Neurotoxicology of Nanomaterials
- 1 April 2020
- journal article
- review article
- Published by American Chemical Society (ACS) in Chemical Research in Toxicology
- Vol. 33 (5), 1121-1144
- https://doi.org/10.1021/acs.chemrestox.0c00050
Abstract
The remarkable advances coming about through nanotechnology promise to revolutionize many aspects of modern life, however, these advances come with a responsibility for due diligence to assure that they are not accompanied by adverse consequences for human health or the environment. Many novel nanomaterials (having at least one dimension < 100 nm) could be highly mobile if released into the environment and are also very reactive, which has raised concerns for potential adverse impacts including, among others, the potential for neurotoxicity. Several lines of evidence led to concerns for neurotoxicity, but perhaps none more than observations that inhaled nanoparticles impinging on the mucosal surface of the nasal epithelium could be internalized into olfactory receptor neurons and transported by axoplasmic transport into the olfactory bulbs without crossing the blood brain barrier. From the olfactory bulb there is concern that nanomaterials may be transported deeper into the brain and affect other brain structures. Of course, people will not be exposed to only engineered nanomaterials, but rather such exposures will occur in a complex mixture of environmental materials, some of which are incidentally generated particles of a similar inhalable size range to engineered nanomaterials. To date, most experimental studies of potential neurotoxicity of nanomaterials have not considered the potential exposure sources and pathways that could lead to exposure, and most studies of nanomaterial exposure have not considered potential neurotoxicity. Here, we present a review of potential sources of exposures to nanoparticles, along with a review of the literature on potential neurotoxicity of nanomaterials. We employ the linked concepts of an Aggregate Exposure Pathway (AEP) and an Adverse Outcome Pathway (AOP) in order to organize and present the material. The AEP includes a sequence of Key Events progressing from material sources, release to environmental media, external exposure, internal exposure, and distribution to the target site. The AOP begins with toxicant at the target site causing a Molecular Initiating Event and, like the AEP, progress sequentially to actions at the level of the cell, organ, individual and population. Reports of nanomaterial actions are described at every key event along the AEP and AOP, except for changes in exposed populations that have not yet been observed. At this last stage, however, there is ample evidence of population level effects from exposure to ambient air particles which may act similarly to engineered nanomaterials. The data give an overall impression that current exposure levels may be considerably lower than those reported experimentally to be neurotoxic. This impression, however, is tempered by the absence of long-term exposure studies with realistic routes and levels of exposure to address concerns for chronic accumulation of materials and/or damage. Further, missing across the board are “Key Event Relationships”, which are quantitative expressions linking the Key Events of either the AEP or the AOP, making it impossible to project quantitatively the likelihood of adverse neurotoxic effects from exposure to nanomaterials, or to estimate margins of exposure for such relationships.Keywords
This publication has 193 references indexed in Scilit:
- Biopersistence of silver nanoparticles in tissues from Sprague–Dawley ratsParticle and Fibre Toxicology, 2013
- Silver nanoparticles (AgNPs) cause degeneration of cytoskeleton and disrupt synaptic machinery of cultured cortical neuronsMolecular Brain, 2013
- Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticlesToxicology Letters, 2012
- Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cellsToxicology and Applied Pharmacology, 2011
- Engineered nanomaterials: exposures, hazards, and risk preventionJournal of Occupational Medicine and Toxicology, 2011
- Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral SclerosisArchives of Neurology, 2010
- Air pollution: mechanisms of neuroinflammation and CNS diseaseTrends in Neurosciences, 2009
- Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticlesToxicology Letters, 2009
- Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammationProceedings of the National Academy of Sciences of the United States of America, 2008
- Phototoxicity and cytotoxicity of fullerol in human lens epithelial cellsToxicology and Applied Pharmacology, 2008