Revisiting the evidence for genotoxicity of acrylamide (AA), key to risk assessment of dietary AA exposure
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REVIEW ARTICLE
Revisiting the evidence for genotoxicity of acrylamide (AA), key to risk assessment of dietary AA exposure Gerhard Eisenbrand1 Received: 14 April 2020 / Accepted: 20 May 2020 © The Author(s) 2020
Abstract The weight of evidence pro/contra classifying the process-related food contaminant (PRC) acrylamide (AA) as a genotoxic carcinogen is reviewed. Current dietary AA exposure estimates reflect margins of exposure (MOEs) 100 µg/kg b w). At variance, in the dose range below 100 µg/ kg b.w. down to levels of average consumers exposure, DNA N7 -Gua lesions were found only sporadically, without dose dependence, and at levels close to the lower bound of similar human background DNA N7-Gua lesions. No DNA damage was detected by the comet assay within this low dose range. GA is a very weak mutagen, known to predominantly induce DNA N7-GA-Gua adducts, especially in the lower dose range. There is consensus that DNA N7-GA-Gua adducts exhibit rather low mutagenic potency. The low mutagenic potential of GA has further been evidenced by comparison to preactivated forms of other process-related contaminants, such as N-Nitroso compounds or polycyclic aromatic hydrocarbons, potent food borne mutagens/carcinogens. Toxicogenomic studies provide no evidence supporting a genotoxic mode of action (MOA), rather indicate effects on calcium signalling and cytoskeletal functions in rodent target organs. Rodent carcinogenicity studies show induction of strain- and species-specific neoplasms, with MOAs not considered likely predictive for human cancer risk. In summary, the overall evidence clearly argues for a nongenotoxic/nonmutagenic MOA underlying the neoplastic effects of AA in rodents. In consequence, a tolerable intake level (TDI) may be defined, guided by mechanistic elucidation of key adverse effects and supported by biomarker-based dosimetry in experimental systems and humans. Keywords Acrylamide · Glycidamide · Mode of action · Non genotoxic · Process related contaminants · Dietary exposure
Introduction Acrylamide (AA) is one of several so-called process-related contaminants (PRCs) occurring in heat-processed food worldwide. Further dietary PRCs of similar widespread occurrence encompasses glycidol and glycidol esters, chlorinated propanols (MCPD) and their esters, furans and * Gerhard Eisenbrand [email protected]‑kl.de 1
University of Kaiserslautern, Germany (Retired), Kühler Grund 48/1, 69126 Heidelberg, Germany
substituted furans and, depending on the type of process and the temperatures applied to food, heterocyclic aromatic amines (HAA), N-Nitroso compounds (NOC) and polycyclic aromatic hydrocarbons (PAH). This list may not be exhaustive and further PRC may come into focus. Of note, assembling these contaminants into one group is merely reflecting their mode of generation. They are formed from food constituents during the various heat treatment processes foods may be exposed to. These include cooking, microwaving, frying, baking, grilling, roasting, smoking, and/or other forms of industrial and household
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