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Abstract
1. The absorption, elimination and metabolism of 14C-trichloroethylene (Tri) was studied in adult female Wistar rats and NMRI mice after administration of 200, 20 and 2mg/kgTri.
2. Dose-dependent biotransformation of Tri to metabolites was observed in both species. Induction of hepatic mono-oxygenases by phenobarbital or polychlorinated biphenyls resulted in a higher rate of biotransformation after a single oral dose of 200 mg/kg 14C-Tri to rats.
3. An increase in radioactivity covalently bound to liver and kidney macromolecules of induced rats as compared to control rats parallels the toxic effects of Tri on these organs after induction of cytochrome P-450.
4. The urinary metabolites were analysed by h.p.l.c. In both species, 1,1,1-trichloro compounds (trichloroacetic acid, trichloroethanol and its glucuronide, comprising 88.9±93.5% of the radioactivity excreted in the urine) constituted the main metabolites; in addition, N-(hydroxyacetyl)-aminoethanol (4.1–7.2%), dichloroacetic acid (0.1–2.0%) and oxalic acid (0.7–1.8%) were identified. The pattern of metabolites in the 72 h urine remained constant for each species in the dose range studied and no change was induced by pretreatment.
5. The percentage of radioactivity exhaled as 14CO2 increased with dose in mice, which may indicate dose-dependent formation of dichloroacetic acid and saturation of deactivating mechanisms for reactive intermediates in mice.