Comparative acute toxicity of four nickel compounds to F344 rat lung

Abstract

Nickel subsulfide (Ni 3S 2), nickel chloride (NiCl 2), nickel sulfate (NiSO 4), and nickel oxide (NiO) are compounds of widely differing solubility encountered in the nickel-refining and electroplating industries. Inhalation is a common route of exposure and toxicity to the respiratory tract is possible. The purpose of this study was to evaluate the biochemical, cytological, and morphological changes in lung following administration of these compounds by intratracheal instillation. F344/Crl rats were administered a single dose of nickel compound containing 0.0, 0.01, 0.10, or 1.0 μmol Ni by intratracheal instillation. Rats were sacrificed at 1 or 7 days after compound administration, with half the animals in each exposure group taken for determination of nickel lung burden and the remaining half used for evaluation of biochemical, cytological, and histological changes. In the latter group, the right lung was lavaged and the fluid obtained was analyzed for indicators of pulmonary inflammation: lactate dehydrogenase (LDH), β-glucuronidase (BG), total protein (TP), glutathione reductase (GR), glutathione peroxidase (GP), and sialic acid (SA). Total and differential cell counts on cells recovered in lavage fluid were also determined. The left lobe was examined for morphological changes. Clearance of nickel from the lung was most rapid for NiCl 2 and NiSO 4, followed by Ni 3S 2 and NiO. Minimal changes in all parameters were observed at 1 day after exposure. No significant changes in any parameter occurred in rats exposed to NiO, while Ni 3S 2, NiSO 4, and NiCl 2 caused increases in LDH, BG, TP, GR, SA, and total nucleated cells at 7 days. Alveolitis was also observed histologically in Ni 3S 2-, NiSO 4-, and NiCl 2-exposed animals at 7 days. Results indicated the following toxicity ranking for the four compounds: Ni 3S 2 ∼ NiSO 4 ∼ NiCl 2 ⪢ NiO. Toxicity appears to be related to the solubility of these compounds.