Effect of pretreatment of rats with carbon tetrachloride on tolerance development

Abstract

To evaluate the effect of pretreatment of rats with CCl4 on tolerance development to subsequent exposures, rats were exposed 25-7500 ppm of CCl4 vapor or given CCl4 orally, 3.25 mg/g body weight. Forty-eight hours later these rats were reexposed to a normally lethal 7500 ppm CCl4 concentration. Mortality, blood clotting time, serum bilirubin, serum and liver triglycerides, and CCl4 and CHCl3 concentrations in tissues and in the whole rat were used as a measure of the response to CCl4 exposure. Conversion of CCl4 to CHCl3 in vitro was also determined in normal and pretreated animals. It was found that animals exposed to 4000 ppm for 6 hr or given 3.25 mg/g of CCl4 orally developed tolerance to subsequent normally lethal CCl4 exposures. Serum bilirubin levels in animals protected by CCl4 pretreatment were significantly lower than in those receiving only a single exposure to CCl4. Blood clotting times in protected animals were normal, while in those not protected by pretreatment, they were greatly prolonged. Serum triglyceride levels in protected animals were normal whereas they were considerably depressed in the nonprotected animals. Liver triglycerides were elevated in both protected and nonprotected, but were not as high in the protected animals. Carbon tetrachloride conversion to CHCl3 was slower in protected than in the non-protected animals. Tolerance to CCl4 developed in animals whose ability to metabolize CCl4 had been depressed by pretreatment with the same compound. This suggests that the toxicity of CCl4 is related to its metabolic pathway or to the production of toxic intermediates.