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Developmental Neurotoxicity Testing: A Path Forward
Citation:
CROFTON, K. M., W. R. MUNDY, AND T. J. SHAFER. Developmental Neurotoxicity Testing: A Path Forward . Yuji Nakajima (ed.), Congenital Anomalies. Wiley-Blackwell, Hoboken, NJ, 52(3):140-146, (2012).
Impact/Purpose:
A major problem in toxicology is the lack of adequate information to perform data based assessment and management decisions. A new integrated evaluation strategy is proposed that provides a framework to encourage more efficient use of resources in assessing the exposure and health hazards of environmental contaminants. Examples are presented for the use of this strategy for DNT screening, including in silico models, in vitro methods, targeted testing approaches, and resource intensive systems based models. There are many challenges to achieving the goal of a truly efficient integrated evaluation strategy for chemical testing. There are many areas of biology for which new methods and models must be developed, including in vitro HTS and targeted testing. These new methods will require validation, which must be done for the intended purpose (Hartung, 2010). Finally, we will need to development tiered decision logic flows that include regulatory acceptance.
Description:
Great progress has been made over the past 40 years in understanding the hazards of exposure to a small number of developmental neurotoxicants. Lead, PCBs, and methylmercury are all good examples of science-based approaches to characterizing the hazard to the developing nervous systems from environmental contaminants. However, very little effort has been spent to address the challenge of assessing the potential developmental neurotoxic hazard of the thousands of other chemicals in common commercial use. The extensive time, financial and animal resource requirements for current regulatory testing guideline methods make this an untenable solution to this challenge. A new testing paradigm is needed that uses time and cost-efficient methods to screen large numbers of chemicals for developmental neurotoxicity (DNT). In silico models are needed to provide rapid chemical structure-based screening. In vitro techniques are being developed to provide rapid and efficient testing in cell-free and cell-based systems. In addition, the use of alternative species, such as zebrafish, will provide efficient models for testing the effects of chemicals in an organism with intact developing nervous systems. Finally these methods and models need to be used in an integrated fashion to provide the data needs for hazard assessment in a manner that is problem driven and cost-efficient. This paper summarizes discussions on these issues from the symposium “Developmental neurotoxicity testing: Scientific approaches towards the next generation to protecting the developing nervous system of children” held at the 2011 annual meeting of the Japanese Teratology Society.
