Summary of the Toxicity of Soluble Nickel

European regulatory activity in the first decade of the new millennium has resulted in soluble nickel compounds being classified as human inhalation carcinogens. However, the precise role of soluble nickel in human carcinogenicity is still uncertain. Epidemiologic information suggests that an increased risk of respiratory cancer associated with refinery process exposure to soluble nickel compounds primarily occurs at levels in excess of 1 mg Ni/m3. However, a few recent studies have noted that exposures slightly lower than this (around 0.5 mg Ni/m3) may have been associated with the excess respiratory cancers observed in workers exposed to soluble nickel.

Well-conducted inhalation animal studies where rats and mice were exposed to soluble nickel at workplace equivalent concentrations up to 2-6 mg Ni/m3 did not show any evidence of carcinogenicity. However, at workplace equivalent levels above 0.1 mg Ni/m3, chronic respiratory toxicity was observed. Respiratory toxicity due to soluble nickel exposures may have enhanced the induction of tumors by less soluble nickel compounds or other inhalation carcinogens seen in refinery workers. This mode of action is in agreement with mechanistic information indicating that nickel ions from soluble nickel compounds will not be bioavailable at target respiratory nuclear sites because they have inefficient cellular uptake and are rapidly cleared from the lungs.

With respect to non-malignant respiratory effects in humans, the evidence for soluble nickel salts being a causative factor for occupational asthma, while not overwhelming, is more suggestive than it is for other nickel species. Such evidence arises mainly from a small number of case reports in the electroplating industry and nickel catalyst manufacturing. It should be noted, however, that exposure to soluble nickel can only be inferred in some of the cases and confounding factors (exposure to chromium, cobalt, and plating solutions of low pH) often have not been taken into account.

Aside from asthma, the only other non-carcinogenic respiratory effect reported in nickel workers exposed to soluble nickel is that of fibrosis. Evidence that soluble nickel may act to induce pulmonary fibrosis comes from a recent study of nickel refinery workers that showed modest abnormalities in the chest X-rays of workers. An association between the presence of irregular opacities (ILO1 =1/0) in chest X-rays and cumulative exposures to soluble nickel, sulfidic nickel, and possibly metallic nickel, was reported. The significance of these results for the clinical diagnosis of fibrosis remains to be determined.

Historically, workplaces where prolonged contact with soluble nickel has been high, have shown high risks for allergic contact nickel dermatitis. For example, nickel dermatitis was common in the past among nickel platers. Due to improved industrial and personal hygiene practices, however, over the past several decades, reports of nickel sensitivity in workplaces, such as the electroplating industry, have been sparse.

(1) Based on a chest radiographs from the International Labor Organization (ILO) set of standard chest X-rays.