There are no studies of nickel workers exposed solely to nickel alloys in the absence of metallic or oxidic nickel. Clearly, however, workers in alloy and stainless steel manufacturing and processing will likely have some low level exposure to nickel alloys. In general, most studies on stainless steel and nickel alloy workers have shown no significant occupationally-related excess risks of respiratory cancer (Cox et al., 1981; Polednak, 1981; Cornell, 1984; Svensson et al., 1989; Moulin et al., 1993, 2000; Hansen et al., 1996; Jakobsson et al., 1997; Arena et al., 1998). There have been some exceptions, however, in certain groups of stainless steel welders (Gerin et al., 1984; Kjuus et al., 1986) where excess lung tumors were detected. Further analyses of these and other stainless steel workers as part of a large international study on welders (>11,000 workers) failed to show any association between increased lung cancer mortality and cumulative exposure to nickel (Siminato et al., 1991). A later analysis of this same cohort (Gerin et al., 1993) showed no trend for lung cancer risk for three levels of nickel exposure. Likewise, no nickel-related tumors were observed in a group of German arc welders exposed to fumes containing chromium and nickel (Becker, 1999). As noted above and in the discussion on metallic nickel, some of these studies involved thousands of workers (Arena et al., 1998; Siminato et al., 1991). Hence, these studies suggest an absence of nickel-related excess cancer risks in workers exposed to nickel-containing alloys.
Limited data are available to evaluate respiratory carcinogenicity of nickel alloys in animals. One intratracheal instillation study looked at two types of stainless steel grinding dust. An austenitic stainless steel (6.8% nickel) and a chromium ferritic steel (0.5% nickel) were negative in hamsters after repeated instillations (Muhle et al., 1992). In another study, grinding dust from an austenitic stainless steel (26.8% nickel) instilled in hamsters was also negative (Ivankovic et al., 1988). In this same study, an alloy containing 66.5% nickel, 12.8% chromium, and 6.5% iron showed some evidence of carcinogenic potential at the higher doses tested. A significant shortening in survival time in one of the high dose groups compared to untreated controls, however, raises the question of toxicity and its possible confounding effect on tumor formation. As noted in the discussion of metallic nickel, intratracheal instillation studies must be carefully interpreted in light of their artificial delivery of unusually large and poten- tially toxic doses of chemical agents to the lung (Driscoll et al., 2000).
In total, there is little evidence to suggest that nickel alloys act as respiratory carcinogens. For many alloys, this may be due to their corrosion resistance which results in reduced release of metal ions to target tissues.
With respect to non-carcinogenic respiratory effects, no animal data are available for determining such effects, and the human studies that have looked at such endpoints have generally shown no increased mortality due to non-malignant respiratory disease (Polednak, 1981; Cox et al., 1981; Simonato et al., 1991; Moulin et al., 1993, 2000; Arena et al., 1998).