Enterohepatic recirculation of trichloroethanol glucuronide as a significant source of trichloroacetic acid. Metabolites of trichloroethylene.

Journal Article · Thu May 01 00:00:00 EDT 1997 · Drug Metabolism and Disposition

OSTI ID:1728618

Stenner, Robert D. ^[1]; Merdink, James L. ^[2]; Stevens, Doug ^[3]; Springer, David L. ^[1]; Bull, Richard J. ^[4]

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1. BATTELLE (PACIFIC NW LAB)
2. Washington State University Tri-Cities
3. Washington State University
4. SELF-EMPLOYED CONSULTANTS

Trichloroacetic acid (TCA) is a metabolite of trichloroethylene (TRI) thought to contribute to its hepatocarcinogenic effects in mice. Recent studies have shown that peak blood concentrations of TCA do not occur until approximately 12 hr after an oral dose of TRI; however, blood concentrations of TRI reach a maximum within 1 hr and is nondetectable after 2 hr. The objective of this study was to examine quantitatively enterohepatic recirculation of trichloroethanol (TCEOH) and TCA as a possible 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 intraduodenal 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 blood 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 total TCEOH in bile, after an intraduodenal dose of TRI, are over 5 times higher than peak concentrations of total TCEOH in systemic blood. Peak concentrations of TCEOH glucuronide in bile are approximately 200 times higher than peak concentrations of TCEOH glucuronide in systemic blood.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1728618
• Report Number(s): PNWD-SA-5351
• Journal Information: Drug Metabolism and Disposition, Journal Name: Drug Metabolism and Disposition Journal Issue: 5 Vol. 25
• Country of Publication: United States
• Language: English