EFFECT OF EMULPHOR, AN EMULSIFIER, ON THE PHARMACOKINETICS AND HEPATOTOXICITY OF ORAL CARBON-TETRACHLORIDE IN THE RAT

Emulphor, a polyethoxylated vegetable oil, is now being used widely to Incorporate volatile organic compounds (VOCs) and other lipophilic co mpounds into aqueous solutions for biochemical, pharmacokinetic, and t oxicological studies. Previous work in this laboratory demonstrated th at 0.25% Emulphor did not alter the kinetics or hepatotoxicity of low doses of CCl4 compared to when the halocarbon was given to rats orally in water. The present study was undertaken as there was concern that higher concentrations of Emulphor (necessary to maintain lipophilic VO Cs in stable aqueous emulsions for extended periods) might alter the V OCs' absorption, disposition, and/or toxicity. Dosages of 10 and 180 m g CCl4/kg bw were given, as an aqueous emulsion using 1, 2.5, 5, or 10 % Emulphor, by gavage to fasted male Sprague-Dan ley rats, Serial micr osamples of blood were collected from an indwelling cannula in unanest hetized, freely moving rats at intervals of 2-60 min for up to 12 hr. The samples' CCl4 content was measured by headspace gas chromatography . Thereby, it was possible to obtain blood CCl4 concentration-versus-t ime profiles. Animals were euthanized 24 hr postdosing and blood was c ollected for measurement of serum enzymes as indices of hepatotoxicity . No toxicologically significant differences in pharmacokinetic parame ters as a function of Emulphor concentration were found. Similarly the hepatotoxic potency of 10 and 180 mg/kg CCl4, as re reflected by elev ation in serum enzyme activities, did not vary significantly with the concentration of Emulphor utilized. Hence, it can be concluded that Em ulphor, in concentrations as high as 10% (equivalent to 260 mg Emulpho r/kg bw) in aqueous emulsions, does not significantly affect the absor ption, disposition, or acute hepatotoxicity of CCl4 in male Sprague-Da wley rats. (C) 1997 Society of Toxicology.