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Evaluating Neurotoxicity of a Mixture of Five OP Pesticides Using a Composite Score
NYIRABAHIZI, E., C. GENNINGS, AND V. C. MOSER. Evaluating Neurotoxicity of a Mixture of Five OP Pesticides Using a Composite Score. Presented at Annual meeting of the Society of Tocicology, Baltimore, MD, March 15 - 19, 2009.
The evaluation of the cumulative effects of neurotoxic pesticides often involves the analysis of both neurochemical and behavioral endpoints. Multiple statistical tests on many endpoints can greatly inflate Type I error rates. Multiple comparison adjustments are often overly conservative leading to reduced power to detect effects of interest. Furthermore, identification of the most sensitive endpoint may be chemical dependent so that neurotoxicity may be most evident on a per animal basis by evaluating many endpoints. Use of a composite score focuses the inference and avoids inflated type I error rates. Coffey et al (2007) describe the development of an overall score based on desirability functions for the many types of outcomes measured in neurobehavioral toxicology experiments. Our objective was to evaluate the neurotoxicity of a mixture of five pesticides (Moser et al, 2005). In particular, the desirability functions for neurochemical (blood and brain cholinesterase activity) and behavioral (motor activity, gait score, tail-pinch response score) endpoints were calculated for single chemical (acephate, diazinon, dimethoate, chlorpyrifos, and malathion) and mixture dose response data, and a composite score of neurotoxicity was determined. Both an additivity model using single chemical data and a model for an environmentally-relevant fixed-ratio mixture were estimated. Focusing in the low dose region using a 5%, 10% and 20% benchmark responses (BMRs), departure from additivity was found at the 20% BMR with all five pesticides in the mixture; additivity was observed at the lower BMRs. Using the same relevant mixing ratio but without the most common chemical, malathion, we found departure from additivity at all three BMRs. Thus, malathion significantly influences the interactions of the remaining chemicals in the mixture. This methodology is therefore useful in evaluating the overall neurotoxicity of pesticide mixtures. This is an abstract of a proposed presentation and does not reflect US EPA policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/POSTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
NEUROBEHAVIORAL TOXICOLOGY BRANCH