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Program - Society of Toxicology

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<strong>Society</strong> <strong>of</strong> <strong>Toxicology</strong> 2011<br />

Continuing Education (Continued)<br />

• Evaluating Epigenetic Changes Using Bisulfite Deep Sequencing,<br />

Russell S. Thomas, The Hamner Institutes for Health Sciences,<br />

Research Triangle Park, NC<br />

• Population-Based DNA Methylation Pr<strong>of</strong>iling in Exposure-Related<br />

Disease, Carmen Marsit, Brown University, Providence, RI<br />

Sunday Afternoon, March 6<br />

1:15 PM to 5:00 PM<br />

First and Second Level (See signage at CE Booths for room<br />

locations)<br />

Toxicity Testing: State <strong>of</strong> Science and Strategies to<br />

Improve Public Health<br />

Quantitative In Vitro to In Vivo Extrapolation: The Essential<br />

Element <strong>of</strong> In Vitro Assay-Based Risk Assessment<br />

PM13<br />

CE Basic<br />

Chairperson(s): Harvey J. Clewell, III, The Hamner Institutes for Health<br />

Sciences, Research Triangle Park, NC, and Bastiaan Johan Blaauboer,<br />

Utrecht University, Utrecht, Netherlands.<br />

Sponsor:<br />

Risk Assessment Specialty Section<br />

Endorsed by:<br />

Biological Modeling Specialty Section<br />

In Vitro and Alternative Methods Specialty Section<br />

Nanotoxicology Specialty Section<br />

There is increasing recognition <strong>of</strong> the need to use efficient approaches to<br />

assess the risk assessment <strong>of</strong> high numbers <strong>of</strong> chemicals in a short time.<br />

The reliance on approaches consisting <strong>of</strong> animal experimentation has its<br />

drawbacks in terms <strong>of</strong> ethical, economical, and—not least—scientific<br />

limitations in assessing risks in a high-throughput mode. The quantitative<br />

interpretation <strong>of</strong> toxic effects <strong>of</strong> compounds in in vitro studies, using<br />

in silico approaches such as systems biological descriptions <strong>of</strong> toxicity<br />

pathways and physiologically based pharmacokinetic modeling (PBPK),<br />

are a necessary component <strong>of</strong> the National Academy <strong>of</strong> Sciences vision<br />

on toxicity testing in the 21st Century. The limited studies performed with<br />

this approach to date have shown that good predictions for the risk <strong>of</strong> the<br />

use <strong>of</strong> chemicals can be made. However, a number <strong>of</strong> limitations have<br />

also become clear and more standardization <strong>of</strong> methods is needed before<br />

implementation <strong>of</strong> quantitative in vitro-in vivo extrapolations (QIVIVE) in<br />

risk assessments can be achieved.<br />

In this course, the following elements <strong>of</strong> the approach for assessing risks<br />

on the basis <strong>of</strong> in vitro toxicity data will be discussed:<br />

1. How can we improve the applicability <strong>of</strong> in vitro methods by determining<br />

the real concentrations that come into contact with the cells<br />

in vitro, both for chemical compounds and for particles?<br />

2. How can we effectively and efficiently integrate the metabolism <strong>of</strong><br />

compounds, for clearance as well as for bioactivation?<br />

3. How can we provide a flexible and yet robust scheme for integrating<br />

the different elements in a high-throughput environment?<br />

• The Use <strong>of</strong> In Vitro Metabolism Data and Biokinetic Modeling to<br />

Conduct QIVIVE for Chemicals, Bastiaan Johan Blaauboer, Utrecht<br />

University, Utrecht, Netherlands<br />

• Characterizing Free Test Chemical Concentration during In<br />

Vitro Toxicity Assays, Nynke Kramer, Utrecht University, Utrecht,<br />

Netherlands<br />

• Particokinetic Modeling to Support QIVIVE for Particle Toxicity<br />

Assays, Justin G. Teeguarden, Pacific Northwest National Laboratory,<br />

Richland, WA<br />

• QIVIVE in a High-Throughput Environment, Harvey J. Clewell,<br />

III, The Hamner Institutes for Health Sciences, Research Triangle<br />

Park, NC<br />

Sunday Afternoon, March 6<br />

1:15 PM to 5:00 PM<br />

First and Second Level (See signage at CE Booths for room<br />

locations)<br />

Novel Approaches to Preclinical Safety Assessment:<br />

Bridging the Gap between Discovery and the Clinic through<br />

Translational <strong>Toxicology</strong><br />

Stem Cell Utility in <strong>Toxicology</strong> Screening<br />

PM14<br />

CE Basic<br />

Chairperson(s): Manu M. Sebastian, Columbia University, New York, NY,<br />

and Zaher A. Radi, Pfizer Global Research and Development, Cambridge,<br />

MA.<br />

Sponsors:<br />

<strong>Society</strong> for Toxicologic Pathology<br />

Toxicologic and Exploratory Pathology Specialty Section<br />

The development <strong>of</strong> toxicological screening tools for evaluating toxicity<br />

<strong>of</strong> new drug candidates has been a major focus in the pharmaceutical<br />

industry. Human embryonic stem (hESC) cells and induced pluripotent<br />

stem (iPS) cells and their lineage cells can be used as tools to predict<br />

developmental and other toxicities <strong>of</strong> drug candidates since several <strong>of</strong><br />

the human biochemical pathways are active in these cells. In addition,<br />

stem cells can also be used to help in the mechanistic understanding <strong>of</strong><br />

how a specific class <strong>of</strong> compounds leads to toxicity. Participation in this<br />

course will provide a basic overview <strong>of</strong> the utility <strong>of</strong> stem cells in drug<br />

discovery and update toxicologists on a variety <strong>of</strong> stem cells applications<br />

as screening tool for evaluating toxicity in multiple organ systems,<br />

thereby giving toxicologists a better understanding <strong>of</strong> the potential practical<br />

application <strong>of</strong> these in vitro methods for safety and risk assessment.<br />

• Introduction: Stem Cells As Tools for <strong>Toxicology</strong> Screening, Manu<br />

M. Sebastian, Columbia University, New York, NY<br />

• Metabolomics <strong>of</strong> Human Embryonic Stem Cells and Predictive<br />

Biomarkers <strong>of</strong> Developmental Toxicity, Gabriela Cezar, University<br />

<strong>of</strong> Wisconsin, Madison, WI<br />

• Stem Cells and Mice with Humanized Livers: New Tools for Drug<br />

Metabolism and <strong>Toxicology</strong>, Stephen Strom, University <strong>of</strong> Pittsburgh<br />

Medical School, Pittsburgh, PA<br />

• Using Embryonic Stem Cell Models to Pr<strong>of</strong>ile Potential<br />

Developmental Toxicants, E. Sidney Hunter III, U.S. EPA, Research<br />

Triangle Park, NC<br />

• Stem Cells in Preclinical Drug Development, Hirdesh Uppal,<br />

Genentech, Inc., South San Francisco, CA<br />

• Concluding Remarks, Zaher A. Radi, Pfizer Global Research and<br />

Development, Cambridge, MA<br />

CE<br />

up-to-date information at www.toxicology.org<br />

95

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