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Toxicological information

Carcinogenicity

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Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

READ ACROSS CONCEPT

Valid toxicological data on carcinogenicity 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 compounds is proposed based on the following reasoning:

Read-across to Sr(NO3)2, SrCl2and Strontium ranelate, 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, strontium dichloride and/or strontium ranelate. 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)

-        strontium ranelate is moderately water soluble with 800 mg/L at 25°C (solubility at pH 1.5; 39.5 g/L at 37°C)

In comparison, the water solubilityof 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, strontium dinitrate and strontium ranelate 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.

Data on strontium:

Strontium ranelate:According to the EMEA report 2005 (see study summary "s_EMEA_2005 -rat" and "s_EMEA_2005 -mice") the results of a 105 weeks carcinogenicity in male and female rats, indicate some increased incidences of C-cell carcinoma in thyroids of male rats in the low (LD) and high dose (HD) groups. It is stated that it cannot completely be excluded that a subtle increase in plasma cation levels may have, in some individual rats, affected the progression of thyroid C-cell hyperplasia/adenoma to carcinoma. However, taking the totality of the data into account, there is no clear evidence that the finding of increased incidences of C-cell carcinoma in LD and HD males in the main carcinogenicity study in the rat are related to strontium ranelate treatment. Moreover, there are some differences between human and rat with respect to calcitonin regulation, such as the age-related increased increase in calcitonin in rats, whereas the opposite occurs with increasing age in humans, which indicate that the tumour findings are of minor clinical relevance. In addition, the incidence of C-cell tumours was not increased in female rats and in male and female mice, and male F344 rats treated over 52 weeks with doses as in the carcinogenicity studies had no increase in thyroid C-cell proliferative lesions. In conclusion and in accordance with theregulation (EC) 1907/2006 Annex X column 2 a carcinogenicity study is not proposed since there is no evidence that the substance has mutagenetic or carcinogenic effects. The data provided in this section are sufficient for the evaluation and classification / non classification of the substance.

Strontium nitrate and Strontium chloride, respectively:There is an absence of any published evidence on the formation of tumours in humans after exposure to stable strontium compounds. Information is available on the action of strontium inin-vivoandin-vitroscreening systems for the prediction of mutagenicity or carcinogenicity of metal salts. The DNA synthesis in nuclear epithelia of kidney and liver was not inhibited by intra-peritoneal injection of strontium nitrate to mice (s_Amlacher_1983). Investigations in anin-vitroscreening system showed that strontium chloride did not affect the accuracy of the DNA synthesis (s_Sirover, 1976).

Data on sulfides:There is no conclusive evidence for any carcinogenic potential of H2S in the public domain, despite that it is well-known that H2S can elicit local effects in the respiratory tract. Upon systemic availability, sulfides are rapidly oxidised and excreted renally as sulfates. Regarding sulfur and sulfates, there is a general opinion that these compounds are essential for life and do not pose a risk for humans.

Thus, in the absence of any conclusive human or animal evidence for any carcinogenic effect, the complete lack of genotoxicity of sulfides, and given the metabolic profile and natural geogenic ubiquitous presence of sulfides in the environment, there is no need for the conduct of a carcinogenicity study, and this data a requirement should therefore be waived. A full expert statement on carcinogenicity is included in the technical dossier and in the CSR.

Reference:

EMEA (2012): CJMP Type II variation assessment report, procedure no. EMEA/H/C/000560/II/0031, 2012-05-24

Anonymous (2009): Solfuro di strontio, ECOL Studio S. R. L., Via Dei Bichi 293, 55100 Lucca, Italia, 2009-12-30

Justification for classification or non-classification

Taken together, the results discussed in the above area it can be concluded that strontium sulfide is not identified as potential mutagen or carcinogen. Hence, no classification and labelling of the substance as carcinogenic substance is necessary.