Fate of Inhaled Nickel Oxide and Nickel Subsulfide in F344/N Rats

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Abstract
The fates of inhaled nickel oxide (NiO, green oxide calcined at 1200°C) and nickel subsulfide (Ni3S2), two occupationally relevant nickel compounds, have been studied in male F344/N rats. Groups of rats underwent pernasal exposure to 9.9 mg NiO/m3 or to 5.7 mg Ni3S2/m3 for 70 and 120 min, respectively. The activity median aerodynamic diameters (geometric standard deviation) of the NiO and Ni3S2 aerosols were 1.3 μm (2.0) and 1.3 μm (1.5), respectively. End points evaluated included total and regional respiratory tract deposition of the aerosols, lung clearance of deposited material, distribution of solubilized material to extrarespiratory tract tissue, and pathways of Ni excretion from the body. The fractions of the inhaled NiO and Ni3S2 aerosols that deposited in the respiratory tract were 0.11 and 0.13, respectively. The fractions of the inhaled aerosol that deposited in the lungs were 0.05 for both aerosols. Inhaled NiO cleared slowly from the lungs, with a half-life of approximately 120 days. Following NiO exposures, Ni was not distributed to the extrarespiratory tract tissue, and the material was excreted only in the feces during the first few days after the exposure. Inhaled Ni3S2 cleared rapidly from the lungs, with a clearance half-time of approximately 4 days. Nickel was detected in several extrarespiratory tract tissues of Ni3S2-exposed rats within a few hours after the end of the exposure, and was detected in lung and kidneys up to 16 days postexposure. Results of this study indicate that two occupationally relevant Ni compounds formed during the refining of Ni ore have significantly different lung retention and tissue distribution patterns. As expected, the high-temperature NiO behaves as a relatively insoluble particle and is retained in lung, while Ni3S2 behaves as a relatively soluble particle, with fairly rapid dissolution in lung and distribution of Ni to extrarespiratory tract tissues.