Mouse Lung Tumor Workshop (Jan 2014)
EPA conducted a State-of-the-Science Workshop on Chemically-induced Mouse Lung Tumors: Applications to Human Health Assessments. The purpose of this workshop was to discuss the available data and interpretation of results from studies of mouse bronchiolar-alveolar adenomas and carcinomas (lung tumors) following exposure to chemical agents, and the relevance of such tumors in mice to human cancer risk. Several lines of research have investigated whether or not these types of lung tumors are formed by a mode of action (MOA) which is specific to mice and are relevant to tumor formation or other toxicity in humans.
Background:
This two-day, state-of-the-science workshop covered a broad range of evidence from human, animal, and in vitro studies with a focus on specific chemicals (ethylbenzene, naphthalene, and styrene) causing lung tumors in mice and implicated in a proposed species-specific mode of action (MOA) based on metabolic and physiological susceptibility. The workshop was sponsored and organized by EPA with input from (1) a volunteer committee of outside experts (including representatives from academic institutions, State agencies, other Federal organizations, NGOs, and industry), and (2) an internal working group of experts from EPA and other Federal partners. The workshop included four separate sessions examining individual topic areas in detail, beginning with and continually referring back to the human relevance of data from animal and in vitro studies.
- A Session Abstracts document was made available to provide context and define the scope for the discussions. It was also developed to provide the introductory material and facilitate a quick engagement in fruitful discussions from the very beginning of the workshop with a minimum of introductory presentations. This document of preliminary materials remains useful following the workshop.
- The Health and Environmental Research Online (HERO) literature database includes a publicly-available project page specifically for the MLTW which provides the available literature relevant to the workshop.
Workshop Goals and Scope:
The goals of the workshop:
- Identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice and how such evidence informs human health assessments.
- Identify approaches for analyzing and interpreting the evidence.
- Identify commonalities, linkages, or differences between the evidence from various disciplines.
This workshop was conducted to inform the development of assessments for chemicals where mouse lung tumors are an issue (e.g., ethylbenzene, naphthalene, styrene). EPA did not seek consensus, recommendations, or guidance during the workshop.
Date/Time:
EPA's Mouse Lung Tumor Workshop (MLTW) was held from 8:30 AM - 5:00 PM eastern time on January 7-8, 2014.
Location:
US EPA Auditorium (Room C111)
109 TW Alexander Drive
Research Triangle Park, NC 27711
Final Agenda
Links to individual slide sets or a more detailed abstract for a presentation are provided; click on the title of a presentation to open the link.
Tuesday, January 7, 2013
Opening and Overview |
|
| 8:30 am | Registration |
| 9:00 am | Welcome and Introductory Remarks - John Vandenberg, PhD; NCEA RTP Division Director |
| 9:20 am | Goals and Scope of the Workshop - George Woodall, PhD; Workshop Chair and Project Leader |
| 9:50 am | Workshop Logistics (On-site and On-line Interactions) - Channa Keshava, PhD; Project Co-Leader |
Session 1: Human Cancer Epidemiology and Pathophysiology |
|
| Co-Chairs: Jason Fritz | US EPA Eric Garshick | Harvard Medical School/VA Boston Healthcare System |
Panelists: James Collins, PhD | Dow Chemical Company Brigitte Gomperts, MD | University of California, Los Angeles Daniel Krewski, PhD | University of Ottawa |
| 10:00 am | Session Overview Jason Fritz and Eric Garshick
|
| 10:05 am | Approaches to Determining Carcinogenic Risks in Humans Eric Garshick | Harvard Medical School/VA Boston Healthcare System
|
| 10:20 am | Guided discussion |
| 10:30 am | Epidemiological Studies of Human Lung Cancer Dan Krewski | University of Ottawa
|
| 10:45 am | Guided discussion |
| 10:55 am | Lung Cancer Mortality: Worker Exposed to Styrene, Ethylbenzene, or Naphthalene Jim Collins | Dow Chemical Company
|
| 11:10 am | Guided discussion |
| 11:20 am | Human Lung Cancer Pathology and Cellular Biology Brigitte Gomperts | University of California, Los Angeles
|
| 11:35 am | Guided discussion |
| 11:45 am | Session Summary Discussion |
| 12:00 pm | Lunch |
Session 2: Comparative Pathology |
|
| Co-Chairs: Charles Wood | US EPA Mark Miller | Wake Forest University |
Panelists: Gary A. Boorman | Covance, Inc. Laura Van Winkle | University of California, Davis Arun Pandiri | Experimental Pathology Laboratories, Inc. |
| 1:00 pm | Session Overview Charles Wood and Mark Miller |
| 1:15 pm | Comparative lung pathology Gary Boorman | Covance, Inc. |
| 1:30 pm | Guided discussion |
| 1:45 pm | Mouse lung tumor model considerations Mark Miller | Wake Forest University
|
| 2:00 pm | Guided discussion |
| 2:15 pm | Rodent lung tumors in NTP studies Arun Pandiri | Experimental Pathology Laboratories, Inc. |
| 2:30 pm | Guided discussion |
| 2:45 pm | Break |
| 3:00 pm | Species Difference in Response and Cell of Origin Laura Van Winkle | University of California, Davis |
| 3:15 pm | Guided discussion |
| 3:30 pm | Animal and Human Tumour Site Concordance Dan Krewski | University of Ottawa |
| 3:45 pm | Guided discussion |
| 4:00 pm | Session Summary Discussion |
| 5:00 pm | Adjourn for the Day |
Wednesday, January 8, 2014
Session 3: Biological Mechanisms |
|
| Co-Chairs: Paul Schlosser | US EPA Ron Melnick | Ron Melnick Consulting |
Panelists: Tim Fennell | Research Triangle Institute Kathy Burns | ScienceCorps LLC Ernest Hodgson | North Carolina State University |
| 8:30 am | Session Overview Paul Schlosser | EPA
|
| 8:35 am | A Framework for Considering the CYP2F2 MOA Hypothesis & Relevance of Mouse Lung Tumors to Humans Ron Melnick | Ron Melnick Consulting |
| 8:45 am | Hypothesis-Driven MOA Analysis: CYP2F2 George Cruzan | ToxWorks |
| 9:05 am | Clarifying Q&A |
| 9:15 am | Pharmacokinetics and Pharmacodynamics of Ethylbenzene Ernest Hodgson | North Carolina State University |
| 9:25 am | Clarifying Q&A |
| 9:30 am | Pharmacokinetics and Pharmacodynamics of Naphthalene Laura Van Winkle | University of California, Davis |
| 9:40 am | Clarifying Q&A |
| 9:45 am | Pharmacokinetics and Pharmacodynamics of Styrene Tim Fennell | Research Triangle Institute |
| 10:00 am | Clarifying Q&A |
| 10:10 am | Break |
| 10:30 am | Related Chemicals: CYP2F2 Substrates & Other Mouse Lung Tumorigens Paul Schlosser | US EPA
|
| 10:40 am | Clarifying Q&A |
| 10:45 am | Integration of Cross Cutting Issues John Lipscomb, PhD | US EPA |
| 10:55 am | Session-wide Open Discussion |
| 11:30 am | Lunch |
Session 4: Evidence for Cellular, Genetic, and Molecular Toxicity |
|
| Co-Chairs: Nagu Keshava | US EPA Gary Stoner, PhD | Medical College of Wisconsin |
Panelists: David Eastmond, PhD | University of California, Riverside Andrew Kligerman, PhD | US EPA, NHEERL Andrew Salmon, PhD | CalEPA, OEHHA |
| 12:30 pm | Session Overview Nagu Keshava and Gary Stoner
|
| 12:40 pm | An Overview of the Genotoxicity of Aromatic Hydrocarbons and their Reactive Intermediates Stephen Nesnow | Independent Consultant
|
| 1:00 pm | Guided discussion |
| 1:10 pm | Mouse Lung Carcinogens, Reactive Metabolites and Toxicity David Eastmond | University of California, Riverside
|
| 1:30 pm | Guided discussion |
| 1:40 pm | Overview of New and Developing Omic Technologies: Assessing Molecular Toxicity and Disease Susceptibility Brian Chorley| US Environmental Protection Agency, RTP
|
| 2:00 pm | Metabolomics Timothy Fennel | RTI International |
| 2:10 pm | Break |
| 2:25 pm | Integration of Sessions 3 and 4 Gary Stoner | Medical College of Wisconsin |
| 2:45 pm | Guided discussion |
| 3:00 pm | Session Summary Discussion |
Summary Session |
|
| Workshop Chair: George Woodall | US EPA |
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| 3:30 pm | Summaries of Key Points from each Workshop Session Session Co-chairs and Workshop Chair
|
| 4:30 pm | Next Steps Workshop Chair to lead the discussion
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| 5:00 pm | Adjourn Workshop |
Panelists, Speakers and Project Team
Provided below are short bio-sketches for the Workshop Chair, and the Co-chairs, Panelists, and Invited Speakers for each Workshop Session. Bios are also provided for the Workshop Project Team.
Session 1. Human Cancer Epidemiology and Pathophysiology
Co-Chairs: Jason Fritz (US EPA) and Eric Garshick (Harvard Medical School/VA Boston Healthcare System)
| Panelist | Title | Affiliation |
|---|---|---|
| Jason Fritz, PhD | Toxicologist | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| After service as a U.S. Marine, Jason Fritz received his baccalaureate in Biochemistry from the University of Denver, and then completed his graduate training at the University of Colorado Anschutz Medical Campus, where he received a Ph.D. in Toxicology studying the effects of chronic inflammation on lung carcinogenesis. Dr. Fritz also received post-doctoral training at UC-AMC, prior to a fellowship in the National Center for Environmental Assessment, part of the Office of Research and Development, within the U.S. Environmental Protection Agency. He is an actively contributing member of the Society of Toxicology, the American Association for Cancer Research, and the Society for Risk Analysis. He also serves as an ad-hoc reviewer for the journal Carcinogenesis, and as reviewer and member of the editorial board for Toxicology Mechanisms and Methods. At the time of this event, Dr. Fritz was a staff Toxicologist, assessment manager and co-chair of the Toxicity Pathways workgroup within the Integrated Risk Information System (IRIS) Division, where he was engaged in evaluating the health hazards associated with chronic exposure to agents such as acrylonitrile, formaldehyde, and benzo(a)pyrene. He also advised on recent promulgations of National Emission Standards for Hazardous Air Pollutants regarding the production of acrylic/modacrylic fibers, polymers and resins, in support of EPA's ongoing mission to protect human health and the environment. | ||
| Eric Garshick, MD, MOH | Associate Professor of Medicine/Physician | Harvard Medical School/VA Boston Healthcare System |
| Dr. Garshick received his Bachelor's degree in Chemical Engineering and Biology in 1975 and his MD degree in 1979, all from Tufts University. He received training in epidemiology at the Channing laboratory, Brigham and Women's Hospital, and received a Masters of Occupational Health degree from the Harvard School of Public Health in 1984. He trained in Internal Medicine at Beth Israel Hospital in Boston and in Pulmonary Medicine at the Brigham and Women's, Beth Israel, and West Roxbury VA Hospitals, and is Board Certified in Internal Medicine, Pulmonary Diseases, and Critical Care Medicine. In addition to practicing Pulmonary and Critical Care Medicine at VA Boston, he has been the principal investigator of two NIH studies examining lung cancer mortality in relation to diesel exhaust exposure in railroad workers and trucking company workers and participated in the IARC assessment regarding diesel exhaust and cancer. He served as a consultant to the EPA Clean Air Scientific Advisory Committee regarding diesel exhaust, and served on the Institute of Medicine's Committee on Gulf War and Health assessment of environmental particulates and pollutants. He has also served a grant reviewer for NIH from 2005-2011 as a member of the Infectious Diseases, Reproductive Health, Asthma, and other Pulmonary Diseases Study Section, and has served as a reviewer on the VA Merit Review Panel for the Rehabilitation Research and Development since 2008. He has published 98 peer-reviewed papers. |
||
| James J. Collins, PhD | Director of Epidemiology | Dow Chemical Company |
| Dr. James Collins received his PhD in 1981 from the University of Illinois at Urbana-Champaign and is a Fellow in the American College of Epidemiology. He is currently the Director of Epidemiology at the Dow Chemical Company in Midland, Michigan. He is also an Adjunct Research Professor at the University of Pittsburgh, School of Public Health and at Saginaw Valley State University. Prior to joining Dow, he directed epidemiology programs at Solutia, Monsanto, Ford, and American Cyanamid and worked at Argonne National Laboratory. His major research interest is the impact of occupational and environmental exposures on health including exposures from dioxins, benzene, acrylonitrile, acrylamide, formaldehyde, styrene, and glutaraldehyde. He has published more than 100 papers in these areas. He is currently on the Editorial Boards for Environmental Health Perspectives, Journal of Environmental and Occupational Medicine, and the Open Epidemiology Journal. He has also has served on several science advisory committees. | ||
| Brigitte Gomperts, MD | Associate Professor | University of California-Los Angeles, Department of Pediatrics |
| Dr. Brigitte Gomperts received her medical degree from the University of the Witwatersrand, Johannesburg, South Africa, and her training as a Pediatric Hematologist-Oncologist at Washington University in St. Louis. She is currently an Associate Professor at the University of California, Los Angeles and a member of the Jonsson Comprehensive Cancer Center and the Broad Stem Cell Research Center. She is also a member of the American Thoracic Society. Her lab studies lung repair and regeneration from stem cells in health and disease. She has published more than 30 peer-reviewed papers in this area. Her lab is interested in understanding the mechanisms of airway basal stem cell repair and how this process goes awry during the development of premalignant lesions. She is also interested in identifying driver mutations that are associated with the stepwise progression of premalignant lesions to squamous non-small cell lung cancer. Her lab has developed novel in vivo and in vitro human and mouse models to study the process of stepwise progression to lung cancer in order to study these processes. | ||
| Daniel Krewski, MHA, MSc, PhD | Director | McLaughlin Centre for Population Health Risk Assessment, University of Ottawa |
| Dr. Daniel Krewski is Professor and Director of the R. Samuel McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa, where he is involved in a number of activities in population health risk assessment within the new Institute of Population Health. Dr. Krewski has also served as Adjunct Research Professor of Statistics in the Department of Mathematics and Statistics at Carleton University since 1984. Prior to joining the Faculty of Medicine at the University of Ottawa in 1998, Dr. Krewski was Director, Risk Management in the Health Protection Branch of Health Canada. While with Health Canada, he also served as Acting Director of the Bureau of Chemical Hazards and as Chief of the Biostatistics Division in the Environmental Health Directorate. Dr. Krewski obtained his Ph.D. in statistics from Carleton University and subsequently completed an M.H.A. at the University of Ottawa. His professional interests include epidemiology, biostatistics, risk assessment, and risk management. | ||
Session 2. Comparative Pathological Evidence for Lung Tumors
Co-Chairs: Charles Wood (US EPA) and Mark S. Miller (Wake Forest University)
| Panelist | Title | Affiliation |
|---|---|---|
| Charles E. Wood, DVM, PhD, DACVP | Research Biologist | US Environmental Protection Agency, National Health Effects and Environmental Research Laboratory |
| Dr. Wood is a research scientist and pathologist within the Carcinogenesis Branch of the National Health and Environmental Effects Research Laboratory at the US Environmental Protection Agency (EPA) in Research Triangle Park, NC. He received his DVM from the University of Georgia, College of Veterinary Medicine and completed a fellowship in Comparative Pathology and PhD in Molecular and Cellular Pathobiology from the Wake Forest University School of Medicine, where he then served as a faculty member in the Department of Pathology with a joint appointment in Translational Science prior to joining EPA. Dr. Wood's background is in comparative/translational pathology and cancer biology. His research interests relate broadly to cancer risk modeling and mechanisms of carcinogenesis, with recent emphasis on prospective applications of the mode of action framework to improve chemical prioritization efforts. This work supports EPA programs related to chemical safety and water and air quality. In recent years he has served on various scientific advisory boards, expert review panels, and grant review sections related to this work. He currently serves as a member of the Cancer Assessment Review Committee for the US EPA Office of Pesticide Programs and as an ad hoc pathology advisor for several EPA science councils. Other professional activities include participation in various pathology work groups and scientific societies. | ||
| Mark Steven Miller, PhD | Professor of Cancer Biology | Wake Forest School of Medicine |
| Dr. Miller received his Bachelor's degree in the Biological Sciences from Fordham University in New York and then completed his graduate training at Columbia University, where he received a PhD in Pharmacology in 1983. Dr. Miller received additional postdoctoral training in the Laboratory of Toxicology at the Massachusetts Institute of Technology from 1983 to 1986 and in the Laboratory of Comparative Carcinogenesis at the National Cancer Institute from 1986-1990. He previously held a faculty position at the University of Tennessee and joined the faculty at the Wake Forest University School of Medicine in 1996, where he currently holds the position of Professor of Cancer Biology and Physiology/Pharmacology. Dr. Miller has served on NIH, DOD, and EPA grant review panels, as well as serving as Chair of the IRIS Assessment of Nitrobenzene for the EPA; as a member of the Alcohol and Toxicology study section for the NIH, is an ad hoc reviewer for several journals and NIH and EPA study sections, and has served as an officer in the Society of Toxicology and the Genetic and Environmental Mutagenesis Society. He has published more than 75 articles in peer-reviewed journals. His research interests have focused on the interaction between environmental and genetic factors in determining the molecular pathogenesis of lung cancer utilizing a variety of in vivo animal models. Recent studies from have focused on (1) determining environmental/genetic interactions that affect an organism's susceptibility to lung cancer formation, particularly as it relates to the effects of environmental chemicals on the developing fetus; (2) the development of novel chemopreventive agents to prevent lung cancer formation in high risk individuals; and (3) use of imaging techniques to assess early lesion development. He has expertise with murine models of lung cancer and the analysis of tumors by biochemical and molecular techniques. | ||
| Gary A. Boorman, DVM, PhD, DABT, DACLAM, DACVP | Toxicologic Pathologist | Covance, Inc. |
| Gary Boorman received his Doctorate of Veterinary Medicine from the University of Minnesota, spent a year in mixed practice in Wisconsin followed by a Laboratory Animal Residency at the University of Michigan where he received a Masters in Pathology. This was followed by four years at the Institute for Experimental Gerontology, TNO in Rijswijk, The Netherlands. Gary did a pathology residency at the University of California, Davis where he received his PhD in Pathology. He spent 30 years at the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences (NIEHS) with a focus mainly on Rodent Carcinogenicity Studies. Gary currently works with non-clinical studies at Covance Inc. located in Chantilly, Virginia. Gary is a Diplomate of American Board of Toxicology (ABT), American College of Veterinary Pathologists (ACVP), and the American College of Laboratory Animal Medicine (ACLAM), and a Fellow, International Academy of Toxicologic Pathology (IATP). In 2006, Gary was recognized as a Distinguished Research Alumnus of the College of Veterinary Medicine, University of Minnesota. He was recognized as a Distinguished Member, American College of Veterinary Pathologists in 2010. In 2012 Gary was given the Lifetime Achievement Award by the Society of Toxicologic Pathology. Gary's currents interests are rodent pathology and the use of genomic technologies to enhance our understanding of the morphological changes we find in non-clinical studies. | ||
| Laura Van Winkle, PhD | Adjunct Professor | University of California at Davis |
| Dr. Laura Van Winkle is currently an Adjunct Professor in the Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California (UC) at Davis. She is also a Research Cell Biologist in the Center for Health and the Environment, John Muir Institute of the Environment also at UC Davis. She received her PhD in 1995 and has been a Diplomate of the American Board of Toxicology since 2002. She is a respiratory toxicologist with specialized training in airway cell biology, respiratory disease, and pathology of conducting airway epithelial injury and repair. Her research includes the study of air pollutants, ingested chemicals, allergens, and engineered nanomaterials and their effects on the adult and developing lung. She served as a peer review panel member of the EPA review of naphthalene carcinogenicity in 2004. She has reviewed grants for NIH and the Florida Department of Health and served as a councilor for the Inhalation and Respiratory Specialty Section of the Society of Toxicology. Professional affiliations include the American Society for Cell Biology, Society of Toxicology, American Physiologic Society and the American Thoracic Society, where she currently serves on the ATS Environmental Health Policy Committee. She has published over 60 papers in peer reviewed journals. She has 20 years of experience studying naphthalene pathology and mechanism of action. | ||
| Arun Pandiri, BVSc&AH, MS, PhD, Diplomate ACVP, ABT | Pathologist | Experimental Pathology Laboratories, Inc. (Contractor to NTP, NIEHS) |
| Dr. Arun Pandiri is a pathologist at the Experimental Pathology Laboratories, Inc. in Research Triangle Park, North Carolina and provides on-site contract support for the Cellular and Molecular Pathology Branch of the National Toxicology Program within the National Institute of Environmental Health Sciences. He received his Veterinary Medical degree from ANGR Agricultural University, Hyderabad, India, and his PhD from Michigan State University. He completed his pathology residency training at North Carolina State University and is a diplomate of the American College of Veterinary Pathologists. He has interests in chemical-induced tumorigenesis and lung and gastrointestinal pathology. He is an active member in the Societies of Toxicologic pathology (STP) and Toxicology (SOT). | ||
Session 3: Biological Mechanisms
Co-chairs: Paul Schlosser (US EPA) and Ronald Melnick (Ron Melnick Consulting)
| Panelist | Title | Affiliation |
|---|---|---|
| Paul Schlosser, PhD | Environmental Health Scientist | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| Paul Schlosser received his Bachelors of Science (1982) and PhD (1988) from the University of Rochester, with a Masters of Applied Science (1984) from the University of Toronto, all in Chemical Engineering. He then conducted three years of postdoctoral research in Biochemical Engineering at the California Institute of Technology, developing methods to identify limiting factors in biochemical pathways used in industrial fermentation and cell cultures. In 1991 Paul joined the Chemical Industry Institute of Toxicology (later the CIIT Centers for Health Research, now The Hamner Institutes), and conducted research on the modeling of xenobiotic metabolism and dosimetry, with applications in risk assessment. Because of his background training in chemical engineering which includes transport phenomena, one focus of this work was inhalation dosimetry, particularly that of formaldehyde. Dr. Schlosser came to the U.S. EPA, National Center for Environmental Assessment (NCEA) in 2004 as an Environmental Health Scientist. Dr. Schlosser now co-chairs the NCEA's Pharmacokinetic Workgroup (PKWG), which is tasked with evaluating and guiding or conducting the application of PBPK and PK models in risk assessment. He has been a primary contributor to the completed Toxicological Reviews for dichloromethane and methanol (non-cancer). Paul also worked on developing methods to quantify variability and uncertainty in PBPK model predictions. In professional society service, he has served as councilor of Biological Modeling Specialty Section (BMSS) of the Society of Toxicology (SOT); secretary/treasurer of North Carolina Chapter, SOT; vice-president, president-cycle and trustee-at-large of the DRSG; and president-cycle and board member of the Research Triangle Chapter, SRA. | ||
| Ronald Melnick, PhD | Director | Ron Melnick Consulting, LLC |
| Ron Melnick received his Ph.D. from the University of Massachusetts in Amherst and was a postdoctoral fellow at the University of California in Berkeley. He was an assistant professor of Life Sciences at the Polytechnic Institute of New York, and then spent 28+ years as a toxicologist at the National Institute of Environmental Health Sciences (NIEHS)/National Toxicology Program. At NIEHS, he was involved in the design, monitoring and interpretation of toxicity and carcinogenesis studies, and conducted mechanistic research to characterize potential health effects of environmental and occupational agents. He spent a year as an agency representative to the White House Office of Science and Technology Policy to work on interagency assessments of health risks of environmental agents and on risk assessment research needs in the federal government. Dr. Melnick has organized several national and international symposiums and workshops on health risks associated with exposure to toxins. After retiring from NIEHS, he established Ron Melnick Consulting, LLC. He has served on numerous scientific review boards and advisory panels, including those of the International Agency for Research on Cancer and EPA. He was the recipient of the American Public Health Association's 2007 David P. Rall Award for science-based advocacy in public health. | ||
| Timothy Fennel, PhD | Director of the RTI Center for Nanotechnology Health Implications Research | Research Triangle Institute |
| Timothy Fennell trained as a biochemist and has extensive experience in understanding the metabolism of chemicals and the role of metabolism in toxicity. He has conducted investigations of the metabolism of a wide variety of chemicals, including styrene. He has more than 30 years of experience in mechanistic-based research and is recognized as an expert in biomarkers, particularly in the area of reactive chemicals/metabolites and exposure assessment via protein- and DNA-adduct measurement. Dr. Fennell serves as the director of the RTI Center for Nanotechnology Health Implications Research funded by the National Institute of Environmental Health Sciences. He holds a PhD in Biochemistry and a BSc in Biochemistry (Honors) from the University of Surrey, Great Britain. | ||
| Kathleen Burns, PhD | Director | ScienceCorps LLC |
| Dr. Burns is a toxicologist who specializes in chemical risk assessment focused on mode of action, threshold, elevated susceptibility and related concepts. She worked for state and federal agencies for 20 years before founding Sciencecorps in 2004. She assisted EPA in the development of air and water regulations, the TRI program, TSCA regulations, cost benefit methods, RSEI and other agency programs. She manages investigative teams and conducts environmental justice and epidemiological studies and risk assessments of chemical and radiological contamination of air, water, soil, consumer products, food and workplaces. She provides public health support to communities, litigation support on water contamination cases and assisted in drafting state and federal legislation. Dr. Burns has policy, science and public health degrees and training from the University of Chicago, the University of Illinois Medical Center in Chicago, Harvard University, and Northwestern University Medical School. She is a member of the American College of Occupational and Environmental Medicine and the International Society for Environmental Epidemiology. | ||
| Ernest Hodgson, PhD | Distinguished Professor Emeritus | Department of Environmental & Molecular Toxicology, NC State University |
| Dr. Ernest Hodgson is a Distinguished Professor Emeritus at North Carolina State University and Executive Director of the Foundation for Toxicology and Agromedicine. Dr. Hodgson has conducted research on xenobiotic biochemistry for several decades, has authored c. 400 peer-reviewed papers in this area, and is editor and part author of several monographs. Most recently his research has focused on human studies utilizing human hepatocytes and sub-cellular preparations. He is currently involved in RNAseq studies of genome-wide effects of environmental chemicals. Dr. Hodgson is also editor and contributing author of toxicology textbooks (Textbook of Modern Toxicology and Molecular and Biochemical Toxicology, both currently in their 4th editions). He has been recognized by awards from the Society of Toxicology, the American Chemical Society, the International Society for the Study of Xenobiotics, the Consolidated University of North Carolina, and North Carolina State University. | ||
| Invited Speaker | Title | Affiliation |
|---|---|---|
| George Cruzan, PhD | President | ToxWorks |
| Dr. George Cruzan provides toxicology consulting to a variety of companies and trade associations. Projects have included regulatory interactions and comments on proposed actions; toxicologic evaluation, including assessment of database, design of research programs, monitoring of studies, and integration into mode of action presentations, and presentations to regulatory agencies. Styrene health effects and mode of action (MOA) has been a major focus of his activities since 1989. He served as chairman of the Science and Technology Task Group of the Styrene Information and Research Center (SIRC) from 1991 to 1995, and has provided science consulting to SIRC since 1995. He was a member of the IARC Panel that reviewed styrene and naphthalene in 2002. He is the lead author on five publications on the MOA of mouse lung tumors from styrene. He has been certified in Toxicology by the American Board of Toxicology since 1980 and a member of the Society of Toxicology since 1986. | ||
| John Lipscomb, PhD | Toxicologist | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| Dr. Lipscomb was a toxicologist and risk assessor in the National Center for Environmental Assessments. At the time of this event, his activities and interests centered on replacing default options with science-based decisions. With over 20 years experience in toxicology and risk assessment, including the US EPA, US FDA/NCTR and uniformed service in the US Air Force, he has published 62 articles, 10 book chapters, 31 government reports, edited a text on Toxicokinetics and Risk Assessment, written risk assessment guidance for the US EPA and the WHO's International Programme on Chemical Safety, and served as a technical advisor to the American Water Works Association for its research on drinking water disinfection byproducts. | ||
Session 4. Evidence for Cellular, Genetic, and Molecular Toxicity
Co-chairs: Nagu Keshava (US EPA) and Gary Stoner, PhD (Medical College of Wisconsin, Division of Hematology and Oncology)
| Panelist | Title | Affiliation |
|---|---|---|
| Nagu Keshava, PhD | Toxicologist | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| Dr. Keshava is currently a Senior Toxicologist at the Center for Public Health and Environmental Assessment (CPHEA), Office of Research and Development (ORD), Environmental Protection Agency (EPA), Washington DC, USA. Prior to moving to EPA, she was at Centers for Disease Control - National Institute for Occupational Safety and Health (CDC/NIOSH). She graduated with a Ph.D. from West Virginia University majoring in Genetics and Developmental Biology. Her areas of scientific expertise and interests include genetic toxicology, mode of action, risk assessment and cancer biology. At EPA, she has led or contributed to risk assessments of various chemicals including 1,2-dichloroethane, trichloroethylene, ethylene oxide, tetrachloroethylene, and formaldehyde. Dr. Keshava has provided scientific support to program offices within EPA and other federal agencies. She has received several awards including the Gold and Bronze medals from U.S. Environmental Protection Agency. She is a member of professional societies including Environmental Mutagenesis and Genomics Society, Society of Toxicology, Genetics and Environmental Mutagenesis Society (GEMS). She has authored or co-authored over 40 peer-reviewed articles and book chapters in journals including Cancer Research and Proceedings of National Academy of Sciences. She has also contributed to numerous governmental and intergovernmental reports. Dr. Keshava has served on several committees, organized and chaired workshops and symposium at the Environmental Mutagenesis and Genomics Society, Genetics and Environmental Mutagenesis society. She is a past president of GEMS. | ||
| Gary Stoner, PhD | Professor of Medicine | Medical College of Wisconsin, Division of Hematology and Oncology |
| Dr. Gary Stoner is Professor of Medicine at the Medical College of Wisconsin Division of Hematology and Oncology, specializing in the fields of chemical carcinogenesis and cancer chemoprevention. He currently serves as Director of the Molecular Carcinogenesis and Chemoprevention Program in the newly developing Cancer Center. Dr. Stoner received his PhD in microbiology from the University of Michigan in 1970 and subsequently became a post-doctoral fellow and research scientist at the University of California-San Diego. While at UCSD, his research focused on the development of the A/J mouse model of lung cancer for identification of environmental carcinogens and mechanistic studies of lung carcinogenesis. He then joined the Laboratory of Human Carcinogenesis at the National Cancer Institute where he conducted research on the metabolism of tobacco carcinogens in human lung tissues and developed human lung cell culture systems for investigations of carcinogen/oncogene-induced cell transformation. He later became involved in chemoprevention research at the Medical College of Ohio. His research is documented in more than 350 peer-reviewed publications and book chapters, and he has edited several books. Dr. Stoner has served on several grant and contract review committees including the NIH Chemical Pathology Study Section, the NCI Cancer Biology and Immunology Contract Review Committee, and as Chair of the NIH Chemo/Dietary Prevention Study Section and the American Cancer Society Advisory Committee on Carcinogenesis, Environment and Nutrition. He has also served as President of the Carcinogenesis and Molecular Biology Specialty Sections of the American Society of Toxicology and of the Ohio Valley Society of Toxicology. He has received numerous awards including the NIH MERIT award, and the Distinguished Alumni Award and Honorary Doctorate from Montana State University. He is also a Fellow in the American Association for the Advancement of Science. | ||
| David Eastmond, PhD | Chair, Cell Biology & Neuroscience; Professor of Cell Biology & Toxicologist | University of California Riverside |
| Dr. David A. Eastmond is a professor and chair of the Department of Cell Biology and Neuroscience at the UC Riverside. He received his B.S. and M.S. degrees from Brigham Young University in Provo, Utah and his Ph.D. from the University of California, Berkeley. From 1987 to 1989, he was appointed as an Alexander Hollaender Distinguished Postdoctoral Fellow at Lawrence Livermore National Laboratory. Shortly thereafter, Dr. Eastmond joined the faculty at UC Riverside where he is actively involved in research and teaching in the areas of toxicology and risk assessment. The research in Dr. Eastmond's laboratory focuses on the mechanisms involved in the toxicity and carcinogenesis of environmental chemicals. His research has centered on the metabolism and chromosome-damaging effects of various environmental chemicals including benzene, a widely used industrial chemical and environmental pollutant, and ortho-phenylphenol, a commonly used fungicide and disinfectant. Dr. Eastmond served as the president of the Environmental Mutagen Society and as a Jefferson Science Fellow in the State Department. He has also participated on a variety of review or advisory panels related to chemical mutagenesis, carcinogenesis and risk assessment including panels for EPA, the US Food and Drug Administration, the National Toxicology Program, the International Programme for Chemical Safety, the International Agency for Research on Cancer, the Organisation for Economic Cooperation and Development, Health Canada, and the International Working Group for Genotoxicity Testing. He currently serves as a member of the Carcinogen Identification Committee for the California Environmental Protection Agency. | ||
| Andrew Salmon, PhD | Scientific Advisor | California EPA, Office of Environmental Health Hazard Assessment |
| Dr. Salmon is currently a Scientific Advisor in Cal/EPA's Office of Environmental Health Hazard Assessment (OEHHA), Scientific Affairs Division, working on special assignments for research collaboration, recruitment and training. Previously, he was Chief of the Air Toxicology and Risk Assessment Unit, in the Air Toxicology and Epidemiology Section of OEHHA. He has worked in OEHHA for the past 25 years doing public health risk assessment, initially for Proposition 65 and more recently in support of the California Air Resources Board's Toxic Air Contaminants program. Current interests include mechanism of action of inhaled toxicants, methodology for cancer and non-cancer risk assessment, identification and estimation of special risks to children's health from air pollutants and potentially toxic contaminants in biogas. He was previously a Lecturer in Industrial Toxicology in the TUC Centenary Institute of Occupational Health at the London School of Hygiene and Tropical Medicine. He has also worked on the metabolism and toxicity of carcinogenic chemicals at University College Hospital Medical School, London, at the University of California, Berkeley and for an industrial toxicology research laboratory in England. Dr. Salmon holds an undergraduate degree in Biochemistry, and a doctorate, from the University of Oxford, England. | ||
| Andrew Kligerman, PhD | Research Biologist/Genetic Toxicologist/Cytogeneticist | US EPA, National Health and Environmental Effects Research Laboratory |
| Dr. Andrew Kligerman is a research biologist in the Integrated Systems Toxicology Division at EPA in Research Triangle Park, NC. He has been a cytogeneticist and genetic toxicologist at the EPA for more than 24 years. He is currently doing an informal rotation with the National Center for Computational Toxicology at EPA, where he is investigating the sensitivity and specificity of high-throughput tests for determining the genetic toxicology of chemicals. For the vast majority of his research career at EPA, he has studied the genotoxicity of important environmental and commodity chemicals. For the previous 10 years, his research has concentrated on investigating the mode of action of arsenicals in inducing genetic damage and cancer. Prior to joining EPA, Dr. Kligerman was a program leader at EHRT, Inc. and staff cytogeneticist at CIIT. Dr. Kligerman received his BS from Duke University in Zoology (1971). He attended Cornell University where he obtained an MS (1974) and PhD (1977) in Animal Cytogenetics in the Laboratory of Dr. Stephen Bloom studying SCEs and chromosome breakage in the mudminnow. Dr. Kligerman completed a Post-doctoral fellowship at Duke University in the Department of Pathology under Dr. George Michalopolous developing co-culture methods using primary rat hepatocytes and human fibroblasts to study genetic damage. Dr. Kligerman has received EPA's Bronze Medal and Levels I and II Scientific Achievement Awards and the EMS Special Service Award. | ||
| Invited Speaker | Title | Affiliation |
|---|---|---|
| Stephen Nesnow, PhD | Director | Stephen Nesnow, Consulting |
| Stephen Nesnow, Ph.D., is a retired Senior Scientist from the U.S. Environmental Protection Agency's (EPA) National Health and Environmental Effects Research Laboratory. Dr. Nesnow received his Ph.D. from New York University. After post-doctoral fellowships at the Sloan-Kettering Institute for Cancer Research and the McArdle Laboratory for Cancer Research, he joined the faculties of the University of Wisconsin and then the University of North Carolina. Dr. Nesnow served as the Branch Chief of the Biochemistry and Pathobiology Branch, EPA for over 20 years and then as a Senior Scientist until retirement. Dr. Nesnow has published more than 240 scientific publications in the area of chemical carcinogenesis, with specialties in metabolism, tumorigenesis, DNA adducts, toxicogenomics, pesticides, and complex mixtures. Dr. Nesnow has been an invited speaker to many national and international symposia and has served as organizer and session chairman at many of these meetings. He has served on national and international panels and committees including many International Agency for Research on Cancer (IARC) Working Groups as a member and as a Workgroup Sub-Chair. He has received awards from the EPA including a Distinguished Career Service Award, two Bronze Medals, and fourteen Scientific and Technological Achievement Awards. He currently serves as Director of Stephen Nesnow, Consulting. | ||
| Brian Chorley, PhD | Molecular Biologist | US Environmental Protection Agency, National Health Effects and Environmental Research Laboratory |
| Dr. Brian Chorley is molecular biologist with fourteen years of laboratory research training in cellular biology and genomics. Dr. Chorley completed his PhD in 2005 from North Carolina State University under the mentorship of Dr. Kenneth Adler where he studied the signaling mechanisms of inflammation and mucin production in airway epithelial cells. He continued his research as a postdoctoral fellow at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, NC where he studied NRF2 antioxidant signaling pathway activation and single nucleotide polymorphisms which can alter regulation of NRF2 target genes. During his time at NIEHS, Dr. Chorley became interested in the environmental effects on human health and individual genetic susceptibility to disease and other adverse outcomes. In 2010, this experience led him to his current position as Principal Investigator in the National Health and Environmental Effects Research Laboratory (NHEERL) at the US Environmental Protection Agency where he currently studies genetic and epigenetic biomarkers of adverse outcomes after chemical exposure. He has authored over ten publications in peer-reviewed journals and has contributed to numerous scientific articles and intramural reports. He is a member of the American Association for the Advancement of Science (AAAS), American Association for Cancer Research (AACR) and a lifetime GEMS member and current councilor. Dr. Chorley currently lives in Raleigh, NC with his wife and two sons. | ||
Workshop Project Team
| Team Member | Title | Affiliation |
|---|---|---|
| George M. Woodall, Jr., PhD | Workshop Chair and Project Lead; Chemical Manager for Styrene | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| Dr. Woodall has been working in environmental and public health for over twenty-five years. He received his doctorate in Toxicology from North Carolina State University in 1996, and previously attained a Masters of Science in Environmental Health from East Tennessee State University (1985) and a Bachelor of Science in Microbiology and Cell Science (1983) from the University of Florida. Dr. Woodall served as a Toxicologist at the National Center for Environmental Assessment (NCEA) of the US EPA, where he worked under the Human Health Risk Assessment Program in performing chemical risk assessments, and developing and improving risk assessment methods. He is the current Chemical Manager for the IRIS assessment in the Center for Public Health and Environmental Assessment (CPHEA), working on an assessment for styrene and has been active in review and analysis of the potential neurotoxic and cancer effects from styrene exposure. He also provides scientific support to the Office of Air Quality Planning and Standards of the US EPA for the Risk and Technology Review program for regulation of hazardous air pollutants. He also actively co-leads an interagency Information Management Working Group which strives to provide a basis for collaborative approaches and sharing of the key information relevant to developing human health risk assessments. Dr. Woodall has served on the National Advisory Committee for Acute Exposure Guideline Levels (AEGLs) for the EPA, and has served on or chaired several expert panels for the OECD. He received the 2008 Science and Technology Achievement Award for the paper: A review of the mutagenicity and rodent carcinogenicity of ambient air, co-authored with Larry Claxton. He previously held the position of Senior Toxicologist with the American Petroleum Institute (API); while in that position, he led the organization for and chaired a symposium (Co-sponsored by the API, the US EPA, the Chemical Industry Institute of Toxicology, and the American Forest & Paper Association) on health research and risk assessment for hydrogen sulfide. He is author or co-author of over 20 peer-reviewed articles and book chapters, and numerous governmental and intergovernmental reports. Dr. Woodall is also active as an officer in the Risk Assessment Specialty Section of the Society of Toxicology (current Secretary-Treasurer; SOT Member since 1988), is a current Councilor for the Genetic and Environmental Mutagenesis Society (GEMS), and a past-chair of the Dose Response Specialty Group of the Society for Risk Analysis (SRA; member since 2002). | ||
| Channa Keshava, PhD | Project Co-Lead; Chemical Manager for Naphthalene | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| Dr. Keshava is currently a Senior Health Scientist in the Integrated Risk Information System (IRIS) program with a background in genetic toxicology and toxicogenomics. He obtained his Ph.D. in 1995 from West Virginia University, Department of Genetics and Developmental Biology Program. Following his postdoctoral training at the Emory University School of Medicine, Atlanta, GA, he joined as a staff scientist at the National Institute for Occupational Safety and Health (NIOSH), Center for Disease Control and Prevention, Morgantown WV. At NIOSH, he conducted research on understanding the carcinogenic effects of environmental pollutants including benzo(a)pyrene, diesel particulate matter, asphalt fumes etc. Dr. Keshava then moved to EPA in 2004 and continued to work in the fields of genetic toxicology, toxicogenomics and risk assessment. He currently works in support of ORD's human health assessment program which evaluates information on health effects that may result from exposure to environmental contaminants. Through the IRIS Program, EPA provides the highest quality science-based human health assessments to support the Agency's regulatory activities. Dr. Keshava is currently chemical manager for naphthalene IRIS assessment. He also provides genetic toxicology support to other IRIS assessments. Dr. Keshava serves as an ad-hoc reviewer for several journal articles including Mutation Research, Environmental Molecular Mutagenesis, Polycyclic Aromatic Compounds, and Carcinogenesis. He is a member of professional societies including Environmental Mutagenesis and Genomics Society, Society of Toxicology, and Genetics and Environmental Mutagenesis Society. He has received many awards including the Bronze Medal from EPA and the Distinguished Alumni Award from West Virginia University. He has made several invited presentations at the national and international meetings and organized and chaired sessions in the area of genetic toxicology and toxicogenomics. Dr. Keshava has led and participated in technical panels, scientific committees and risk assessment work groups. He is current President-elect for the Genetic and Environmental Mutagenesis Society. He has published over 30 peer reviewed journal articles in the field of genetic toxicology and toxicogenomics. | ||
| Paul Reinhart, PhD | Chemical Manager for Ethylbenzene | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| Dr. Reinhart received his PhD in Toxicology from the University of Kentucky in 1993 followed by several years of post-doctoral study at Wayne State University, Detroit, Michigan. His research has focused on the cellular and molecular components of pulmonary toxicity from a variety of agents. Dr. Reinhart is a long-standing member of the Society of Toxicology and is a Diplomate of the American Board of Toxicology. He has been a Toxicologist with the USEPA since 2005 and serves as the Chemical Manager for ethylbenzene. | ||
| Nagu Keshava, PhD | Planning Liaison; Co-chair for Session 4 | US Environmental Protection Agency, Center for Public Health and Environmental Assessment (CPHEA), formerly known as the National Center for Environmental Assessment (NCEA) |
| Dr. Keshava is currently a Senior Toxicologist at the Center for Public Health and Environmental Assessment (CPHEA). Prior to moving to EPA, she was at Centers for Disease Control - National Institute for Occupational Safety and Health (CDC/NIOSH). She graduated with a Ph.D. from West Virginia University majoring in Genetics and Developmental Biology. Her areas of scientific expertise and interests include genetic toxicology, mode of action, risk assessment and cancer biology. At EPA, she has led or contributed to risk assessments of various chemicals including 1,2-dichloroethane, trichloroethylene, ethylene oxide, tetrachloroethylene, and formaldehyde. Dr. Keshava has provided scientific support to program offices within EPA and other federal agencies. She has received several awards including the Gold and Bronze medals from U.S. Environmental Protection Agency. She is a member of professional societies including Environmental Mutagenesis and Genomics Society, Society of Toxicology, Genetics and Environmental Mutagenesis Society (GEMS). She has authored or co-authored over 40 peer-reviewed articles and book chapters in journals including Cancer Research and Proceedings of National Academy of Sciences. She has also contributed to numerous governmental and intergovernmental reports. Dr. Keshava has served on several committees, organized and chaired workshops and symposium at the Environmental Mutagenesis and Genomics Society, Genetics and Environmental Mutagenesis society. She is a past president of GEMS. | ||