH 1.5; 465.9 g/L at 37°C)

-        strontium dinitrate is highly water soluble with ≤ 802 g/L at 25°C/pH ca. 6 (solubility at pH 1.5; 668.6 g/L at 37°C)

In comparison, the water solubility of strontium sulfide is 120.6 g/L at 24°C/pH 12.9 (solubility at pH 1.5; 4.9 g/L at 37°C)

In conclusion, read across from strontium chloride and strontium dinitrate to strontium sulfide is considered as justified since the toxicity of these substances may reasonably be considered to be determined by the availability of Sr cations. It is noted that although SrS is a strong base (pH 12.6 for a 1% solution - source: Anonymous, 2009), substantial neutralisation in the gastrointestinal tract at pH-levels of approx.1.5 – 2 may nevertheless be anticipated.

Strontium

in vitro clastogenicity

Strontium nitrate did not induce micronuclei in cultured human peripheral blood lymphocytes when tested in excess of the limit of solubility in both the absence and presence of S9 Mix according to Draft OECD Guideline 487 (in vitro micronucleus test, Lloyd, M. (2010).

in vitro gene mutation

Strontium nitrate did not induce mutation at the hprt locus of L5178Y mouse lymphoma cells when tested under the conditions in accordance with OECD 476 (in vitro mammalian cell gene mutation test, Lloyd, M. (2010)). These conditions included treatments up to precipitating concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S9 mix).

SrCl₂*6H₂O 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 (Thompson, P. W. (1997).

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 (S9 mix) in accordance with OECD Guideline 471 (Bacterial reverse mutation assay).

Sulfides

in vivo clastogenicity

Based on the outcome of a guideline-compliant study, sodium sulfide does not induce chromosome aberrations in mammalian erythrocytes, when tested in NMRI male and female mice up a concentration of 96.1 mg/kg (Gocke (1981).

in vitro gene mutation

In a reliable in-vitro Ames test (reverse gene mutation assay) it is concluded that sodium sulfide is not mutagenic under the experimental conditions. The test concentrations were chosen up to 5000 µg/plate(Engelhardt (1989).

Sodium sulfide anhydrous was assayed for mutation at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus (6 -thioguanine [6TG] resistance) in mouse lymphoma cells (Stone (2010)..When tested up to toxic concentrations in the absence and presence of S9 mix in Experiments I and II, there were no significant increases in mutant frequency at any concentration analysed. A weak but statistically significant linear trend was observed in the presence of S9 mix in Experiment II but, in the absence of any marked increases in mutant frequency at any test article concentration analysed in this experiment, this observation was not considered biologically relevant.

The REACH requirements according to the endpoints in section 8.4, Annex VII-X in Regulation (EC) 1907/2006 are fulfilled. No further testing is required.

Justification for selection of genetic toxicity endpoint
Data of the genetic toxicity are available for strontium compounds and inorganic sulfides (SrCl2/Sr(NO3)2 and Na2S)

Short description of key information:
In-vitro studies:
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 nitrate is not to be classified as mutagenic.
Sodium sulfide has been tested in bacterial reverse mutation assays and in vitro gene mutation tests. The tests show a negative response.
In-vivo studies:
Chromosome aberration of sodium sulfide has been tested in-vivo in a micronucleus assay performed in mice similar to OECD guideline 474 (Gocke_1981). This study was rated as reliable with restrictions (RL=2) and is used as a key study. The study had a negative result.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

All reliable studies available showed no genetic toxicity for strontium and sulfide. Thus, according to Directive EEC 67/548 and to Regulation (EC) No 1272/2008, strontium sulfide should not be considered to have a mutagenic potential, and hence no classification or labelling is required.