Program - Society of Toxicology

Society of Toxicology 2011
Continuing Education (Continued)
Today toxicologists must select appropriate model organisms, manage
abundant high-throughput data, understand legacy data, and develop
pathway-based understanding of environmental factors influencing
biological systems. Mastery of these concepts improves toxicity prediction
while providing insights into environmentally influenced diseases
and phenotypes. A clear understanding of the diverse on-line data resource
aims and limitations equips the researcher with the best combination of
resources to effectively address their questions.
• Reactome Knowledgebase, Marc E. Gillespie, St. Johns University,
Jamaica, NY
• Comparative Toxicogenomics Database (CTD), Carolyn J.
Mattingly, Mount Desert Island Biological Laboratory, Salisbury Cove,
ME
• PharmGKB, Teri E. Klein and Li Gong, Stanford University Medical
Center, Stanford, CA
• Mouse Genome Informatics Database, Susan M. Bello, Jackson
Laboratory, Bar Harbor, ME
Sunday Morning, March 6
8:15 AM to 12:00 NOON
First and Second Level (See signage at CE Booths for room
locations)
Epigenetic Mechanisms
Epigenetics in Toxicology: Introduction, Mechanistic
Understanding, and Applications in Safety Assessment
AM05
CE Basic
Chairperson(s): Mayurranjan S. Mitra, Washington University School of
Medicine, St. Louis, MO, and Thomas Sussan, Johns Hopkins University
Bloomberg School of Public Health, Baltimore, MD.
Sponsor:
Molecular Biology Specialty Section
Endorsed by:
Carcinogenesis Specialty Section
Cardiovascular Toxicology Specialty Section
Mechanisms Specialty Section
Epigenetics refers to molecular mechanisms that cause heritable changes
in gene expression without altering the DNA sequence. The most
widely studied epigenetic mechanisms encompass DNA methylation,
histone modifications, and gene regulation by non-coding RNAs, such
as microRNAs. Typically, these mechanisms are required for normal
cellular development and differentiation; however, perturbations in
them can lead to diseases, notably cancer. Increasing evidence suggest
that environmental factors such as diet, stress, and exposure to radiation
and xenobiotics can induce heritable changes in the epigenetic status,
potentially affecting the health of the present and future generations.
Importantly, the long-term and life-threatening consequences of environment/chemical-induced
changes in epigenetics, makes this field a critical
area for future exploration by toxicologists. The course will begin by
introducing the fundamental concepts of epigenetics and reviewing the
various underlying mechanisms. Methods to assess epigenetic changes
will be discussed, followed by a discussion of the role of DNA cytosine
methylation in the regulation of carcinogen-inducible CYP450 genes.
Mechanistic understanding of the role of microRNAs in the regulation
of cellular toxicity and the influence of environment on epigenetics that
cause developmental effects will also be presented. Finally, the future of
epigenetics in toxicology and its potential applications for safety assessment
will be discussed. Students as well as toxicologists working in
academia, federal and pharmaceutical industries, and researchers interested
in mechanistic toxicology will benefit from taking this course.
• Introduction, Mayurranjan S. Mitra, Washington University School of
Medicine, St. Louis, MO
• Introduction and Overview of Epigenetics, James G. Herman, The
Johns Hopkins School of Medicine, Baltimore, MD
• Role of Epigenetics in the Regulation of Carcinogen-Metabolizing
Enzymes, Oliver Hankinson, University of California Los Angeles,
Los Angeles, CA
• Retroelements and MicroRNAs in the Epigenetic Regulation of
Cellular Differentiation, Proliferation, and Toxicity, Kenneth S.
Ramos, University of Louisville, Louisville, KY
• Epigenetic Gene Regulation: Linking Early Developmental
Environment to Adult Disease, Dana Dolinoy, University of
Michigan, Ann Arbor, MI
• What We Need to Know Prior to Incorporating an Epigenetic
Evaluation into Safety Assessments, Jay I. Goodman, Michigan State
University, East Lansing, MI
Sunday Morning, March 6
8:15 AM to 12:00 NOON
First and Second Level (See signage at CE Booths for room
locations)
Integration of Toxicological and Epidemiological Evidence
to Understand Human Risk
Protecting Human Health: Use of Toxicological and
Epidemiological Data in Determining Safe Levels for Human
Exposure
AM06
CE Basic
Chairperson(s): Eileen P. Hayes, EP Hayes Toxicology Services LLC,
Longmont, CO, and Terry Gordon, New York University School of
Medicine, Tuxedo Park, NY.
Sponsor:
Occupational and Public Health Specialty Section
Toxicological and epidemiological data are the basis for risk assessment
processes used to determine acceptable levels of exposure. This is the
case for the general public who may be exposed to pollutants via ambient
air and/or drinking water, for workers who may be exposed to chemicals
in the workplace, and for patients who may have exposure to both active
pharmaceutical ingredients (API) and impurities that may be present in
the product. The goal of this course is to provide students with an understanding
of the regulatory background and the practical application of
both toxicological and epidemiological information in setting exposure
levels considered to be protective of public health. The objectives of this
course are 1) to describe the regulatory requirements that underlie development
of acceptable levels of exposure for either the general population
or select populations (workers, patients) via the media described above;
and 2) to describe the evaluation of toxicological and epidemiological
data in determining acceptable levels of exposure. Case studies of representative
compounds will illustrate the processes. The U.S. Environmental
Protection Agency (U.S. EPA) has well-defined processes for establishing
both National Ambient Air Quality Standards (NAAQS) under the Clean
Air Act and drinking water Maximum Contaminant Levels (MCLs) under
the Safe Drinking Water Act. The Occupational Health and Safety Administration
(OSHA) promulgates permissible exposure limits (PELs) for the
workplace. The American Conference of Government Industrial Hygienists
(ACGIH), a nonprofit, non-governmental organization publishes
Threshold Limit Values (TLVs) that are used globally by many public and
private-sector employers to protect the health of their employees. Additionally,
many employers have established programs to derive acceptable
levels of workplace exposure for compounds not specifically regulated
by government agencies. Acceptable identification, reporting, and safety
thresholds for impurities in drug products are governed under guidance
CE
up-to-date information at www.toxicology.org
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