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Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium

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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.

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Acknowledgments

This project was supported by a Grant-in-Aid for Scientific Research (24590752) from the Japan Ministry of Education, Culture, Sports, Science, and Technology, and a grant provided by The Uehara Memorial Foundation in 2009.

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Mio Miyake, Yuki Ito, Himiko Suzuki & Michihiro Kamijima

  2. Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan

    Masato Sawada & Kazunobu Sawamoto

  3. Nagoya City Public Health Research Institute, Nagoya, 467-8615, Japan

    Kiyoshi Sakai

  4. Chukyo University School of Health and Sport Science, Toyota, 470-0393, Japan

    Tatsuo Sakamoto

Authors
  1. Mio Miyake
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Correspondence to Yuki Ito or Michihiro Kamijima.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Supplemental figure

Mouse respiratory epithelium after exposure to 0 (CON) and 150 (HIGH) ppm 2E1H for 1 week (1 W), 1 month (1 M), and 3 months (3 M). Typical photographs in each group are given here. No toxic changes were observed in the respiratory epithelium. Scale bar indicates 50 µm. (TIFF 34074 kb)

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Miyake, M., Ito, Y., Sawada, M. et al. Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium. Arch Toxicol 90, 1949–1958 (2016). https://doi.org/10.1007/s00204-016-1699-6

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  • DOI: https://doi.org/10.1007/s00204-016-1699-6

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