ACRYLAMIDE - A REVIEW OF ITS GENOTOXICITY AND AN ASSESSMENT OF HERITABLE GENETIC RISK

An updated review of the genotoxicity studies with acrylamide is provi ded. Then, using data from the studies generating quantitative informa tion concerning heritability of genetic effects, an assessment of the heritable genetic risk presented by acrylamide is presented. The revie w offers a discussion of the reactions and possible mechanisms of geno toxic action by acrylamide and its epoxide metabolite glycidamide. Sev eral genetic risk approaches are discussed, including the parallelogra m, direct (actually a modified direct), and doubling dose approaches. Using data from the specific-locus and heritable translocation assays, the modified direct and doubling dose approaches are utilized to quan titate genetic risk. Exposures of male parents to acrylamide via inhal ation, ingestion, and dermal routes are also quantitated. With these a pproaches and measurements and their underlying assumptions concerning extrapolation factors (including germ cell stage specificity, DNA rep air variability, locus specificity), number of human loci associated w ith dominant disease alleles, and spontaneous mutation rates, an asses sment of heritable genetic risk for humans is calculated for the three exposure scenarios. The calculated estimates for offspring from fathe rs exposed to acrylamide via drinking water are up to three offspring potentially affected with induced genetic disease per 10(8) offspring. Estimates for inhalation or dermal exposures suggest higher risks for induced genetic disease in offspring from fathers exposed in occupati onal settings.