Subchronic Inhalation Toxicity of Nickel Subsulfide to Rats and Mice

Abstract

Inhalation studies conducted on nickel subsulfide (Ni₃S₂ have shown this compound to be highly toxic to the respiratory tract of rats and mice exposed for 12 d. To assess the subchronic inhalation toxicity of Ni₃S₂, groups of F344/N rats and B6C3F₁ mice were exposed to 0, 0.11, 0.22, 0.44, 0.88, and 7.8 mg Ni/m³ (as Ni₃S₂), 6 h/d, 5 d/wk, for 13 wk. Concentrations of Ni in lungs of rats and mice exposed for 73 wk were similar, but the incidence and severity of the toxic effects of Ni₃S₂ exposure were greater among rats than mice. Exposure resulted in depressed weight gain and increased lung weights. Inhalation of Ni₃S₂ did not affect motility, viability or morphology of sperm in males, nor did it alter the estrous cycle length of females. Major histopathological lesions related to nickel exposure occurred in the nose, lung, and lung-associated lymph nodes of both species. The major findings were focal chronic inflammation of the lung, atrophy of the olfactory epithelium, and hyperplasia of the bronchial and mediastinal lymph nodes. In addition, focal interstitial fibrosis developed in lungs of mice exposed to 0.88 and 7.8 mg Ni/m³. The lowest exposure concentrations resulting in respiratory tract lesions were 0.44 mg Ni/m³ for mice and 0.11 mg Ni/m³ for rats. Results indicate that subchronic inhalation exposure of rats and mice to Ni₃S₂ concentrations below the current threshold limit value VLVI for nickel produces significant lesions in the respiratory tract.