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2003 Continuing Education Courses

The Continuing Education Program offers a widerange of courses that cover stateoftheart knowledge in toxicology, as well as new developments in toxicology and related disciplines. Courses can be applied toward certifying and licensing board requirements and may also be used for recertification with the American Board of Toxicology (ABT). Both basic and advanced course topics are offered. The basic course is intended to provide a broad overview of an area or to assist individuals in learning new techniques or approaches. The advanced course is intended to be of interest to individuals with previous knowledge of the subject or already working in the field.

Application of Stem Cells in Biomedical Research

Sunrise MiniCourse 1 Basic

Chairperson(s): Julio C. Davila, Pharmacia Corporation, St. Louis, MO.

Endorsed by:
In Vitro Specialty Section
Molecular Biology Specialty Section

In recent years stem cells are a subject of increasing scientific interest because of their potential utility in numerous biomedical applications. Stem cell technology has provided unprecedented opportunities not only for studying and understanding human development but also for changing the way we potentially will discover and develop new drugs, as well as test them for safety. This presentation will provide an overview on the evolving concept of applying stem cell technology to biomedical research, derivation of diverse tissuespecific cell types, and specific example of stem cell applications in biomedical research. This minicourse will be of interest to all toxicologists and related scientists from industry, academia, and government who are interested in the application of in vitro approaches using stem cells to predict the impact of drug exposure in humans as well as the generation of cells and tissues that could be used as therapies.

  • An Overview of Stem Cell Technology and Its Potential Applications, Clive N. Svendsen, University of Wisconsin, Madison, WI.

Essential Informatics for Toxicologists

AM 2 Basic

Chairperson(s): William B. Mattes, Pharmacia Corporation, Kalamazoo, MI.

Endorsed by:
Molecular Biology Specialty Section

The combination of the Internet, automated data acquisition, and genomic information has transformed the role of the computer in the modern scientistŐs life. A familiarity with word processing and simple spreadsheets is simply not adequate preparation for dealing with large datasets such as those generated by toxicogenomics or highthroughput screens. Increasingly, the software tools used to deal with such data require an understanding of basic concepts in computer science, database design, bioinformatics and statistics. This basic level course hopes to provide the beginnings of such an understanding. Thus the first lecture will cover some of the essential concepts of operating systems, file and data concepts and programming concepts. This will be followed by a talk discussing the essentials of database design and use, contrasting flatfile and relational databases. A third lecture will provide an overview of how to work with protein and nucleic acid sequences: homology searching and sequence alignment. The final lecture will cover concepts of visual analysis of large data sets, and contrast some of the various approaches used. Hopefully after this course the student will be conversant in informatics to the level of effectively interacting with computer scientists, as well as collecting and manipulating datasets with reasonable skill. Exercises will be included that the attendee can review and practice on their own computer in order to better understand the principles discussed.

  • Basics of Operating Systems, Data, and Data Handling, William B. Mattes, Pharmacia Corporation, Kalamazoo, MI.
  • Essentials of Database Principles and Use, Lyle Burgoon, Michigan State University, East Lansing, MI.
  • Basic Sequence Alignment and Searching, Russell Thomas, Kalypsys, Inc., La Jolla, CA.
  • Visual Analysis of Large Datasets, Jennifer Fostel, Pharmacia Corporation, Kalamazoo, MI.

Unfolding the Secrets in Culturing Brain Cells: Theory, Techniques, and Beyond

AM 3 Basic

Chairperson(s): Timothy J. Shafer, U.S. EPA, Research Triangle Park, NC and Wei Zheng, Purdue University School of Health Sciences, West Lafayette, IN.

Endorsed by:
In Vitro Specialty Section
Neurotoxicology Specialty Section
Mechanisms Specialty Section

In vitro culture of selected cell types of the CNS is an indispensable tool in modern neuroscience research. Rapid development in theories and techniques has revolutionized the traditional way in culturing neurons, neuroglia, and brain barrier cells. For example, coculture techniques make it possible to investigate molecular mechanisms underlying regeneration of neurons, interaction between neurons and neuroglia, and induction of brain barriers. Recent advancement in stem cell research provides an additional dimension toward the reproduction of nearly all brain cell types. The fastpaced progress in in vitro culture of brain cells has presented itself as the most dynamic and rapidly advancing field in neuroscience. It is for that matter that molecular mechanisms are rarely elucidated without evidence obtained from studies using cell cultures. This course will provide comprehensive reviews of cutting edge technology in culturing brain cells beginning with a brief introduction to tissue culture theory and practice. Subsequent lectures will focus on three major cell types of the CNS, i.e., neurons, astrocytes, and barrier cells, and discuss in detail the techniques to establish a primary culture, to maintain an established cell line, and to create an immortalized cell line. The theory and practice of stem cell cultures in neurotoxicological studies will also be addressed. Application of these techniques in basic research, regulatory monitoring, and industrial R&D will be discussed. This course serves as an ideal introduction to students, postdoctoral fellows, and industrial researchers beginning in their culture research, and also is suitable to those who want to improve in vitro culture techniques in their own laboratories. For experienced researchers, the course will provide a comprehensive review of the most recent progress in cell culture techniques.

  • Introduction: Basic Principles of Tissue Culture, Timothy J. Shafer, U.S. EPA, Research Triangle Park, NC.
  • Neurons: Primary and Clonal, William R. Mundy, U.S. EPA, Research Triangle Park, NC.
  • Glial Cultures and Glial/Neuron CoCultures, Michael Aschner, Wake Forest University School of Medicine, WinstonSalem, NC.
  • Brain Barriers in Test Tubes: Primary Culture, Immortalization, and TransBarrier Transport, Wei Zheng, Purdue University School of Health Sciences, West Lafayette, IN.
  • The Utility of Stem Cells in Neurotoxicology and Other Disciplines, Mark Noble, University of Rochester Medical Center, Rochester, NY.

The Nuts and Bolts of Genetically Engineered Mice in Toxicology

AM 4 Basic

Chairperson(s): Wanda M. HaschekHock, University of Illinois, Urbana, IL and Jeffrey I. Everitt, GlaxoSmithKline, Research Triangle Park, NC.

Endorsed by:
Comparative and Veterinary Specialty Section
Toxicologic and Exploratory Pathology Specialty Section

The recent advent of genetic engineering techniques has allowed intentional engineering of novel animal models for human diseases. This has had a profound impact on basic biomedical research and has accelerated the pace at which pharmaceutical and biotechnology firms can discover new targets and innovative drug candidates. In addition it has greatly enhanced the study of mechanisms of toxicity. This course will provide an overview of how genetic engineering is used to create such models, specific issues related to management of such animals, the identification of phenotypic alterations and their evaluation in the development of models, and the use of these models in the pharmaceutical industry for discovering new targets for therapy interventions and developing new drug candidates. The course will be presented at the basic level and will provide information for scientists of all toxicology disciplines who are considering the use genetically engineered models in their research or need to understand the information provided by the use of such models. It will especially be of use to those who are not currently working with whole animals or such genetically engineered models.

  • Overview of Genetically Engineered Mice, Niles W. Fox, Lilly Research Laboratories, Indianapolis, IN.
  • Management and Infectious Disease Issues in Genetically Engineered Mice, Lela K. Riley, University of Missouri, Columbia, MO.
  • Phenotyping and Pathology Issues, Charles A. Montgomery, ComPath, Conroe, TX.
  • Use of Genetically Engineered Rodents in Drug Discovery and Development, Brad Bolon, Amgen, Inc., Thousand Oaks, CA.

Fundamentals of Risk Assessment and Applications of Recent Methodologies to Difficult Problems

AM 5 Advanced

Chairperson(s): Dennis J. Paustenbach, Exponent, Inc., Menlo Park, CA.

Endorsed by:
Biological Modeling Specialty Section
Carcinogenesis Specialty Section
Food Safety Specialty Section
Neurotoxicology Specialty Section
Risk Assessment Specialty Section

The field of risk assessment has evolved at a fairly rapid pace over the past 45 years. Fifteen years ago, it was not uncommon for risk assessments to be conservative descriptions of the plausible risks posed by chemicals; often the approach was dictated by regulatory guidance or criteria. Today, the approach to characterizing risks is more flexible than in years past. This course will include an introductory lecture on the fundamentals of risk assessment with an emphasis on the changes in risk assessment procedures that have occurred over the past five years (e.g., new EPA cancer guidelines, children's health guidelines, monte carlo techniques, aggregate and cumulative risk, etc.). The four basic parts of a risk assessment will be described (hazard identification, doseresponse assessment, exposure assessment, and risk characterization) and stateoftheart approaches to each will be presented. This lecture is followed by three case studies. The first will discuss one of the most complex risk assessments ever conducted. It involves a former government facility which used and emitted both chemical and radiological agents. The second will present an analysis of the risks to children posed by CCA treated wood. The last case study will present several examples of how to evaluate some of the hazards posed by consumer products. Applicable regulatory guidance (both domestic and international) will be cited in the various talks.

  • Fundamentals of Risk Assessment, Dennis J. Paustenbach, Exponent, Inc., Menlo Park, CA. and Pamela Williams, Exponent, Inc., Boulder, CO.
  • Conducting a Retrospective Risk Assessment of a Site with Both Chemical and Nuclear Wastes, Thomas E. Widner, ENSR International, Alameda, CA.
  • Conducting Risk Assessments of Consumer Products, Thomas Brennan, U.S. EPA, Washington, DC.
  • Conducting Risk Assessments of Consumer Products, Gregory P. Broby, Exponent, Inc., Oakland, CA.
  • Assessing Arsenic Exposure to Children from Treated Wood, Joyce S. Tsuji, Exponent, Inc., Bellevue, WA.

Cutaneous Toxicity—Current Methods and Concepts in Safety Evaluation and Relevance to Human Exposure

AM 6 Basic

Chairperson(s): Nancy A. MonteiroRiviere, North Carolina State University, Raleigh, NC and Carol S. Auletta, Huntingdon Life Sciences, East Millstone, NJ.

Endorsed by:
Dermal Toxicology Specialty Section
In Vitro Specialty Section
Regulatory and Safety Evaluation Specialty Section

Humans are exposed to a large number of potentially toxic substances through the skin. Cutaneous exposure may occur intentionally, as with use of pharmaceuticals and consumer products, or accidentally, as a result of industrial or environmental exposure. Evaluation of the safety of these substances is an important function of toxicologists. It has been several years since SOT presented a continuing education course on this topic. The course will provide presentations and discussions of the current status of cutaneous toxicity safety evaluation, using in vitro and in vivo (animal model) systems as well as clinical evaluations in humans. Areas covered will include irritation, toxicity and phototoxicity. Regulatory aspects, current protocols, guidance on study design and interpretation of results will be discussed as will the relevance to human exposure. This would be a basic course of interest to toxicologists who may work with materials with a potential for cutaneous exposure (pharmaceuticals, consumer products, chemicals). It will provide an overview of the topic for those with little or no experience in this area and will provide updates, with information on current ideas and methods in the field, for those currently working in dermal toxicology. The presentation on in vitro assays will be of special interest to scientists specializing in this area. Presentations on human testing and CDER/U.S. FDA practice will be of interest to those with concerns in the areas of drug development and regulatory affairs.

  • Anatomical Considerations for Model Selection, Nancy A. MonteiroRiviere, North Carolina State University, Raleigh, NC.
  • In Vitro Assays: What's New? What Works? What Doesn't?, Cynthia A. Ryan, Procter & Gamble Company, Cincinnati, OH.
  • In Vivo Assays—Current Protocols, Procedures and Animal Models, Carol S. Auletta, Huntingdon Life Sciences, East Millstone, NJ.
  • Human Assays—Clinical Relevance of In Vivo and In Vitro Assays, Howard Maibach, UC San Francisco, San Francisco, CA.
  • Regulatory Perspectives—U.S. FDA Guidance on Test Selection, Data Interpretation and Clinical Relevance, Abigail C. Jacobs, U.S. FDA, Rockville, MD.

Medicinal Herbals and Dietary Supplements

AM 7 Advanced

Chairperson(s): Alfred F. Fuciarelli, Battelle Toxicology Northwest, Richland, WA and William T. Allaben, National Center for Toxicological Research, Jefferson, AR.

Endorsed by:
Food Safety Specialty Section
Regulatory and Safety Evaluation Specialty Section

Medicinal herbals and other dietary supplements are consumed by an estimated onethird of the U.S. population. Over 1500 botanicals are sold as dietary supplements or ethnic traditional medicines. Their use has increased substantially since passage of the 1994 Dietary Supplement Health and Education Act. Herbal formulations are not subjected to FDA premarket toxicity testing to assure their safety or efficacy. However, there is an increased public awareness of the need to conduct toxicity studies on herbs and herbal ingredients and many government and private laboratories are contributing to this effort. Perhaps the largest single effort in this area is being conducted by the National Toxicology Program where studies are being conducted on the following medicinal herbals and compounds found in herbs: aloe vera gel, black cohash, comfrey, ginseng and ginsenosides, goldenseal, kava kava, pulegone, thujone, and extracts of grape seed, pine bark, black walnut, Echinacea purpurea, Ginkgo biloba and milk thistle. In this course, speakers will present information relevant to toxicity testing for safety and efficacy. Presentations describe the ongoing efforts in chemical analyses and dosing/formulation issues; safety assessment including carcinogenicity, reproductive toxicity, immunotoxicity, neurotoxicity, and effects associated with acute exposure to high doses and chronic exposures to low doses; adverse human health effects with an emphasis on circumstances under which the adverse reactions may occur; interactions with pharmaceutical products; and perspectives on research needs and priorities for safety assessment of herbal medicines and dietary supplements.

  • Characterization and Use of Herbal Medicines and Dietary Supplements in Bioassays, Cynthia S. Smith, National Institutes of Environmental Health Sciences, Research Triangle Park, NC.
  • Toxicity and LongTerm Effects of Herbal Medicines and Dietary Supplements, Elizabeth A. Yetley, U.S. FDA, College Park, MD.
  • The Nature of Safety: Classification of Adverse Events to Botanical Dietary Supplements, Joseph Betz, NIH, Bethesda, MD.
  • Natural ProductDrug Interactions, Gayle N. Scott, Eastern Virginia Medical School, Norfolk, VA.

Genomic and Proteomic Array Formats on the Cutting-Edge

PM 8 Advanced

Chairperson(s): Mary Jane Cunningham, Molecular Mining Corporation, Kingston, Canada.

Endorsed by:
In Vitro Specialty Section
Mechanisms Specialty Section
Molecular Biology Specialty Section

Microarrays are now being used to explore gene expression from a variety of tissues and cells on the scale of tens of thousands of genes. They have been used in toxicology over the past three to four years to investigate and predict toxic effects and explore the mechanisms of action by which compounds cause these effects. Several past courses and seminars have detailed the most common formats: oligonucleotide and cDNA arrays. In this course, new formats which are on the cuttingedge and in some cases, in development, will be explored. These formats include optic fiber, electronic, tissue and protein microarrays. Each format presented has its own advantages and limitations but can offer a more defined look at gene and protein expression compared to the current common formats. Optic fiber and electronic arrays offer instantaneous hybridization and detection. Protein arrays offer a quicker scan of protein activity with better resolution than the more traditional method of performing twodimensional electrophoresis and annotating by mass spectroscopy. Tissue arrays are essentially a microarray of histology and can be used to detect DNA, RNA or protein. Each format will be presented in detail with how it is applied to current genomic and proteomic issues. Specific applications or perceived applications to issues in toxicology will be presented.

  • Fiberoptic Microarrays, Jason Epstein, Tufts University, Medford, MA.
  • Electrokinetic Microarrays: The Advantages and Limitations, Marc Madou, University of California, Irvine, CA.
  • Global Analysis of Biochemical Activities using Proteome Chips, Paul Bertone, Yale University, New Haven, CT.
  • Tissue Microarrays: Histopathology Genomics, Mark Basik, UniversitŽ de MontrŽal, DŽpartement de Chirurgie, Bethesda, MD.

Integrating Toxicologic Pathology into Compound Evaluation and Risk Assessment II

PM 9 Basic

Chairperson(s): Douglas C. Wolf, U.S. EPA, Research Triangle Park, NC.

Endorsed by:
Comparative and Veterinary Specialty Section
Toxicologic and Exploratory Pathology Specialty Section

The contribution of pathology assessment to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is determined. Therefore, it is important that the general toxicology community understands current concepts and nomenclature of toxicologic pathology. Toxicologic pathology is a discipline that changes and adapts over time including methods of analysis and nomenclature of lesions. As risk assessments are reevaluated and updated on commodity chemicals, frequently the older literature must be evaluated. This course will present ideas on how to evaluate terminology and diagnoses in light of current standards, diagnostic drift, and changed interpretation. Then a continuation of a systems approach to toxicologic pathology assessment will continue with a review of the cardiovascular system, neuropathology, and the eye. Lectures will cover normal structure, function, diagnostic terminology, and specific case examples.

  • The Ebb and Flow of Diagnostic Drift, Peter Mann, Experimental Pathology Laboratory Northeast, Galena, MD.
  • Integrating Cardiovasular Pathology into Toxicity Evaluation, William Kerns, Pharma Consulting, Inc., Harvard, MA.
  • Integrating Central Nervous System Pathology into Toxicity Evaluation, Andrew Fix, Procter & Gamble Company, Cincinnati, OH.
  • Integrating the Pathology of the Eye into Toxicity Evaluation, Robert L. Peiffer, Merck Research Laboratories, West Point, PA.

Choice and Application of Classical, Population or PhysiologicallyBased PK for Chemical Assessment and Pharmaceutical Development

PM 10 Advanced

Chairperson(s): John C. Lipscomb, U.S. EPA, Cincinnati, OH and Rakesh Dixit, Merck Research Laboratories, West Point, PA.

Endorsed by:
Biological Modeling Specialty Section
Regulatory and Safety Evaluation Specialty Section
Risk Assessment Specialty Section

Both toxicity and therapeutic effectiveness are dictated by the delivery of a chemical to its target (pharmacokinetics, PK) and the response (pharmacodynamics, PD) which follows the molecular interaction between xenobiotic and target molecule. This session will instruct participants in proper methods to conduct investigations and interpret PK findings. It will contain an overview of PK in risk and safety assessment and four lectures on topics critical to the identification of PK models and their proper application to derive toxicologically, risk and safetyrelevant measures. Lecture content will be aimed at instructing the selection of therapeutic doses; identification of margins of safety; methods applicable to the extrapolation of doses; the separate benefits of classical versus physiologicallybased PK models; and proper methodology to collect, interpret and employ measures of population PK variance. PK is a critical modulator of toxicity, and is a fundamental component in risk assessments, safety assessment and drug development. This advanced level course is intended to educate professionals who are considering or have recently begun to increase their studies of PK; it will guide the development of toxicity studies which can also collect useful PK information. The course has been designed to address the interests of scientists involved in the design of basic toxicity and pharmacokinetic studies, preclinical and clinical studies, and those scientists conducting safety and/or risk assessments.

  • Introduction and Overview, John C. Lipscomb, U.S. EPA, Cincinnati, OH.
  • Pharmacokinetic Information in Drug Development, Rakesh Dixit, Merck Research Laboratories, West Point, PA.
  • Population Pharmacokinetics: Methods, Interpretation of Results and Dose Prediction, Samir Gupta, ScheringPlough Research Institute, Kenilworth, NJ.
  • The PBPK Approach in Species Dose and Route Extrapolation, Hugh A. Barton, U.S. EPA, Research Triangle Park, NC.
  • Benefits of Classical and PhysiologicallyBased PK Models in the Assessment of Therapeutics, David R. Plowchalk, Pfizer, Inc., Groton, CT.

Evaluation of Immunomodulation in Safety Assessment

PM 11 Basic

Chairperson(s): Dori R. Germolec, NIEHS, Research Triangle Park, NC and Robert V. House, DynPort Vaccine Company, Frederick, MD.

Endorsed by:
Immunotoxicology Specialty Section

Assessment of adverse effects on the immune system is of considerable importance in the safety evaluation of investigational new drugs. This course will cover the practical aspects of immunotoxicology for pharmaceutical development and is targeted to toxicologists in the industry. Although it will focus on safety assessment of therapeutics, the concepts discussed are also applicable to a variety of test materials. The course will be introduced with a session on the historical role that immunotoxicology has played in drug development, the types of adverse events that have been reported in both clinical trials and nonclinical toxicology studies and the growing importance of this field of study in safety assessment. The second speaker will discuss basic methods for assessing immune function in rodents, including which tests may be combined with standard 28day toxicity studies, assays to evaluate specific immune targets, as well as special studies that may be informative or necessary to conduct when immune effects are observed. The third speaker will cover immune assessment in nonhuman primates, and will focus on species selection, testing strategies, and technical issues specific to primates. The final speaker will discuss the current international regulatory requirements for immunotoxicology in submission of new drugs. Although this is a basic course, it is assumed that the participants will have a basic knowledge of immunology.

  • Past, Present, and Future: The Evolution of Immunotoxicology Assessment in Pharmaceutical Development, Jack Dean, SanofiSynthelabo, Malvern, PA.
  • Assessment of Immunomodulation in Rodent Models, Robert V. House, DynPort Vaccine Company, Frederick, MD.
  • Assessment of Immunomodulation in NonHuman Primates, Jeanine Bussiere, Immunex Corporation, Seattle, WA.
  • Immunotoxicology in Drug Development: A Regulatory Perspective, Kenneth Hastings, U.S. FDA, Rockville, MD.

The Effects of NonReproductive Hormones on the Reproductive System and the Implications for Toxicology

PM 12 Advanced

Chairperson(s): Robert Chapin, Pfizer Global Research and Development, Groton, CT and Kimberley Treinen, ScheringPlough Research Institute, Lafayette, NJ.

Endorsed by:
Reproductive and Developmental Specialty Section

More and more, we are coming to understand the degree of interconnectedness that ties together organ and hormone systems that were previously thought to be separate. This interconnectedness is important in both human health and in animal toxicology studies. The mammalian reproductive system undergoes basic activation events during development, and then constant finetuning as adults. This activation and finetuning rely on hormones and growth factors which can have effects both subtle and profound. This course is designed to give both the general and specialist audience a better appreciation of the impact of several different hormonal systems on male and female reproduction, and how we can use these to explain mechanisms of toxicity in the reproductive systems. John Meredith will provide a background understanding of the signaling events in reproductive tissues by reviewing normal mechanisms of endocrine interaction and signaling. Patricia Morris will then describe the complex and intriguing world of cytokines, with their pleiotropic effects on all aspects of mammalian reproduction. Paul Cooke will show how the thyroid hormones significantly impact the reproductive system both developmentally and in adults. Finally, Raphael Witorsch will explore what is known about the effects of glucocorticoids on various stages of reproduction. At the end of the course, the student will have an improved understanding of how these other hormone systems impinge on reproduction, and will be better able to determine their involvement in a lesion when puzzling out mechanisms of toxicity.

  • Basic and New Concepts in the Regulation of the Male and Female Reproductive Endocrine Axis, John Meredith, ScheringPlough Research Institute, Lafayette, NJ.
  • Thyroid Hormone Regulation of Male and Female Gonadal Development and Function, Paul Cooke, University of Illinois, Urbana, IL.
  • Physiologic Role and Toxicologic Effects of Glucocorticoids on Reproduction, Raphael J. Witorsch, Medical College of Virginia, Richmond, VA.
  • Nonlactogenic Actions of Prolactin: A Review of the Most Versatile Pituitary Hormone, Paul W. Sylvester, University of Louisiana at Monroe, Monroe, .

Epigenetics of Cancer

PM 13 Basic

Chairperson(s): Ruth Roberts, Aventis Pharma, Vitry sur Seine, France and Jay Goodman, Michigan State University, East Lansing, MI.

Endorsed by:
Carcinogenesis Specialty Section

For the past few decades, research has focused on understanding the mechanisms of genotoxic or nongenotoxic carcinogenesis. However, recent evidence suggests that gene expression can be markedly altered via several epigenetic mechanisms that can lead to permanent or reversible changes in cellular behavior. Thus, cancer may develop as a result of interplay between genetic alteration and epigenetic changes. Developing an understanding of the role played by epigenetic modulation of gene expression is a key element in understanding the response of cells and organisms to toxicants, in particular carcinogens. This course will bring together several leading speakers in this area to address the different aspects of epigenetics ranging from methylation through to proposed nongenomic modes of action for transcription factors such as ER and PPAR. This is of interest to all toxicologists, particularly those interested in the mechanisms of rodent and human cancer. This basic course is intended to assist investigators who may want to incorporate a consideration of epigenetics into their research and/or teaching. Through the use of appropriate examples, emphasis will be placed upon the conceptual and theoretical basis of epigenetics. Furthermore, there will be a focus on practical aspects concerning safety assessment, e.g., how an epigenetic mechanism of action might provide information concerning extrapolation from species to species and the shape of the doseresponse curve at low doses.

  • Overview on the Interplay Between Genetics and Epigenetic Abnormalities in Cancer, James Trosko, Michigan State University, East Lansing, MI.
  • Altered DNA Methylation—A Secondary Mechanism in Carcinogenesis, Jay Goodman, Michigan State University, East Lansing, MI.
  • Regulating Gene Expression—Reading the Chromatin Code, Jonathan Moggs, Syngenta Central Toxicology Laboratory, Macclesfield, United Kingdom.
  • Transcriptional and Notranscriptional Responses to PPAR Ligands, Ruth Roberts, Aventis Pharma, Vitry sur Seine, France.