Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues

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Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)
Board on Environmental Studies and Toxicology (BEST)

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. "Appendix E Peroxisome Proliferators and Liver Cancer." Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues . Washington, DC: The National Academies Press, 2006.

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Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues

TABLE E-1 Characteristic Effects of Peroxisome Proliferator Compounds

Morphologic changes

Hepatomegaly

Increase in number and size of peroxisomes

Hepatocarcinogenesis (tumor promotion)

Biochemical changes

Decrease in serum lipids, triacylglycerols, and cholesterol

Peroxisomal protein induction (acyl-CoA oxidase, bi/trifunctional protein, carnitine acetyltransferase)

Mitochondrial protein induction (acyl-CoA dehydrogenase, carnitine palmitoyl transferase)

Microsomal protein induction (CYP4A)

Cytosol protein induction (acyl-CoA hydrolase, malic enzyme, fatty acid binding protein)

Other characteristics of biochemical changes

Species differences: (rat, mouse > hamster, guinea pig > rabbit, dog, monkey)

Sex differences: (male > female)

Target organ specificity (liver > kidney, heart, small intestine > other organs)

TABLE E-2 Representative Peroxisome Proliferators

Commercial Category	Compound
Hypolipidemic drug (approved in U.S. and elsewhere)	Gemfibrozil (U.S.) Clofibrate (U.S. and others) Ciprofibrate (France) Fenofibrate (Other countries, not U.S.)
Hypolipidemic drug (not approved)	Wy-14,643 Nafenopin BR-931 Methylclofenepate
Herbicide	Lactofen Fomasafen 2,4-Dichlorophenoxyacetic acid 2,4,5-Trichlorophenoxyacetic acid
Plasticizers and polymerizers	Di-(2-ethylhexyl)phthalate Di-(2-ethylhexyl)adipate Di-n-butyl phthalate Perfluorooctanoic acid Perfluorooctanesulfonate
Solvents	Trichloroethylene Perchloroethylene
Miscellaneous pharmaceutical	Valproic acid (antimania, approved U.S. and elsewhere) LY-171,883 (leukotriene D4 receptor antagonist [not approved]) Dehydroepiandrosterone (dietary supplement and human adrenal steroid, approved in U.S. and elsewhere)