Developmental Effects of Fish Borne Toxicants in the Rat

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Recent epidemiological studies suggest a relationship between consumption of contaminated Great Lakes fish by pregnant women and developmental and cognitive deficits in their infants and children. Although polychlorinated biphenyl (PCB) exposure is correlated with these dysfunctions, recent data we have collected from rats perinatally exposed to diets containing lyophilized Great Lakes salmon suggest that the observed neuropsychological effects may be due to other neuroactive contaminants in the fish or to synergistic interactions between PCBs and other contaminants. </P>
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In order to determine which toxicants present in Great Lakes fish induce neurobehavioral alterations following perinatal exposure we will: <ol>
<li> measure concentrations of the organic and inorganic contaminants in Lake Ontario (LO) salmon and in Pacific Ocean (PO) salmon, which will serve as a control in all experiments; </li>
<li> determine neurobehavioral effects in rats perinatally exposed to lyophilized LO salmon (contains all contaminants) or a sulfuric acid extract of LO salmon (contains all organic contaminants). If the neurobehavioral effects of the lyophilized LO salmon and the solvent extract are equal we will assume that the non-extractable components (including MeHg) are not involved in mediating the effects and we will go on to; </li>
<li> determine the neurobehavioral effects of two florisil column fractions of the LO solvent extract -- one containing the majority of the PCBs, DDE, HCB, mirex and chlordanes, and the other containing the coplanar PCBs, dioxins, dibenzofurans and polar pesticides and; </li>
<li> determine regio-specific neurochemical changes in animals exposed to the behaviorally active fraction(s). </li></ol>
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Alternatively, if the results obtained (2) indicate that the unfractionated solvent extract does not yield effects equivalent to those of the lyophilized LO salmon, we will conduct studies to determine which endogenous (fatty acids, selenium) and exogenous (MeHg, arsenic, lead) non-extractable components must be added to the solvent extract to result in behavioral equivalence. </P>
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These experiments will allow us to determine which class(es) of contaminants are responsible for the neuropsychological changes seen in perinatally-exposed humans. The findings will aid in the risk assessment process and will also form the basis for later studies to determine the mechanisms responsible for the behavioral alterations.</p>