A better approach to in vivo developmental neurotoxicity assessment: Alignment of rodent testing with effects seen in children after neurotoxic exposures
Autor: | Samantha L. Regan, Michael T. Williams, Jenna L.N. Sprowles, Charles V. Vorhees |
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Rok vydání: | 2018 |
Předmět: |
Adolescent
Neurogenesis Child Behavior Neuropsychological Tests 010501 environmental sciences Toxicology Risk Assessment 01 natural sciences 03 medical and health sciences Child Development 0302 clinical medicine Species Specificity In vivo Toxicity Tests Animals Humans Medicine Child 0105 earth and related environmental sciences Neurons Pharmacology Developmental neurotoxicity Behavior Animal Working memory business.industry Age Factors Cognitive flexibility Brain Infant Cognition Executive functions Child Preschool Models Animal Neurotoxicity Syndromes Reproductive toxicity business Neurocognitive 030217 neurology & neurosurgery Clinical psychology |
Zdroj: | Toxicology and Applied Pharmacology. 354:176-190 |
ISSN: | 0041-008X |
Popis: | High throughput screens for developmental neurotoxicity (DN) will facilitate evaluation of chemicals and can be used to prioritize those designated for follow-up. DN is evaluated under different guidelines. Those for drugs generally include peri- and postnatal studies and juvenile toxicity studies. For pesticides and commercial chemicals, when triggered, include developmental neurotoxicity studies (DNT) and extended one-generation reproductive toxicity studies. Raffaele et al. (2010) reviewed 69 pesticide DNT studies and found two of the four behavioral tests underperformed. There are now many epidemiological studies on children showing adverse neurocognitive effects, yet guideline DN studies fail to assess most of the functions affected in children; nor do DN guidelines reflect the advances in brain structure-function relationships from neuroscience. By reducing the number of test ages, removing underperforming tests and replacing them with tests that assess cognitive abilities relevant to children, the value of DN protocols can be improved. Testing for the brain networks that mediate higher cognitive functions need to include assessments of working memory, attention, long-term memory (explicit, implicit, and emotional), and executive functions such as cognitive flexibility. The current DNT focus on what can be measured should be replaced with what should be measured. With the wealth of data available from human studies and neuroscience, the recommendation is made for changes to make DN studies better focused on human-relevant functions using tests of proven validity that assess comparable functions to tests used in children. Such changes will provide regulatory authorities with more relevant data. |
Databáze: | OpenAIRE |
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