Special Sessions

Plenary Lecture: Risk Communication—The Perception Gap, an Unrecognized Aspect of Risk
Monday, March 6, 8:30 AM–9:15 AM
Lecturer: David Ropeik, Harvard School of Public Health, Harvard University, Boston, MA.

This talk will propose that the classic definition of Risk = Hazard x Exposure is incomplete. A definition that more fully reflects all aspects of risk is Hazard x Exposure x Perception. While it is often said that people are wrong or irrational when their fears don’t match the facts, their fears are real, and those fears often lead to behaviors that compound the risk to themselves and to society. The scientific understanding of the roots of risk perception will be explained. More effective risk communication, based on a respect for the realities of risk perception, will be offered as a vital tool for closing ‘The Perception Gap’ and encouraging people to make more informed and healthier choices.

View the Plenary Lecture slide presentation

Special Session: Using Animals for Toxicological Research and Testing: Best Practices for Assuring Compliance with Animal Welfare Regulations, Policies, and Guidelines
Monday, March 6, 4:30 AM–6:00 PM
Chairperson(s): Jan Oberdoerster, Bristol-Myers Squibb, East Syracuse, NY and William Stokes, NIEHS, NIH, DHHS, Research Triangle Park, NC

Toxicological research and testing often require the use of animals to investigate mechanisms of toxic action and to accomplish regulatory safety assessments. This animal use must be conducted in accordance with applicable animal welfare laws, policies, and regulations. Additionally, many organizations participate in voluntary accreditation programs, which also necessitates adherence to best practice standards based on guidelines published in the NRC/ILAR Guide for the Care and Use of Laboratory Animals. These requirements and guidelines seek to ensure that investigators use animals in the most humane and judicious manner consistent with successful attainment of the research or testing objectives, and consistent with current best practices for animal care and use.

However, institutions face challenges in assuring adherence to best practices in the face of changing research and testing objectives, priorities, techniques, and animal species, such as in response to recent major bioterrorism research initiatives. They are also faced with adhering to evolving changes in best practices for animal care and use in areas such as environmental enrichment, consideration and use of alternatives, humane endpoints, management of pain and distress, and animal caging and environment. This workshop will review the most common animal care and use deficiencies and suggestions for improvement cited by regulatory and accreditation authorities, and the current best practices used as benchmarks by these organizations for inspections and site visits of animal care and use programs and facilities. Perspectives on compliance issues and current best practices will be provided by U.S. DA APHIS/Animal Care (Animal Welfare Act regulations), NIH Office of Laboratory Animal Welfare (PHS Policy on the Humane Care and Use of Laboratory Animals), and the Association for the Assessment and Accreditation of Laboratory Animal Care International. The Canadian Council on Animal Care and the UK Home Office will provide international perspectives. Increased understanding of current animal care and use compliance issues and expected best practices will facilitate optimization of humane animal care and use by investigators and laboratory animal veterinarians, and minimize the likelihood of disruptive mandatory corrective actions.

• U.S. DA Perspective—Regulatory Compliance Issues for Animals Used in Toxicological Research and Testing, Jodie Kulpa-Eddy, U.S. DA Animal and Plant Health Inspection Service, U.S. DA, Riverdale, MD.

• Using Animals for Toxicological Research and Testing: Best Practices for Assuring Compliance with Animal Welfare Regulations, Policies, and Guidelines, Axel Wolff, NIH, Bethesda, MD.

• AAALAC Perspective: Common Animal Care and Use Program and Facility Recommendations for Improvement for Toxicological Research and Testing Facilities, John Miller, AAALAC, Rockville, MD.

• Canadian Council on Animal Care Perspective: Compliance Issues and Best Practices for Animals Used for Toxicological Research and Testing, Clement Gauthier, Canadian Council on Animal Care, Ottawa, ON, Canada.

• The UK Home Office Perspective: Regulatory Compliance Issues and Best Practices for Animals Used for Toxicological Research and Testing, Jon Richmond, UK Home Office Animals Scientific Procedures Division, UK Home Office, London, United Kingdom.

Medical Research Council (MRC) Lecture: Cell Death and Neurodegeneration
Tuesday, March 7, 8:00 AM–8:50 AM
Lecturer: Dr. Junying Yuan, Harvard Medical School

The UK Medical Research Council (MRC) sponsored lecture at the SOT Annual Meeting reflects the long tradition of support by the MRC for basic sciences and their translation to medicine.

Dr. Junying Yuan will present the MRC lecture on cell death and neurodegeneration. Dr. Yuan is currently a professor of Cell Biology at Harvard Medical School. She initially trained at Fudan University, Shanghai, China and subsequently obtained her PhD in Neuroscience at Harvard University working with the Nobel Prize winner H.R. Horvitz. She continued as an Instructor and Assistant Professor of Medicine at Harvard Medical School, then became Associate and now full Professor of Cell Biology. Professor Yuan has pioneered studies concerning the mechanism of degeneration, regulation and cell death first in C. elegans and then in mammalian systems and has made fundamental contributions by discovering the caspase family of proteases and subsequently by relating them to neurodegenerative conditions. More recently she has used unbiased chemical genetic screens to identify new regulatory machineries controlling the process leading to cell death. She has identified both new death pathways and chemicals that may be used to prevent the onset of non-apoptotic cell death. Her work is of great relevance to cell biology, medicine and toxicology. Dr. Yuan has published an impressive number of high-quality papers and is regarded as one of the leading figures in the research field of cell death.

The MRC was established in 1913 and scientists funded by the MRC at its Units and institutes as well as in several UK universities have discovered fundamental processes in cell biology and medicine. The MRC supports research carried out in universities and other academic establishments in the UK and through its intramural programme supports strategic research in Units and Institutes. The MRC Toxicology Unit was formed in 1947 and is currently located at the University of Leicester where it integrates competitive research areas in cell biology, molecular biology, genetics and medicine. The Unit is pleased to sponsor a lecture at the SOT Annual Meeting to acknowledge the importance of fundamental sciences and its medical applications to the field of toxicology.

Issues Session: Safety Assessment of the Major Human Metabolites
Tuesday, March 7, 12:00 NOON–1:30 PM
Chairperson(s): Rakesh Dixit, Johnson and Johnson PRD, San Diego, CA
Round-Table Discussion Panel Members: Rakesh Dixit, Johnson & Johnson PRD, San Diego, CA. Sidney Nelson, University of Washington, Seattle, WA. Alfred Tonelli, Johnson and Johnson PRD, Raritan, NJ. Martin David Green, U.S. FDA, Rockville, MD. Andrew Parkinson, XenoTech, Lenexa, KS.

Metabolites can be responsible for the desired efficacy as well as the adverse effects. While qualitatively both phase I and phase II metabolic reactions are fairly conserved across laboratory safety species and humans, there are often important quantitative differences in the rate and the extent of metabolism between safety species and humans. If a metabolite is responsible for toxicity, the quantitative differences in exposure to a major toxic metabolite between humans and laboratory animals can lead to misrepresentation of safety margins based on the parent drug exposure. Non-clinical safety assessment studies are critical to identifying potential toxicity signals for humans and for providing a reasonable assurance related to the test drug’s safety at proposed clinical doses. Given the use of high doses (large multiples of the projected human doses) in safety studies and the fact that the rates of most phase I and phase II reactions are relatively greater in non-clinical safety species than in humans, it is expected that in the vast majority of cases there will be adequate coverage of metabolites both qualitatively and quantitatively in safety studies. In a small number of cases, when the major vs. minor pathways of metabolism are dissimilar across species, there may be human specific “unique” or “dominant metabolites” that may not have been be adequately tested in non-clinical safety studies.

The U.S. Food and Drug administration has recently issued “Guidance for Industry: Safety Testing of Drug Metabolites.” The document makes a serious regulatory attempt to define the major human metabolite(s) and provides scientific guidance on the safety testing of the major human metabolites in non-clinical studies. However, the guidance document has also raised ambiguity and concerns regarding the definition of the major metabolites as well as the extent of safety studies with human dominant or unique metabolites. The round-table discussion will provide an academic, industrial and federal regulatory perspective on the proposed guideline, including the definition of the major metabolite and the safety testing of the major metabolites. It is hoped that this scientific round-table discussion will provide a path forward for an adequate testing the safety of metabolites.

• Introduction on the Safety Assessment of the Major Metabolites, Rakesh Dixit, Johnson and Johnson PRD, San Diego, CA.

• An Academic Perspective on the Safety Testing of the Major Metabolites, Sidney Nelson, University of Washington, Seattle, WA.

• An Industry Perspective on the Safety Testing of the Major Metabolites, Alfred Tonelli, Johnson and Johnson, PRD, Raritan, NJ.

• The U.S. FDA Regulatory Perspective and the Rationale for the Guideline, M. David Green, U.S. FDA, CDER, Rockville, MD.

SOT/EUROTOX Debate
Motion: 'Omics' Research Does Not Add Substantially to the Safety Assessment of Chemicals
Wednesday, March 8, 8:00 AM to 8:50 AM
Sponsored by: SOT (Society of Toxicology) and EUROTOX (European Societies of Toxicology)
Debaters: (Pro) EUROTOX: Alan Boobis, Imperial College London, London, United Kingdom.
(Con) SOT: Dan Nebert, University of Cincinnati, Cincinnati, OH.

The 2006 Eurotox debate continues a very informative series in which the points and respective counterpoints on a given topic are addressed by well known toxicologists. Dr. Daniel W. Nebert and Prof. Alan R. Boobis will present differing views on the contribution of ‘omic’ technologies for assessing chemical safety as it applies to assessing human risk.

Special Session: Meet the Directors Session: Update of Activities of Selected Government Agencies
Wednesday, March 8, 12:00 NOON–1:30 PM

The Meet the Directors Session is a special 90 minute session that provides an opportunity for the leaders of several major federal agencies to engage in a panel discussion of emerging trends in toxicology research and its funding. The objective of this session is to provide meeting attendees a better understanding of the toxicology research activities sponsored by agencies like the EPA, NIEHS, and NTP. There will be a strong emphasis on change of direction and new initiatives that may impact the practice of toxicology in the near and long term. Speakers will identify opportunities where non-agency toxicologists may be able to participate in initiatives of their agencies, and will answer questions of attendees.

Special Session: Town Hall Meeting: Recent Changes in Participation Requirements on Government Advisory Groups/Panels
Wednesday, March 8, 4:30 PM–6:00 PM
Chairperson(s): David B.Warheit, Dupont Haskell Laboratories, Newark, DE

This special session will focus on the issues of conflict of interest and perception of bias, and how those issues play out in the selection of members for peer review panels. In particular, the focus will be on the processes utilized for selection of peer review panels for The International Agency for Research on Cancer (IARC), National Academy of Sciences, American Chemistry Council—Long Range Research Initiative and the U.S. Environmental Protection Agency—Science Advisory Board working groups. Dr. Vincent Cogliano will describe the rationale for changes regarding selection of Working Panels recently implemented at IARC. Dr. Carol Henry will discuss the procedures implemented for funding industry-sponsored research. Dr. Vanessa Vu, Director of the EPA Science Advisory Board will discuss conflict of interest/peer review issues as they relate to the EPA Science Advisory Board. Finally, peer review/report review procedures at the National Academy of Sciences will be presented.

• Introduction to the Issue, David Warheit, Dupont Haskell Laboratories, Newark, DE.

• Recent Changes at International Agency for Research on Cancer, Vincent Cogliano, Cedex, France.

• Conflict of Interest: Peer Review Issues at the Long Range Research Initiative and National Academy of Sciences, Carol Henry, American Chemistry Council, Arlington, VA.

• Conflict of Interest: Peer Review Issues at the EPA Science Advisory Board, Vanessa Vu, U.S. EPA, Washington, DC.

• Report Review: Peer Review Issues at the National Academy of Sciences, TBA.

Special Session: Hurricane Katrina: Interface Between Response and Research
Thursday, March 9, 9:00 AM–12:00 NOON
Chairperson(s): Harold Zenick, U.S. EPA, Research Triangle Park, North Carolina and Henry Falk, Coordinating Center for Environmental Health and Injury Prevention, CDC, Atlanta, Georgia.

This symposium session will set the stage and describe what conditions were encountered on the ground, initial response(s) including trade offs and follow up related to Hurricane Katrina. The panelist will also discuss the nature of the information and research that might better help reduce uncertainties in decision making for future disasters. This session will end with a roundtable discussion with the audience.

• Welcome and Introduction, Hal Zenick, National Health and Environmental Effects Research Laboratory, ORD/EPA, Research Triangle Park, North Carolina and Henry Falk, Coordinating Center for Environmental Health and Injury Prevention, CDC, Atlanta, Georgia.

• Challenges and Health Needs in New Orleans, Kevin Stephens, the Director for Health, NO Department of Health, New Orleans, Louisiana.

• Making Timely Risk Management Decision – Need for Appropriate Health Benchmarks, Bob Olexssy, National Risk Management Research Laboratory, ORD/U.S. EPA, Cincinnati, OH.

• Clean up: Occupational and Public Health Risks – Max Kiefer2, National Institute of Occupational Safety and Health.

• Mold and Related Indoor Health Risks, Tom Sinks or Howard Frumkin, National Center for Environmental Health/Agency for Toxic Substances Disease Registry, CDC, Atlanta, GA.

• Assessing Damage to Coastal Ecological Resources, William Benson, Gulf Ecology Division, ORD/U.S. EPA, Gulf Breeze, FL.