Intraluminal hexadecane enhances large intestinal excretion of tissue hexachlorobenzene in rats.

In young adult female rats with a cecal stoma, administration of hexadecane into the stomach (750 or 500 mg) and into the ligated colon (250 mg) enhanced 2- to 3-fold the intestinal excretion of [14C]hexachlorobenzene. Apparent sites of increased transferral from the blood into luminal contents were (caudal) ileum, cecum and colon. Presence of nonabsorbed hexadecane in luminal contents seems to be a prerequisite for the effects. Results support previous reports that enhancement of intestinal excretion of lipophilic chemicals by liquid paraffins takes place in the large intestine

Enhanced fecal elimination of stored hexachlorobenzene from rats and rhesus monkeys by hexadecane or mineral oil.

The effect of various dietary treatments on the fecal excretion of [14C]-hexachlorobenzene (HCB) was studied in rats and rhesus monkeys. Cholestyramine and sesame oil failed to influence fecal excretion of HCB and/or metabolites. However, dietary administration of n-hexadecane (5%) increased fecal excretion of radioactivity 4-13-fold in rats and rhesus monkeys. Similarly, mineral oil in the diet (5%) of rhesus monkeys elicited a 6-9-fold increase in fecal excretion of HCB and/or metabolites. As a result of the mineral oil treatment, an enhanced depletion of HCB from blood and also of the stored HCB from adipose tissue was observed. The concentration of HCB in the blood declined in accordance with decreasing storage levels of HCB in adipose tissue. The major site of elimination of HCB and/or metabolites seemed to be the intestine; in particular, the cecum and the colon ascendens. Both hexadecane and mineral oil appeared to stimulate specifically this elimination pathway

Relationship of body weight to disposition of hexachlorobenzene in rats.

Male rats of various body weights were dosed twice with [14C]hexachlorobenzene (50 mg/kg, p.o.) in olive oil by gavage on 2 consecutive days. During 2 weeks after dosage, cumulative excretion into urine was about 1% of the dose and unrelated to body weight. Cumulative excretion into feces was 30 ± 10% of the dose and decreased with increasing body weight. In contrast, the concentration of hexachlorobenzene in urine, feces, kidney, liver and adipose tissue 14 days after dosing was higher in larger than in smaller animals. However, the relative concentration, i.e. the concentration of hexachlorobenzene in urine, feces or tissue divided by the concentration of hexachlorobenzene in adipose tissue, eliminated most of the variability among individual animals. This allows direct comparison of dispositional data of animals with greatly differing body burdens

Mineral oil in the diet enhances fecal excretion of DDT in the rhesus monkey.

Seven days after dosing of two rhesus monkeys with 14C-DDT (50 mg/kg) per os, one monkey was put on a diet containing 5% mineral oil for 35 days, whereas the other animal served as control. During 5 weeks both urinary and fecal excretion of radioactivity was more than doubled in the treated as compared to the untreated animal. At the end of the treatment, concentration of DDT in adipose tissue of the mineral oil treated animal was about half of that found in the control. The data represent further support of previous reports that mineral oil reduces body burdens of refractory lipophilic chemicals

Stimulation of nonbiliary, intestinal excretion of hexachlorobenzene in rhesus monkeys by mineral oil.

Four rhesus monkeys were administered various doses of hexachlorobenzene (HCB) po, to achieve widely varying adipose tissue levels. One month later, each animal was provided with a bile duct bypass allowing for interruption of the enterohepatic circulation (EHC). Effects of mineral oil-supplemented diet and/or interruption of the EHC on urinary, biliary, and fecal excretion of HCB and its metabolites were quantified. Urinary excretion of HCB was not affected by mineral oil but was reduced 20 to 60% by interruption of the EHC. Similarly, biliary excretion of HCB was also reduced 25 to 60% by interruption of the EHC and was not altered by mineral oil. Fecal excretion was increased about fivefold by mineral oil, whereas interruption of the EHC had no effect on the amount of HCB in feces. Results demonstrate that interruption of the EHC reduced urinary and biliary excretion of HCB metabolites, whereas mineral oil specifically stimulated intestinal excretion of the parent compound

Enhanced intestinal excretion of hexachlorobenzene in rats by intraluminal injection of hexadecane.

The effect of hexadecane on the intestinal excretion of hexachlorobenzene was studied in female Sprague-Dawley rats dosed twice with 14C-hexachlorobenzene at 50 mg kg-1 per os. Injection of 75 mg n-hexadecane into ligated and unligated segments of the intestine increased concentrations of hexachlorobenzene in intestinal contents by about two- or three-fold in jejunal and ileal segments, and about two-fold in the cecal-colon segment. The jejunum appeared to be the site of greatest excretion of hexachlorobenzene, followed by the ileum, the cecum and the colon. This order is opposite to our previous data from animals with an undistributed intestinal passage. The apparently greater excretion of hexachlorobenzene into the small intestine is probably due to its much larger surface area than that of the large intestine. However, the residency time of luminal contents in the large intestine normally exceeds that in the small intestine by about 20-40-fold, which apparently more than compensates for the difference in relative surface area between small and large intestine. Thus, residency time appears to be a more important factor than surface area in determining the intestinal elimination of hexachlorobenzene. These results with hexachlorobenzene are probably typical of physiological disposition of lipophilic halogenated hydrocarbons generally

Effects of cholestyramine on the disposition of pentachlorophenol in rhesus monkeys.

Three male rhesus monkeys were provided with a bile duct by-pass and dosed twice with 14C-pentachlorophenol (50 mg/kg po) 4 wk apart. During the first day after each dose, the monkeys excreted about 20, 0.5, and 20% of the dose into urine, feces, and bile, respectively. While the animals continued to receive basal diet after the first dose, starting 24 h after the second dose their diet was supplemented with 4% cholestyramine for 6 consecutive days. A comparison of control to treatment period (d 2-6) shows that cholestyramine reduced the urinary excretion of pentachlorophenol from 35 to 5% and increased the fecal excretion from 3 to 54% of the dose administered. Cholestyramine, in addition to changing the major route of excretion of pentachlorophenol elimination, also markedly reduced the body burden of pentachlorophenol as total excretion (urinary plus fecal) was enhanced by 40%. Up to 30% of the dose was excreted into bile in 1 d during the control period, indicating considerable enterohepatic circulation of pentachlorophenol. Cholestyramine decreased the amount of pentachlorophenol in the bile from 70 to 52% of the dose, which coincided with a similar decrease in the urine. This effect suggests that a considerable portion of pentachlorophenol in urine originates from the enterohepatic circulation. Moreover, the increase in the fecal excretion (52% of dose) of pentachlorophenol, as a result of the treatment, exceeded by far the decrease seen in the urine (30% of dose) or bile (18% of dose), suggesting that, in addition to interfering with the enterohepatic cycle of pentachlorophenol, cholestyramine also increases its elimination directly across the intestinal wall