title: Developmental neurotoxicity of engineered nanomaterials: identifying research needs to support human health risk assessment.
abstract: Increasing use of engineered nanomaterials (ENM) in consumer products and commercial applications has helped drive a rise in research related to the environmental health and safety (EHS) of these materials. Within the cacophony of information on ENM EHS to date are data indicating that these materials may be neurotoxic in adult animals. Evidence of elevated inflammatory responses, increased oxidative stress levels, alterations in neuronal function, and changes in cell morphology in adult animals suggests that ENM exposure during development could elicit developmental neurotoxicity (DNT), especially considering the greater vulnerability of the developing brain to some toxic insults. In this review, we examine current findings related to developmental neurotoxic effects of ENM in the context of identifying research gaps for future risk assessments. The basic risk assessment paradigm is presented, with an emphasis on problem formulation and assessments of exposure, hazard, and dose response for DNT. Limited evidence suggests that in utero and postpartum exposures are possible, while fewer than 10 animal studies have evaluated DNT, with results indicating changes in synaptic plasticity, gene expression, and neurobehavior. Based on the available information, we use current testing guidelines to highlight research gaps that may inform ENM research efforts to develop data for higher throughput methods and future risk assessments for DNT. Although the available evidence is not strong enough to reach conclusions about DNT risk from ENM exposure, the data indicate that consideration of ENM developmental neurotoxic potential is warranted.
authors.affiliation: Office of Research and Development, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Powers
authors.forename: Ambuja S
authors.initials: AS
authors.lastname: Bale
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kraft
authors.forename: Susan L
authors.initials: SL
authors.lastname: Makris
authors.forename: Jordan
authors.initials: J
authors.lastname: Trecki
authors.forename: John
authors.initials: J
authors.lastname: Cowden
authors.forename: Andrew
authors.initials: A
authors.lastname: Hotchkiss
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Gillespie
mesh_terms: D000818:Animals; D006801:Humans; D049329:Nanostructures / Q000633:toxicity*; D009420:Nervous System / Q000187:drug effects* / Q000196:embryology; D018570:Risk Assessment
keywords: developmental neurotoxicity; engineered nanomaterials; risk assessment research.