Program - Society of Toxicology

Society of Toxicology 2011
Program Description (Continued)
Abstract #
#1714 3:35 MACROPHAGE DIVERSITY PROMOTES
TUMOR PROGRESSION AND METASTASIS. ​
J. W. Pollard. Department of Developmental and
Molecular Biology, Albert Einstein College of
Medicine Yeshiva University, New York. Sponsor: D.
Laskin.
4:05 PANEL DISCUSSION/Q&A.
Tuesday Afternoon, March 8
1:30 PM to 4:15 PM
Room 147
Integration of Toxicological and Epidemiological Evidence
to Understand Human Risk
Symposium Session: When Is Exposure Not Exposure?
Defining the Dose-Response Region between “Effect” and
“Adverse Effect” Implications for Human Health Risk
Assessment
Chairperson(s): Caroline English, NSF International, Ann Arbor, MI, and
Edward Ohanian, U.S. EPA, Washington, D.C.
Sponsor:
Risk Assessment Specialty Section
Endorsed by:
Molecular Biology Specialty Section
‘Omics technologies demonstrate global changes in gene regulation and
expression following chemical exposure, causing toxicologists to revisit the
question, what is an adverse effect and what isn’t. Dose-dependent transitions
in genomic and related responses reflect the levels of exposure that
cause detectable perturbations to the biological system under study. We
will focus on two transitions, having both dose and temporal dimensions,
which are advanced as being pivotal to understanding mode of action and
prediction of toxicity. The first transition is from no-detectable-effect on the
biological system relative to unexposed controls, to the first-perceptibleeffect
at the global genome level; observed as up- and down-regulation
of genes that regulate adaptive responses. The second transition is from
the adaptive response region to the first adverse response or critical effect
region of the dose-response relationship. We will explore if and how ‘omic
phenomena elicited by chemical exposures translate into useful information
for risk assessors. Consideration of the adaptive capacity of the biological
system and severity of the effect might further inform our definition of
the term adverse and inform the magnitude of traditional uncertainty
factors used. Understanding dose-dependent transitions combined with
dosimetry models that characterize the exposure-tissue concentration relationship
might permit risk assessors to define exposures delimited by safe
and adverse boundaries. We will conclude by describing emerging advances
in high-throughput quantitative ‘omic technologies, and findings from
studies with endogenous and exogenous compounds and nanoparticulates, to
address how we move from the vast array of ‘omic data generated to practical
risk assessment applications.
#1715 1:30 WHEN IS EXPOSURE NOT EXPOSURE?
DEFINING THE DOSE-RESPONSE REGION
BETWEEN “EFFECT” AND “ADVERSE
EFFECT” IMPLICATIONS FOR HUMAN
HEALTH RISK ASSESSMENT. ​C. English. NSF
International, Ann Arbor, MI.
1:30 INTRODUCTION. ​Caroline English
#1716 1:39 USE OF THE HIERARCHICAL OXIDATIVE
STRESS PARADIGM FOR HAZARD AND
RISK ASSESSMENT IN RESPONSE TO
AMBIENT ULTRAFINE AND ENGINEERED
NANOPARTICLE TOXICITY. ​A. E. Nel.
Medicine, University of California Los Angeles, Los
Angeles, CA. Sponsor: A. Nel.
Abstract #
#1717 2:05 HUMAN EXPOSURE CONTEXT FOR
NANOPARTICLE TOXICITY ASSESSMENT
BY BIOLOGICAL PATHWAY BASED DOSE-
RESPONSE MODELING. ​J. G. Teeguarden 1 ,
M. N. Costa 2 , K. M. Waters 2 and J. E. McDermott 2 .
1
Biological Monitoring and Modeling, Pacific
Northwest National Laboratory, Richland, WA and
2
Computational Biology and Bioinformatics, Pacific
Northwest National Laboratory, Richland, WA.
#1718 2:31 TIME-DEPENDENT CHANGES IN THE
TRANSCRIPTOME: AN APPROACH FOR
IDENTIFYING TRANSCRIPTIONAL
PROFILES ASSOCIATED WITH THE ONSET
OF CHRONIC PHENOTYPIC CHANGES. ​
D. C. Wolf. NHEERL/ORD, U. S. EPA, Research
Triangle Park, NC.
#1719 2:57 FORMALDEHYDE: DOSE-DEPENDENT
TRANSITIONS FOR AN ENDOGENOUS
COMPOUND WITH HIGH DOSE
CARCINOGENICITY. ​M. E. Andersen.
Computational Biology, The Hamner Institutes for
Health Sciences, Research Triangle Park, NC.
#1720 3:23 ENVIRONMENTAL EPIGENOMICS AND
RISK ASSESSMENT: WHAT CONSTITUTES
AN ADVERSE EFFECT AND ISSUES OF
NONLINEARITY. ​D. C. Dolinoy. Environmental
Health Sciences, University of Michigan, Ann Arbor,
MI.
#1721 3:49 INTERPRETING DOSE-RESPONSE
INFORMATION ON INTERMEDIATE
STAGES OF CAUSAL CASCADES IN
TOXICITY MODE OF ACTION. ​L. R.
Rhomberg. Gradient, Cambridge, MA.
Tuesday Afternoon, March 8
1:30 PM to 4:15 PM
Room 150
Workshop Session: Nonclinical to Clinical Abuse Liability
Assessment of Drugs: Current Practices, Challenges, and
Impact of Recent Regulatory Guidance
Chairperson(s): Brian Gemzik, Bristol-Myers Squibb, Princeton, NJ, and
Carrie Markgraf, Merck, Lafayette, NJ.
Sponsor:
Regulatory and Safety Evaluation Specialty Section
Endorsed by:
Drug Discovery Toxicology Specialty Section
Neurotoxicology Specialty Section
An increased level of attention has been focused on the assessment of abuse
liability for drugs that affect the central nervous system as a consequence
of recent regulatory guidances from the EMEA, ICH, as part of M3(R2),
and U.S. FDA (draft). It is therefore critical to understand the current
issues facing the pharmaceutical research and regulatory communities in
the evaluation of new drug candidates for abuse and dependence potential.
Nonclinical and clinical evaluations each contribute to the assessment of
a drug for class scheduling, and to the information in the product label.
Animal models for the study of drugs with pharmacologic mechanisms
known to be associated with abuse are well characterized, and clinical trial
protocols enrolling experienced users of abused drugs have been widely
utilized in risk assessment. However, unique challenges are encountered
in both nonclinical and clinical discovery and development settings when
evaluating drugs with novel mechanisms of action. In recognition of the
need for a broad and integrated understanding in the toxicology community,
this symposium will blend current topics in this field of growing interest,
Tuesday
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