Developmental Neurotoxicity of Chlorpyrifos: Mechanistic Information and Predictive Safety Assessment Applications.

Abstract

Over the last decade a considerable body of evidence has emerged indicating that chlorpyrifos (CPF) targets important processes during nervous system development causing developmental neurotoxicity. These processes include neuronal proliferation, differentiation, axonogenesis, synaptogenesis, myelination and apoptosis. This book chapter attempts to collate mechanistic information derived from in vivo and in vitro studies investigating the neurotoxic properties of CPF in developing nervous system. Furthermore, this existing mechanistic knowledge will be organized accordingly and linked to distinct adverse outcomes that CPF can cause in developing organisms such as motor, sensory and cognitive deficits. These neurodevelopmental effects vary in severity, duration and time of onset and can be reversible or can have permanent, life-long consequences. Thus, the developmental neurotoxicity induced by CPF is complex and here there will be also presented a chemical-specific predictive risk assessment approach that will encompass all the available mechanistic as well as complementary toxicokinetic information. Additionally, this book chapter will revise all the information available from several risk assessment reports performed by different international organizations regarding the neurodevelopmental effects of CPF. An analysis of the various outcomes and the differences in diverse aspects of these assessments will be provided. Finally, the implications of these evaluations across different regulatory frameworks will be also described.