Program - Society of Toxicology

44 th Annual Meeting
and ToxExpo
Continuing Education
IMMUNOLOGY FOR TOXICOLOGISTS
AM 05
BASIC
Chairperson(s): Ian Kimber, Syngenta Central Toxicology Laboratory,
Macclesfield,Cheshire, United Kingdom and Dori R. Germolec, National
Institute for Environmental Health Sciences, Research Triangle Park, NC.
Endorsed by:
Immunotoxicology SS*
Risk Assessment SS
The adaptive immune system that is found in mammals comprises a dedicated
interacting system of tissues, cells and molecules that work in concert to provide
specific immune responses and host resistance to pathogenic microorganisms
and transformed cells. Specific immunity is supplemented by, and works in
harmony with, the phylogenetically more ancient innate immune system.
Immunotoxicology describes the study of adverse health effects that may result
from the interaction of xenobiotics with one or more components of the immune
system. Such health effects may take a variety of forms. These include frank
immunotoxicity where there is functional impairment of the immune system.
The concern here is that compromised immune function may translate into an
increased susceptibility to infectious and/or malignant disease. A second potential
consequence of the interaction of chemicals or proteins with the immune
system is allergy; defined as the adverse health effects that may arise from the
stimulation of a specific immune response. Allergic disease may take a variety
of forms, those of greatest significance for toxicologists being skin sensitization
and allergic contact dermatitis, allergic sensitization of the respiratory tract,
food allergy and idiosynctratic allergic drug reactions. Finally, xenobiotics have
been implicated in the induction or exacerbation of autoimmune reactions and
autoimmune disease. This course will provide a grounding in fundamental and
clinical aspects of immunology, and will describe the basic elements immunotoxicity,
allergy and autoimmunity. The objective is deliver an accessible guide
to the immune system and immunotoxicology for general toxicologists.
• An Introduction to Immunology: Fundamental and Clinical Aspects,
Ian Kimber, Syngenta Central Toxicology Laboratory, Macclesfield,
Cheshire, United Kingdom.
• Elementary Immunotoxicology, Robert House, DynPort Vaccine
Company, Frederick, MD.
• Allergy and Allergic Disease, MaryJane Selgrade, U.S. EPA, Research
Triangle Park, NC.
• Autoimmunity and Autoimmune Disease, Dori R. Germolec, National
Institute for Environmental Health Sciences, Research Triangle Park, NC.
EVALUATION OF CARDIAC DRUG TOXICITY IN
PHARMACEUTICAL DISCOVERY AND DEVELOPMENT
AM 06 (REPEATS AS PM 12)
BASIC
Chairperson(s): Brian Short, Allergan, Irvine, CA and Y. J. Kang, University
of Louisville, Louisville, KY.
Endorsed by:
Comparative and Veterinary SS
HESI Biomarkers Technical Committee
Mechanisms SS
Regulatory and Safety Evaluation SS
Student Advisory Committee
Toxicologic and Exploratory Pathology SS
The heart is an important potential target organ to evaluate in nonclinical and
clinical studies during drug development as well as a therapeutic site of action
for many cardiovascular diseases. There are examples in almost every therapeutic
class of drugs that produced unanticipated cardiotoxicity leading to
market withdrawal or cessation of development. Toxicologists are an integral
part of an interdisciplinary group, including physiologists, pharmacologists,
pathologists, clinicians, and regulators, which assess cardiac safety. As such,
toxicologists play a critical role in the screening of pharmaceutical agents for
cardiotoxicity as well as in establishing an adequate margin of safety and
working basis for monitoring therapeutic endpoints and clinical safety of trial
participants. The goal of this continuing education course is to illustrate the integration
of physiology, pharmacology, toxicology, and pathology of the heart
addressing both recent scientific advances and practical knowledge in pharmaceutical
company setting. This course will cover in vitro and in vivo models of
drug-induced cardiac injury and recent advances in biomarkers of cardiac injury
to improve the strategy for detection and nonclinical and clinical monitoring of
drug-related cardiotoxicity. This CE course will provide current understanding
of the physiology of the heart with a focus on normal and drug-induced disturbances
in cardiac electrophysiology and cardiac function, as well as testing
strategies for assessing potential cardioactive drug candidates prior to entry into
clinical trials. It will also cover basic and advanced knowledge of pathology of
the heart, including a review of cardiac pathological evaluation, and provide
case examples of the integration of physiological and pathological parameters
and risk assessment to humans. Biochemical, cellular and molecular mechanisms
of cardiac toxicity, including recent work in experimental animal studies
and novel approaches directed toward understanding mechanisms of druginduced
cardiac injury, cardiomyopathy and cardiac hypertrophy will be
presented. Finally, biomarkers of drug-induced cardiac injury will be discussed.
This will include a review of the findings of the Expert Working Group on
Biomarkers of Drug-Induced Cardiac Toxicity, an in-depth look at serum
troponins, and related work currently in progress under the ILSI-sponsored
Subcommittee on the Development and Application of Biomarkers of Toxicity.
• Physiological Basis for Cardiac Drug Toxicity and Evaluation, Robyn L.
Phelps, Allergan, Irvine, CA.
• Integrating Cardiac Pathology into Drug Discovery and Development,
Calvert Louden, AstraZeneca Pharmaceuticals, Wilmington, DE.
• Mechanisms of Drug-Induced Cardiotoxicity, Y. J. Kang, University of
Louisville, Louisville, KY.
• Biomarkers of Drug-Induced Cardiac Toxicity, Malcolm J. York,
GlaxoSmithKline, Ware, Hertfordshire, United Kingdom.
CE
up-to-date information at www.toxicology.org 41