CARCINOGENICITY ASSESSMENT OF SELECTED NICKEL COMPOUNDS

The early epidemiological data indicated different carcinogenic risks from inhalation of different nickel compounds, but it was not clear wh at characteristics governed the intrinsic carcinogenic hazard of the v arious nickel compounds. Based on the earlier results, all soluble and insoluble nickel compounds were assumed to have the same carcinogenic mechanism albeit different potencies, Recent in vivo and in vitro stu dies challenged this assumption. In this paper an attempt is made to i ntegrate the most relevant human, animal, and in vitro data into a gen eral model that can help understand the different carcinogenic potenti als of the various nickel compounds. In this perspective, it is recogn ized that there are two main components that could contribute to the d evelopment of lung cancer via exposure to certain nickel compounds, Th e first component corresponds to the heritable changes (genetic or epi genetic) derived from the direct or indirect actions of nickel compoun ds, The second component may be the promotion of cell proliferation el icited by certain nickel compounds. The different contributions of thr ee nickel compounds to these two components are presented. This paper emphasizes the importance of recognizing the individuality of the diff erent nickel species in reaching regulatory decisions and the fact tha t different risk assessment considerations may apply for compounds tha t appear to produce immortality and cancer by genetic/epigenetic mecha nisms (like nickel subsulfide), compounds that may present a threshold for the induction of tumors in rats (like high-temperature nickel oxi de), or compounds that may only have an enhancing effect on carcinogen icity (like nickel sulfate). (C) 1997 Academic Press.