Chronic toxicity and carcinogenicity of olestra in Swiss CD-1 mice.

Two 2-yr feeding studies were conducted in Swiss CD-1 mice to evaluate the oral toxicity and carcinogenicity potential of olestra, a fat substitute consisting of a mixture of the hexa-, hepta- and octaesters of sucrose formed with long-chain fatty acids. In a dose-response study olestra was fed at 0, 2.5, 5 or 10% (w/w) of the diet. In a companion study conducted to confirm equivocal effects, olestra was fed at 0 or 10% (w/w) of the diet. Olestra-containing diets were supplemented with fat-soluble vitamins A, D, E and K to maintain the nutritional status of the olestra-fed mice at a level similar to that of the control mice. 100 mice/sex were placed in each group. 50 mice/sex/group were predesignated to the carcinogenicity portion of the study and all survivors were killed at 24 months. 15 mice/sex/group were predesignated to the toxicity portion of the study and were killed at 12 months. 35 mice/sex/group were included as sentinel animals to be used for monitoring nutritional status. Ophthalmoscopic examinations were conducted before the test and at 12 and 24 months. Body weights and feed consumption were determined weekly. Gross observations, clinical chemistry and haematology data were obtained on animals killed at 12 and 24 months. Complete gross post-mortem examinations, including organ weight and organ-to-body and organ-to-brain weight ratios were performed on all animals. Histopathology was conducted on a full complement of tissues from all animals allocated to the carcinogenicity portions of the studies. There were no olestra-related effects on any of the endpoints measured, including survival, time-to-tumour or tumour incidence, ophthalmology, clinical chemistry, haematology, organ weights or tissue morphology. These results indicate that olestra is not toxic or carcinogenic when fed to mice at up to 10% of the diet for 2 yr.