Food and Drug Administration risk assessment--process and toxicologic pathology.

A general outline of the risk assessment process at the Center for Food Safety and Applied Nutrition (CFSAN) of the Food and Drug Administration based on the toxicologic evaluation of data is described. Examples of recent pathology evaluations are presented to illustrate primarily the pathology review process at the CFSAN. These examples include the review of data from rodent studies from proposed indirect food additives and data from dog studies submitted in support of an investigational new drug, a short-acting opioid, proposed as an anesthetic in humans.

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.

Hepatocellular foci--a regulator's Gordian.

Recently, the Food and Drug Administration has received several petitions which raise the question of the significance of an increased number of treated rats with foci of hepatocellular alteration. Study pathologists are responsible for defining the diagnostic criteria used in any study to diagnose proliferative changes in the liver. Similarly, study pathologists, based on their observations of the overall liver findings, are responsible for assessing the biological significance of any lesion observed and including their appraisal in the written pathology narrative which should accompany any petition sent to a regulatory agency.

Forestomach lesions induced by butylated hydroxyanisole and ethylene dibromide: a scientific and regulatory perspective.

Selected pathology lesions from 9 studies, 5 with butylated hydroxyanisole (BHA) and 4 with ethylene dibromide (EDB) are reviewed and their relative importance in regulatory evaluation is discussed. When Fischer 344 (F344) rats were fed BHA at 0.5% and 2.