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In vitro Alternative Methodologies for Central Nervous System Assessment: A Critique using Nanoscale Materials as an Example.
Citation:
Yorkel, R. AND R. C. MACPHAIL. In vitro Alternative Methodologies for Central Nervous System Assessment: A Critique using Nanoscale Materials as an Example. Presented at 2011 Toxicology and Risk Assessment Conference, Cincinnati, OH, April 25 - 28, 2011.
Impact/Purpose:
There are numerous challenges in testing and interpreting the results of nanoscale materials
Description:
Identifying the potential health hazards to the central nervous system of a new family of materials presents many challenges. Whole-animal toxicity testing has been the tradition, but in vitro methods have been steadily gaining popularity. There are numerous challenges in testing and interpreting the results of nanoscale materials. Some of them are: 1) There are multiple physical forms of nanoscale materials, comprised of different primary materials, with novel forms being continuously created; 2) Nanoscale materials have physicochemical properties different from small soluble ligands that can significantly alter their kinetics and dynamics, including surface coating and protein adsorption (opsonization), adhesion, phagocytic uptake, and formation of persistent intracellular agglomerations; 3) The most appropriate exposure metric has yet to be identified; 4) There is remarkably little information on dose/concentrationresponse; and 5) Little information about their penetration, distribution and persistence in the brain -and nothing about the spinal cord. Classical approaches to estimate pharmacokinetic parameters appear inadequate. Failure to appreciate the unique properties of nanomaterials may lead to inaccurate risk estimates when interpreting 'observations and research results. Exposure and toxicological assessments of nanoscale materials will likely require a broad approach incorporating systems-biology and material-characterization components, including in vivo confirmation of acellular and in vitro findings, along with novel toxicokinetic models. (This is an abstract of a presentation and does not imply EPA policy.)