Toxicological Sciences 58, 195-207 (2000)
Copyright © 2000 by the Society of Toxicology
Safety Evaluation |
The Effects of Diet, ad Libitum Feeding, and Moderate and Severe Dietary Restriction on Body Weight, Survival, Clinical Pathology Parameters, and Cause of Death in Control Sprague-Dawley Rats
Department of Safety Assessment, Merck Research Laboratories,
* 63963 Clermont-Ferrand Cedex 9, France; and
West Point, Pennsylvania 19486
A 2-year study was conducted in Sprague-Dawley rats to compare the effects of ad libitum (AL) feeding and dietary restriction (DR) on body weight, survival, cause of death, and clinical pathology parameters. Three groups of 120 rats/sex each received the following daily rations of a maintenance rodent diet: ad libitum (AL group); 75% of adult AL food consumption (25% DR group); and 45% of adult AL food consumption (55% DR group). Among the 3 groups, there were generally no differences in relative (food intake per gram of body weight) food consumption. Compared to the AL group, decreased body weight gain occurred in DR groups and was associated with an increase in survival proportional to the DR rate. The main cause of death was pituitary adenomas in all groups. Decreases in total leukocyte, segmented neutrophil, lymphocyte, and platelet counts occurred in the 55% DR group. In serum biochemistry, there were decreases in total protein, albumin, total and HDL cholesterol, and total calcium, and increases in alkaline phosphatase activities and chloride in 55% DR females, as well as decreases in triglycerides in the 55% DR group and in 25% DR females. Results of urinalyses showed decreases in urine volume and protein, and increases in urinary pH in both DR groups. In conclusion, a DR rate of approximately 25% appears to be appropriate for Sprague-Dawley rats in toxicity and carcinogenicity assays to improve survival without impairing growth and routine clinical pathology parameters.
Key Words: Sprague-Dawley rat; dietary restriction; body weight; survival; cause of death; clinical pathology.
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