Handbook of Developmental Neurotoxicology

Dr. William Slikker, Jr. was the director of FDA’s National Center for Toxicological Research (NCTR) before his retirement. He received his Ph.D. in pharmacology and toxicology from the University of California at Davis. Dr. Slikker holds adjunct professorships in the Department of Pediatrics, as well as the Department of Pharmacology and Toxicology at the University of Arkansas for Medical Sciences. He has held committee chairmanships or elected offices in several scientific societies including the Teratology Society (serving as president) and the American Society for Pharmacology and Experimental Therapeutics (chair, Developmental Pharmacology Section and member, Program Committee). Dr. Slikker is also the co-founder and past president of the MidSouth Computational Biology and Bioinformatics Society. He is currently associate editor for NeuroToxicology and associate editor for the “Environmental Health” section of Experimental Biology and Medicine. He is the past president of The Academy of Toxicological Sciences and the Society of Toxicology. He is a recipient of the 2014 George H. Scott Memorial Award from The Toxicology Forum and was invited to present the Warkany Lecture at the 2015 annual meeting of the Teratology Society. In early 2019, the Academy of Toxicological Sciences selected Dr. Slikker to receive the prestigious Mildred S. Christian Career Achievement Award. The Society for Birth Defects Research and Prevention selected Dr. Slikker to be the recipient of the 2022 Edward W. Carney Distinguished Service Award. Dr. Slikker has authored or co-authored over 380 publications in the areas of transplancentalpharmacokinetics, developmental neurotoxicology, neuroprotection, systems biology, and risk assessment. Dr. Slikker’s recent research has highlighted the concern for thousands of infants and toddlers who undergo longer-duration general anesthesia. He has performed research with his team and published over 25 peer-reviewed papers outlining the issue of brain-cell death and cognitive-function deficits in animal models that may result from several hours of anesthesia at a critical time of development. He has also, with the use of in vitro and in vivo techniques in rodents and nonhuman primates, defined possible mechanisms of toxicity and protective pathways to prevent the detrimental effects of general anesthesia. Through these and related scientific contributions, he has identified and characterized a host of minimally invasive biomarkers of neurotoxicity including the use of preclinical imaging (MRI, MicroPET/CT), genomic and lipidomic analysis, and modeling approaches to characterize and quantify adult and developmental neurotoxicity. He has also served on several national/international advisory panels for ILSI, HESI, CIIT, EPA, NIEHS, NAS, NIH and WHO. Dr. Paule received his B.S. in Biochemistry and his Ph.D. in Pharmacology and Toxicology at the University of California at Davis. In 1983 he began work at the FDA’s National Center for Toxicological Research in Jefferson, Arkansas, where he remains today. He attained certification as one of FDA’s Senior Biomedical Research Scientists in 2000 and in 2005 became the Director of the Division of Neurotoxicology at NCTR. Dr. Paule has played a major role in developing an automated system for monitoring multiple complex brain functions in nonhuman primates, children, and rodents. Utilization of similar or identical behavioral tasks across species serves to facilitate the interspecies extrapolation of exposure data and, thus, the risk assessment process. He is past President of the Behavioral Toxicology Society, the Neurobehavioral Teratology Society and the Neurotoxicology Specialty Section of the Society of Toxicology and Associate Editor for the journals NeuroToxicology and Neurotoxicology and Teratology. Dr. Paule has published over 225 research articles and 30 book chapters and holds Adjunct Professorships at the University of Arkansas for Medical Sciences in the Departments of Pharmacology and Toxicology and in Pediatrics. He is an elected Fellow in the Academy of Toxicological Sciences and in the International Behavioral Neuroscience Society. Cheng Wang, M.D., Ph.D. is a Senior Scientist at the National Center for Toxicological Research (NCTR)/US Food and Drug Administration (FDA). He is also an Adjunct Faculty member in the Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences (UAMS). Dr. Wang is the P.I. of protocols (grants) supported by the NCTR/FDA, National Toxicology Program and NICHD. He is currently responsible for leading a research team that provides unique and highly specialized skills in neural toxicology, pharmacology, systems biology and stem cell biology research. Dr. Wang has published more than 80 peer-reviewed research articles in prestigious journals and 20 book chapters. Dr. Wang is a Co-Editor-in-Chief of the book entitled “Developmental Neurotoxicology Research: Principles, Models, Techniques, Strategies, and Mechanisms” and “Neural Cell Biology”. He also serves as Editor-in-Chief for Journal of Evolving Stem Cell Research (JESR) and Global Journal of Anesthesiology. Dr. Wang was awarded the Outstanding Performance Award at the Society of Toxicology 44th Annual Meeting and the 2007 FDA Scientific Achievement Award for Excellence in Laboratory Science. He also was awarded a 2008 FDA Group Recognition Award for his participation in the Pediatric Anesthesia Research Group. Research Interests Neural Stem Cell Biology Application of Systems Biology in Neurotoxicological Studies during Development Activity-induced Synaptic Plasticity and Neural Cell Adhesion Molecule Potential Pediatric Anesthetic-induced Neural Cell Death and the Potential Role of Neurotransmission (Mechanistic Studies) Mitochondrial DNA Damage and Expression Levels of DNA Repair Enzymes

PART I. CELLULAR AND MOLECULAR MORPHOGENESIS OF THE NERVOUS SYSTEM PART II. DEVELOPMENTAL NEUROBIOLOGY/TOXICOLOGY PART III. SYNAPTOGENESIS AND NEUROTRANSMISSION PART IV. NUTRIENT AND CHEMICAL DISPOSITION PART V. BEHAVIORAL ASSESSMENT PART VI. CLINICAL ASSESSMENT AND EPIDEMIOLOGY PART VII. SPECIFIC NEUROTOXIC SYNDROMES PART VIII. RISK ASSESSMENT