| Summary: | Statement of Problem- The pesticides lindane, chlordane, endrin, dieldrin, toxaphene, and DDT as well as the industrial compounds hexachlorobenzene(HCB), polychlorinated biphenyls (PCBs), polychlorodibenzo-p-dioxins (PCDDs), and polychlorodibenzofurans (PCDFs) are globally distributed environmental organochlorine contaminants. This class of compounds are persistent and possess potent biological effects including immunosuppression, teratogenicity, carcinogenicity, reproductive toxicity, neurotoxicities, and disturbances in energy metabolism which produce a wasting syndrome. To date little information is available on the sensitivity of pinnipeds (seals) to these organochlorine contaminants and their spectrum of toxic effects. Control of energy metabolism in seals is of key importance for survival of these marine mammals. We are determining the sensitivity of five different species of seals, located along the western coast of the United States, to the toxic effects of PCBs on energy metabolism (wasting syndrome). The protected status of pinnipeds preclude in vivo toxicological testing. In vitro methodologies for examining toxicity, which use more readily obtainable tissues (e.g., blood and in the case of the seals, adipose tissue), have been unavailable. Previously, we investigated the relative sensitivity of the guinea pig, rat, and mouse to the wasting effects of PCBs and PCDDs using sensitive in vitro adipose tissue explant bioassays for glucose transport and lipoprotein lipase activity, both of which play critical roles in wasting syndrome. These bioassays correctly identify the relative sensitivity of these three species. We are using these in vitro bioassays to compare the sensitivity of five species of seals with the well characterized guinea pig, rat, and mouse. The toxic, 3,3',4,4' tetrachlorobiphenyl congener is being used as our principal model compound. PCBs are tested, in vitro, in replicates of adipose and blood tissue explant cultures from seals side by side with cultures from the sensitive guinea pig, and less sensitive rat, and mouse. This data is being analyzed to determine the relative sensitivity of seals to PCBs. Levels of organochlorine contaminants in seal adipose tissue used in these experiments are being quantified to determine if environmental exposure to organochlorine contaminants is affecting glucose transport and lipoprotein lipase activity in these animals. Levels of circulating thyroid hormones,T4 and T3, are being determined in concert with levels of organochlorine contaminants in blood to ascertain if environmental exposures to PCBs and other organochlorine contaminants are affecting thyroid function in these animals. This project is providing a measure of the relative sensitivity of different species of seals to the adverse effects of PCBs on energy metabolism. Levels of circulating thyroid hormones, T4 and T3 are also being evaluated as a potential biomarker of exposure to these compounds. This information can be used to identify species of seals at greater risk from these contaminants. This information will also aid in the recovery and rehabilitation of stranded animals, which often exhibit weight loss, skin lesions resembling chloracne produced by these contaminants, and have relatively high levels of these compounds in their adipose tissue.
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