Kinetic and mechanistic data needs for a human phsiologically based pharmacokinetic (PBPK) model for acrylamide: pharmacokinetic model for acrylamide.
A pharmacokinetic (PBPK) model has been developed for acrylamide (AMD) and its oxidative metabolite, glycidamide (GLY), in the rat based on available information. Despite gaps and limitations to the database, model parameters have been estimated to provide a relatively consistent description of the kinetics of acrylamide and glycidamide using a single set of values (with minor adjustments in some cases). Future kinetic and mechanistic studies will need to focus on the collection of key data for refining certain model parameters and for model validation, as well as for conducting studies that elucidate the mechanism of action. Development of a validated human AMD/GLY PBPK model capable of predicting target tissue doses at relevant dietary AMD exposures, in combination with expanding data on modes of action, should allow for a substantive improvement in the risk assessment of acrylamide in food.
Andersen
Melvin E
ME
CllT Centers for Health Research, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA. MAndersen@ciit.org
Scimeca
Joseph
J
Olin
Stephen S
SS
D020106:Acrylamide / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D019540:Area Under Curve; D018736:DNA Adducts; D004852:Epoxy Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D015233:Models, Statistical; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D012107:Research Design; D018570:Risk Assessment / Q000379:methods*; D014018:Tissue Distribution
D018736:DNA Adducts; D004852:Epoxy Compounds; D020106:Acrylamide; C071834:glycidamide; D010100:Oxygen