Project Summary (2000-2005)

This project is identifying the cellular mechanisms underlying the developmental neurotoxicity of the organic pesticide chlorpyrifos, as well as the adverse behavioral outcomes consequent to developmental exposure. This information is being used to develop appropriate biomarkers with which to estimate the NOAEL. Researchers are using two models, one for mammalian neurotoxicity (rat) and one for piscine neurotoxicity (zebrafish). The mammalian model provides a closer model for human health effects and the piscine model provides a potential biomarker for environmental monitoring. The zebrafish model is also valuable because the processes of neurodevelopment are readily observable in the transparent embryo. In both cases, the focus is on the specific targeting of brain development at exposure levels below the threshold for dysmorphogenesis or standard teratogenesis. Specifically, researchers are determining the cellular mechanisms by which chlorpyrifos disrupts mammalian neural cell replication and differentiation, determining the functional consequences of chlorpyrifos' effects on cell development, and developing a non-mammalian model of developmental neurotoxicity of chlorpyrifos for estimation of NOAEL in ecotoxicologic settings. Molecular mechanisms of developmental neurotoxicity are being identified and linked to eventual alterations in behavioral performance.