Histopathological changes in the olfactory epithelium of mice during four-week recovery after 2-ethyl-1-hexanol inhalation

Volatile organic compound 2-ethyl-1-hexanol (2EH) causes the sick building syndrome. Inhalation exposure to 2EH causes olfactory epithelium (OE) degeneration and olfactory neuron loss in mice, which recover temporarily despite continued exposure but subsequently experience similar toxic effects. However, the exact course of recovery after 2EH cessation remains unknown. Therefore, in this study, we aimed to evaluate the histopathological changes in OE after 2EH inhalation cessation. Male ICR mice were exposed to 70 ppm 2EH for 8 hr daily, five days a week, for four weeks, followed by a recovery period of up to four weeks. Histopathological changes in mouse OE on the first (D1) and third (D3) days and first (W1), second (W2), and fourth (W4) weeks of the recovery period were analyzed. Notably, 2EH induced OE degeneration at W2, enlarged the Bowman’s glands at W1 and W2, and decreased the olfactory marker protein-positive cell proportions at W1 and W2. Total leukocytes, neutrophils, and lymphocytes were abundant at both W1 and W2, with no significant differences. Proliferating cell nuclear antigen-positive basal cell number increased; they were distributed throughout the OE on D1 but subsequently lined up the basement membrane and remained at low levels thereafter. Number of growth-associated protein-43-positive immature olfactory neurons increased from D3 to W2. In conclusion, OE was not immediately repaired; the toxic effects appeared 1–2 weeks after 2EH cessation, as indicated by the OE tissue damage with decreased olfactory marker protein-positive cell proportions, followed by proper recovery.