Respiratory tract toxicity of inhaled hydrogen sulfide in Fischer-344 rats, Sprague–Dawley rats, and B6C3F1 mice following subchronic (90-day) exposure

Abstract The goal of this study was to characterize the toxicity of hydrogen sulfide (H 2 S), including nasal and pulmonary effects, in adult male and female Fischer-344 and Sprague–Dawley rats and B 6 C 3 F 1 mice. Animals underwent whole-body exposure to 0, 10, 30, or 80 ppm H 2 S for 6 h/day for at least 90 days. Exposure to 80 ppm H 2 S was associated with reduced feed consumption during either the first exposure week (rats) or throughout the 90-day exposure (mice). Male Fischer-344 rats, female Sprague–Dawley rats, and female B 6 C 3 F 1 mice exposed to 80 ppm H 2 S had depressed terminal body weights when compared with air-exposed controls. Subchronic H 2 S inhalation did not result in toxicologically relevant alterations in hematological indices, serum chemistries, or gross pathology. Histologic evaluation of the nose showed an exposure-related increased incidence of olfactory neuronal loss (ONL) and rhinitis. ONL occurred following exposure to ≥30 ppm H 2 S in both sexes of all experimental groups, with one exception, male Sprague–Dawley rats demonstrated ONL following exposure to 80 ppm H 2 S only. A 100% incidence of rhinitis was found in the male and female B6C3F1 mice exposed to 80 ppm H 2 S. In the lung, exposure to H 2 S was associated with bronchiolar epithelial hypertrophy and hyperplasia in male and female Sprague–Dawley rats following exposure to ≥30 ppm H 2 S and in male Fischer-344 rats exposed to 80 ppm H 2 S. Our results confirm that the rodent nose, and less so the lung, are highly sensitive to H 2 S-induced toxicity, with 10 ppm representing the NOAEL for ONL following subchronic inhalation.