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NEUROTOXICOLOGICAL AND STATISTICAL ANALYSES OF A MIXTURE OF FIVE ORGANOPHOSPHORUS PESTICIDES USING A RAY DESIGN.
Citation:
Moser, V C., A. Hamm, M. Casey, W. H. Carter, C. Gennings, AND J E. Simmons. NEUROTOXICOLOGICAL AND STATISTICAL ANALYSES OF A MIXTURE OF FIVE ORGANOPHOSPHORUS PESTICIDES USING A RAY DESIGN. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Pesticide application patterns generally result in exposure to mixtures instead of single chemicals. Of particular importance in the estimation of pesticide mixture risks is the detection and characterization of their interactions. This research tested for interaction(s) in a mixture of five organophosphorus (OP) pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion). The ratio of pesticides in the mixture reflected the relative dietary exposure estimates projected by the US EPA Dietary Exposure Evaluation Model (DEEM). The approach first required characterization of dose-response curves for each OP alone to build an additivity model. Neurochemical (blood and brain cholinesterase [ChE] activity) and behavioral (motor activity [MA], gait score, tail-pinch response score) endpoints were assessed in adult male Long-Evans rats following acute oral exposure. The additivity model was used to predict the effects of the pesticide mixture along a ray of increasing total doses (full ray, 10-450 mg/kg), using the same fixed ratio of components. The mixture data were similarly modeled and statistically compared to the additivity model along the ray. To evaluate the influence of malathion, a second pesticide mixture was tested using the same proportions of OPs but without malathion (reduced ray, 2-79 mg/kg). Analysis of the full ray revealed significant synergism for all endpoints except the tail-pinch response, which was additive. For gait score, the reduced ray was additive, indicating that the non-additivity detected before was due to malathion in the mixture. For blood ChE and MA, the curves for the full and reduced rays were different from each other, but for brain ChE they were not. Therefore, there is evidence that malathion interacts with the other OPs, at least in terms of the effects on blood ChE, MA, and gait; however, the deviation from additivity cannot fully be attributed to the malathion in the mixture. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy