Relationship of Behavioral Deficits to Traditional and Novel Biomarkers Following Chronic Organophosphorus Pesticide Exposures

Introduction: Organophosphorus pesticides (OPs) are considered our most toxic pesticides due to their established neurotoxic effects following extended exposures in animals and humans, and they are among the most widely used pesticides throughout the world.  They are also believed to be likely terrorism agents.  Several studies have reported correlations of the adverse neurotoxic effects in humans to measures of cholinesterase inhibition and dialkylphosphates in urine, but most have not been significant.  Correlations of the deficits with years of exposure have been more successful.  We conclude that the cholinesterase and dialkylphosphate biomarkers do not correlate with the neurobehavioral deficits because they are not mechanistically related to the neurotoxic damage produced by the pesticide exposures.  

Methods: Egyptian pesticide application teams with a broad range of (chronic) exposures to chlorpyrifos, an organophosphorus pesticide, have been studied to identify potential neurotoxic effects, demonstrated by performance on neurobehavioral tests of memory, attention and coordination.  In linked experimental animal research, chlorpyrifos was administered subcu over 21 days to rats trained to perform behavioral tests of functions parallel to those used in our human studies; we have correlated their performance to novel biomarkers of inflammation and oxidative stress related to adverse effects in some OP studies in animals.  Based on the animal research, the most promising novel biomarker will be measured in banked samples from the pesticide applicator teams studied and correlated with their behavioral performance.  Results: Performance on some behavioral tests in the Egyptian applicator teams revealed dose response relationships, the first reported in the human organophosphorus literature.  Cholinesterase measures, the chlorpyrifos-specific urine metabolite 3,5,6-trichloro-2-pyridinol (TCPy), and novel biomarkers were/will be correlated with performance in the Egyptian applicators.  

Discussion: This research will be the first to correlate human behavioral performance with traditional and novel OP biomarkers in the same population.  (R01 ES 16308:Anger & Lein, MPIs)