Chronic inhalation exposure to 0.5 ppm of 2-ethyl-1-hexanol induces histopathological changes in olfactory, respiratory, and skin tissue of mice.

OBJECTIVES

2-Ethyl-1-hexanol (2EH) is a volatile organic compound that can cause sick building syndrome and can be released from flooring materials for more than 10 years through the hydrolysis of compounds with 2-ethylhexyl moieties. Previous studies using mice have raised concerns about tissue-damaging effects on the olfactory epithelium (OE), olfactory bulb (OB), brain, lungs, and skin. A subchronic mouse study observed degeneration of OE at concentrations as low as 20 ppm. However, the effects of long-term exposure to 2EH remain unclear. This study aimed to elucidate the histopathological effects of chronic exposure to 2EH relative to its airborne concentration.

METHODS

Ten-week-old male ICR mice were exposed to 0, 0.5, 10, or 100 ppm 2EH by inhalation for 8 h/d, 5 d/wk, for 6 months. Subsequently, histopathological analysis was conducted.

RESULTS

At 0.5 ppm, acute and chronic inflammation were observed in the OE and alveoli, with tissue repair in the OE, and thickening of the epithelium and smooth muscle in the bronchi. Metaplasia of OE in the respiratory epithelium was induced at 10 and 100 ppm. At all concentrations, the number of mature neurons in the OE and immature neurons in the OB decreased, suggesting that olfactory nerve activity was suppressed. Fibroblasts increased in the dorsal skin. Microglia in the hippocampus and amygdala increased in number.

CONCLUSIONS

Chronic inhalation exposure at airborne concentrations of 2EH as low as 0.5 ppm caused inflammation in the OE, OB, segmental bronchi, and alveoli, and affected the target area of OB neurons.