Exposure to sub‐parts per million levels of vinyl chloride can increase the risk of developing liver injury

نویسنده

  • Ryoichi Fujiwara
چکیده

Vinyl chloride is a manufactured substance that is used to make polyvinyl chloride (PVC) plastic products, such as pipes, wire coatings, packaging materials, and cigarette filters. Because vinyl chloride usually exists in a gaseous state, the most common way of taking vinyl chloride into the human body is inhalation. People whowork at or near a facility thatmanufactures vinyl chloride and PVC products, hazardous waste sites, and landfills can therefore be exposed to vinyl chloride. Studies of humans and animals have indicated that exposure to high amounts of vinyl chloride increased risks of developing several types of cancer, including liver cancer, brain cancer, and lung cancer, and as a consequence, vinyl chloride has been recognized as a carcinogen and ranked fourth on the Substance Priority List prepared by the Agency for Toxic Substances and Disease Registry. Currently, the Occupational Safety and Health Administration (OSHA) regulates levels of vinyl chloride in the workplace to no greater than 1 ppm averaged over any 8-hour period. Although trace levels of vinyl chloride can be detected in various environmental matrices, such as drinking water, groundwater, and cigarette smoke, the impact of chronic exposure to subppm levels of vinyl chloride is still largely unknown. Steatosis, inflammation, fibrosis, and necrosis, in addition to cancer, have been associated with exposure to high levels of vinyl chloride. In this issue of Hepatology Communications, Lang et al. used a mouse model to investigate the effect of vinyl chloride at levels below the OSHA limit on the susceptibility to liver injury. Six-week-old mice were fed either a low-fat diet (LFD) or high-fat diet (HFD) for 12 weeks with and without inhalation of 0.85 ppm vinyl chloride for 6 hours per day, 5 days per week. The vinyl chloride exposure had a significant impact in the HFD-fed group, enhancing liver damage, neutrophil infiltration, apoptosis, oxidative stress, and endoplasmic reticulum stress, indicating that diet-induced obesity or the HFD itself sensitizes the liver for injury induced by sub-ppm levels of vinyl chloride. However, the most interesting observation in the study was that the sub-ppm levels of vinyl chloride dramatically dysregulated metabolic homeostasis and impaired mitochondrial function even in the LFD-fed mice. These findings indicate that exposure to sub-ppm levels of vinyl chloride can sensitize the liver to stressors and potentially lead to the onset of liver injury, including steatohepatitis, in both LFDand HFD-fed animals. In fact, workers handling vinyl chloride have a greater risk of developing liver disease. Therefore, the risk of developing various types of liver disease in humans, such as nonalcoholic fatty liver disease, might be lowered by minimizing the potential exposure to even a sub-OSHA level of vinyl chloride. In the liver, vinyl chloride is primarily metabolized to chloroethylene oxide by cytochrome P450 (CYP) 2E1. The metabolite spontaneously undergoes rearrangement to chloroacetaldehyde or is metabolized to Abbreviations: CYP, cytochrome P450; HFD, high-fat diet; LFD, low-fat diet; OSHA, Occupational Safety and Health Administration; PVC, polyvinyl chloride.

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عنوان ژورنال:

دوره 2  شماره 

صفحات  -

تاریخ انتشار 2018