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Carcinogenicity

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Description of key information

No carcinogenicity study on Be metal with a full evaluation of proper endpoints is available. A total of 11 publications with relevance to carcinogenic potential of Be metal are available but only three of these are considered reliable. The publication by Groth et al addresses carcinogenic potential of various Be species (including metal) while the study by Finch et al (1998a) is relevant due to the long observation period (350 days). Finch et al (1998b) supports the findings of the latter study. 

Key value for chemical safety assessment

Additional information

Only three studies are considered reliable for the purpose of evaluating carcinogenic potential of Be metal. In the study by Groth (1980), an increase in lung neoplasms was observed in rats following exposure to Be metal, passivated Be metal and a 60 % BeAl alloy. While the number of animals in the dose groups are relatively small due to canibalism, there is still a relatively clear increase in the number of lung neoplasms. This is further supported by a weak dose-response effect and the observation that the number of neoplasms in animals exposed to Be alloys containing less Be (< 4 %) was significantly less than in animals exposed to Be metal. This study is considered of relevance to humans.

The study by Finch (1998a) does not address fully a carcinogenic endpoint but was included due to the long exposure period. Mice were significantly less suscpetible to toxicity (histopathological changes of lung). Whether this can also be extended to carcinogenicity can not be concluded. Since the observation was limited to 350 days, it can not be excluded that an effect would be manifested later. This finding is further supported by Finch (1998b) where no lung neoplasms were observed in p53 (+/+) mice following exposure to Be metal via inhalation. In p53(+/-) mice only the high dose caused a slight increase in neoplasms (4/28 animals) while no effect was seen in low dose animals.

The remaining studies are not considered reliable or relevant. Nevertheless, the general trend in these studies is an increase in neoplasms in rats following exposure to Be-metal by inhalation while mice are relatively resistant to this effect. In two rat studies, mutations in the K-ras gene was found at a very low rate. No changes were found in p53 or c-raf-1, indicating that these pathways are not involved in the effects of Be-metal in rats. In conclusion, animal models of carcinogenicity of Be-metal are not conclusive and should be interpreted carefully.

Justification for classification or non-classification

The studies are not appropriate for classification purposes.