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Olfactory Neuron Loss in Adult Male CD Rats Following Subchronic Inhalation Exposure to Hydrogen Sulfide

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, brenneman{at}ciit.org

R. Arden James

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709

Elizabeth A. Gross

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709

David C. Dorman

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709

Dysosmia and anosmia are reported to occur following human exposure to hydrogen sulfide (H₂S) gas. The clinical association between H₂S exposure and olfactory dysfunction in humans necessitates evaluation of the nasal cavity and olfactory system in experimental animals used to study H₂S toxicity. The purpose of this study was to subchronically expose 10-week-old male CD rats to relatively low concentrations of H₂S and to histologically evaluate the nasal cavity for exposure-related lesions. Rats (n = 12/ group) were exposed via inhalation to 0, 10, 30, or 80 ppm H₂S 6 h/d and 7 d/wk for 10 weeks. Following exposure to 30 and 80 ppm H₂S, a significant increase in nasal lesions limited to the olfactory mucosa was observed. The lesions, which consisted of olfactory neuron loss and basal cell hyperplasia, were multifocal, bilaterally symmetrical, and had a characteristic rostrocaudal distribution pattern. Regions of the nasal cavity affected included the dorsal medial meatus and the dorsal and medial portions of the ethmoid recess. The no observed adverse effect level for olfactory lesions in this study was 10 ppm. For perspective, the American Conference of Governmental Industrial Hygienists threshold limit value (TLV) recommendation for H ₂S is currently 10 ppm (proposed revision: 5 ppm), so the concentrations employed in the present study were 3 and 8 times the TLV. These findings suggest that subchronic inhalation exposure to a relatively low level of H₂ S (30 ppm) can result in olfactory toxicity in rats. However, because of differences in the breathing style and nasal anatomy of rats and humans, additional research is required to determine the significance of these results for human health risk assessment.

Key Words: Hydrogen sulfide • olfactory neuron loss • olfactory basal cell hyperplasia • rat • subchronic • inhalation exposure • toxicity

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