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© 1990 Oxford University Press

other

Interactions of Water Contaminants I. Plasma Enzyme Activity and Response Surface Methodology following Gavage Administration of CCl4 and CHCl3 or TCE Singly and in Combination in the Rat 1,2

JOSEPH F. BORZELLECA*,3, TODD M. O'HARA*, CHRIS GENNINGS{dagger}, R. HUGH GRANGER{ddagger}, MELISSA A. SHEPPARD* and LYMAN W. CONDIE, JR.§

*Departments of Pharmacology and Toxicology, Medical College of Virginia Box 613, MCV Station, Richmond, Virginia 23298 {dagger}Biostatistics, Medical College of Virginia Box 613, MCV Station, Richmond, Virginia 23298 {ddagger}Departments of Pathology, Medical College of Virginia Box 613, MCV Station, Richmond, Virginia 23298 §U.S. Environmental Protection Agency Cincinnati, Ohio 45268

Received April 10, 1989; accepted October 26, 1989

Interactions of Water Contaminants. I. Plasma Enzyme Activity and Response Surface Methodology following Gavage Administration of CCl4 and CHCl3 or TCE Singly and in Combination in the Rat. BORZELLECA, J. F., O'HARA, T. M., GENNINGS, C, GRANGER, R. H., SHEPPARD, M. A., AND CONDIE, L. W., JR. (1990). Fundam. Appl. Toxicol. 14, 477–190. The joint hepatotoxicity of CCU and CHC13 or TCE in male CD rats following simultaneous oral administration has been investigated. Rats with chronic indwelling arterial cannulas were administered a single oral dose of COl4, and CHCl3 or CCl4 and TCE in 5% Emulphor at doses of 0 to 700 mg/kg. Hepatotoxicity was evaluated by measuring the activity of AST, ALT, and SDH in plasma at 0, 3, 6, 12, 24, 36, 48, and 72 hr postgavage. Response data were analyzed for interaction using response surface methodology. CCl4 alone displayed dose-dependent toxicity. TCE demonstrated little evidence of hepatotoxicity. In combination, both CCl4/CHCl3 and CCl4/TCE displayed a synergistic (supraadditive) response for peak plasma enzyme activity.


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