Acrylamide (ACR) is a widely used monomer in the polymer industry. The polymeric form is widely utilized as a flocculent in the waste and water treatment industry. Historically, concerns regarding occupational and environmental exposures have centered around its well-documented neurotoxic effects. Recent studies have implicated ACR as a male reproductive toxicant in rats at doses that failed to produce peripheral neuropathies in these males. The purpose of this proposal is to further extend these findings through a number of investigations. The first investigations are aimed at determining the stages of spermatogenesis most adversely affected by ACR and establishing a no effect limit of exposure to ACR. To accomplish these aims two dominant lethal studies had to be carried out. Results from the first study are presented in the preliminary studies section. A second dominant lethal study to extend the dose range downward and the next investigation to assess the factors that contribute to apparent pre-implantation loss are in progress. The apparent pre-implantation loss investigation will evaluate copulatory dysfunction which may result in abnormal mating behavior and sperm transport. In addition, spermatotoxic effects may result from ACR exposure and these will be assessed. The third investigation will examine where ACR interferes with fertilization or subsequent zygote development (i.e. produces """"""""true"""""""" preimplantation loss). The fourth investigation will initiate studies into the potential mechanism underlying pre- and post-implantation loss and will evaluate the potential binding of ACR to sperm and sperm DNA. The last investigation will seek to characterize the effect of dose and rate of exposure on the expression of reproductive damage. This proposal is important for a number of reasons. First, it will give greater insight into the mechanism of ACR-induced dominant lethality. It will, also, provide important information to better understand the significance of pre- and post-implantation loss. In addition, it will establish a dose relationship associated with ACR's reproductive effects. Finally, the results determined by these studies may provide information useful in identifying other occupational and/or environmental exposures which here-to-fore have been unrecognized as reproductive toxicants.
