title: Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity.
abstract: The discovery of acrylamide (AA) in many common cooked starchy foods has presented significant challenges to toxicologists, food scientists, and national regulatory and public health organizations because of the potential for producing neurotoxicity and cancer. This paper reviews some of the underlying experimental bases for AA toxicity and earlier risk assessments. Then, dietary exposure modeling is used to estimate probable AA intake in the U.S. population, and physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling is used to integrate the findings of rodent neurotoxicity and cancer into estimates of risks from human AA exposure through the diet. The goal of these modeling techniques is to reduce the uncertainty inherent in extrapolating toxicological findings across species and dose by comparing common exposure biomarkers. PBPK/PD modeling estimated population-based lifetime excess cancer risks from average AA consumption in the diet in the range of 1-4 x 10 (-4); however, modeling did not support a link between dietary AA exposure and human neurotoxicity because marginal exposure ratios were 50-300 lower than in rodents. In addition, dietary exposure modeling suggests that because AA is found in so many common foods, even big changes in concentration for single foods or groups of foods would probably have a small impact on overall population-based intake and risk. These results suggest that a more holistic analysis of dietary cancer risks may be appropriate, by which potential risks from AA should be considered in conjunction with other risks and benefits from foods.
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, USA. daniel.doerge@fda.hhs.gov
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.forename: John F
authors.initials: JF
authors.lastname: Young
authors.forename: James J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dinovi
authors.forename: Sara H
authors.initials: SH
authors.lastname: Henry
mesh_terms: D020106:Acrylamide / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000737:chemistry; D004032:Diet; D004781:Environmental Exposure / Q000032:analysis; D005506:Food Contamination / Q000032:analysis; D006358:Hot Temperature; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced; D018570:Risk Assessment
chemical_list: D002273:Carcinogens; D020106:Acrylamide