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)



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