The proposed research centers about the initial distribution of selected persistent xenobiotic chemicals and their translocation from storage depots. The major goals are to determine whether pregnancy and lactation in mammals or vitellogenesis and spawning in fish or the hormones responsible for the initiation and/or maintenance of these physiological conditions, alter the distribution of xenobiotics in female mice and rainbow trout, and whether chemicals are, in turn, accumulated by their offspring. Implicit in this goal is an evaluation of the mode and control of transfer of xenobiotics from their storage sites. Specifically, since a number of lipophilic chemicals have been shown to bind to plasma lipoproteins and since pregnancy and lactation in mammals and vitellogenesis in fish alter plasma lipoprotein profiles and/or lipid metabolism the possibility exists that these lipoproteins may direct the translocation of xenobiotics from storage depots to the fetus and/or nursing offspring or to yolk. The information obtained from these studies will indicate whether xenobiotic chemicals which have been sequestered in storage sites are available for transfer to offspring and whether the alterations in the endocrine milieu associated with reproductive function determine their redistribution. In general, the experimental approach involves the determination of half-lives, ultimate fate, and induction of hepatic drug metabolizing enzyme activity by selected radiolabeled persistent chemicals in control, pregnant, lactating and hormonally pretreated mice and in control (non-vitellogenic), prespawning, and hormonally pretreated rainbow trout. Whether plasma lipoproteins are involved in the redistribution of xenobiotic chemicals from storage depots will be determined in vivo and in vitro.
