Title: | Inhalation exposure to 2-ethyl-1-hexanol causes hepatomegaly and transient lipid accumulation without induction of peroxisome proliferator-activated receptor alpha in mice |
Author(s): | Wakayama T; Ito Y; Miyake M; Nomasa K; Sakai K; Oya N; Sato H; Ohno H; Kamijima M; |
Address: | "Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Japan. Department of Environmental Health, Nagoya City Public Health Research Institute, Japan. Research Fellow of Japan Society for the Promotion of Science, Japan" |
DOI: | 10.2486/indhealth.2020-0252 |
ISSN/ISBN: | 1880-8026 (Electronic) 0019-8366 (Print) 0019-8366 (Linking) |
Abstract: | "2-Ethyl-1-hexanol (2EH) is a volatile organic compound known to cause sick building syndrome. However, 2EH-induced hepatotoxicity has been mainly evaluated in experiments orally administering 2EH as a metabolite of di(2-ethylhexyl) phthalate. To evaluate the hepatotoxicity risk of 2EH as an indoor air pollutant, we exposed 10-wk-old male ICR mice to 2EH by inhalation for 8 h/d, 5 d/wk for 3 months (0, 20, 60, or 150 ppm) or 6 months (0, 0.5, 10, or 100 ppm). In both experiments, relative liver weights significantly increased in the highest exposure groups. The 3-month exposure increased histopathological lipid droplets in the liver in a dose-dependent manner, hepatic triglyceride at all exposure levels, hepatic phospholipid at 150 ppm, and microsomal triglyceride transfer protein at 60 and 150 ppm; however, these changes were not observed following the 6-month of exposure. Following the 3-month exposure, alanine transaminase and peroxisomal bifunctional proteins, known markers of liver injury and peroxisome proliferation, respectively, remained unaltered. Therefore, in the present study, the inhalation concentration range of 2EH induced a toxic hypertrophic change, revealing a limited role of peroxisome proliferator-activated receptor alpha (PPARalpha). The liver weights may have presumably increased via a mechanism independent of PPARalpha activation" |
Keywords: | "Animals *Hepatomegaly/chemically induced *Hexanols Inhalation Exposure Lipid Metabolism Male Mice Mice, Inbred ICR *PPAR alpha 2-Ethyl-1-hexanol Hepatic enlargement Lipid droplet Peroxisome proliferator-activated receptor alpha (PPARalpha) Volatile organi;" |
Notes: | "MedlineWakayama, Takanari Ito, Yuki Miyake, Mio Nomasa, Karin Sakai, Kiyoshi Oya, Naoko Sato, Hirotaka Ohno, Hiroyuki Kamijima, Michihiro eng Japan 2021/10/01 Ind Health. 2021 Nov 29; 59(6):383-392. doi: 10.2486/indhealth.2020-0252. Epub 2021 Sep 28" |