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Development of a Rabbit Model to Investigate the Effects of Acute Nitrogen Dioxide Intoxication

National Poison Control Centre, Department of Intensive Care and Clinical Toxicology, University Hospital Utrecht, Utrecht, The Netherlands

L. van Bree

Laboratory for Toxicology

J.A.M.A. Dormans

Laboratory for Pathology of the National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven

A.B.T.J. Boink

Laboratory for Toxicology

B. Sangster

National Poison Control Centre, Department of Intensive Care and Clinical Toxicology, University Hospital Utrecht, Utrecht, The Netherlands

1 In previous studies a rat inhalation model was developed to investigate the effects of intervention after acute NO₂ exposure. The object of the present study was to investigate whether acute NO₂ intoxication induced comparable effects in rabbits as it does in rats. Where the effects of intervention in both species are similar, then the conclusions drawn from these studies may have more relevance for the treatment of man.

2 Biochemical variables in bronchoalveolar lavage and supernatant from lung homogenate, which may be relevant for the evaluation of lung injury and repair, were investigated and compared with histology.

3 After NO ₂ exposure for 10 min, the pulmonary effects observed became more pronounced with increasing NO₂ concentrations (0, 125, 175, 250, 400, 600 or 800 ppm) [1 ppm NO₂ is 1.88 mg m^-3]. The effects in rabbits were found to be broadly comparable with those in rats.

4 To achieve severe lung injury in rabbits without mortality, enabling investigations of the effects of intervention over several days, exposure to a NO₂ concentration of 600 ppm for 10 min was most appropriate, while a concentration of 175 ppm NO₂ was needed to attain comparable effects in rats.

5 The repair phase starts later, namely at 3 days after exposure in rats, compared to 5 days in rabbits.

Human & Experimental Toxicology, Vol. 13, No. 11, 749-758 (1994)
DOI: 10.1177/096032719401301103


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