Dilanthanum tricarbonate

Carcinogenicity

Description of key information

There is no evidence, that the substance is carcinogenic. Lanthanum carbonate does not carry any structures suggesting a carcinogenic potency. Moreover, the results of the perfomed in vitro and in vivo genotoxicity studies were negative indicating that carcinogenicity by a direct genotoxic mechanism can be excluded. Finally, in the repeated dose toxicity studies, there was no evidence for pre-neoplastic lesions.

Justification for classification or non-classification

The data on carcinogenicity by the oral route is conclusive but not sufficient for classification according to the criteria of Directives 67/548/EEC (DSD) and 1272/2008/EC (CLP).

Additional information

In a carcinogenicity study - only available as short abstract - rats were given daily up to 1500 mg/kg bw/day Lanthanum III carbonate hydrate by gavage for 104 weeks (Läkemedelsverket, 2006). In this study the NOAEL regarding carcinogenicity was considered to be 1500 mg/kg bw/day. This was based on the fact that no increased incidences of malignant tumours were observed. Although some histocytic sarcomas in a few rats were found, these were regarded as of spontaneous origin rather than induced by Lanthanum carbonate.

In a similar study CD-1 mice were treated orally with up to 1500 mg/kg bw/d Lanthanum III carbonate hydrate for 2 years (Läkemedelsverket, 2006). No increased incidences of malignant tumours were observed although there was a dose-dependent increase in the incidence and severity of non-neoplastic lesions in the stomach. These lesions progressed to benign gastric adenoma in four high-dose males and one high-dose female. However, these findings were considered to be related to an exacerbation of spontaneous pathological stomach changes in CD-1 mice since it is known that aging CD-1 mice are predisposed to the development of sponataneous adenomatous hyperplasia. Adenomatous hyperplasie was also seen in control mice and the hyperplastic lesions in treated mice showed no atypical cytological alterations suggestive of pre-malignancy.

No gastric mucosal changes were seen in long-term dog studies (Läkemedelsverket, 2006). The positive finding only in a particularly sensitive mouse strain and negative findings in rats (hyperplasia but no tumours) and dogs (no hyperplasia) indicate that the neoplastic response in the mouse has little toxicological significance.

 

Moreover, based on the observations in the subchronic feeding study with Lanthanum carbonate octahydrate performed according to OECD 408 (Reißmüller, 2006) there is no indication of treatment-related histopathological changes since observations occurred at a comparable frequency and severity grade among control and animals treated with up to and including 1480.4 mg/kg bw/day for 90 days in the diet.