Identification of Environmental Chemicals Associated With the Development of Toxicant-associated Fatty Liver Disease in Rodents

Toxicol Pathol. 2015 Jun;43(4):482-97. doi: 10.1177/0192623314549960. Epub 2014 Oct 16.

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.

Keywords: CEBS; NAFLD; TASH; ToxRefDB; pesticides; steatohepatitis; steatosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Environmental Pollutants / toxicity*
  • Liver / drug effects*
  • Non-alcoholic Fatty Liver Disease / chemically induced*
  • Pesticides / toxicity
  • Toxicity Tests

Substances

  • Environmental Pollutants
  • Pesticides