ENTEROHEPATIC RECIRCULATION OF TRICHLOROETHANOL GLUCURONIDE AS A SIGNIFICANT SOURCE OF TRICHLOROACETIC-ACID - METABOLITES OF TRICHLOROETHYLENE

Trichloroacetic acid (TCA) is a metabolite of trichloroethylene (TRI) thought to contribute to its hepatocarcinogenic effects in mice. Recen t studies have shown that peak blood concentrations of TCA do not occu r until similar to 12 hr after an oral dose of TRI; however, blood con centrations of TRI reach a maximum within 1 hr and is nondetectable af ter 2 hr. The objective of this study was to examine quantitatively en terohepatic recirculation of trichloroethanol (TCEOH) and TCA as a pos sible mechanism responsible for the delayed production of TCA. Jugular vein, duodenum, and bile duct-cannulated Fischer 344 rats were used, with the collection of blood, bile, urine, and feces samples after int raduodenal and intravenous dosing of animals with TRI, TCEOH, and TCA. Samples were analyzed by GC for TCA, total TCEOH, and free TCEOH. The results show that, after an intravenous dose of TCEOH (100 mg/kg), 36 % of the TCEOH in brood is attributable to enterohepatic recirculation . With the same treatment, 76% of the TCA in blood is attributable to enterohepatic recirculation of metabolites. Peak concentrations of tot al TCEOH in bile, after an intraduodenal dose of TRI, are over 5 times higher than peak concentrations of total TCEOH in systemic blood. Pea k concentrations of TCEOH glucuronide in bile are similar to 200 times higher than peak concentrations of TCEOH glucuronide in systemic bloo d.