Laila Al-Eryani1, Banrida Wahlang1, K C Falkner2, J J Guardiola3, H B Clair4, R A Prough5, Matt Cave6. 1. Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA. 2. Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, Louisville, Kentucky, USA. 3. University of Louisville School of Medicine, Louisville, Kentucky, USA. 4. University of Louisville School of Medicine, Louisville, Kentucky, USA Department of Biochemistry & Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA. 5. Department of Biochemistry & Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA. 6. Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, Louisville, Kentucky, USA University of Louisville School of Medicine, Louisville, Kentucky, USA Department of Biochemistry & Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA Robley Rex Louisville VAMC, Louisville, Kentucky, USA matt.cave@louisville.edu.
Abstract
BACKGROUND: Toxicant-associated fatty liver disease (TAFLD) is a recently identified form of nonalcoholic fatty liver disease (NAFLD) associated with exposure to industrial chemicals and environmental pollutants. Numerous studies have been conducted to test the association between industrial chemicals/environmental pollutants and fatty liver disease both in vivo and in vitro. OBJECTIVES: The objective of the article is to report a list of chemicals associated with TAFLD. METHODS: Two federal databases of rodent toxicology studies-Toxicological Reference Database (ToxRefDB; Environmental Protection Agency) and Chemical Effects in Biological Systems (CEBS, National Toxicology Program)-were searched for liver end points. Combined, these 2 databases archive nearly 2,000 rodent studies. Toxicant-associated steatohepatitis (TASH) descriptors including fatty change, fatty necrosis, Oil red O-positive staining, steatosis, and lipid deposition were queried. RESULTS: Using these search terms, 123 chemicals associated with fatty liver were identified. Pesticides and solvents were the most frequently identified chemicals, while polychlorinated biphenyls (PCBs)/dioxins were the most potent. About 44% of identified compounds were pesticides or their intermediates, and >10% of pesticide registration studies in ToxRefDB were associated with fatty liver. Fungicides and herbicides were more frequently associated with fatty liver than insecticides. CONCLUSION: More research on pesticides, solvents, metals, and PCBs/dioxins in NAFLD/TAFLD is warranted due to their association with liver damage.
BACKGROUND: Toxicant-associatedfatty liver disease (TAFLD) is a recently identified form of nonalcoholic fatty liver disease (NAFLD) associated with exposure to industrial chemicals and environmental pollutants. Numerous studies have been conducted to test the association between industrial chemicals/environmental pollutants and fatty liver disease both in vivo and in vitro. OBJECTIVES: The objective of the article is to report a list of chemicals associated with TAFLD. METHODS: Two federal databases of rodent toxicology studies-Toxicological Reference Database (ToxRefDB; Environmental Protection Agency) and Chemical Effects in Biological Systems (CEBS, National Toxicology Program)-were searched for liver end points. Combined, these 2 databases archive nearly 2,000 rodent studies. Toxicant-associatedsteatohepatitis (TASH) descriptors including fatty change, fatty necrosis, Oil red O-positive staining, steatosis, and lipid deposition were queried. RESULTS: Using these search terms, 123 chemicals associated with fatty liver were identified. Pesticides and solvents were the most frequently identified chemicals, while polychlorinated biphenyls (PCBs)/dioxins were the most potent. About 44% of identified compounds were pesticides or their intermediates, and >10% of pesticide registration studies in ToxRefDB were associated with fatty liver. Fungicides and herbicides were more frequently associated with fatty liver than insecticides. CONCLUSION: More research on pesticides, solvents, metals, and PCBs/dioxins in NAFLD/TAFLD is warranted due to their association with liver damage.
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