Estimation of safe dietary intake levels of acrylamide for humans.
Acrylamide (AA), a human neurotoxicant and rat tumorigen, is produced in starchy foods when cooked. AA is also an industrial chemical used in polyacrylamide production. A safety evaluation of ingested AA by humans was conducted using a newly developed, state-of-the-art physiologically-based toxicokinetic (PBPK or PBTK) model to compare internal doses of AA and its metabolite glycidamide (GA) in humans and rats. Based on modes of action (MoA), a nonlinear dose-response approach was applied for neurotoxicity (non-genotoxicity) and carcinogenicity (mixed: genotoxicity and epigenetic MoA). Tolerable daily intake (TDI) for neurotoxicity from AA was estimated to be 40 microg/kg-day; TDIs for cancer were estimated to be 2.6 and 16 microg/kg-day based on AA or GA, respectively. Margins of exposure (MoE) were calculated for average AA consumers to be 300 and 500 based on AA and GA, respectively; for cancer, the MoE for average AA consumers was estimated to be 200 and 1200 based on AA and GA, respectively. For high consumers of AA, MoEs were somewhat less.
Tardiff
Robert G
RG
The Sapphire Group, Inc., Bethesda, Maryland 20814, USA. rgt@thesapphiregroup.com
Gargas
Michael L
ML
Kirman
Christopher R
CR
Carson
M Leigh
ML
Sweeney
Lisa M
LM
D020106:Acrylamide / Q000493:pharmacokinetics* / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis*; D004852:Epoxy Compounds / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005506:Food Contamination; D006801:Humans; D008297:Male; D008452:Maximum Allowable Concentration; D009498:Neurotoxins / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D018570:Risk Assessment
D002273:Carcinogens; D004852:Epoxy Compounds; D009498:Neurotoxins; D020106:Acrylamide; C071834:glycidamide