Excretion of chlordecone by the gastrointestinal tract: Evidence for a nonbiliary mechanism

Abstract

Workers exposed to chlordecone (Kepone), a toxic organochlorine pesticide, excreted larger amounts of chlordecone in bile than in stool, suggesting that it may undergo enterohepatic recirculation, We found in a single subject that equal amounts of chlordecone and of its reduced metabolite, chlordecone alcohol, were excreted in bile at a rate four times as great as in stool. When biliary contents were diverted from the intestine through a T tube, fecal excretion of chlordecone alcohol was abolished, presumably due to interruption of its passage via bile to intestine. This change was not accompanied by disappearance of chlordecone from the stool. The amount of chlordecone in stool when bile was diverted was increased six-to tenfold over that when diverted bile was continuously infused into the duodenum. Analogous experiments with [14C]-chlordecone-treated rats in which bile flow was exteriorized through a plastic cannula showed thal the excretion of radioactivity in feces was in the same range when bile was reinfused in the duodenum or was totally diverted. Moreover, in rats with bile diverted, cholestyramine, an anion-exchange resin which binds chlordecone in vitro, doubled the excretion of radioactivity in stool. A similar effect was observed in intact animals. We conclude that chlordecone enters the intestinal lumen from a nonbiliary source, probably the gut, and that net excretion of chlordecone from this source can be augmented by cholestyramine.

Factors affecting the storage and excretion of toxic lipophilic xenobiotics

“…Excretion data obtained from humans exposed to chlordecone and rats that were administered the compound are consistent with this route as a significant excretory pathway (58,59). The authors observed that fecal excretion of chlordecone was maintained or increased when bile flow was diverted relative to that seen while bile flow was intact.…”

Atsdr Evaluation of Health Effects of Chemicals

“…Chlordecone and chlordecone alcohol (chlordecol) are excreted in the bile and eliminated via the feces of humans occupationally exposed to chlordecone Cohn et al, 1978;Boylan et al, 1979;Guzelian et al, 1981). A substantial enterohepatic recirculation of chlordecone exists, however, that curtails its excretion ( Cohn et al, 1978;Boylan et al, 1979;Guzelian et al, 1981 ).…”

“…A substantial enterohepatic recirculation of chlordecone exists, however, that curtails its excretion ( Cohn et al, 1978;Boylan et al, 1979;Guzelian et al, 1981 ). Only 5-10% of the biliary chlordecone entering the lumen of the duodenum appeared in the feces (Cohn et al, 1978;Guzelian et al, 1981).…”

“…Chlordecone was not detected in the sweat and was detected in only minor quantities in urine, saliva, and gastric juice (Cohn et al, 1978). Similarly, stool contained 11-34% of the quantities excreted in bile for workers exposed for six months (Boylan et al, 1979). When biliary contents were diverted, fecal excretion of chlordecone alcohol fell to low or undetectable levels; however, chlordecone excretion in feces persisted, suggesting a nonbiliary mechanism for the excretion of chlordecone into the intestine and feces (Boylan et al, 1979).…”

Enterohepatic circulation of organochlorine compounds: a site for nutritional intervention☆

“…This nonbiliary mechanism has been observed for OCs, such as chlordecone. Fecal excretion of chlordecone was found to be the same in rats with or without biliary diversion [11]. Presumably OCs enter the intestine by secretion out of the enterocyte, or by turnover of enterocytes that contain significant amounts of OCs.…”