Pulmonary clearance and toxicity of zinc oxide instilled into the rat lung

Abstract

Pulmonary toxicity of zinc oxide (ZnO) was evaluated by investigating the metabolic fate and inflammatory potency of ZnO instilled into the rat lung. Groups of three rats received single intratracheal instillations of ZnO suspension at a dose of 100 micrograms Zn/rat in the time-course experiment or received 20, 50, 100, 200, 500 and 1000 micrograms Zn/rat and were killed 2 days after treatment in the dose-response experiment. It was suggested that ZnO particles were solubilized in the bronchoalveolar milieu and cleared from the lung with a half-life of 14 h. Metallothionein (MT) was induced with a peak at 2 days. The content of MT was proportional to the dose of ZnO, but contributed little for the accumulation of Zn in the lung. A dose of 20 micrograms Zn/rat was sufficient to develop maximum responses for beta-glucuronidase activity and surfactant content in the bronchoalveolar lavage fluid. Moreover, the activity of lactate dehydrogenase and protein content in the lavage fluid increased significantly at 20 micrograms Zn/rat. These results suggest that the recommended ZnO concentration in the work-place atmosphere of 5 mg/m3 might not be adequate.

Zinc exposure in Chinese foundry workers

“…Studies in rats have indicated that zinc oxide is cleared from the lung with an estimated half-life of 14 hr following intratracheal instillation [Hirano et al, 1989]. No estimates of the half-life of zinc in circulation could be identified.…”

“…Ulvik proposed a sequestering of circulating zinc from plasma into the liver. Hirano et al [1989] demonstrated a dose-dependent induction of the low molecular protein metallothionein following intratracheal instillation of zinc oxide in the lung. Leber and Miya [1976] have shown that zinc induces the synthesis of hepatic metallothionein in mice, suggesting a possible role for metallothionein in this process.…”

Toxicological Profile for Zinc

“…The aerosol had a mass median diameter of 0.17 µm. The retention of zinc in lungs was dose related in male Wistar rats administered a single intratracheal instillation of 0.07-3.7 mg zinc/m 3 as zinc oxide (Hirano et al 1989). A half-life of 14 hours was calculated.…”

“…Information regarding the absorption of zinc in animals following inhalation exposure was limited to lung retention data (Gordon et al 1992;Hirano et al 1989). However, there was information to assess the extent of absorption following oral exposure (Davies 1980;Galvez-Morros et al 1992; Johnson et al…”

“…Toxicokinetic studies have been performed in both humans and animals following oral exposure; however, data are limited for inhalation and dermal exposures. The animal model used most often to evaluate the toxicokinetics of zinc are rats (Agren et al 1991;Alexander et al 1981;Galvez-Morros et al 1992;Hirano et al 1989;Weigand and Kirchgessner 1992) and may be a good model for assessing the kinetics of zinc in humans.…”