title: Enterohepatic recirculation of trichloroethanol glucuronide as a significant source of trichloroacetic acid. Metabolites of trichloroethylene.
abstract: 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.
authors.affiliation: Pacific Northwest National Laboratory (operated by Battelle Memorial Institute), Richland, WA 99352, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Stenner
authors.forename: J L
authors.initials: JL
authors.lastname: Merdink
authors.forename: D K
authors.initials: DK
authors.lastname: Stevens
authors.forename: D L
authors.initials: DL
authors.lastname: Springer
authors.forename: R J
authors.initials: RJ
authors.lastname: Bull
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D002849:Chromatography, Gas; D004764:Enterohepatic Circulation; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D005965:Glucuronates / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014238:Trichloroacetic Acid / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D014241:Trichloroethylene / Q000378:metabolism*
chemical_list: D005965:Glucuronates; D014241:Trichloroethylene; D014238:Trichloroacetic Acid; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol; C041653:urochloralic acid