Hepatotoxicity Caused by Repeated and Subchronic Pulmonary Exposure to Low-Level Vinyl Chloride in Mice

Abstract

Vinyl chloride (VC) is classified as a group 1 carcinogen to humans by the International Agency for Research on Cancer, and inhalation is considered to be an important route of occupational exposure. In addition, increasing numbers of studies have observed adverse health effects in people living in the vicinity of petrochemical complexes. The objective of this study was to investigate the adverse in vivo health effects on the lungs and liver caused by pulmonary exposure to low-level VC. BALB/c mice were repeatedly intranasally administrated 50 µL/mouse VC at 0, 1, and 200 ng/mL (5 days/week) for 1, 2, and 3 weeks. We observed that exposure to 1 and 200 ng/mL VC significantly increased the tidal volume (μL). Dynamic compliance (mL/cmH2O) significantly decreased after exposure to 200 ng/mL VC for 3 weeks. Total protein, lactate dehydrogenase (LDH), and interleukin (IL)-6 levels in bronchoalveolar lavage fluid (BALF) significantly increased after exposure to 200 ng/mL VC for 2 and/or 3 weeks. Significant decreases in 8-isoprostane and caspase-3 and an increase in IL-6 in the lungs were found after VC exposure for 2 and/or 3 weeks. We observed that aspartate aminotransferase (AST), alkaline phosphatase (ALKP), albumin (ALB), and globulin (GLOB) had significantly increased after three weeks of VC exposure, whereas the ALB/GLOB ratio had significantly decreased after 3 weeks of exposure to VC. IL-6 in the liver increased after exposure to 1 ng/mL VC, but decreased after exposure to 200 ng/mL. IL-1β in the liver significantly decreased following exposure to 200 ng/mL VC, whereas tumor necrosis factor (TNF)-α and caspase-3 significantly increased. Hepatic inflammatory infiltration was confirmed by histological observations. In conclusion, sub-chronic and repeated exposure to low levels of VC can cause lung and liver toxicity in vivo. Attention should be paid to all situations where humans are frequently exposed to elevated VC levels such as workplaces or residents living in the vicinity of petrochemical complexes.