Development of a rabbit model to investigate the effects of acute nitrogen dioxide intoxication.
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 NO2 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.
National Poison Control Centre, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
J
J
Meulenbelt
L
L
van Bree
J A
JA
Dormans
A B
AB
Boink
B
B
Sangster
D000818:Animals; D001273:Atmosphere Exposure Chambers; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009585:Nitrogen Dioxide / Q000506:poisoning*; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D009585:Nitrogen Dioxide