Developmental neurotoxicity of organophosphates: a case study of chlorpyrifos
The chapter addresses the case of chlorpyrifos as a specific example of how knowledge of the systemic toxicity of an organophosphate in adults can be misleading with regard to its potential to act as a developmental neurotoxicant. A case study of the developmental neurotoxicity of chlorpyrifos reveals important lessons for future work, and for the human health relevance of animal and in vitro studies. First, the known mechanisms for systemic toxicity in an adult prove to be inadequate and misleading in evaluating the developmental neurotoxicity of chlorpyrifos, and likely for other organophosphates as well. Second, there is no mechanism for the adverse effects of chlorpyrifos on nervous system development, but, rather, a family of mechanisms, thus attacking multiple stages of brain cell maturation, disparate regions and cell types, and encompassing a wide window of vulnerability. Third, adverse effects on general aspects of cell signaling extend the types of alterations that can be expected to include signals required for peripheral functions so that agents acting as developmental neurotoxicants may also affect cardiovascular, metabolic, immune, or endocrine function as equally relevant end points. Fourth, there may be predisposing factors that create subpopulations that are especially vulnerable to developmental neurotoxicants, including not only obvious genetic polymorphisms, but also prior exposures to drugs and chemicals that target similar processes in brain cell development. Finally, recent work has addressed the essential issue of whether these kinds of studies really relate to the human condition. © 2006 Elsevier Inc.
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