EFFECT OF DOSING VEHICLE ON THE HEPATOTOXICITY OF CCL4 AND NEPHROTOXICITY OF CHCL3 IN RATS

There are conflicting results in the literature concerning the effect of gavage vehicle, corn oil (GO) versus aqueous suspension, on the tox icity of haloalkanes. The purpose of our study was to assess the influ ence of oral dosing vehicle on the acute hepatotoxicity of CCl4 and ne phrotoxicity of CHCl3. Male Sprague-Dawley rats, fed ad libitum, were treated (po) with single doses of CCl4, or CHCl3, using corn oil (CO), or an aqueous preparation (5%) of Emulphor (EL620) or Tween-85 (Tw-85 ) as vehicle (10 ml/kg). Rats were killed 48 h after treatment Blood w as collected for plasma alanine aminotransferase (ALT) determination a nd renal cortical slices were prepared for p-aminohippuric acid (PAH) incorporation. The comparison, between gavage vehicles, of the slopes and ED50 of the dose-response curves, although not significantly diffe rent, indicated clear trends for enhanced potency with CO for CHCl3, n ephrotoxicity but not for CCl4, hepatotoxicity. However, ALT values, a measure of the severity of effect for CCl4, also indicated that CO, w hen compared to EL620 and Tw-85, tended to enhance CCl4, hepatotoxicit y at low toxicity incidence. Furthermore, CO clearly enhanced the seve rity of effect for CHCl4 nephrotoxicity, as measured by the slice-to-m edium PAH ratios, al high dosage. The,greater severity of the lesion p roduced by exposure to these chemicals, when administered in CO, is co nsistent with the trends observed for their potency (dose-response cur ves). Our results agree with an increased toxicity of haloalkanes by t he gavage vehicle CO reported in the literature. Thus, CO should be co nsidered a potential confounder in hepato- and nephrotoxicity assays.