Assessment of exposure to hazardous chemicals is handicapped by inadequate monitoring methods. This proposal will evaluate an immunologically based test for adducted hemoglobin that will ultimately be used to assess exposure to acrylamide. Acrylamide, a classical neurotoxin and reproductive toxin that humans are exposed to in the workplace and by ingesting contaminated water, distributes preferentially to the erythrocytes. Since acrylamide-hemoglobin adducts accumulate for the 120 day life span of the erythrocyte, hemoglobin adducts represent a dosimeter that is detectable long after the insulting toxin is eliminated. The investigators have identified an acrylamide hemoglobin adduct and prepared a synthetic adducted peptide to represent the hemoglobin adduct. Acrylamide-adducted peptide was used to immunize rabbits and generate antisera against the adducted peptide. An immunologically-based hemoglobin adduct assay has been developed and will be evaluated in animals treated acutely and subchronically with acrylamide to determine the lowest detectable exposure dose detected by their method. Two routes of exposure will be evaluated: dermal and oral. Validation of this methodology will include testing humans exposed to acrylamide in the workplace. Subjects will donate blood specimens when actively working with acrylamide-based products in research laboratories and then again after a period of non-exposure. Control subjects will be age- matched laboratory workers that are not knowingly exposed to acrylamide at work. Effects of covariate exposures will also be examined. Specifically, this work will enable assessment (using reliable, rapid methodology) of individuals exposed to an industrial chemical with multitargeted toxicological properties; universally, this work will serve as a model for developing biomonitors for additional chemicals of environmental importance.
