An Integrated Computational Framework for the Interpretation of Organophosphorus Pesticide Biomarkers (sponsored by EPA STAR)
Although various biomarkers have been used to assess exposure to and poisoning from organophosphorus (OP) pesticides/insecticides, the complexity of OP absorption, distribution, metabolism and elimination, especially for mixtures of these chemicals, warrants integration of computational modeling tools with the biomarker data for more accurate quantitation and assessment of actual whole body exposures and target tissue dosimetry. The objective of this project is to create a computer-assisted framework to aid in the identification, characterization, and understanding of biomarkers resulting from human exposure to mixtures of OP insecticides, using chlorpyrifos and diazinon as the initial test compounds. The framework will use existing human biomarker data, along with information about population and exposure variability and uncertainty, to reconstruct absorbed dose and exposure scenarios, as well as to predict levels of biomarkers resulting from known exposures to one or multiple OP insecticides. The software tool developed, and targeted data acquired, will be useful in the interpretation of biomarkers indicative of exposure to OP insecticide mixtures, including the effects of population and dose variability and uncertainty. Therefore, the outcome of this project will be a more accurate approach to the assessment of exposure from these mixtures in the cumulative risk assessment process, and therefore the overall benefit will be an improvement of EPA’s ability to protect public health.