New Nonpurified Diet (NTP-2000) for Rodents in the National Toxicology Program's Toxicology and Carcinogenesis Studies

Abstract

The NIH-07 open-formula nonpurified diet was the selected diet for rodents in the National Toxicology Program's toxicology and carcinogenesis studies from 1980 to 1994. Protein and mineral concentrations of the NIH-07 diet may have increased some diet- and age-associated lesions such as nephropathy. A number of experimental nonpurified diets with lower protein and higher fat and fiber (∼15% protein, 7–8.5% fat, and 9–14% crude fiber) than the NIH-07 diet were formulated and evaluated in Fischer 344 (F344) rats. Decreasing protein content of the diet decreased protein consumption by ∼30% and decreased severity of nephropathy without affecting growth. Increased fat intake seemed to have decreased the incidence or severity of leukemia, a lethal neoplasm of F344 rats. Increasing fiber content without decreasing the caloric density lowered body weight gain and slowed growth of mammary tumors. Higher fat and/or fiber intake decreased the incidences of adrenal pheochromocytomas and medullary hyperplasia in male rats. Nonpurified diets with lower protein and higher fat and fiber concentrations than the NIH-07 diet decreased or delayed diet- and age-associated lesions and increased survivals in 2-y studies. On the basis of these results, a new cereal-based nonpurified diet, designated as NTP-2000, was formulated with ∼14.5% protein, ∼8.2% fat, ∼9.3% fiber and a calcium:phosphorus molar ratio of ∼1.3. The NTP-2000 diet was compared with the NIH-07 diet in a 13-wk study in F344 rats. The NTP-2000 diet was adequate for growth, did not affect the hematological parameters and did not cause substantial changes in blood chemistry, serum enzyme or serum electrolyte values. The NTP-2000 diet decreased liver and kidney weights, prevented nephrocalcinosis and decreased the severity of diet- and possibly age-associated lesions.