RT Journal Article
SR Electronic
T1 Demonstration of major metabolic pathways for chlordecone (kepone) in humans.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 434
OP 438
VO 8
IS 6
A1 M W Fariss
A1 R V Blanke
A1 J J Saady
A1 P S Guzelian
YR 1980
UL http://dmd.aspetjournals.org/content/8/6/434.abstract
AB The hypothesis that liver is the site of the previously demonstrated chlordecone alcohol formation in man was tested. Human bile obtained from chlordecone-poisoned factory workers contained substantial amounts of free chlordecone, but little free chlordecone alcohol. However, when the same bile specimens were pretreated with beta-glucuronidase before analysis by gas-liquid chromatography, large amounts of chlordecone alcohol appeared, accounting for 75% of total organochlorine compounds. Confirmation of the identity of chlordecone and chlordecone alcohol was made by using gas liquid chromatography-mass spectrometry. Whereas biliary chlordecone alcohol was present predominantly as its glucuronide conjugate (93%), chlordecone was excreted primarily as the unaltered compound (72%) with only a small portion conjugated with glucuronic acid (9%). The remaining fraction of the total chlordecone measured in bile appeared to be a stable polar metabolite resistant to beta-glucuronidase. This unidentified metabolite could be converted to free chlordecone only by acid hydrolysis under harsh conditions. In contrast to human bile, rat bile contained only trace amounts of chlordecone alcohol (less than 0.5% of total chlordecone), thus indicating that hepatic metabolism of chlordecone is species-specific. We conclude that in man, the major metabolic route for chlordecone is its reduction in the liver followed by glucuronidation.