Toxicological Sciences 66, 7-15 (2002)
Copyright © 2002 by the Society of Toxicology
BIOTRANSFORMATION AND TOXICOKINETICS |
Predicted Regional Flux of Hydrogen Sulfide Correlates with Distribution of Nasal Olfactory Lesions in Rats
CIIT Centers for Health Research, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, North Carolina 27709–2137
Hydrogen sulfide (H2S) is a toxic gas that is released by both natural and industrial sources. H2S selectively targets the olfactory system in humans and rodents. The purpose of this study was to test the hypothesis that the distribution of H2S-induced nasal pathology is correlated with the location of high-flux areas within the upper respiratory tract. To investigate whether the location of the olfactory lesion is dependent on regional gas uptake patterns, a comparison was made between lesion locations and regions of high H2S flux predicted using a 3-dimensional, anatomically accurate computational fluid dynamics (CFD) model of rat nasal passages. Rats were exposed by inhalation to 0, 10, 30, or 80 ppm H2S for 6 h/day for 70 days. The regional incidence of olfactory lesions and predicted H2S flux were determined at the mid-dorsomedial meatus and the middle portion of the ethmoid recess, and their rank correlation was evaluated. At these 2 levels, regions lined by respiratory epithelium were predicted to exhibit the highest mass flux values; however, H2S exposure elicited little or no response in this tissue. In contrast, regions lined by olfactory epithelium showed a close correlation between H2S flux and lesion incidence (p < 0.005) for both the 30 and 80-ppm exposure groups. These results indicate that airflow-driven patterns of H2S uptake within the inherently sensitive olfactory epithelium play an important role in the distribution of H2S-induced lesions and should therefore be taken into consideration when extrapolating from nasal lesions in rats to estimates of risk to human health.
Key Words: hydrogen sulfide; rat; inhalation; pharmacokinetics; computational fluid dynamics; olfactory toxicity.
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