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.

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