As with above-mentioned species of nickel, the critical health effect of interest in relation to occupational exposure to oxidic nickel is respiratory cancer. Unlike metallic nickel, which does not appear to be carcinogenic in humans or animals, and soluble nickel, whose carcinogenic potential currently appears to be the opposite in humans and animals, the evidence for the carcinogenicity of certain oxidic nickel compounds is more compelling. That said, there is still some uncertainty regarding the forms of oxidic nickel that induce tumorigenic effects. Although oxidic nickel is present in most major industry sectors, it is of interest to note that epidemiological studies have not consistently implicated all sectors as being associated with respiratory cancer. Indeed, excess respiratory cancers have been observed only in refining operations in which nickel oxides were produced during the refining of sulfidic ores and where exposures were relatively high (>5 mg Ni/ m3). At various stages in this process, nickel-copper oxides may have been formed. In contrast, no excess respiratory cancer risks have been observed in workers exposed to lower levels (<2 Ni/m3) of oxidic nickel free of copper during the refining of lateritic ores or in the nickel-using industry.
A high calcining temperature nickel oxide administered to rats and mice in a two-year inhalation study did show some evidence of carcinogenicity in rats. In intraperitoneal studies, nickel-copper oxides have appeared to be as potent as nickel subsulfide in inducing tumors at injection sites. There is, however, no strong evidence to indicate that black (low temperature) and green (high temperature) nickel oxides differ substantially with regard to tumor-producing potency.
There is no single unifying physical characteristic that differentiates oxidic nickel compounds with respect to their in vitro genotoxicity or carcinogenic potential. Some general physical characteristics which may be related to carcinogenicity include: particle size =5 µm, large particle surface area, presence of metallic or other impurities and/ or amount of Ni (III), and the ability to induce reactive oxygen radicals. Phagocytosis appears to be a necessary, but not sufficient condition for carcinogenesis. Solubility in biological fluids will also affect how much nickel ion is delivered to target sites (i.e., cell nucleus).
With respect to non-malignant respiratory effects, oxidic nickel compounds do not appear to be respiratory sensitizers. Based upon numerous epidemiological studies of nickel-producing workers, nickel alloy workers, and stainless steel workers, there is little indication that exposure to oxidic nickel results in excess mortality from chronic respiratory disease. In the few instances where excess risks of non-malignant respiratory disease did appear – for example, among refining workers in Wales – the excesses were seen only in workers with high nickel exposures (>10 mg Ni/ m3), in areas that were reported to be very dusty. With the elimination of these dusty conditions, the risk that existed in these areas seems largely to have disappeared by the 1930s. In two studies of nickel workers using lung radiographs, there was no evidence that oxidic nickel dusts caused a significant fibrotic response.
Dermal exposures to oxidic nickel are believed to be of little consequence to nickel workers. While no data are directly available on the effects of oxidic nickel compounds on skin, little skin absorption of nickel ions is expected due to their low water solubility.