Toxicological Sciences, Vol 52, 24-34, Copyright © 1999 by Society of Toxicology
K Keenan, G Ballam, K Soper, P Laroque, J Coleman and R Dixit
The diet can significantly alter the results of toxicity and
carcinogenicity studies. <it>Ad libitum (AL) overfeeding
of excessive calories to sedentary adult rodents is one of the most poorly
controlled variables affecting the current rodent bioassay. AL-overfed
rodents develop an early onset of adverse metabolic events,
endocrine-disruptive degenerative diseases, and tumors that result in early
morbidity and mortality. AL food consumption is extremely variable, but has
a strong correlation with adult body weight, obesity, and survival. AL
feeding of diets with modified protein, fiber, and energy content are not
as effective as simple, moderate dietary (caloric) restriction (DR) in
controlling these study variables. Moderate DR (70-75% of adult AL) is
operationally simple and controls adult body weights, prevents obesity, and
improves health and survival by reducing or delaying diet-related
endocrine, renal, and cardiac diseases. Moderate DR provides a uniform
rodent model, increases treatment exposure time, and increases the
statistical sensitivity of these chronic bioassays to detect true treatment
effects. Feeding a balanced diet by a moderate DR regimen of 70-75% of the
maximum, unrestricted adult AL food intake is recommended for conducting
well-controlled toxicity and carcinogenicity studies.Keywords:
overfeeding; dietary restriction; nutrition; carcinogenesis;
toxicology
ARTICLES
Diet, caloric restriction, and the rodent bioassay
Department of Safety Assessment and Biometrics, Merck Research Laboratories, WP45-222, Sumneytown Pike, West Point, PA 19486, USA; Riom, France; Purina Mills, Inc., St Louis, Missouri 63116, USA; Corresponding author; Fax: (215) 652 7718; E-mail: kevin_keenan@merck.com
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