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 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).
Oller
A R
AR
Nickel Producers Environmental Research Association, Durham, North Carolina 27713, USA.
Costa
M
M
Oberdörster
G
G
D000280:Administration, Inhalation; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004785:Environmental Pollutants; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics; D008452:Maximum Allowable Concentration; D009532:Nickel / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D018570:Risk Assessment
D002273:Carcinogens; D004785:Environmental Pollutants; D009532:Nickel