The present project was undertaken to develop new methodologies for biological monitoring of exposure to the toxicant acrylamide in laboratory animals as well as humans. Methods were developed to measure the adducts of acrylamide and its epoxide metabolite glycidamide to cysteine in rat hemoglobin and to valine in human hemoglobin by means of gas chromatography/mass spectrometry. Studies in rats indicated that both acrylamide and glycidamide adducts are formed following acute or chronic exposure to acrylamide, while only the glycidamide adducts are formed after exposure to glycidamide. Both adducts, in addition to acrylonitrile adducts, were measured in a group of Chinese workers exposed to acrylamide during its synthesis and polymerization. Significant signs of neurotoxicity were also found in this population. Additional studies in rats indicated that acrylamide, but not glycidamide, is the proximate neurotoxicant while glycidamide may be responsible for the male reproductive and genotoxic/carcinogenic effects of acrylamide. These studies suggest that these novel biomarkers to assess exposure to acrylamide are useful to assess potential health hazards (including possible cancer risks) due to exposure to acrylamide in occupationally exposed workers as well as in the general population.

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