BIOTRANSFORMATION OF ALLYL CHLORINE IN THE RAT - INFLUENCE OF INDUCERS ON THE URINARY METABOLIC PROFILE

Allyl chloride (AC) is used as intermediate in the synthesis of epichl orohydrin (ECH). We investigated the biotransformation of AC in rats t o select potential urinary biomarkers of exposure. For this purpose, w e developed analytical methods to measure different selected urinary m etabolites of AC. The earlier described urinary metabolites of AC [all yl mercapturic acid (ALMA) and 3-hydroxypropyl mercapturic acid (HPMA) ], as well as two urinary metabolites of ECH [alpha-chlorohydrin (alph a-CH) and 3-chloro-2-hydroxypropyl mercapturic acid (CHPMA)], were det ermined in this study. After intraperitoneal administration of AC, in doses ranging from 66 to 590 mu mol/kg, control rats excreted 30 +/- 6 .5% of the AC dose as ALMA. HPMA was a minor urinary metabolite of AC (<3% of the AC dose), and, for this metabolite, no clear dose-excretio n relationship was found. Two other minor urinary metabolites were als o found as well, namely CHPMA and alpha-CH, suggesting the formation o f ECH. CHPMA excretion was linear from 66 to 330 mu mol/kg AC and amou nted to 0.21 +/- 0.08% of the AC dose. alpha-CH excretion was linear i n the dose range used and was excreted for 0.13 +/- 0.02% of the AC do se. In addition, we investigated the influence of three different enzy me inducers on the urinary metabolite profile of AC, namely pyrazole, beta-naphthoflavone, and phenobarbital. Pyrazole only increased the ur inary excretion of alpha-CH. beta-Naphthoflavone induction only enhanc ed the ALMA excretion significantly. Phenobarbital inducted both the e xcretion of CHPMA and alpha-CH. From these studies, we conclude that u rinary excretion of ALMA, CHPMA, and alpha-CH can be used as biomarker s in humans potentially exposed to AC. However, ALMA seems to be the m ore appropriate biomarker, because enzyme induction may play a confoun ding role if CHPMA or alpha-CH is used.