Program - Society of Toxicology

50 th Anniversary Annual Meeting and ToxExpo
Program Description (Continued)
Thursday
Abstract # Abstract #
system combined with complex genetic susceptibilities are considered
crucial. In case of systemic hypersensitivity to drugs, i.e. drug allergy,
immune responses to non-self drug-modified antigens may be intermingled
with responses to self-antigens. Immune responses against self-antigens are
hallmark of autoimmune diseases; however, a low level of self-reactivity
is present in healthy individuals and is considered important for immunological
homeostasis. The distinction between allergic and autoimmune
responses induced by chemicals may be a very fine line, reflecting the
relative antigenicity of the novel- and self-proteins involved. Importantly,
development of allergic or autoimmune clinical phenomena, including
nature and type, may depend on individual susceptibilities (i.e. genetic
polymorphisms), or coinciding environmental triggers (e.g. microbial
interactions). The complex etiology and lack of mechanistic knowledge is a
challenge for risk assessment as at present no single model is available that
may predict chemical-induced autoimmunity and systemic allergy. Hazard
and risk assessment of these phenomena will likely require a more holistic
translational approach. Exploring the similarities and differences between
chemical-induced autoimmunity and systemic allergy is an important step
to establish a methodological framework to identify chemicals with the
potential to induce these immune system toxicities. Therefore we will focus
on the complex relationship between chemical-induced autoimmunity and
systemic allergy and the identification of methods, mechanistic commonalities
and strategies that would be useful for risk assessment.
#2682 9:00 AUTOIMMUNITY VERSUS SYSTEMIC
HYPERSENSITIVITY: COMMONALITIES
USEFUL FOR IMMUNOTOXICITY
TESTING. ​R. Pieters 1 and D. Germolec 2 . 1 IRAS,
Utrecht University, Utrecht, Netherlands and
2
Toxicology Branch, National Toxicology Program,
NIEHS, Research Triangle Park, NC.
9:00 INTRODUCTION. ​Raymond Pieters
#2683 9:05 AUTOIMMUNITY AND AUTOIMMUNE
DISEASE. ​N. Rose. Johns Hopkins University,
Baltimore, MD. Sponsor: R. Pieters.
#2684 9:37 AUTOIMMUNITY VS. ALLERGY: A
CRITICAL NEED IN SAFETY TESTING. ​R.
R. Dietert. Microbiology and Immunology, Cornell
University, Ithaca, NY.
#2685 10:09 MECHANISMS UNDERLYING
HEXACHLOROBENZENE-INDUCED
IMMUNOTOXICITY: COMPARISON WITH
IDIOSYNCRATIC DRUG REACTIONS. ​J.
Ezendam 1 and R. Pieters 2 . 1 National Institute for
Public Health and the Environment, Bilthoven,
Netherlands and 2 Institute for Risk Assessment
Sciences, Utrecht, Netherlands.
#2686 10:41 AUTOIMMUNITY IN IDIOSYNCRATIC
DRUG REACTIONS. ​J. Uetrecht. University of
Toronto, Toronto, ON, Canada.
#2687 11:13 TRICHLOROETHYLENE-INDUCED
AUTOIMMUNITY; DEPENDENCE
ON METABOLISM AND GENETIC
SUSCEPTIBILITY. ​K. Gilbert 1,2 . 1 Microbiology
and Immunology, Arkansas Children’s Hospital
Research Institute, Little Rock, AR and 2 University
of Arkansas for Medical Sciences, Little Rock, AR.
Thursday Morning, March 10
9:00 AM to 11:45 AM
Room 145
Integration of Toxicological and Epidemiological Evidence
to Understand Human Risk
Workshop Session: PBPK Model Use in Risk Assessment:
Why Being Published Is Not Enough
Chairperson(s): Paul Schlosser, U.S. EPA, Research Triangle Park, NC,
and Eva McLanahan, U.S. EPA, Research Triangle Park, NC.
Sponsor:
Biological Modeling Specialty Section
Endorsed by:
Mixtures Specialty Section
Risk Assessment Specialty Section
While publication of a physiologically-based pharmacokinetic (PBPK)
model in a peer-review journal is a mark of good science, evaluation of
published models and the supporting computer code can identify issues
or shortcomings that can be barriers to their use in risk assessment. The
quality of human health risk assessments must be sustained, including use
of appropriate PBPK models and other quantitative tools for dose-response
evaluation and interspecies extrapolation. A published model can be modified
to address assessment-specific issues, and having clear criteria can
reduce the number of review and revision iterations and hence the time
needed to bring a model to application. As probabilistic (population) PBPK
models are being implemented, parameter choices to fully characterize
population variability become critical. Thus a thorough but efficient process
for the review and implementation of PBPK models is necessary. While
a typical process and set of criteria were created specifically for PBPK
models, the principles may be applied to other types of computational
models (e.g., dose-response) as they are developed. We have convened a
panel of experts in biologically-based modeling and relevant quantitative
methods to not only describe and discuss model evaluation and criteria, but
also issues and choices that arise in model application and assuring reasonable
certainty, as well as computational tools now available for improving
model quality. Addressing issues identified during the review and application
of PBPK models for human health risk assessments provides an
opportunity to improve the science of PBPK modeling as a whole. Attendees
will obtain knowledge to improve their models for use in risk assessment,
evaluate when and how a model can be applied with a fair degree of
certainty, and better understand the constraints and requirements that may
otherwise limit use of a PBPK model. Finally, we will conclude with a panel
discussion and dialogue on the criteria, processes, methods, and choices that
can best assure the use of quality PBPK models in future risk assessments.
#2688 9:00 PBPK MODEL USE IN RISK ASSESSMENT:
WHY BEING PUBLISHED IS NOT ENOUGH. ​
E. D. McLanahan. ORD/NCEA, U.S. EPA, Research
Triangle Park, NC.
9:00 INTRODUCTION. ​Eva McLanahan
#2689 9:05 A PROCESS FOR THE EVALUATION AND
IMPLEMENTATION OF PBPK MODELS IN
HUMAN HEALTH RISK ASSESSMENTS. ​H.
A. El-Masri. NHEERL, U.S. EPA, Research Triangle
Park, NC.
#2690 9:37 APPLICATION-SPECIFIC
CONSIDERATIONS IN EVALUATION
OF PHYSIOLOGICALLY-BASED
PHARMACOKINETIC (PBPK) MODELS. ​L.
M. Sweeney. TERA, Cincinnati, OH.
356
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