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 μg Zn/rat in the timecourse experiment or received 20, 50, 100, 200, 500 and 1000 μg 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 μg Zn/rat was sufficient to develop maximum responses for β-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 μg Zn/rat. These results suggest that the recommended ZnO concentration in the work-place atmosphere of 5 mg/m3 might not be adequate.
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Amdur MO, Corn M (1963) The irritant potency of zinc ammonium sulfate of different particle sizes. Am Ind Hyg Assoc J 24: 326–333
Amdur MO, McCarthy JF, Gill MW (1982) Respiratory response of guinea pigs to zinc oxide fume. Am Ind Hyg Assoc J 43: 887–889
Amdur MO, McCarthy Jf, Gill MW (1983) Effect of mixing conditions on irritant potency of zinc oxide and sulfur dioxide. Am Ind Hyg Assoc J 44: 7–13
Conner MW, Rogers AE, Amdur MO (1982) Response of guinea pig respiratory tract to inhalation of submicron zinc oxide particles generated in the presence of sulfur dioxide and water vapor. Toxicol Appl Pharmacol 66: 434–442
Eaton DL, Toal BF (1982) Evaluation of the Cd/hemoglobin affinity assay for the rapid determination of metallothionein in biological tissues. Toxicol Appl Pharmacol 66: 134–142
Finckel AJ, Hamilton A, Hardy HL (1983) Zinc. In: Industrial toxicology. John Wright PSG Inc, Massachusetts
Gupta S, Pandey SD, Misra V, Viswanathan PN (1986) Effect of intratracheal injection of zinc oxide dust in guinea pigs. Toxicology 38: 197–202
Hammond PB, Beliles RP (1980) Metals. In: Doull J, Klaassen CD, Amdur MO (eds) Toxicology. Macmillan Publishing, New York
Hirano S, Tsukamoto N, Kobayashi E, Suzuki KT (1989a) Toxicity of cadmium oxide instilled into the rat lung. I. Metabolism of cadmium oxide in the lung and its effects on essential elements. Toxicology 55: 15–24
Hirano S, Tsukamoto N, Higo S, Suzuki KT (1989b) Toxicity of cadmium oxide instilled into the rat lung. II. Inflammatory responses in broncho-alveolar lavage fluid. Toxicology 55: 25–35
Kobayashi E, Hirano S, Tsukamoto N, Tamagawa H, Suzuki KT (1988a) Effects of heavy metals instilled intratracheally into rats. IV. Metabolism of zinc acetate in the lung (in Japanese). Eisei Kagaku 34: 560–564
Kobayashi E, Hirano S, Tsukamoto N, Suzuki KT (1988b) Effects of heavy metals instilled intratracheally into rats. V. Inflammatory responses in broncho-alveolar lavage fluid after instillation of zinc acetate (in Japanese). Eisei Kaguku 34: 524–530
Lam HF, Peisch R, Amdur MO (1982) Changes in lung volumes and diffusing capacity in guinea pigs exposed to a combination of sulfur dioxide and submicron zinc oxide mixed in a humidified furnace. Toxicol Appl Pharmacol 66: 427–433
Lam HF, Conner MW, Rogers AE, Fitzgerald S, Amdur MO (1985) Functional and morphologic changes in the lungs of guinea pigs exposed to freshly generated ultrafine zinc oxide. Toxicol Appl Pharmacol 78: 29–38
Lam HF, Chen LC, Ainsworth D, Peoples S, Amdur MO (1988) Pulmonary function of guinea pigs exposed to freshly generated ultrafine zinc oxide with and without spike concentrations. Am Ind Hyg Assoc J 49: 333–341
Linn WS, Kleinman MT, Bailey RM, Medway DA, Spier CE, Whynot JD, Anderson KR, Hackney JD (1981) Human respiratory responses to an aerosol containing zinc ammonium sulfate. Environ Res 25: 404–414
Lockard VG, Kennedy RE (1976) Alterations in rabbit alveolar macrophages as a result of traumatic shock. Lab Invest 35: 501–506
Nriagu JO, Pacyna JM (1988) Quantitative assessment of worldwide contamination of air, water and soils by trace metals. Nature 333: 134–139
Raab OG, Yeh HC, Newton GJ, Phalen RF, Velasquez DJ (1977) Deposition of inhaled monodisperse aerosols in small rodents. In: Walton WH (ed) Inhaled particles IV, part 1. Unwin Brothers Limited, Old Working Surrey, UK
Toshima N, Akino T (1972) Alveolar and tissue phospholipids of rat lung. Tohoku J Exp Med 108: 253–263
Wróblewski F, LaDue JS (1955) Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 90: 210–213
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Hirano, S., Higo, S., Tsukamoto, N. et al. Pulmonary clearance and toxicity of zinc oxide instilled into the rat lung. Arch Toxicol 63, 336–342 (1989). https://doi.org/10.1007/BF00278649
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DOI: https://doi.org/10.1007/BF00278649