Draft Action Plan Acrylamide in food：食品中丙烯酰胺的行动计划草案.pptVIP

Toxicology Component of FDA’s Action Plan for Acrylamide Richard Canady, PhD DABT US Food and Drug Administration Center for Food Safety and Applied Nutrition Goal of the toxicity component of FDA’s action plan Examine the likelihood that adverse health effects are caused by exposure to acrylamide-containing foods. Context for toxicology research Ongoing assessment of knowledge base for acrylamide Past assessments for Food contact materials, cosmetics, water treatment, pesticide inert ingredient, specialized grout, monomer/polymer manufacture, coal mining, cigarette smoke Knowledge has changed with regard to How we are exposed Ingestion from food, not just water The levels to which we are exposed Data gap evaluations World Health Organization/ Food and Agriculture Organization (WHO/FAO) consultation in June Interagency meeting in September Joint Institute for Food Safety and Applied Nutrition (JIFSAN) workshop in October Expert panel at Emerging Neurotoxicology Conference in November Workshop for germ cell mutagen risk assessment Spring 2003 Outline of presentation of what we know, need, and are planning Toxicokinetics Animal carcinogen Human neurotoxicant Reproductive/developmental effects Safety/risk assessment 1. What we know for toxicokinetics Absorbed orally Degree of absorption from food has not been studied Most toxicity information from drinking water or injections Wide and uniform distribution (oral exposure, high dose) Metabolism understood for 1000 micrograms per kilogram of body weight (mcg/kg) doses Saturable (CYP2E1) conversion to glycidamide Glutathione conjugation Elimination occurs in hours to days But protein binding (-SH) and potential for cumulative damage Exposure duration affects neurotoxic dose 1. Toxicokinetics data needs Bioavailability of acrylamide from food Dose-response for toxicity, disposition, and binding Dose metrics, critical events, mode of action DNA to hemoglobin adduct relationship DNA and protein binding as a marker of