Problems in consideration of rodent hepatocarcinogenesis for regulatory purposes

Hepatoproliferative lesions of rodents are frequently reported in petitions containing pathology data from chronic toxicity and carcinogenicity studies submitted to the Center for Food Safety and Applied Nutrition of the Food and Drug Administration. The Pathology Branch of the Office of Scientific Analysis and Support evaluates these data, which are submitted in support of the safe use of food additives, color additives, and other regulated products. Data are reviewed for the adequacy of the information provided, the terminology used to describe the reported lesions, and the overall scientific rationale used in interpreting the biological significance of the observed lesions. When questions arise during the review process, additional data, information, or clarification are sought from the petitioner. Microslides may be requested from the petitioner so that an independent evaluation of the lesions may be conducted. Several examples of recent evaluations of hepatoproliferative lesions are presented to illustrate some of the problems encountered during the review process and to demonstrate the procedures and approaches used in the evaluation of hepatocellular lesions within the center.