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Carcinogenicity

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Description of key information

Taken together all results discussed it can be concluded that strontium is not identified as potential mutagen or carcinogen.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Justification for classification or non-classification

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

Additional information

Studies conducted with strontium ranelate (EMEA report 2005):

Read across to studies where the oral route is implemented is envisaged due to the fact that possible effects occurred could be regarded as strontium ion related effects. Due to the fact that as a first surrogate for bioavailability, the water solubility of a test substance may be used and since both substances (strontium ranelate and strontium hydroxide) could be regarded as "soluble" in the gastrointestinal tract, any read- across from strontium ranelate to strontium hydroxide is considered to be justified. It is noted; although Sr(OH)2is a strong base (pH 13.1 for a 1 % solution) it will be neutralised within thegastrointestinal tract.

 

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 progress on 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.

 

Studies conducted with strontium chloride and strontium nitrate:

Read across is envisaged due to the fact that possible effects occurred could be regarded as strontium ion related effects. All three substances (SrCl2, Sr(NO3)2 and Sr(OH)2) are "very soluble" in the gastrointestinal tract. Hence, it could be concluded that read across is possible.

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 in in-vivo and in-vitro screening 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 an in-vitro screening system showed that strontium chloride did not affect the accuracy of the DNA synthesis (s_Sirover, 1976).