FDA Points-to-Consider Documents: The Need for Dietary Control for the Reduction of Experimental Variability within Animal Assays and the Use of Dietary Restriction to Achieve Dietary Control

摘要: Standard protocols for conducting chronic toxicity and carcinogenicity studies have been refined over the years to carefully control many variables. Nevertheless, last 2 decades, there has a steady increase in variability, decrease survival, an tumor incidence rates, average body weight of animals among various rodent species strains used testing. These observations prompted evaluation study designs determine what factor(s) may be responsible such confounding changes. Ad libitum feeding selection successful breeders with rapid offspring growth is believed at least partially heavier, obese rodents which laboratories are coping today. As result these changes, some safety deemed inconclusive or inadequate regulatory purposes either additional supportive requested and/or per se repeated. Research on molecular mechanisms caloric restriction agent-induced Food Drug Administration (FDA) National Center Toxicological stimulated first international conference biological effects dietary 1989; this was followed 1993 by FDA workshop exploring utility controlling reduced survival tests 1994 implications community using support sponsor's submission risk assessments. The outcome that FDA's commitment develop Points-to-Consider documents address issue studies.