51st Annual Meeting & ToxExpo - Society of Toxicology

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Society of Toxicology 2012 Scientific Workshops The Thematic Track information can be found on pages 8–9. • Enzymatic Functions Defined by Tracking Redox Reactions: The Example of Manganese Superoxide Dismutase. Marcelo Bonini, University of Illinois at Chicago, Chicago, IL. • Intra- and Intercellular Signaling Pathways As Modulators of Free Radical Toxicity. Lars-Oliver Klotz, University of Alberta, Edmonton, Alberta, Canada. • Free Radicals and Oxidized Macromolecules: Roles in Biomarker Toxicology. Maria Kadiiska, NIEHS/NIH, Research Triangle Park, NC. • Distinguishing Free Radical Metabolites of Aromatic Amine Drugs Based on Reactivity and Their Potential In Vivo Toxicity. Arno Siraki, University of Alberta, Edmonton, Alberta, Canada. Clinical Toxicology from Bedside to the Bench and Back Chelation Therapy: A Focus on the Risks and Benefits Wednesday, March 14, 9:00 AM to 11:45 AM Chairperson(s): Carl Herbrandson, Minnesota Department of Health, Saint Paul, MN, and Richard Wang, Centers for Disease Control and Prevention, Atlanta, GA. Sponsor: Occupational and Public Health Specialty Section Endorsed by: Clinical and Translational Toxicology Specialty Section Metals Specialty Section Chelation is a very important therapy to lessen the occurrence of health consequences from the exposure to high levels of metals including selected radionuclides. However, the efficacy of treatment long after exposure has not been consistently demonstrated. Chelation in cases where exposures are limited can compromise health. Furthermore, chelation has been used in attempts to treat diseases for which it has not been proven effective (e.g., arteriosclerosis and autism). On the surface, the idea of removing toxic metals from the body is appealing, but serious health consequences can occur when chelation is improperly used. Consideration of the perspectives of medical and public health practitioners on chelation practices are important. • Chelation Therapy at Different Stages of Life. Deborah Cory- Slechta, University of Rochester Medical Center, Rochester, NY. • Chelation Therapy: A Cautionary Tale. Mary Jean Brown, Centers for Disease Control and Prevention, Atlanta, GA. • Experimental Evidence of Efficacy and Harm: The Good and Bad of Chelation Therapy. Donald Smith, University of California, Santa Cruz, CA. • Chelation Controversy: What Does This Laboratory Test Mean? Charles McKay, University of Connecticut School of Medicine, Hartford, CT. • Chelation for Heavy Metal Intoxication: A Medical Toxicology Perspective. Michael Kosnett, University of Colorado School of Medicine, Denver, CO. Cooperative Epidemiology and Toxicology Research: HEI’s National Particle Component Toxicity (NPACT) Initiative Wednesday, March 14, 9:00 AM to 11:45 AM Chairperson(s): Matthew J. Campen, University of New Mexico, Albuquerque, NM, and Geoffrey Sunshine, Health Effects Institute, Boston, MA. Sponsor: Cardiovascular Toxicology Specialty Section Endorsed by: Disease Prevention Task Force Inhalation and Respiratory Specialty Section Occupational and Public Health Specialty Section In 2006, the Health Effects Institute (HEI) funded two major studies to address the comparative toxicity of components of particulate matter (PM) at multiple places across the United States where PM components and the sources of PM would differ. The goal of the program was to integrate toxicological and epidemiological approaches to address this issue. Both teams, one led by Sverre Vedal at the University of Washington, the other by Mort Lippmann at New York University (NYU), investigated the effects of PM components on cardiovascular endpoints in the same strain of mouse, ApoE knockout, but took contrasting approaches. In research conducted at Lovelace Respiratory Research Institute, Dr. Vedal’s team exposed the mice to well-characterized, lab-generated pollutant atmospheres that included vehicular—diesel + gasoline engine emissions—resuspended road dust, and secondary nitrates and sulfate particles. Dr. Lippmann’s team exposed the mice to particles concentrated from ambient air at four sites across the US. The NYU team also collected PM samples of different size ranges—ultrafine, fine, and coarse—at these sites to evaluate cardiovascular effects in another strain of mice. The epidemiological analyses in both studies used well-established cohorts with participants throughout the US and with some overlap between the locations studied by both groups. Dr. Vedal’s team focused on evaluating associations between long-term exposure to PM components with cardiovascular endpoints in participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and Women’s Health Initiative (WHI) studies. Dr. Lippmann’s team evaluated associations in multiple cities between PM components and daily mortality and hospital admissions endpoints, as well as between exposures to components and annual mortality in the American Cancer Society Thematic Session 94 SOT’s 51 st Annual Meeting
51 st Annual Meeting and ToxExpo The Thematic Track information can be found on pages 8–9. Workshops Scientific (ACS) cohort. These integrated studies provide important lessons on how to design and execute population and laboratory-based research in a cooperative manner. • The University of Washington (UW)—Lovelace Respiratory Research Institute (LRRI) NPACT Initiative on the Cardiovascular Health Effects of PM2.5 Components. Sverre Vedal, University of Washington, Seattle, WA. • Cardiovascular Toxicology of Simulated Complex Air Pollution Atmospheres. Jacob D. McDonald, Lovelace Respiratory Research Institute, Albuquerque, NM. • Overview of the NYU NPACT Initiative on the Health Effects of PM Components. Morton Lippmann, New York University, Tuxedo Park, NY. • Alterations of Cardiac Function and Plaque Progression in ApoE−/−Mice by Subchronic Inhalation Exposure of Concentrated Ambient PM2.5: The Roles of PM Components and Source Categories. Lung Chi Chen, New York University, Tuxedo Park, NY. • In Vitro and In Vivo Effects of PM: Influence of Size, City, and Season. Terry Gordon, New York University, Tuxedo Park, NY. Clinical Toxicology from Bedside to the Bench and Back Progress in Developing New Biomarkers of Drug- Induced Liver Injury (DILI): What You Don’t Know Can Hurt You Wednesday, March 14, 9:00 AM to 11:45 AM Chairperson(s): Douglas A. Keller, sanofi-aventis US, Malvern, PA, and Ina Schuppe-Koistinen, AstraZeneca, Södertälje, Sweden. Sponsor: Drug Discovery Toxicology Specialty Section Endorsed by: Clinical and Translational Toxicology Specialty Section Regulatory and Safety Evaluation Specialty Section Toxicologic and Exploratory Pathology Specialty Section Current biomarkers of drug-induced liver injury (DILI) are able to identify damage once it has occurred and when it becomes severe. Serum ALT and bilirubin are the accepted standards for hepatocellular injury and impaired liver function, respectively. The use of combined ALT and bilirubin levels (Hy’s Law) is considered a useful hallmark of whether an individual drug may cause severe DILI, which results in a 10–50% chance of transplantation or mortality. However, many patients who exhibit combined drug-induced ALT and bilirubin elevations do not develop severe DILI but rather adapt; therefore these biomarkers do not reliably predict risk of severe liver injury in man. Also, during the preclinical drug development phase, ALT can increase in the absence of injury and this can result in a program delay or termination. More specific markers that distinguish true injury from these false signals would improve liver injury signal detection and provide novel therapies to patients faster. The C-Path Preclinical Safety Testing Consortium and the IMI SAFE-T program are in the process of identifying and qualifying novel biomarkers of liver injury and function. Other liver biomarker discovery and qualification efforts are under way in academic, industrial, and government laboratories, such as the National Center for Toxicological Research. The greatest need is to find biomarkers for adaptation to liver injury, and to identify patients who will progress to DILI before the injury is severe and resolve false ALT signals. Our panel of experts will provide information and foster discussion on the major needs for DILI biomarkers, and highlight major areas of research under way on DILI biomarker discovery and qualification efforts. • Qualification of Preclinical Biomarkers of DILI: Current Gaps, Research Efforts and Future Directions. Wendy Bailey, Merck & Co. Inc., West Point, PA. • Qualification of Clinical Biomarkers of DILI: Current Gaps, Research Efforts, and Future Directions. Michael Merz, Novartis, Basel, Switzerland. • Multiple ‘Omics Approach for Assessing Classical and Idiosyncratic Hepatotoxicants in Preclinical Species. William Salminen, US FDA, Jefferson, AR. • Biomarkers of BSEP Inhibition Relating to DILI. Gerry Kenna, AstraZeneca, Macclesfield, United Kingdom. • New Predictive Biomarker Profiles for Human DILI. Ina Schuppe- Koistinen, AstraZeneca, Södertälje, Sweden. Regulatory Science: Bridging the Gap between Discovery and Product Availability Advancing Food Safety in a Global Marketplace Wednesday, March 14, 1:30 PM to 4:15 PM Chairperson(s): Nicola Stagg, Dow AgroSciences LLC, Indianapolis, IN, and Michael Bolger, US FDA, College Park, MD. Sponsor: Food Safety Specialty Section Endorsed by: Global Strategy Task Force Mixtures Specialty Section Regulatory and Safety Evaluation Specialty Section Risk Assessment Specialty Section Advancements in packaging technology, such as those that extend food shelf-life, agricultural products including pesticides and genetically modified crops, and a more integrated and global marketplace up-to-date information at www.toxicology.org 95 Thematic Session
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Scientific Posters SNACK BAR 016 11
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