HERL Symposium Announcement

nobody at herlvx.rtpnc.epa.gov nobody at herlvx.rtpnc.epa.gov
Thu May 27 13:38:50 EST 1993

The Health Effects Research Laboratory (HERL) of the U. S.
Environmental Protection Agency is Pleased to Announce a

          Biological Mechanisms and Quantitative Risk Assessment:
             From Experimental Design to Risk Characterization

Regulatory agencies, including EPA, are committed to an
increasing reliance on quantitative risk assessment in support of
major regulatory decisions.  Accurate health-based risk
assessments require an understanding of mechanisms by which
chemicals affect living organisms.  In the past, however, much
information gathered under the umbrella of mechanistic toxicology
has been of little direct value in the risk assessment process. 
Mechanistic research has to be highly focused to address specific
issues in a quantitative form to be useful in these risk

The purpose of the Symposium is to provide an opportunity for
active dialog on the role of mechanistic biological research in
future risk assessment strategies.  Specific goals are to discuss
the following issues:

    Current use of mechanistic biological data in quantitative
     risk assessments

    The changing face of health effects risk assessments in
     response to increasingly sophisticated knowledge of the
     mechanisms of toxic effects and biological function

    Role of mathematical models of biological systems in
     integrating research activities, identifying data gaps,
     designing mechanistic studies, and reducing uncertainties in
     the risk assessment process



TUESDAY, November 2, 1993


This will consist of a short talk from Lawrence Reiter,
Health Effects Research Laboratory (HERL) Director
introducing the Seminar series as well as this
Symposium, and a short talk from a political figure with
interests in risk assessment for environmental

Session I:  Risk Assessment and Research: Setting the Stage

A historical perspective and overview of risk assessment
and its importance to government will be coupled with
a closer examination of pitfalls in current
methodologies.  Research opportunities will be explored
with a critical focus on the role and potential for
mechanistic research to improve the scientific basis for
risk assessment.  This session provides a foundation for
subsequent  discussion of research efforts and the
application of mechanistic  information to risk

John Vandenberg, HERL  and Bill Farland, EPA Office
of Health and Environmental Assessment (OHEA),

  Gil Omenn, University of Washington: Risk Assessment
     and the Federal Government: Is It Important? 
  John Graham, Harvard University: Beyond Default
     Assumptions in Risk Assessment
  Dan Krewski, Health and Welfare, Canada: The Future
     of Mechanistic Research in Risk Assessment:
     Where Are We Going and Can We Get There from

Session II:  Applying Mechanistic Research to Risk

The goal of this session is to describe how biological
research has contributed to improving risk  assessments
and how the clear articulation of a risk assessment
paradigm has focused biological research. Panel
discussions on each of  two major environmental
contaminants will focus on specific advances of our
understanding of the biological action of the agent that
led to improvements in the risk assessment.  This
session will illustrate some of the basics of
contemporary risk assessments, including LMS, PK, and
other mathematical modeling, dosimetry, response, and
extrapolation issues.

Linda Birnbaum, HERL and Dan Krewski, Health and
Welfare, Canada, chairs.

Methylene Chloride Panel
  Robert Maronpot, National Institutes of Environmental
     Health Sciences (NIEHS)
Harvey Clewell, Clement International
Lorenz Rhomberg, OHEA

Dioxin Panel
Mike DeVito, University of North Carolina (UNC)
Lorrene Kedderis, Sphinx Pharmaceutical
Mike Kahn, NIEHS

WEDNESDAY, November 3, 1993

Session III:  Biological Mechanisms and Their
Application to Cancer Risk Assessment

The incorporation of biological information into models
for risk assessment began with cancer risk assessment. 
Many biological processes that need to be understood
for developing realistic cancer models, however, are
common to other toxicologic endpoints.  This session
will present research into mechanisms of xenobiotic
toxicity  that are common to many biological processes,
and describe how this information may be incorporated
into cancer risk assessment models.

Marc Mass, HERL and Henry Pitot, University of
Wisconsin, chairs

  Henry Pitot, University of Wisconsin: Derivation of the
     Parameters of the Moolgavkar-Knudson Cancer
     Incidence Equation Using a Rat Liver
     Carcinogenesis Model.
  Sam Cohen, University of Nebraska: Cell Proliferation
     in the Bladder and Implications for the Construction
     of Cancer Risk Assessment Models.
  Suresh Moolgavkar, Fred Hutchinson Cancer Research
     Center: Contrasting Biologically-Based and Non-
     Biologically-Based Low-Dose Extrapolation Models
     and Their Impact on the Cancer Risk Assessment
     Process; Applications of the Moolgavkar-Knudson
  Curtis Travis, Oak Ridge National Laboratories: Cancer
     Risk Assessment Modeling in the 2-AAF
     Megamouse Study; the Impact of Cell Proliferation.

Session IV:  Biological Mechanisms and Their
Application to Non-Cancer Risk Assessment

Relative to recent events in carcinogen risk assessments,
little attention has been paid to incorporating
mechanistic data into risk assessments for non-
carcinogens.  This session will explore the similarities
and differences in mechanisms of cancer versus non-
cancer health effects at the level of  tissue response,
describe how biologically based models of metabolic
pathways and receptor interactions can be developed and
utilized for non-cancer effects, and explore the potential
contributions of mechanistic based models using
examples from developmental toxicity and neurotoxicity.

Robert Kavlock, HERL, and Carol Henry, California
EPA, chairs

  Rory Conolly, Chemical Industry Institute of
     Technology (CIIT): Cancer and Non-Cancer Risk
     Assessment: Not So Different if You Consider
  William Jusko, University of Buffalo: Receptor-
     Mediated Pharmacodynamics of Corticosteroids:
     Models for Risk Assessment
  Robert. C. Jackson, Agouron Pharmaceutical, Inc.:
     Toxicity Prediction from Metabolic Pathway
  Dana Shuey, UNC, and John Rogers, HERL: Biological
     Modelling of 5-Fluorouracil Developmental
  Jim Stratton, California EPA, and Stephanie Padilla,
     HERL: Regulatory and Research Issues Related to
     Cholinesterase Inhibition

THURSDAY, November 4, 1993

Session V:  Emerging Research Areas in Health
Effects Risk Assessment

Many current areas of research develop information that
should be incorporated into quantitative risk
assessments.  This session will sample some of these
research areas, with discussions of how this information
could be used in models for risk assessment.
Mel Andersen, HERL, and Bill Greenlee, Purdue
University, chairs

  John Groopman, Johns Hopkins University: Aflatoxin
     Exposures and Human Biomarkers of Exposure and
  Curtis Harris, National Cancer Institute: P53 Tumor
     Suppressor Gene: At the Crossroads of Molecular
     Carcinogenesis, Molecular Epidemiology, and
     Human Risk Assessment.
  Bill Greenlee, Purdue University: Integrating Molecular,
     Cellular and in vitro Tissue Responses to Dioxin in
     Health Risk Assessments


  Roger McClellan, CIIT: Risk Assessment and Biological
     Mechanisms: Lessons Learned, Future


An opportunity will be provided for attendees to present posters
on topics related to the theme of the Symposium.  Guidelines for
submissions of abstracts will be sent to those indicating their

For further information, please contact:

          HERL Symposium Coordinator
          Research and Evaluation Associates, Inc.
          100 Europa Drive, Suite 590
          Chapel Hill, North Carolina 27514


           H E R L
           Advancing Environmental Health


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