Metabolism of acrylamide in humans and biomarkers of exposure to acrylamide

Absorption of acrylamide is fast from the gastrointestinal tract, and then it is metabolized and excreted in urine, for the most part as metabolites. Acrylamide is widely distributed to all tissues and also to placenta and milk. It is partly transformed to its genotoxic metabolite glycidamide through phase I metabolism. Both acrylamide and glycidamide are electrophilic compounds, which can react with cellular nucleophiles. Acrylamide and glycidamide are detoxified by conjugation with glutathione through phase II metabolism. The conjugates are excreted in urine as mercapturic acid derivatives, which are biomarkers of short-term exposure to acrylamide. Acrylamide and glycidamide react with the N-terminal valine residue of hemoglobin forming covalent adducts. The life span of erythrocytes is about 4 months in human, and thus the hemoglobin adducts reflect the time-weighted exposure to acrylamide. The hemoglobin adduct of acrylamide can be used in internal dose assessment, and the glycidamide adduct generally shows a genotoxic effect. Nucleophilic nitrogens in DNA are also susceptible to form adducts, especially with glycidamide. Biomarkers of exposure provide information to assess internal dose, bioavailability, metabolism, individual exposure, and changes in levels over time.