title: Olfactory neuron loss in adult male CD rats following subchronic inhalation exposure to hydrogen sulfide.
abstract: 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 H2S 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 H2S (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.
authors.affiliation: Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709-2137, USA. brenneman@ciit.org
authors.forename: K A
authors.initials: KA
authors.lastname: Brenneman
authors.forename: R A
authors.initials: RA
authors.lastname: James
authors.forename: E A
authors.initials: EA
authors.lastname: Gross
authors.forename: D C
authors.initials: DC
authors.lastname: Dorman
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D006862:Hydrogen Sulfide / Q000633:toxicity*; D006965:Hyperplasia; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D019055:No-Observed-Adverse-Effect Level; D009830:Olfactory Bulb / Q000187:drug effects* / Q000473:pathology; D009831:Olfactory Mucosa / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000393:Air Pollutants; D006862:Hydrogen Sulfide