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Rat Model to Investigate the Treatment of Acute Nitrogen Dioxide Intoxication

National Poison Control Centre, P.O. Box 1, 3720 BA Bilthoven, The Netherlands, Department of Intensive Care and Clinical Toxicology, University Hospital Utrecht, Utrecht, The Netherlands

J.A.M.A. Dormans

Laboratory for Pathology, P.O. Box 1, 3720 BA Bilthoven, The Netherlands

M. Marra

Laboratory for Toxicology of the National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA Bilthoven, The Netherlands

P.J.A. Rombout

Laboratory for Toxicology of the National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA Bilthoven, The Netherlands

B. Sangster

National Poison Control Centre, P.O. Box 1, 3720 BA Bilthoven, The Netherlands, Department of Intensive Care and Clinical Toxicology, University Hospital Utrecht, Utrecht, The Netherlands

1 The pulmonary toxic events induced by acute nitrogen dioxide (NO)₂ exposure were studied in the rat to develop an inhalation model to investigate therapeutic measures.

2 A good correlation was observed between the lung weights and severity of the atypical pneumonitis. The pulmonary effects observed, became more pronounced with increasing NO ₂ concentrations (0, 25, 75, 125, 175 or 200 ppm, 1 ppm NO₂=1.88 mg m^-3 NO₂) and exposure times (5, 10, 20 or 30 min).

3 An adequate NO ₂ concentration is 175 ppm, because it can induce a severe lung injury without mortality. This makes it possible to investigate suitable therapeutic interventions for several days.

4 Following acute inhalatory NO₂ intoxication, transformation of NO₂ to nitrate is presumably more notable than transformation to nitrite.

5 The transformation of NO₂ to nitrate in lung tissue causes a slight increase in the serum nitrite concentration, which does not induce measurable formation of methaemoglobin. 6 Presumably, methaemoglobin does not contribute to the toxicity of NO₂ intoxication.

Human & Experimental Toxicology, Vol. 11, No. 3, 179-187 (1992)
DOI: 10.1177/096032719201100306


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