Presystemic elimination of trichloroethylene in rats following environmentally relevant oral exposures.
1,1,2-Trichloroethylene (TCE), a volatile organic contaminant (VOC) of drinking water in the Unites States, is frequently present in trace amounts. TCE is currently classified by the International Agency for Research on Cancer and the U.S. Environmental Protection Agency as a probable human carcinogen, because it produces tumors in some organs of certain strains of mice or rats in chronic, high-dose bioassays. Previous studies (Toxicol Appl Pharmacol 60:509-526, 1981; Regul Toxicol Pharmacol 8:447-466, 1988) used physiological modeling principles to reason that the liver should remove virtually all of a well metabolized VOC, such as TCE, as long as concentrations in the portal blood were not high enough to saturate metabolism. To test this hypothesis, groups of unanesthetized male Sprague-Dawley rats received intravenous injections of 0.1, 1.0, or 2.5 mg TCE/kg as an aqueous emulsion. Other rats were gavaged with 0.0001, 0.001, 0.01, 0.1, 1, 2.5, 5, or 10 mg TCE/kg b.wt. Serial microblood samples were taken via an indwelling carotid artery cannula, to generate blood TCE versus time profiles. Headspace solid-phase microextraction gas chromatography with negative chemical ionization mass spectrometry (limit of quantitation = 25 pg/ml) was used to quantify TCE. TCE was undetectable in rats given 0.0001 mg/kg, but it exhibited linear kinetics from 0.1 to 5.0 mg/kg. Bioavailability was consistent over this dosage range, ranging from 12.5 to 16.4%. The presence of these limited amounts of TCE in the arterial blood disprove the aforementioned hypothesis, yet demonstrate that first-pass hepatic and pulmonary elimination in the rat afford its extrahepatic organs protection from potential adverse effects by the majority of the low levels of TCE absorbed from drinking water.
Liu
Y
Y
College of Pharmacy, University of Georgia, Athens, GA 30602-2352, USA.
Bartlett
M G
MG
White
C A
CA
Muralidhara
S
S
Bruckner
J V
JV
D000818:Animals; D001682:Biological Availability; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D052617:Solid Phase Microextraction; D014018:Tissue Distribution; D014241:Trichloroethylene / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D014481:United States
D014241:Trichloroethylene