Enzymes induced by ethanol differently affect the pharmacokinetics of trichloroethylene and 1,1,1-trichloroethane.
This study was undertaken to clarify the effect of enzymes induced by ethanol consumption on the pharmacokinetics of trichloroethylene (TRI, a highly metabolised substance) and 1,1,1-trichloroethane (1,1,1-TRI, a poorly metabolised substance). Rats maintained on a control liquid diet or a liquid diet containing ethanol (2 g/day/rat) for not less than three weeks were exposed to either TRI (50, 100, 500, and 1000 ppm) or 1,1,1-TRI (50, 100, and 500 ppm) by inhalation for six hours and the concentration of each compound in the blood and the urinary excretion of metabolites (trichloroethanol and trichloroacetic acid) were measured over several hours. Ethanol, which increased the in vitro metabolism of both compounds about fivefold, enhanced the in vivo metabolism of TRI only at high levels of exposure (marginally at 500 and considerably at 1000 ppm), whereas the metabolism of 1,1,1-TRI was enhanced at all concentrations tested. Moreover, there was a definite difference in the effect of induction of enzymes between the two solvents: the enhanced metabolism of TRI in vivo was shown by a decrease in the blood concentration of TRI as well as by an increase in the urinary excretion of its metabolites, whereas that of 1,1,1-TRI was shown by an increase in the urinary excretion of its metabolites alone. These results suggest that the induction of enzymes differentially affects the pharmacokinetics of TRI and 1,1,1-TRI in human occupational exposure: TRI metabolism may be increased only at concentrations much higher than the current occupational exposure limit (mostly 50 ppm), whereas 1,1,1-TRI metabolism may be increased at an exposure similar to occupational exposure.
Kaneko
T
T
Department of Environmental Health, Medical University of Yamanashi, Japan.
Wang
P Y
PY
Sato
A
A
D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D000431:Ethanol / Q000031:analogs & derivatives / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000493:pharmacokinetics*; D014238:Trichloroacetic Acid / Q000652:urine; D014240:Trichloroethanes / Q000493:pharmacokinetics*; D014241:Trichloroethylene / Q000493:pharmacokinetics*
D012997:Solvents; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D014241:Trichloroethylene; D000431:Ethanol; D014238:Trichloroacetic Acid; D003577:Cytochrome P-450 Enzyme System