The early epidemiological data indicated different carcinogenic risks from inhalation of different
nickel compounds, but it was not clear what characteristics governed the intrinsic carcinogenic hazard of the various
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 studies challenged this assumption. In this paper an attempt is made to integrate the most relevant human, animal, and in vitro data into a general model that can help understand the different carcinogenic potentials of the various
nickel compounds. In this perspective, it is recognized that there are two main components that could contribute to the development of
lung cancer via exposure to certain
nickel compounds. The first component corresponds to the heritable changes (genetic or epigenetic) derived from the direct or indirect actions of
nickel compounds. The second component may be the promotion of cell proliferation elicited by certain
nickel compounds. The different contributions of three
nickel compounds to these two components are presented. This paper emphasizes the importance of recognizing the individuality of the different
nickel species in reaching regulatory decisions and the fact that different risk assessment considerations may apply for compounds that appear to produce immortality and
cancer by genetic/epigenetic mechanisms (like
nickel subsulfide), compounds that may present a threshold for the induction of
tumors in rats (like high-temperature
nickel oxide), or compounds that may only have an enhancing effect on carcinogenicity (like
nickel sulfate).