EFFECTS OF PRIOR OR CONCURRENT DIELDRIN EXPOSURE ON TISSUE ATRAZINE METABOLISM

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Exposure to atrazine, one of the widely used herbicides in the United States, has been associated with deleterious effects on various organ systems. However, in order to establish the human health relevancy of these studies, tissue dosimetry and pharmacokinetics studies are needed. In addition, atrazine metabolism is dependent in large measure upon the activities of cytochrome P450 (CYP) mono-oxygenases. Certain pesticides that are now banned, but still widely present in the environment, such as the insecticide dieldrin, are known CYP inducers. The persistence of dieldrin and the high use of atrazine, increase the likelihood of exposure to these two pesticides in combination. Existing analytical methods to analyze atrazine in biological matrices have various drawbacks. We have recently developed an LC-MS method to analyze atrazine and all of its major mammalian metabolites in mouse plasma and urine. In this project, we will optimize this method for determination of atrazine and its metabolites in target tissues and then use it to determine how atrazine¿s tissue disposition and pharmacokinetics are influenced by prior or concurrent dieldrin exposure. Our long-term goal is to understand better how the pharmacokinetics and tissue distribution of environmentally-relevant pesticides changes when organisms are exposed to pesticide mixtures. More specifically, we will determine whether prior/ongoing exposure to dieldrin will alter atrazine¿s pharmacokinetics. When completed, this research is expected to not only delineate the effects of dieldrin exposure on the pharmacokinetics of atrazine, but to also underscore the importance of pesticide interaction in risk assessment.