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EFFECT OF ROUTE AND PATTERN OF EXPOSURE ON THE PHARMACOKINETICS AND ACUTE HEPATOTOXICITY OF CARBON TETRACHLORIDE
Citation:
Sanzgiri, U., H. Kim, S. Muralidhara, C. Sallas, AND J. Bruckner. EFFECT OF ROUTE AND PATTERN OF EXPOSURE ON THE PHARMACOKINETICS AND ACUTE HEPATOTOXICITY OF CARBON TETRACHLORIDE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/541, 1995.
Description:
The objectives of this study were to evaluate the influence of both route and pattern of exposure on the pharmacokinetics and target organ toxicity of a common VOC, carbon tetrachloride (CCl4). ale Sprague-Dawley rats, 325-275 g, inhaled 100 or 1,000 ppm CCl4 for 2 hr through a one-way breathing valve. he total amount of CCl4 retained by each rat (i.e., the systemically absorbed dose) during the 2-hr period was determined to be 17.5 and 179 mg CCl4/kg bw, respectively. Cl4, in doses of 17.5 and 179 mg/kb bw, was administered in an aqueous emulsion by bolus gavage or by constant gastric infusion over 2 hr. erial micro blood samples from the animals were analyzed for CCl4, in order to delineate blood concentration versus time profiles. erum sorbitol dehydrogenase and alanine-amino transaminase activities and total liver microsomal cytochrome P450 level and glucose-6-phosphatase activity were measured 24 hr post dosing as indices of CCl4 hepatotoxicity. he pattern of oral exposure (i.e., dosage regimen) had a significant influence on the pharmacokinetics and acute hepatotoxicity of CCl4. rterial blood levels in the gastric infusion group were substantially lower than in the oral bolus group at does doses, while substantially higher Cmax and AUC. values were manifest in the bolus groups. he extent of hepatotoxicity was also significantly greater in these animals. he route of exposure had a significant effect on the pharmacokinetics of CCl4. oncentrations of CCl4 in the arterial blood were much higher during inhalation than gastric infusion. However, AUC. values for the two groups were not significantly different.