Need for dietary control by caloric restriction in rodent toxicology and carcinogenicity studies.
The conditions under which laboratory animals are maintained can powerfully influence the results of toxicological studies utilized for risk assessment. Nutrition is of importance in toxicological bioassays and research, because diet composition and the conditions under which it is fed can affect the metabolism and activity of xenobiotic test substances and alter the results and reproducibility of long-term studies. It is known that ad libitum (AL) overfed sedentary laboratory rodents suffer from an early onset of degenerative disease and diet-related tumors that lead to poor survival in chronic bioassays. AL-fed animals are not well-controlled subjects for any experimental studies. Examination of study-to-study variability in food consumption, body weight, and survival in carcinogenicity studies for the same strain or stock of rodents shows tremendous laboratory-to-laboratory variability. However, a significant correlation between average food (calorie) consumption, adult body weight, and survival has been clearly established. The use of moderate dietary restriction (DR) results in a better controlled rodent model with a lower incidence or delayed onset of spontaneous diseases and tumors. Operationally simple, moderate DR significantly improves survival, controls adult body weight and obesity, reduces age-related renal, endocrine, and cardiac diseases, increases exposure time, and increases the statistical sensitivity of these expensive, chronic bioassays to detect a true treatment effect. A moderate DR regimen of 70-75% of the maximum unrestricted AL food intake is recommended as a nutritionally intelligent, well-established method in conducting well-controlled toxicology and carcinogenicity studies.
Keenan
K P
KP
Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Laroque
P
P
Dixit
R
R
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D004032:Diet; D004195:Disease Models, Animal; D002149:Energy Intake; D009752:Nutritional Status; D051381:Rats; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D018675:Toxicity Tests / Q000379:methods*