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Neurotoxicol Teratol. 2016 May-Jun;55:38-44. doi: 10.1016/ Epub 2016 Apr 2.

Unmasking silent neurotoxicity following developmental exposure to environmental toxicants.

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National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. Electronic address:
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Environmental Medicine, University of Rochester Medical School, Rochester, NY, USA.
Departments of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Department of Environmental Health and Center for Neurodegenerative Disease, Emory University, Atlanta, GA, USA.
National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.


Silent neurotoxicity, a term introduced approximately 25years ago, is defined as a persistent change to the nervous system that does not manifest as overt evidence of toxicity (i.e. it remains clinically unapparent) unless unmasked by experimental or natural processes. Silent neurotoxicants can be challenging for risk assessors, as the multifactorial experiments needed to reveal their effects are seldom conducted, and they are not addressed by current study design guidelines. This topic was the focus of a symposium addressing the interpretation and use of silent neurotoxicity data in human health risk assessments of environmental toxicants at the annual meeting of the Developmental Neurotoxicology Society (previously the Neurobehavioral Teratology Society) on June 30th, 2014. Several factors important to the design and interpretation of studies assessing the potential for silent neurotoxicity were discussed by the panelists and audience members. Silent neurotoxicity was demonstrated to be highly specific to the characteristics of the animals being examined, the unmasking agent tested, and the behavioral endpoint(s) evaluated. Overall, the experimental examples presented highlighted a need to consider common adverse outcomes and common biological targets for chemical and non-chemical stressors, particularly when the exposure and stressors are known to co-occur. Risk assessors could improve the evaluation of silent neurotoxicants in assessments through specific steps from researchers, including experiments to reveal the molecular targets and mechanisms that may result in specific types of silent neurotoxicity, and experiments with complex challenges reminiscent of the human situation.


Behavior; Delayed-onset; Development; Environmental health; Neurotoxicity; Risk assessment

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