Influence of organic solvents on the anticoagulant response to warfarin in rats.

Exposure to styrene (S), trichloroethylene (TCE), and carbon tetrachloride (CT) is known to produce hepatotoxic effects in animals and humans. Warfarin (W), the coumarin anticoagulant, is mostly eliminated by hepatic biotransformation and the site of its anticoagulant action is located in the liver. Therefore, the effects of the above solvents on the anticoagulant response to W were studied in male Sprague-Dawley rats. Groups of rats were given i.p. injections of either S (6 and 12 mmole/kg) or TCE (5.6 and 11.2 mmole/kg) or CT (1 mmole/kg) in corn oil 24 h prior to or simultaneously with W (1 mg/kg, s.c.) and the animals were sacrificed 24 h after W. Doses of solvents used in this study showed hepatotoxic effects as verified by significant increases in serum transaminases response. A significant increase in prothrombin time (P.T.) was seen when W was treated simultaneously with S or TCE at any dose level, but not so with CT. An increase in the P.T. of W was also noticed in the groups pretreated with the highest dose of S or TCE and with CT group. Solvents alone had no effect on the P.T. So, acute exposure to organic solvents may lead to enhanced anticoagulant response to W.