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 compounds into aqueous solutions for biochemical, pharmacokinetic, and toxicological studies. Previous work in this laboratory demonstrated that 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 VOCs in stable aqueous emulsions for extended periods) might alter the VOCs' absorption, disposition, and/or toxicity. Dosages of 10 and 180 mg CCl4/kg bw were given, as an aqueous emulsion using 1, 2.5, 5, or 10% Emulphor, by gavage to fasted male Sprague-Dawley rats. Serial microsamples of blood were collected from an indwelling cannula in unanesthetized, 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-time profiles. Animals were euthanized 24 hr postdosing and blood was collected for measurement of serum enzymes as indices of hepatotoxicity. No toxicologically significant differences in pharmacokinetic parameters as a function of Emulphor concentration were found. Similarly the hepatotoxic potency of 10 and 180 mg/kg CCl4, as reflected by elevation in serum enzyme activities, did not vary significantly with the concentration of Emulphor utilized. Hence, it can be concluded that Emulphor, in concentrations as high as 10% (equivalent to 260 mg Emulphor/kg bw) in aqueous emulsions, does not significantly affect the absorption, disposition, or acute hepatotoxicity of CCl4 in male Sprague-Dawley rats.
Sanzgiri
U Y
UY
College of Pharmacy, University of Georgia, Athens, Georgia 30602-2356, USA.
Bruckner
J V
JV
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000493:pharmacokinetics*; D056486:Chemical and Drug Induced Liver Injury; D004347:Drug Interactions; D007064:L-Iditol 2-Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D010938:Plant Oils / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010938:Plant Oils; D002251:Carbon Tetrachloride; D007064:L-Iditol 2-Dehydrogenase; D000410:Alanine Transaminase