Abstract
Diet is an important variable in rodent toxicology and carcinogenicity studies. Several diet models are now available for selection in rodent toxicology studies. Abundant data have clearly established a signi cant correlation between average food (calorie) consumption, nutrient composition of the diet, adult body weight, the onset and incidences of speci ed pathological endpoints, and survival (2, 3). Ad libitum feeding of common diets to rodents on long-term studies results in overeating, excessive caloric intake, higher body weights, decreased activity patterns, and earlier onset and higher incidences of some spontaneous degenerative diseases (nephropathy and cardiomyopathy), neoplasia (eg, pituitary and mammary tumors), and reduced survival. Reduced survival of the control animals in 2-year studies, often signi cantly less than 50%, has heightened the industry’s awareness of these diet-related issues (2). The overeating problems in long-term rodent studies have been addressed by two different approaches: dietary modi cation (change the nutrient contents of the diet) and dietary restriction (control the amount of food the animals can eat). Some of the early studies using dietary modi cation were inconclusive, but more recently scientists at the National Toxicology Program and others have shown that control of the formulation of an ad libitum, nonpuri ed diet source for laboratory animals (diet modi cation) has a signi cant effect on survival and the incidence and severity of several dietary and possibly age-associated pathology. More speci cally, a diet (NTP-2000) with lower protein and higher fat and ber ( 15% protein, 7–8.5% fat, and 9–14% crude ber), when fed ad libitum to F344 rats, enhanced survival and reduced the incidence and/or severity of several common age-related
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