Lime (chemical), hydraulic

Carcinogenicity

Description of key information

Calcium (when administered orally in feed as Ca-lactate) is not carcinogenic. Neither toxicity nor carcinogenic activity was observed in rats at the highest dose tested.

The NOAEL of lime (chemical) hydraulic, converted from Ca taking into account the respective molecular weights, has been determined at 592.5 mg/kg bw/d (the highest dose tested).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

592.5 mg/kg bw/day

Study duration:

chronic

Species:

rat

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No increased rate of tumour formation was observed in studies on calcium lactate in rats. Lime (chemical) hydraulic does not contain any main constituents or major impurities that are known to be carcinogenic. Calcium, and in consequence hydraulic lime is not considered to be carcinogenic. Classification for carcinogenicity is not warranted.

Additional information

The long-term toxicity/carcinogenicity of calcium lactate was examined in F344 rats. Calcium lactate was given ad libitum in the drinking water at levels of 0, 2.5 or 5% to groups of 50 male and 50 female rats for two years. Animals were examined daily for clinical signs and mortality. Body weights were measured once a week for the first 13 weeks and every four weeks thereafter. Water intake was measured three times a week, when the calcium lactate solutions were replaced with freshly prepared solutions. Haematology and clinical chemistry analyses were performed at the end of the study. At week 113, all surviving animals were killed and autopsied. An autopsy was performed immediately on rats that died (or were killed when moribund) during the study and those killed at the end of the study. The animals were then examined macro- and microscopically for the presence of non-neoplastic and neoplastic lesions. All organs and / or tissues were routinely fixed in 10 % buffered formalin, sectioned and stained with haematoxylin and eosin. The mortality rate in high-dosed females was slightly higher than those in the two other groups, but the difference was not statistically significant. There was a dose-dependent decrease in body weight gain for both males and females. No specific dose-related changes of haematological or biochemical parameters were observed. Females of the high-dose group exhibited slightly, but significantly, higher kidney weights. Histologically, however, there was no difference in the severity of chronic nephropathy. A significant dose-dependent increase was observed in the relative brain weights of both male and female rats although no histological change was detected. A number of non-neoplastic lesions (e.g. myocardial fibrosis, bile-duct proliferation, hepatic microgranulomas and chronic nephropathy) were observed in all groups, with no difference in their incidence and/or degrees. None of the experimental groups showed a significant increase in the incidence of any specific tumours compared with the corresponding control value, and no positive trend was noted in the occurrence of any tumour. Male rats of the high-dose group showed a slightly higher incidence of pheochromocytomas and adrenal medullary hyperplasia, however, there were no carcinogenic effects observed. Calcium lactate did not cause toxicity or carcinogenic activity in F344 rats. Thus, the high dose of 5 % represents the NOAEL for tumour formation in this study. The concentration of 5 % corresponds to calcium lactate doses of 2150 and 2280 mg/kg bw/d to male and female rats, respectively, which are 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.

According to the specification lime (chemical) hydraulic contains 66 % calcium as oxide equivalent (CaO). Considering the molecular weight of calcium (40.078 g/mol), and calcium oxide (56.077 g/mol) the content of calcium in lime (chemical) hydraulic is 47.17 % Ca. Lime (chemical) hydraulic does not contain any main constituents or major impurities that are known to be carcinogenic. The NOAEL for hydraulic lime is obtained by converting the NOAEL for calcium, considering the content of calcium in hydraulic lime. The NOAEL is therefore 592.5 mg/kg bw/d.

A human clinical study (Baron, 1999; 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.

Furthermore, epidemiological data on cement workers (cement used as a surrogate for lime; s_Vestbo_1991_cement dust) indicate no increased overall cancer risk due to inhalation of cement dust in this population.