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.