HEPATOTOXICITY OF ATRAZINE AND ITS DEGRADATION PRODUCTS

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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. Atrazine is one of the herbicides that are most heavily used in the world. The proposed research is focused on studying the hepatotoxicity of atrazine and its degradation products. In the funding period from 6/05 to 5/06, we studied the metabolism of atrazine in rat liver microsome incubation system to identify the major phase I metabolites of atrazine. HPLC-MS/MS based analytical methods were developed and used in our lab for these purposes. After incubation with rat liver microsome for 2 hours at 37 0C, atrazine degradation products including deethylatrazine and deisopropylatrazine were detected by using an advantageous tandem mass spectrometry-based analytical method. This was the first report on the detection of these atrazine degradation products in this biological incubation system. This past year we also started to study the effects of atrazine and its degradation products on Fe(III)-NADPH induced lipid peroxidation in rat liver microsome so that hepatotoxicity of atrazine and its degradation products would be more precisely assessed. Five peer-reviewed publications from this group are acknowledging the RCMI grant (12RR13459) in this funding period. Next year, we plan to continue the study on phase I metabolites of atrazine in rat liver microsome using the HPLC-MS/MS procedures established in our lab. Hepatotoxicity of newly identified atrazine degradation products will be assessed and comparatively studied against their parent compounds. The study will be focused on the effects of these agrochemicals on NADPH induced lipid peroxidation in rat liver microsome incubation system.