Intestinal excretion of toxic substances

Chemicals can be eliminated from body via feces by two major mechanisms, namely biliary and intestinal excretion. The relative importance of these processes in the elimination of a highly lipophilic xenobiotic such as hexachlorobenzene (HCB) has been studied. It has been demonstrated that fecal (90%) rather than urinary (10%) excretion is the major route of elimination of HCB in most species. It has been shown also that the bile of HCB dosed animals contained HCB metabolites only whereas fecal excretion consisted primarily of the parent compound. These findings suggested that the bile could not be the source of fecal HCB. Indeed, bile duct ligation in rats increased rather than decreased the fecal excretion of HCB. Experiments in rhesus monkeys with complete biliary bypass confirmed the conclusion that the source of fecal HCB is not the bile, suggesting that most of the fecal HCB originated from intestinal excretion. Exfoliation of intestinal epithelium and exudation across the intestinal mucosa are the two major nonbiliary mechanisms whereby xenobiotics can enter the intestinal lumen. The contribution of desquamation and exudation to fecal excretion of HCB was estimated in jejunectomized and hemicolectomized rats. Removal of 50% of the jejunum did not influence fecal excretion of HCB, whereas excision of 50% of the large intestine reduced it by 40%. These data suggest that the source of fecal HCB is nonbiliary, intestinal transfer (exudation) from blood into the intestinal contents, which occurs primarily in the large intestine. Fecal elimination of HCB is significantly enhanced by dietary treatments with mineral oil or hexadecane.(ABSTRACT TRUNCATED AT 250 WORDS)