Annual Meeting Program - Society of Toxicology

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Society of Toxicology 2008 Program Description (Continued) Abstract # #2028 2:12 TARGETED DISRUPTION OF THE NUCLEAR FACTOR-E2-RELATED FACTOR-2 (NRF2) GENE PREVENTS FORMATION OF CHOLESTEROL GALLSTONES IN MICE. A. Slitt 1 , Q. Cheng 1 , H. Jiang 2 , S. Kulkarni 1 , J. Y. Chan 3 and D. Q. Wang 2 . 1 Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, 2 Department of Medicine, Harvard Medical School, Boston, MA and 3 Department of Pathology, University of California, Irvine, CA. Sponsor: J. Manautou. #2029 2:33 HEPATOCYTE-SPECIFIC DELETION OF KEAP1 ALTERS EXPRESSION OF HEPATIC DRUG METABOLIZING ENZYMES AND TRANSPORTERS. Q. Cheng 1 , L. M. Aleksunes 2 , J. E. Manautou 2 , N. J. Cherrington 3 , K. Taguchi 4 , M. Yamamoto 4 and A. L. Slitt 1 . 1 Biomedical and Pharmaceutical Sciences, Univesity of Rhode Island, Kingston, RI, 2 Pharmaceutical Sciences, Univerisity of Connecticut, Storrs, CT, 3 Pharmacology and Toxicology, Univerisity of Arizona, Tucson, AZ and 4 Graduate School of Comprehensive Human Sciences, Univerisity of Tsukuba, Tennoudai, Tsukuba, Japan. #2030 2:54 THE NRF2 ACTIVATOR OLTIPRAZ ALSO ACTIVATES THE CONSTITUTIVE ANDROSTANE RECEPTOR. M. D. Merrell 1 , J. P. Jackson 1 , L. M. Augustine 1 , C. D. Fisher 1 , A. L. Slitt 2 , J. M. Maher 3 , W. Huang 4 , D. D. Moore 4 , C. D. Klaassen 5 and N. J. Cherrington 1 . 1 Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, 2 Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, 3 TARA center, University of Tsukuba Tennoudai, Tsukuba-sh, Ibaraki, Japan, 4 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX and 5 Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS. #2031 3:15 ACETYLTRANSFERASE P300/CBP REGULATES NRF2-DEPENDENT ANTIOXIDANT RESPONSE THROUGH ACETYLATION-DEPENDENT AND INDEPENDENT MECHANISM. Z. Sun and D. D. Zhang. Department of pharmacology & toxicology, University of Arizona, Tucson, AZ. #2032 3:35 NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2 (NRF2) INHIBITS CYTOKINE PRODUCTION BY ACTIVATED MURINE T CELLS. C. E. Rockwell and C. D. Klaassen. Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS. #2033 3:55 IDENTIFICATION OF NRF2-DEPENDENT AIRWAY EPITHELIAL ADAPTIVE RESPONSE TO PROINFLAMMATORY OXIDANT-HYPOCHLOROUS ACID (HOCL) CHALLENGE BY TRANSCRIPTION PROFILING. L. Zhu 1 , J. Pi 1 , S. Wachi 2 , M. E. Andersen 1 , R. Wu 2 and Y. Chen 1 . 1 The Hamner Institutes, RTP, NC and 2 UC Davis, Davis, CA. Abstract # Wednesday Afternoon, March 19 1:30 PM to 4:15 PM Room 2A PLATFORM SESSION: SELECTIVE DOPAMINERGIC NEUROTOXICITY: GENETICS AND MECHANISMS Chairperson(s): Virgnia Moser, U.S. EPA, Research Triangle Park, NC and Lisa Opanashuk, University of Rochester, Rochester, NY. #2034 1:30 MUTATION OF THE PARKINSON’S GENE DJ-1 INCREASES THE INFLAMMATORY RESPONSE IN MOUSE ASTROCYTES. A. K. Ashley 1 , T. Katoh 2 , J. A. Moreno 1 , W. H. Hanneman 1,2 and M. E. Legare 1,2 . 1 Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO and 2 Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO. #2035 1:54 OXIDATIVE STRESS-INDUCED PHOSPHORYLATION OF PKD1 ACTIVATION LOOP IS REGULATED BY PROTEIN KINASE C-DELTA PROTEOLYTIC ACTIVATION IN CELL CULTURE MODELS OF DOPAMINERGIC DEGENERATION. A. Asaithambi, A. Kanthasamy, V. Anantharam and A. G. Kanthasamy. Biomedical Sciences, Iowa State University, Ames, IA. #2036 2:18 DEFINING “NEUROINFLAMMATION”: LESSONS FROM MPTP- AND METHAMPHETAMINE-INDUCED NEUROTOXICITY. J. P. O’Callaghan. CDC- NIOSH, Morgantown, WV. #2037 2:42 PROLYL HYDROXYLASE INHIBITION PROTECTS AGAINST MPP+ TOXICITY IN VITRO. D. Lee, R. Subramanian and J. K. Andersen. Buck Institute for Age Research, Novato, CA. #2038 3:06 NUCLEAR FACTOR KAPPA B MEDIATES SELECTIVE INDUCTION OF NEURONAL NITRIC OXIDE SYNTHASE IN ASTROCYTES DURING MILD INFLAMMATORY STIMULATION WITH 1-METHYL-4-PHENYL-1, 2, 3, 6-TETRAHYDROPYRADINE. D. L. Carbone and R. B. Tjalkens. Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO. #2039 3:29 ALTERED DOPAMINE LEVELS AND NEURODEGENERATION IN THE SUBSTANTIA NIGRA IN RESPONSE TO INTRANIGRAL INJECTION OF ROTENONE IN MICE. J. Carlsen and J. Eells. Mississippi State University, Mississippi State, MS. Sponsor: M. Ross. #2040 3:52 CHARACTERIZATION OF THE DIFFERENCES IN THE OXIDATIVE EVENTS IN PROTEINS IN TWO DIFFERENT PESTICIDE MODELS OF PD. P. Mastroberardino 1 , A. L. McCormack 3 , D. A. Di Monte 3 , G. W. Miller 2 and J. T. Greenamyre 1 . 1 Neurology, University of Pittsburgh, Pittsburgh, PA, 2 Center for Neurodegenerative Disease, Emory University, Atlanta, GA and 3 Basic Research Department, The Parkinson’s Institute, Sunnyvale, CA. Wednesday up-to-date information at www.toxicology.org 263
47 th Annual Meeting & ToxExpo Program Description (Continued) Wednesday Afternoon, March 19 2:45 PM to 3:45 PM Exhibit Hall 4C-3 Abstract # discuss regulatory issues and status worldwide, recent toxicological findings, relative sources of exposure, biotic and abiotic degradation, and characterization of risk and associated data gaps. Finally, a cost-benefit analysis for DecaBDE will be evaluated. (This abstract does not represent EPA policy) Wednesday Exhibitor Hosted Session: An Alternative to Animal Use: Today and Prospective Presented by: SkinEthic Laboratories SkinEthic is devoted to develop and produce reliable and robust in vitro alternative methods to animal use in cosmetic, chemical and pharmaceutical industries. SkinEthic models provide relevant tools for efficacy and safety screening tests in order to support integrated decision making during research and development phases. Some screening tests are referenced and validated as alternatives to animal use. Others are in the process of validation under ECVAM and OECD guidelines. Wednesday Afternoon, March 19 2:45 PM to 3:45 PM Exhibit Hall 4C-4 Exhibitor Hosted Session: In Vivo Micro- Ultrasound Imaging for Quantification of Anatomical, Functional and Molecular Biomarkers in Preclinical Imaging Presented by: VisualSonics This workshop will describe new developments in in vivo micro-imaging for Quantification of Anatomical, Functional and Molecular Biomarkers in Preclinical Imaging. Specifically, examples of real-time ultrasound imaging for performing detailed studies of abdominal and cardiovascular phenotypes and analyses as well as assessment of teratogenic effects will be reviewed. Possibilities for guided interventional procedures (both therapeutic and toxic) will also be discussed. #2041 4:30 A CASE STUDY ON THE RISKS AND BENEFITS OF DECABDE, A MAJOR BROMINATED FLAME RETARDANT. D. Staskal. ChemRisk, Austin, TX. 4:45 TOXICITY OF DECABDE. Linda Birnbaum 4:58 EXPOSURE TO DECABDE. Tom Webster 5:11 DEGRADATION OF DECABDE VIA ABIOTIC AND BIOTIC PATHWAYS. Heather Stapleton 5:24 RISK CHARACTERIZATION - CONSIDERATIONS FOR BIOAVAILABILITY, PHARMACOKINETICS, AND LIMITATIONS TO INTERPRETING AVAILABLE TOXICITY DATA. Bob Campbell 5:37 COST BENEFIT ANALYSIS MODEL FOR DECABDE AND FIRE SAFETY. Martin van den Berg Wednesday Afternoon, March 19 4:30 PM to 5:50 PM Room 615 INFORMATIONAL SESSION: IMPLEMENTATION OF THE ICH S8 IMMUNOTOXICITY TESTING GUIDELINE Chairperson(s): Thomas Kawabata, Pfizer Global Research and Development, Groton, CT and Pramila Singh, PPD Industries, Inc., Morrisville, NC. Wednesday Afternoon, March 19 4:30 PM to 5:50 PM Room 608 ROUNDTABLE SESSION: A CASE STUDY ON THE RISKS AND BENEFITS OF DECA-BDE—A MAJOR BROMINATED FLAME RETARDANT Chairperson(s): Daniele Staskal, ChemRisk, Inc., Austin, TX and Linda Birnbaum, U.S. EPA, Research Triangle Park, NC. Endorsed by: Occupational and Public Health Specialty Section* Risk Assessment Specialty Section Decabromodiphenyl ether (DecaBDE) is a high production volume chemical used as a flame retardant in a variety of consumer products; examples of uses in high impact polystyrene and textile applications include housing of TVs, audio and video equipment, mobile phones, and upholstery textiles (e.g., sofas, office chairs). It is the only polybrominated diphenyl ether (PBDE) mixture still used commercially as the other formulations have been banned or withdrawn worldwide. However, DecaBDE is the subject of intense scientific and regulatory scrutiny given that recent studies have suggested that 1) DecaBDE is a potential developmental neurotoxicant in rodent models; 2) DecaBDE potentially degrades to lower brominated congeners which appear to be more toxic than DecaBDE itself; and 3) levels of DecaBDE appear to be increasing in humans, wildlife, and the environment. Nonetheless, some scientists suggest that despite these findings, the benefits of using DecaBDE as a flame retardant outweigh the potential health risks. This scientific roundtable will address these topics. Experts will Endorsed by: Immunotoxicology Specialty Section* The ICH S8 Guideline, “Immunotoxicity Studies for Human Pharmaceuticals” provides recommendations for nonclinical safety testing of low molecular weight drugs for potential to induce harmful effects via suppression of the immune system. It applies to new drugs; existing drugs in which intended indication or label changes may result in unaddressed toxicological issues; and drugs in which signs of immunosuppression arise during clinical trials or following market approval. Preparation of the S8 guidance document progressed through the combined efforts of pharmaceutical industry representatives (PhRMA, JPMA, EFPIA) and members from tripartite government regulatory agencies (FDA, MHLW, CHMP) who recognized the need for globally harmonized regulatory guidance on immunotoxicological testing in drug development. Over the years leading up to the adoption of the S8 Guideline by regional regulatory agencies (2005-2006), there was significant debate and even some confusion over the compulsory versus voluntary nature of the testing recommendations and on how to apply the guidance in concert with pharmaceutical industry objectives. The purpose of this informational seminar is to provide a forum for the discussion of the practical implementation of the S8 Guideline including industry case examples and questions that remain unanswered. A panel consisting of members of the ICH S8 Expert Working Group responsible for creating the S8 Guideline and representing the U.S., Europe, and Japan will be available to answer questions from the audience. This session is intended to be an interactive forum with the expert panel, audience, and selected speakers from industry who have comments or questions on the scope and application of the S8 Guideline in current industry practice. The session will begin with a brief introduction followed by an overview of the development of the S8 Guideline and the rationale for the recommendations made. This will be followed by two individual oral presentations by industry professionals with key opinions to consider about the practical application of the Guideline, an open question and answer session, and concluding thoughts. 264 SOT’s 47 th Annual Meeting
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