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© 1989 Oxford University Press

research-article

A CCl4/CHCl3 Interaction Study in Isolated Hepatocytes: Selection of a Vehicle

TODD M. O'HARA, JOSEPH F. BORZELLECA, ELIZABETH C. CLARKE, MELISSA A. SHEPPARD and LYMAN W. CONDIE, JR*

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University Richmond, Virginia 23298 *U.S. Environmental Protection Agency, 26 W Martin Luther King Drive Cincinnati, Ohio 45268

Received January 16, 1989; accepted April 7, 1989

Emulphor, ethanol, and dimethyl sulfoxide (DMSO) were evaluated as vehicles in studying the toxicity of CCl4 and CHCl3 in isolated hepatocytes. The appropriateness of the vehicle was determined by evaluating the following parameters: solubility of CCl4 and CHCl3 in the vehicle, cell injury (intracellular K+), cell death (LDH leakage), and lack of interaction (protection or enhanced toxicity) with CCl4. and CHCl3. The relative toxicity of the vehicles according to maximum no effect levels (v/v) was: emulphor (0.125%) > ethanol (1.0%) > DMSO (5.0%). Emulphor at toxic levels was inadequate to dissolve enough CCl4 to evaluate in this system. Ethanol (5.0, 2.5, 1.0, 0.5%) was more toxic than DMSO and interacted with both CCl4. and CHCl3 to enhance toxicity. DMSO (15.0, 5.0, 2.5%) did not significantly alter the toxicity of CCl4. and CHCl3 no interaction. These data suggest that DMSO should be the vehicle for evaluating the toxicity of CCl4. and CHCl3 and their mechanisms of action in the isolated hepatocyte.


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