DISPOSITION OF INGESTED OLESTRA IN THE FISCHER-344 RAT

Four studies were conducted in the Fischer 344 rat to determine the di sposition of orally gavaged olestra. Twenty-four rats were used for ea ch study. Three olestra samples, differing in the degree of saturation of the fatty acid chains, were tested; one sample was heated to simul ate olestra's intended use in preparing fried foods. In addition, a su crose polyester (SPE) sample containing 28% short-chain penta- and low er polyesters was tested. All test samples were uniformly labeled with C-14 in the sucrose moiety. Urine, feces, and CO2 were continuously c ollected and counted. Urine also was analyzed for [C-14]sucrose by HPL C. If olestra were absorbed and systemically metabolized, [C-14]sucros e would be excreted in the urine. Rats were killed 1, 3, 7, and 21 day s after dosing, and tissues were collected and counted. Tissue lipids were extracted and analyzed for intact olestra or SPE by HPLC. Less th an 0.15% of the dose of C-14 was absorbed from the olestra samples, an d about 1.3% from the SPE sample. The disposition of the absorbed radi olabel suggested that its source was glucose and fructose resulting fr om the intestinal hydrolysis of short-chain penta- and lower sucrose p olyesters. For rats dosed with olestra, <8 X 10(-4)% of the dose of ra diolabel was recovered in the olestra-containing fraction of lipids ex tracted from liver, the target organ for absorbed olestra, and no [C-1 4]sucrose was found in urine, indications that olestra essentially was not absorbed. Heating olestra did not change this result. For rats do sed with SPE, 1 x 10(-3)% of the dose was recovered in the SPE-contain ing fraction of liver lipids and <6 X 10(-3)% was recovered in the suc rose fraction of urine, indications that <7 x 10(-3)% of the dose of S PE was absorbed. It was concluded that it was the penta- and lower pol yesters that were absorbed from the SPE sample. (C) 1995 Society of To xicology.