Chloral hydrate formation in the Japanese medaka minnow

Trichloroethylene (TRI) is a common groundwater contaminant that has been shown to be tumorigenic and toxic in laboratory animals. The toxicity of TRI is increased by inducing the production of cytochrome P-450-dependent metabolites. Cytochrome P450 (CYP) 2E1 metabolizes TRI in mammals; however, this isoform of CYP2E1 does not appear to be expressed in fish. Medaka microsomal protein containing CYP was exposed to TRI and extracted with ethyl acetate. The extract was analyzed using gas chromatography (liquid injection) with an electron capture detector and separately using mass spectrometry. The formation of chloral hydrate, a precursor of toxic metabolites, was confirmed following exposure of hepatic microsomes of the medaka to TRI. These results indicate that medaka catalyze the first step in the formation of toxic metabolites and CYP forms in addition to CYP2E1 which catalyzes this reaction in fish.