Meeting Agenda

CE 1 Toxicologic Pathology of the Developing Central Nervous System

Sunday, June 18, 2006, 8:00 AM–11:55 AM

Chair: Olga Pulido, MD, MSc, A Board Path, FIATP
Bureau of Chemical Safety, Health Products and Food Branch, Health Canada
& University of Ottawa Department of Pathology and Laboratory Medicine
Ottawa, Ontario, Canada

Summary: The developing brain has a distinct set of characteristics resulting in greater sensitivity to damage by toxic agents compared to the adult brain. The consequences of early exposure to neurotoxins in foods, environmental contaminants, therapeutics etc., can be very subtle. Its long-term impact on human health can be serious and may only be evident after prolonged latency. A causal relationship between chemical exposure and neurotoxic effects is therefore often difficult to determine. Neuropathology is an essential component of developmental neurotoxicity assessment for regulatory purposes. The toxicologic pathologist is challenged by the interdependence of the sequence of complex biologic processes underlying the development of the central nervous system and the regional differential structural vulnerability of the immature brain to various chemicals. The methodology, the experimental design, knowledge of developmental neurobiology, mechanistic base neurotoxicology and the clinical functional implications are all important guides to the pathologist in detecting and interpreting chemical induced effects. The objective of this course is to provide general toxicologic pathologists, regulators, toxicologists and related biomedical disciplines with an overview of current knowledge and practices relevant to "Developmental Neuropathology", their implications to “Neurotoxicology and Human Health Risk Assessment”.

Time, Title, and Speaker Description

8:00 AM–8:05 AM Introduction, Olga Pulido, MD, MSc, A Board Path, FIATP

8:05 AM–8:55 AM Developmental Neurotoxicity Studies-Neuropathology Procedures and Pitfalls Robert H. Garman, DVM, DACVP, Charles River Laboratories Pathology Associates, Murrysville, PA

This session provides an overview of procedures followed in the conduct of the neuropathology component of DNT studies in rodents. Topics to be discussed include recommended stains, procedures for obtaining homologous sections, brain regions to be measured, advantages and disadvantages of evaluating brains from young-aged rodents (e.g. PND 12 vs. PND 22), and guidelines for interpreting the biologic significance of morphometry data.

8:55 AM–9:45 AM Developmental Neuropathology of Environmental Agents: The Issue of Silent Neurotoxicity, Michael Aschner, PhD, Vanderbilt University Medical Center, Nashville, TN

The central nervous system is the most vulnerable of all body systems to developmental injury. This lecture will focus on developmental processes by which the nervous system is formed and how those processes are known or suspected to be injured by toxic agents within the context of environmental exposures.

9:45 AM–10:15 AM Break

10:15 AM–11:05 AM Drug-Induced Developmental Neuroapoptosis, John W. Olney, MD, Washington University School of Medicine, St. Louis, MO

Recent evidence documents that exposure of the immature brain to various classes of drugs (including general anesthetics, anticonvulsants and several drugs of abuse) during the period of synaptogenesis can trigger wisespread neuroapoptosis in the developing brain. Methods for studying this newly discovered form of toxicologic pathology will be described.

11:05 AM–11:55 AM Overcoming the Challenges Faced by the General Pathologist Conducting Developmental Neuropathology Studies for Toxicology Assessments Olga Pulido, MD, MSc, A Board Path, FIATP

Children health and the developmental impact of pre- and post-natal toxic exposures to environmental contaminants are key concerns on "Food Chemical Safety and Environmental Toxicology." Neuropathology is a pivotal component of developmental toxicology. Our experience conducting neuropathology assessments for DNT rat studies, relevant to human exposures to chemical contaminants, will provide the basis for discussion.