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 usedwidely to incorporate volatile organic compounds (VOCs) andother lipophilic compounds into aqueous solutions for biochemical,pharmacokinetic, and toxicological studies. Previous work inthis laboratory demonstrated that 0.25% Emulphor did not alterthe kinetics or hepatotoxicity of low doses of CCl₄ comparedto when the halocarbon was given to rats orally in water. Thepresent study was undertaken as there was concern that higherconcentrations of Emulphor (necessary to maintain lipophilicVOCs in stable aqueous emulsions for extended periods) mightalter the VOCs' absorption, disposition, and/or toxicity. Dosagesof 10 and 180 mg CCl₄/kg bw were given, as an aqueous emulsionusing 1, 2.5, 5, or 10% Emulphor, by gavage to fasted male Sprague–Dawleyrats. Serial microsamples of blood were collected from an indwellingcannula in unanesthetized, freely moving rats at intervals of2-60 min for up to 12 hr. The samples' CCl₄ content was measuredby headspace gas chromatography. Thereby, it was possible toobtain blood CCl₄, concentration-versus-time profiles. Animalswere euthanized 24 hr postdosing and blood was collected formeasurement of serum enzymes as indices of hepatotoxicity. Notoxicologically significant differences in pharmacokinetic parametersas a function of Emulphor concentration were found. Similarlythe hepatotoxic potency of 10 and 180 mg/kg CCl₄, as reflectedby elevation in serum enzyme activities, did not vary significantlywith the concentration of Emulphor utilized. Hence, it can beconcluded that Emulphor, in concentrations as high as 10% (equivalentto 260 mg Emulphor/kg bw) in aqueous emulsions, does not significantlyaffect the absorption, disposition, or acute hepatotoxicityof CCl₄ in male Sprague–Dawley rats.