Acrylamide : differences in absorption, metabolism and excretion between rodents and humans

Acrylamide (AM) is a commonly used monomer in the manufacture of polyacrylamide. In addition, AM has been found in heated foods that are rich in starch. The main dietary sources in Sweden tend to be crisps, French fries, fried potatoes, crisp bread, cookies and coffee. Un-fortunately, dietary intake of AM has in several studies been shown to cause cancer in ro-dents. Consequently, the compound is currently regarded as a potential carcinogen in hu-mans. Once in the body, AM may be transformed into the genotoxic compound glycidamide (GA). Research is presently going on to reveal to what extent dietary AM is converted into GA in humans. The main purpose of this research is to outline a foundation for a more accu-rate risk assessment in the future. Since the westernized population is exposed to a significant amount (0.5 μg/kg body weight.), it is essential to attain a better understanding regarding the absorption, metabolism and secretion of dietary AM. Apart from in vivo studies in rodents, lately some in vivo studies have been performed in humans. 13C NMR och LC/MS are two commonly used techniques when analyzing urinary metabolites. With these methods it is possible to gain information regarding the absorption, metabolism, and the extent of elimina-tion of AM. The objective of this thesis was to compile the results and conclusions that have been published on this topic, and subsequently compare the gained information between ro-dents and humans. The absorption is generally considered effective in both humans and ro-dents. In the liver, most of the AM conjugates into N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), followed by secretion. The second main metabolic path way in both humans and rodents is by transformation into GA. In humans, most of GA is hydrolyzed into 2, 3-dihydroxypropionamide (glyceramid) and in rodents conjugated into the two mercapturic ac-ids N-acetyl-S-(2-carbamoyl-2-hydroxy-ethyl)-L-cysteine (GAMA) och N-acetyl-S-(1-carbamoyl-2-hydroxyethyl) cysteine (Iso-GAMA). Since glyceramid is hard to detect, it may result in difficulties when trying to estimate how much of dietary AM that is actually con-verted into the genotoxic GA. During the first 24 hours after dietary intake, more AM is ex-creted in rats than in humans. The conversion into GA in humans is probably around 20-25 % of the conversion that takes place in rats. This is a good reason to believe that a lower risk of cancer is naturally present in humans compared to rodents after dietary intake of AM. Keywords: acrylamide, glycidamide, absorption, metabolism, secretion, urine metabolite