Biochemical responses of rat and mouse lung to inhaled nickel compounds

Nickel subsulfide (Ni3S2), nickel sulfate (NiSO4), and nickel oxide (NiO) are encountered occupationally in the nickel refining and electroplating industries, with inhalation being a common route of exposure. The purposes of this study were to evaluate the biochemical responses of lungs of rats and mice exposed for 13 weeks to occupationally relevant aerosol concentrations of Ni3S2, NiSO4, and NiO, to correlate biochemical responses with histopathologic changes, and to rank the compounds by toxicity. Biochemical responses were measured in bronchoalveolar lavage fluid (BALF) recovered from lungs of exposed animals. Parameters evaluated in BALF were lactate dehydrogenase (LDH), beta-glucuronidase (BG), and total protein (TP). Total and differential cell counts were performed on cells recovered in BALF. All compounds produced an increase in LDH, BG, TP, and total nucleated cells, and an influx of neutrophils, indicating the presence of a cytotoxic and inflammatory response in the lungs of exposed rats and mice. Increases in BG were greater than increases in LDH and TP for both rats and mice. Chronic active inflammation, macrophage hyperplasia, and interstitial phagocytic cell infiltrates were observed histologically in rats and mice exposed to all compounds. Statistically significant increases in BG, TP, neutrophils, and macrophages correlated well with the degree of chronic active inflammation. Results indicated a toxicity ranking of NiSO4 greater than Ni3S2 greater than NiO, based on toxicities of the compounds at equivalent mg Ni/m3 exposure concentrations.