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Current Practices and Future Trends in Neuropathology Assessment for Developmental Neurotoxicity Testing
Citation:
Bolon, B., R. H. Garman, H. Jorgen, G. Gunderson, W. Kaufman, G. Krinke, P. B. Little, S. MAKRIS, M. MELLON, K. K. Sulik, AND K. F. JENSEN. Current Practices and Future Trends in Neuropathology Assessment for Developmental Neurotoxicity Testing. TOXICOLOGIC PATHOLOGY. Society of Toxicology, RESTON, VA, 39(1):289-293, (2011).
Impact/Purpose:
EPA scientists organized and co-chaired a continuing education course on developmental neurotoxicity assessment at the Society of Toxicologic Pathologists in Chicago, ILL on June 20, 2010. This course trained the current and future pathologists in best practices for the conduct developmental neurotoxicity assessments and discussed future technologies that have the potential to dramatically improve and expedite developmental neurotoxicity assessments. This 'mini-review' that is based on the course will be published in the symposium issue of Toxicologic Pathology
Description:
The continuing education course on "Developmental Neurotoxicity Testing" (DNT) was designed to communicate current practices for DNT neuropathology, describe promising innovations in quantitative analysis and non-invasive imaging, and facilitate a discussion among experienced neuropathologists and regulatory scientists regarding suitable DNT practices. Conventional DNT neuropathology endpoints are qualitative histopathology and morphometric endpoints of particularly vulnerable sites (cerebral, cerebellar, or hippocampal thickness). Novel imaging and stereology measurements hold promise for automated analysis of factors that cannot be effectively examined in routinely processed specimens (e.g., cell numbers, fiber tract integrity). The panel recommended that dedicated DNT neuropathology data sets be acquired on a minimum of 8 serial coronal sections (for qualitative assessment) or 3 sections (for quantitative linear and stereological analyses) using a small battery of stains to examine neurons and myelin. Where guidelines permit discretion, immersion fixation is acceptable for younger animals (postnatal day 22 or earlier), and peripheral nerves may be embedded in paraffin or soft plastic. Frequent concerns regarding DNT data sets include false negative outcomes due to processing difficulties (e.g., lack of concordance among sections from different animals) and insensitive analytical endpoints (e.g., qualitative evaluation) as well as false positive results arising from over-interpretation or misreading by inexperienced pathologists.
