GENOTOXICITY AND SUBCHRONIC TOXICITY STUDIES WITH HEATED OLESTRA

Olestra is a class of sucrose-fatty acid polyesters intended for use a s a non-caloric replacement of edible oil. Genotoxicity and subchronic toxicity studies were conducted to determine whether olestra could fo rm genotoxic or toxic breakdown products during simulated commercial u se. Heated olestra was prepared for these studies by batch-frying pota to slices in olestra at 177-185 degrees C for 25-32 hr over 5-7 days. Genotoxicity of this previously heated olestra was assessed in four st andard in vitro assays: (1) Salmonella mutagenesis (Ames test); (2) fo rward mutagenesis of mouse lymphoma cells at the thymidine kinase locu s; (3) unscheduled DNA synthesis in rat hepatocytes; and (4) clastogen icity in cultured Chinese hamster ovary cells. These tests were conduc ted with previously heated olestra at concentrations up to at least 5 mg/ml both in the absence of exogenous bioactivation and, for assays ( 1), (2) and (4) with added liver microsomal (S-9) activation. The Ames and mouse lymphoma assays were performed with olestra (10 mg/ml and 2 3 mg/litre, respectively) either alone or emulsified with the non-toxi c, non-ionic surfactant Pluronics F68, both in the presence and absenc e of metabolic activation. To test for clastogenicity in vivo, rats we re administered previously heated olestra by gavage at 5 g/kg per day for up to 5 days and bone marrow cells were examined for chromosomal a berrations. Heated olestra lacked genotoxic activity detectable by the aforementioned assays. Heated olestra was fed to Fischer 344 rats at up to 10% of the diet (w/w) for 91 days. Evaluation of survival, food consumption, feed efficiency, physical condition, body weight, organ w eight, haematological and clinical chemistry parameters, and histomorp hology revealed no adverse effects attributable to ingestion of heated olestra at exposure levels in excess of those anticipated for human c onsumption. It is concluded that olestra used as a deep-frying medium conveys no genotoxic or toxic hazard at anticipated levels of human co nsumption. Copyright (C) 1996 Elsevier Science Ltd