DISPOSITION OF INGESTED OLESTRA IN THE FISCHER-344 RAT

Four studies were conducted in the Fischer 344 rat to determine the disposition of orally gavaged olestra. Twenty-four rats were used for each study. Three olestra samples, differing in the degree of saturation of the fatty acid chains, were tested; one sample was heated to simulate olestra's intended use in preparing fried foods. In addition, a sucrose polyester (SPE) sample containing 28% short-chain penta- and lower polyesters was tested. All test samples were uniformly labeled with C-14 in the sucrose moiety. Urine, feces, and CO2 were continuously collected and counted. Urine also was analyzed for [C-14]sucrose by HPLC. If olestra were absorbed and systemically metabolized, [C-14]sucrose would be excreted in the urine. Rats were killed 1, 3, 7, and 21 days after dosing, and tissues were collected and counted. Tissue lipids were extracted and analyzed for intact olestra or SPE by HPLC. Less than 0.15% of the dose of C-14 was absorbed from the olestra samples, and about 1.3% from the SPE sample. The disposition of the absorbed radiolabel suggested that its source was glucose and fructose resulting from the intestinal hydrolysis of short-chain penta- and lower sucrose polyesters. For rats dosed with olestra, <8 X 10(-4)% of the dose of radiolabel was recovered in the olestra-containing fraction of lipids extracted from liver, the target organ for absorbed olestra, and no [C-14]sucrose was found in urine, indications that olestra essentially was not absorbed. Heating olestra did not change this result. For rats dosed with SPE, 1 x 10(-3)% of the dose was recovered in the SPE-containing fraction of liver lipids and <6 X 10(-3)% was recovered in the sucrose fraction of urine, indications that <7 x 10(-3)% of the dose of SPE was absorbed. It was concluded that it was the penta- and lower polyesters that were absorbed from the SPE sample. (C) 1995 Society of Toxicology.