title: Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium.
abstract: The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at ≥20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. yukey@med.nagoya-cu.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Sawada
authors.affiliation: Nagoya City Public Health Research Institute, Nagoya, 467-8615, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Himiko
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Chukyo University School of Health and Sport Science, Toyota, 470-0393, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Sawamoto
authors.affiliation: Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. kamijima@med.nagoya-cu.ac.jp.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000441:Hexanols / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D008813:Mice, Inbred ICR; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D009830:Olfactory Bulb / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D013997:Time Factors
chemical_list: D000393:Air Pollutants; D000441:Hexanols; C034017:2-ethylhexanol
keywords: 2-Ethyl-1-hexanol (2E1H); Histopathological changes; Inhalation; Olfactory bulb; Olfactory epithelium