Significant pulmonary response to a brief high-level, nose-only nitrogen dioxide exposure: An interspecies dosimetry perspective

Abstract Brief, high-level nitrogen dioxide (NO 2 ) exposures are major hazards during fires and heat-generating explosions. To characterize the lung response to a brief high-level NO 2 exposure, we exposed two groups ( n = 5) of 325–375 g, male, Sprague–Dawley rats to either 200 ± 5 ppm (376 ± 9 mg/m 3 ) NO 2 or room air for 15 min. The rats were nose-only exposed in a multiport exposure chamber fitted with pressure transducers to monitor their respiration during exposure. One hour after exposure, we euthanized the rats, collected blood samples, lavaged the lungs with warm saline, and then excised them. One lung lobe was cooled to −196°C and used for low-temperature electron paramagentic resonance (EPR) analysis. The remainder was homogenized and used for biochemical analyses. Inspired minute ventilation ( V i ) during exposure decreased 59% ( p 2 . In lung lavage, both total and alveolar macrophage cell counts declined (∼75%, p p p 2 exposure of rats was sufficient to cause significant damage. However, comparison of the exposure dose normalized to rat body weight with previously reported sheep and estimated human values revealed significant differences. This raises a question about interspecies dosimetry and species-specific responses when animal data are extrapolated to humans and used for safety standard setting, particularly with high-level brief exposures.