Print Email Facebook Twitter Regulatory developmental neurotoxicity testing: A model study focussing on conventional neuropathology endpoints and other perspectives Title Regulatory developmental neurotoxicity testing: A model study focussing on conventional neuropathology endpoints and other perspectives Author de Groot, D.M.G. Bos-Kuijpers, M.H.M. Kaufmann, W.S.H. Lammers, J.H.C.M. O'Callaghan, J.P. Pakkenberg, B. Pelgrim, M.T.M. Waalkens-Berendsen, I.D.H. Waanders, M.M. Gundersen, H.J.J. TNO Kwaliteit van Leven Publication year 2005 Abstract Our aim was to investigate a model of the morphologic approach proposed in guidelines for developmental neurotoxicity testing (DNT). Hereto, a limited DNT study [EPA Health Effects Test Guidelines OPPTS 870.6300, 1996a. Developmental Neurotoxicity Study "Public Draft", United States Environmental Protection Agency; Prevention, Pesticides and Toxic Substances (7101); EPA 712-C-96-239, June 1996. http://www.epa.gov/opptsfrs/OPPTS_Harmonized/870_Health_Effects_Test_Guidelines/Drafts/870-6300.pdf was carried out with different doses of methylazoxy methanol acetate (MAM), known to affect brain morphology and neuron numbers in the developing brain. After gross examination, the brains of F1-animals were further dissected along neuro-anatomical landmarks to ensure homology between tissues of different individuals. The (relative) weight of the brain (parts) was determined. One brain half (alternating left/right to avoid lateralization) was further used for microscopic slide reading and measurement of brain layer width (linear morphometry); the other was set aside for stereologic investigation in a later phase of the study. In the offspring, a clear reduction in brain size (gross macroscopy) and weight (MAM high- and top-dose groups) was observed on postnatal days (PN) 22 and 62, but this reduction was hard to pinpoint in the microscope as the changes primarily appeared quantitative in nature, rather than qualitative. Linear measurements of brain layer width appeared very sensitive and efficient. This first step of a project is presented and the perspectives of a further stereologic investigation are discussed. © 2005 Published by Elsevier B.V. Subject ToxicologyToxicology and Applied PharmacologyMethylazoxy methanol acetate (MAM)Microscopy and linear morphometryNeuron numbers and stereologyNeuropathology endpointsOECD 426)OPPTS 870.8600, EPARatRegulatory developmental neurotoxicity (DNT) testing (Guidelines OPPTS 870.6300, EPAmethylazoxymethanol acetateanimal modelanimal tissuebrainbrain developmentbrain sizeconference papercontrolled studydevelopmental neurotoxicity testingdissectionfemalemorphometricsnerve cellneuroanatomyneuropathologyneurotoxicitynonhumanperinatal periodpractice guidelinepriority journalqualitative analysisrattoxicity testingAnimalia To reference this document use: http://resolver.tudelft.nl/uuid:ff0c31aa-9e00-4a14-bd82-85bf367c6855 DOI https://doi.org/10.1016/j.etap.2004.12.039 TNO identifier 238496 ISSN 1382-6689 Source Environmental Toxicology and Pharmacology, 19 (3), 745-755 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.