Moderate food restriction (FR) has been established as a nutritionally appropriate and well-controlled method with long-term beneficial effects in conducting toxicity and carcinogenicity studies in rodents. This study describes the early effects of moderate FR on toxicity study parameters in rats and on the variability of these parameters. Physical signs, body weight, food and water consumption, and clinical pathology parameters were examined in a 4-week study in which rats were moderately food-restricted or fed ad libitum (AL). There were no diet-related differences in physical signs, hematology or urinalysis. FR-related changes were observed in body weight and serum biochemistry; however, most of the changes involved anti-aging alterations and/or physiological adjustment to FR. Moderate FR resulted in low variability and good reproducibility in body weight. The present results indicate that moderate FR does not impair study parameters and increases statistical sensitivity. Therefore, a moderate FR feeding regimen is beneficial not only for long-term but also for short-term toxicity studies in rats.
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