Registration Dossier

Toxicological information

Carcinogenicity

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Administrative data

Description of key information

Calcium (when administered orally in feed as Ca-lactate) is not carcinogenic.
Magnesium (when administered orally in feed as Mg-chloride) is not carcinogenic.
The NOAEL of calcium magnesium carbonate oxide, converted from Ca taking into account the respective molecular weights, has been determined at 979 mg/kg bw/d.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
979 mg/kg bw/day

Justification for classification or non-classification

No increased rate of tumour formation was observed in studies on calcium lactate in rats and magnesium chloride in mice, respectively. Neither calcium nor magnesium nor calcium magnesium carbonate oxide is considered to be carcinogenic. Classification for carcinogenicity is not warranted.

Additional information

There was no evidence of relevant carcinogenic activity of calcium in both sexes of rats receiving 2.5 or 5 % calcium lactate via drinking water for 104 weeks.The NOAEL for tumour formation in this study is represented by the high dose of 5 %, corresponding to calcium lactate doses of 2150 and 2280 mg/kg bw/d to male and female rats, respectively. This is equivalent to calcium doses of approximately 279.5 and 296.4 mg Ca/kg bw/d for male and female rats. Accordingly, the lower NOAEL value of 279.5 mg Ca/kg bw/d (male rats) is established as a NOAEL for carcinogenicity hazard assessment.

A human clinical study (Baron, 1999; technical dossier section 7.10.1) suggests a beneficial effect of calcium supplementation on cancer risk: Calcium supplementation is associated with a significant - though moderate - reduction of the risk of recurrent colorectal adenomas.

Diets containing 2 % MgCl2*6 H2O did not cause carcinogenic effects in B6C3F1 mice of both sex. The NOAELs for tumor formation were 2810 and 3930 mg/kg bw/d for males and females, respectively. These values correspond to doses of 336 and 470 mg Mg/kg bw/d for males and females, respectively.

Accordingly the lower NOAEL value of 336 mg Mg/kg bw/d for male mice, is established as the NOAEL for carcinogenicity hazard assessment. Both NOAELs (Ca and Mg) are used as a basis for deriving an NOAEL for CaCO3MgO.

Considering the molecular weight of magnesium (24.305 g/mol)/ calcium (40.078 g/mol) and CaCO3MgO (140.390 g/mol), this NOAEL can be converted into a NOAEL for calcium magnesium carbonate oxide of 979.07 mg/kg bw/d with respect to calcium and 1941 mg/kg bw/d with respect to magnesium.

Furthermore, epidemiological data on cement workers (cement used as a surrogate for lime; technical dossier section 7.10.1, Vestbo, 1991) indicate no increased overall cancer risk due to inhalation of cement dust in this population.