EMERGING SCIENCE FOR

ENVIRONMENTAL HEALTH DECISIONS

WORKSHOP ON ADVANCESIN CAUSAL UNDERSTANDING

FOR HUMAN HEALTH RISK-BASED DECISION MAKING

March 6–7, 2017National Academies of Sciences, Engineering, and Medicine

National Academy of Sciences Building Lecture Room

2100 Constitution Avenue, NW Washington, DC

This workshop is hosted by the National Academies’ Standing Committee on Use of Emerging Science for Environmental Health Decisions (ESEHD). The ESEHD committee is organized

under the auspices of Board on Life Sciences and the Board on Environmental Studies and Toxicology of the National Academies, and sponsored by the National Institute of

Environmental Health Sciences.

2

Table of Contents

Workshop Agenda………………………………………………...……………….…5

Workshop Information………………………………………………………………7

Speaker Abstracts……………………………………………………………………………………………….7 Speaker and Moderator Biographies…………………………………………………………………13 Planning Committee Roster………………………………………………………………………………24 List of Selected Readings………………………………………………………………………………..…25

Standing Committee Information………………………………………………….26

About the Standing Committee and Committee Statement of Task……………….…26 Standing Committee Roster………………………………………………………………………….…..28 Standing Committee Member Biographies……………………………………………………....29

3

4

Register at http://dels.nas.edu/envirohealth

MONDAY, MARCH 6, 9:00AM-5:15PM

SeSSion 1 An overview of CAuSAl Thinking And new wAyS To ConneCT dATA

9:00 Welcome—Kimberly Thigpen Tart, National Institute of Environmental Health Sciences

9:10 Opening Remarks—Kim Boekelheide, Brown University, Standing Committee Co-Chair

9:30 Causal Inference: New Data, An Old Problem— Jonathan Samet, University of Southern California Institute for Global Health

10:10 Causal Inference from Data—Philip Stark, University of California, Berkeley

10:50 Causal Models in Epidemiology—Paolo Vineis, Imperial College London

11:30 Lunch

SeSSion 2 CASe STudieS of CurrenT ApproACheS for deTermining CAuSAliTy

Moderator: Kevin Elliott, Michigan State University

12:30 The Key Characteristics of Carcinogens—Martyn Smith, University of California, Berkeley, School of Public Health

12:50 Inferring Causality in Observational Epidemiology: Breast Cancer Risk as an Example—Mary Beth Terry, Columbia University Mailman School of Public Health

1:10 Determining Causality in Obesity—Jessie Buckley, Johns Hopkins Bloomberg School of Public Health

1:30 The Negative Control Approach to Detect and Correct for Unobserved Confounding—Eric Tchetgen Tchetgen, Harvard T.H Chan School of Public Health

new moleCulAr And bioinformATiC ApproACheS have advanced understanding of how molecular pathways are affected by exposure and the molecular networks involved in disease. However, these advances are often not yet deemed sufficient to establish causality for public health risk assessments; regulators still rely primarily on traditional apical endpoints, such as those endpoints observed in animal studies. This workshop will discuss the current

thinking surrounding causal models, how novel approaches and tools are relevant for environmental health, and how they can be incorporated into the decision making process. Environmental health experts, toxicologists, statisticians, sociologists, epidemiologists, regulators, will be joined by experts from other fields that utilize different data streams for establishing causality in complex systems.

AGENDA

(continued)

Advances in Causal Understanding for Human Health Risk-Based Decision Making

MARCH 6–7, 2017 THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE

LECTURE ROOM, 2101 CONSTITUTION AVE NW, WASHINGTON, DC

ThiS meeTing will be webCAST

5

MONDAY, MARCH 6, CONTINUED

1:50 Panel Discussion − Martyn Smith, University of California, Berkeley, School of Public Health

− Mary Beth Terry, Columbia University Mailman School of Public Health

− Jessie Buckley, Johns Hopkins Bloomberg School of Public Health

− Eric Tchetgen Tchetgen, Harvard T.H Chan School of Public Health

2:10 Break

SeSSion 3 exploring novel reSeArCh ToolS

Moderators: Margaret Karagas, Dartmouth College and Chirag Patel, Harvard Medical School

2:25 20th Century Causality Frameworks Are Evolving To Fit 21st Century Data—Vincent Cogliano, U.S. Environmental Protection Agency

2:45 The AOP Framework and Causality: Meeting Chemical Risk Assessment Challenges in the 21st Century—Gerald Ankley, U.S. Environmental Protection Agency (remote)

3:15 Computational Causal Discovery—Richard Scheines, Carnegie Mellon University

3:45 A Big Tech Approach to a “Small” Problem: Microbiome Characterization of Raw Food Ingredients to Improve Food Safety—Kristen Beck, IBM Watson (remote)

4:15 Panel Discussion − Gary Ginsberg, Connecticut Department of Public Health

− Martyn Smith, University of California, Berkeley, School of Public Health

− Kathryn Guyton, International Agency for Research on Cancer

− Reza Rasoulpour, Dow Agro Sciences − Stanley Barone, U.S. Environmental Protection Agency

− Meredith Williams, California Department of Toxic Substance Control

TUESDAY, MARCH 7, 9:00AM-12:00PM

SeSSion 4 highlighTing gApS And opporTuniTieS

Moderator: Gary Miller, Emory University

These debates are designed to stimulate candid discussion and present opposing viewpoints of a specific issue or topic related to environmental health. The views expressed in these debates are not necessarily the views of the speaker or the planning committee and should not be taken or quoted as such.

9:00 Welcome—Gary Miller, Emory University

9:10 Debate Scenario 1: Mercury and Cardiovascular Health − Gary Ginsberg, Connecticut Department of Public Health

− Melissa Perry, George Washington University

9:45 Debate Scenario 2: Application of Read-Across Using in vitro Data in Dodecylphenol Risk Assessment − Lesa Aylward, Summit Toxicology, LLP − Patrick McMullen, ScitoVation

10:20 Debate Scenario 3: Application of Human Cell-Based Assays in Toxicity Testing − Reza Rasoulpour, Dow AgroSciences − Norbert Kaminski, Michigan State University

10:55 Panel Discussion to Identify Unifying Themes − Gary Ginsberg, Connecticut Department of Public Health

− Melissa Perry, George Washington University − Lesa Aylward, Summit Toxicology, LLP − Patrick McMullen, ScitoVation − Reza Rasoulpour, Dow AgroSciences − Norbert Kaminski, Michigan State University

11:55 Closing Remarks

12:00 Adjourn Meeting

Workshop Planning Committee MembersKim Boekelheide (Co-Chair), Brown UniversityWeihsueh Chiu, Texas A&M UniversityKristi Pullen Fedinick, Natural Resource Defense CouncilGary Ginsberg, Connecticut Department of Public HealthReza Rasoulpour, Dow AgroSciences

6

Speaker Abstracts

Session 1: An Overview of Causal Thinking and New Ways to Connect Data

Causal Inference: New Data, An Old Problem

Jonathan M. Samet University of Southern California

A starting point in decision-making with regard to management of environmental health hazard is the determination that an exposure increases risk for an adverse outcome. In the Red Book paradigm, this determination corresponds with hazard identification and more generally with causal inference—the assessment of the strength of evidence for a causal association between exposure and outcome. In medicine and public health, the development of approaches for such assessment dates to the 19th century with the Henle-Koch postulates, elaborated to support the determination as to whether an infectious organism causes a particular disease. In the 1950s and 1960s, as non-communicable diseases emerged and epidemiological studies pointed to cigarette smoking as a cause of lung cancer, cardiovascular disease, and chronic obstructive pulmonary disease, guidelines were proposed for causal inference that accommodated reliance on observational evidence; the most notable were those used in the 1964 report of the Surgeon General on smoking and health and those in the 1965 paper by Bradford Hill (see table). The guidelines are the basis for expert judgement, and none are requisite except for temporality. Since the 1960s, these guidelines have been adopted in multiple frameworks for environmental health decision-making and accommodated to new data streams and questions. This presentation will cover that history using a case-study approach, setting out how these guidelines have proved useful for decades while their application has been continually challenged by the evolution of the nature of the evidence considered.

Causal inference from data Philip Stark

University of California, Berkeley What do we mean by "causality?" When are we justified in drawing causal conclusions from data? How much does experimental design matter? Are there algorithms that can draw reliable causal inferences from observational data?

Causal Models in Epidemiology Paolo Vineis

Imperial College London My presentation will address in particular the combined use of the epidemiological design and of laboratory approaches (including molecular biomarkers and omics) to address causality. I refer to the work of Russo and Illari to describe the use of markers according to the concept of information transmission along the causal chain. I will provide a few examples, referring also to the IARC Monograph programme.

7

Session 2: Case Studies of Current Approaches for Determining Causality

The Key Characteristics of Carcinogens Martyn T. Smith

University of California, Berkeley An international collaboration between scientists from IARC, US EPA, the NTP and academia has developed a set of 10 key characteristics of human carcinogens that was published recently in Environmental Health Perspectives (Vol.124; 713-721, 2016). These 10 key characteristics can be used to organize mechanistic data during the evaluation of the carcinogenic hazard of a chemical. They are currently being used by IARC in their evaluations and other authoritative bodies use similar search tools and criteria. We propose that scientists should develop key characteristics for other endpoints such as endocrine disruption and reproductive toxicity as suggested in the recent National Academies report on “Using 21st Century Science to Improve Risk-Related Evaluations.”

Inferring causality in observational epidemiology: Breast Cancer Risk as an Example

Mary Beth Terry Columbia University Mailman School of Public Health

This talk will review what we know about breast cancer prevention and risk assessment and highlight key gaps that need to be addressed. Many epidemiological studies, particularly those using population-based ascertainment, do not include a substantial proportion of subjects with a cancer family history, and are therefore not enriched for underlying genetic susceptibility. This can have an impact on both the precision and ability to identify associations if the risk gradient depends on underlying genetic susceptibility (i.e., gene-environment interactions). Improving precision can be readily accomplished through sampling more individuals. However, increasing the sample size, without ensuring adequate individuals at greater disease susceptibility are included, will limit the ability to detect gene-environment interactions. Thus, the role of a given environmental factor may be under-recognized if gene-environment interactions exist. Using a family-based cohort enriched with individuals across the risk spectrum, we illustrate the importance of having sufficient numbers of individuals across the risk spectrum to properly test the role of environmental factors on cancer risk. We illustrate this concept by estimating the association between polycyclic aromatic hydrocarbons (PAHs) and breast cancer risk as a function of a woman’s underlying genetic risk inferred from her cancer family history.

Determining causality in obesity Jessie Buckley

Johns Hopkins Bloomberg School of Public Health Obesity is a complex disease characterized by positive energy balance. While treatment strategies focus on energy intake and expenditure at the individual level, prevention requires population-based approaches that recognize multiple spheres of influence from cell to society. This presentation will discuss frameworks for evaluating causes of obesity including risk factor identification, causal inference, and systems science approaches. Challenges and opportunities

8

will be discussed with an application to examining early life environmental exposures and childhood obesity.

The negative control approach to detect and correct for unobserved confounding Eric Tchetgen Tchetgen

Harvard T.H. Chan School of Public Health This talk will give a brief overview of the negative control approach for indirect adjustment of unobserved confounding in causal inference from observational data. New sufficient conditions for nonparametric identification of a treatment causal effect subject to unobserved confounding will be discussed, corresponding methods for statistical inference will be described and a number of illustrative examples will be given. Session 3: Exploring novel research tools

20th Century Causality Frameworks Are Evolving To Fit 21st Century Data

Vincent Cogliano U.S. Environmental Protection Agency

Causality frameworks have and will continue to evolve to accommodate novel data sources. The earliest frameworks addressed epidemiologic studies and animal bioassays only. During the 1990s and early 2000s, these frameworks evolved to address mechanistic data, as mechanistic understanding grew and new assays came into use. The advent of 21st century data sources presents similar opportunities. A new paradigm, consistent with a multi-factorial view of disease, identifies key precursor events and pathways leading to an apical health endpoint, then tests whether an agent can perturb these pathways. To make full use of the new data, the scientific community faces several challenges, among them: to develop case studies that test approaches for integrating new data into inferences about causality; to better understand the linkages between human diseases and the pathways through which they develop; to communicate the findings of large data sets to decision makers and other stakeholders; to better understand the uncertainties associated with the use of new data; and to promote discussion among scientists and stakeholders about the use of new data in various decision contexts. This abstract does not necessarily represent the views or policies of the U.S. Environmental Protection Agency.

The AOP Framework and Causality: Meeting Chemical Risk Assessment Challenges in the 21st Century

Gerald Ankley US Environmental Protection Agency

Chemical safety assessments are expanding from a focus on a few chemicals (or chemical mixtures) to the broader “universe” of thousands, if not hundreds of thousands of substances that potentially could impact humans or the environment. This is exemplified in regulatory activities such as the REACH program in Europe, or the recent reauthorization of TSCA in the US, which require consideration of the potential impacts of a much greater number of

9

chemicals than in the past. The data needed to address these types of legislated mandates cannot realistically be obtained solely through using the whole animal testing approaches historically employed for chemical risk assessment. Rather, there needs to be an increased emphasis on cost-effective tools that enable robust prediction of potential chemical impacts when empirical data are lacking. Concurrent with the realization that predictive methods will need to play an increasingly prominent role in regulatory toxicology has been the recent explosion in technology in the biological sciences enabling collection of large amounts of pathway-based molecular and biochemical data. For example, genomic techniques and high-throughput (robotic-based) in vitro testing enable the generation of knowledge concerning the effects of chemical perturbation on biological systems in an increasingly efficient and rapid manner. However, a pressing need stemming from these technological advances is the ability to actually apply the generated data to regulatory decision-making and risk assessment. As such, the adverse outcome pathway (AOP) framework provides the basic translation and communication tool needed to facilitate the application of predictive toxicology techniques to chemical risk assessment. The AOP concept, at its simplest, portrays causal linkages between an initial molecular initiating event (MIE; the first interaction of a chemical with a biological macromolecule such as an enzyme of a receptor) and subsequent measurable responses (termed key events [KEs]) across biological levels of organization that occur as a result of this interaction, which culminate in an adverse outcome—typically at the level of the individual or population—relevant to a given risk assessment scenario. An important—and explicit—component of AOP development involves a weight-of-evidence (WoE)-based analysis of causality between KEs depicted within an AOP. In other words, formal depiction/description of an AOP includes an analysis of the causal linkages between molecular/biochemical responses and those endpoints directly meaningful to risk assessment. The WoE analysis for an AOP is based on modified Bradford-Hill criteria originally developed to assess epidemiology data, and consist of three considerations: (1) biological plausibility, (2) essentiality, and (3) empirical support (e.g., dose-response/time-course data). This presentation will introduce the AOP concept and discuss WoE-based causality in the context of AOP development/description. The contents of this presentation do not reflect USEPA policy or positions.

Computational Causal Discovery

Richard Scheines Carnegie Mellon University

I will discuss computational methods for moving from data (experimental or observational or both) to a set of causal hypotheses that explain these data. Originating in work done in causal graphical models by Judea Pearl and Spirtes, Glymour and Scheines in the early 1990s, these methods have been applied widely, and are now the focus of an NIH Center on Causal Discovery focusing on biomedical research. I will briefly sketch the approach, and illustrate it on fMRI data for categorizing autistic vs. neurotypical subjects, for identifying the genetic drivers of lung disease and of cancer.

10

Session 4: Highlighting Gaps and Opportunities

Debate Scenario 1: Mercury and Cardiovascular Health

Gary Ginsberg, Connecticut Department of Public Health Melissa Perry, George Washington University

Resolved: Methyl Mercury is a Contributing Cause to Cardiovascular Disease; This Effect Should be Considered in Methyl Mercury Cost/Benefit Analyses The developmental neurotoxicity of Methyl mercury is well recognized and has been used in establishing the USEPA RfD and in previous cost-benefit analyses of mercury regulations, as well as in setting fish consumption advisories for pregnant women. There is a body of evidence that methyl mercury can have adverse effects on cardiovascular health although this endpoint has not been used in regulatory standard setting or in public health advisories. Cost/benefit analyses of mercury regulations would likely be more influenced by the cardiovascular than neurodevelopmental endpoint if causal evidence for cardiovascular effects is demonstrated. Evidence for causality includes data on mercury effects on molecular targets and adverse outcome pathways, as well as evidence from human populations indicating perturbations of upstream outcomes that are predictive of subsequent acute myocardial events. However, the epidemiological evidence that methyl mercury is a risk factor for cardiovascular disease or acute myocardial infarct is mixed and some studies have shown an inverse association between mercury biomarkers and cardiovascular mortality. This lack of consistency and the inability to quantify an attributable risk for methylmercury and cardiovascular disease in exposed populations are arguments against the causal inference or utility of this endpoint in risk/benefit analyses.

Debate Scenario 2: Application of Read-Across Using in vitro Data in Dodecylphenol Risk Assessment

Lesa Aylward, Summit Toxicology, LLP Patrick McMullen, ScitoVation

Resolved: Read-across from in vitro data and in-silico modeling provides a sufficient basis for presumption of endocrine activity of dodecylphenol and derivation of health reference values. The recent NAS report, Using 21st Century Science to Improve Risk-Related Evaluations, describes the evolving landscape of 21st Century toxicology and exposure science and the application of new concepts in risk assessment. These applications often involve the use of in vitro and in silico techniques to extend existing risk assessment approaches. Here we explore the possibility for incorporating alternative data streams into chemical read across for inferring compound mode of action and safe exposure levels. The practice of read across is predicated upon an implied structure activity relationship: structurally similar compounds produce similar toxicological effects. While traditionally read across is anchored to in vivo endpoints, here we explore the incorporation of in vitro bioactivity estimates to support classification and health

11

reference value estimation. This debate illustrates application of the NAS report framework and elements of the causal frameworks presented in this workshop to a case study of dodecylphenol, a data-poor high production volume chemical used in the production of numerous chemical products. The approach is supported by available structure-activity relationship information and data from in vitro assays on estrogen receptor binding and activity. Cautions arise from the extension of read-across beyond the structural range of compounds with in vivo data and from differing physical/chemical properties and potential differences in metabolism.

Debate Scenario 3: Application of human cell-based assays in toxicity testing.

Reza Rasoulpour, Dow AgroSciences Norbert E. Kaminski, Michigan State University

Resolved: Animal models provide a sufficient basis for presumption for toxicity in safety testing. Utilization of animals for safety testing has been the gold standard in toxicology since inception of the discipline. Due to ethical reasons, cost and the large number of chemicals and agents requiring safety testing, a significant emphasis has been place on the development of cell-based assays as either an adjunct or alternative to animal testing. Strong arguments have been made that cell-based assays lack the fundamental characteristics of tissues and organ systems inherent in the fundamental physiology of humans. Moreover, there are serious knowledge gaps that raise concerns about reliable extrapolation of data from cell-based assays to the human. Yet, in spite of the many inherent problems associated with cell-based assay systems for assessing safety and toxicity (e.g., absence of metabolism, tissue associated cellular interactions through cell-cell contact and release of soluble mediators), it is also becoming increasingly clear that animal models, especially rodents, are poor surrogates of human physiology. A number of recent studies have compared physiological responses at the cellular and molecular level to exogenous stimuli, and have observed marked differences across animal species, especially at the level of transcriptomics. Efforts such as ENCODE and Mouse Encode are beginning to provide important insights in explaining the underlying mechanisms for cross-species differences in responses to environmental stimuli. The observed differences should not come as a surprise as for example, the mouse and human are believed to have diverged evolutionarily 70 million years ago. Since in most cases it is not ethically possible to conduct safety testing in humans, the strengths and challenges of animal versus cell-based toxicity evaluations will be debated.

12

Speaker and Moderator Biographies

Gerald Ankley, Ph.D. Dr. Gerald (Gary) Ankley is a Senior Research Toxicologist with the USEPA Office of Research and Development at the Mid-Continent Ecology Division in Duluth, Minnesota. He also is an Adjunct Professor with the University of Minnesota. Dr. Ankley received his BS from the Department of Fisheries and Wildlife at Michigan State University, and MS and PhD degrees from the School of Forest Resources at the University of Georgia. He has worked at the Duluth USEPA lab for about 28 years in several areas, including the development of aquatic toxicity test methods for effluents and sediments, assessment of the effects of endocrine-disrupting chemicals on wildlife, and application of predictive toxicology tools to ecological risk assessment. He has authored more than 350 research papers and book chapters on these and related topics, and has been formally recognized as one of the most highly cited scientists in the world in the environmental sciences. Dr. Ankley currently/has represented the USEPA on many national and international efforts related to chemical regulation/risk assessment, including several sponsored by the World Health Organization and the Organization for Economic Cooperation and Development. Dr. Ankley has received more than 50 Science and Technology Achievement Awards for different publications based on recommendations by the Science Advisory Board, an external review panel to the EPA. In 2008 he received the prestigious Founders Award from the Society of Environmental Toxicology and Chemistry, in recognition of an outstanding career in the environmental sciences.

Lesa Aylward, Ph.D.

Lesa L. Aylward, Ph.D., is an Honorary Associate Professor with a joint appointment between Queensland Children’s Medical Research Institute and the National Research Center for Environmental Toxicology (Entox) and a Principal at Summit Toxicology, LLP. Dr Aylward’s research interests include the development and application of toxicokinetic models and the use of biomonitoring for tracking exposure to chemicals in the environment, foods, and consumer products. She has published extensively on the development of tools for the interpretation of biomonitoring data in a risk assessment context and the use of biomonitoring as an exposure assessment tool in epidemiological studies. Her current research interests include evaluation of the sources of and factors influencing inter- and intra-individual variation in chemical biomarker concentrations with a focus on the design and implementation of biomonitoring for exposure characterization in epidemiological studies. She has several current collaborations with Entox researchers on the use of human biomonitoring to characterize chemical exposures in the Australian general population and in occupationally exposed groups.

13

Stanley Barone Jr, MS., Ph.D. Dr. Barone has a MS in endocrinology and Ph.D. in neurobiology from East Carolina University School of Medicine. He came to EPA in 1990 as a developmental neurotoxicologist in the neurotoxicology division of what was to become National Health and Environmental Effects Research Laboratory (NHEERL) in the Office of Research and Development (ORD) in Research Triangle Park, NC. In 2004, Dr. Barone moved to Washington DC and joined the National Center for Environmental Assessment (NCEA) after 14 years in NHEERL. Dr. Barone led an effort to develop and implement a framework for Assessing Health Risks of Environmental Exposures to Children (2006). From 2006-2012, Dr. Barone was Assistant Center Director for Human Health Risk Assessment at NCEA in ORD and National Program Director for Human Health Risk Assessment Program and technical contribution to tetrachloroethylene, trichloroethylene (TCE) and methanol IRIS assessments. Dr. Barone served as branch chief of the science support branch in the risk assessment division of Office of Pollution Prevention and Toxics (OPPT) in Office of Chemical Safety and Pollution Prevention (OCSPP) from May 2012 to February 2014. His key responsibilities include overseeing risk assessment activities related to both new chemicals and existing chemicals programs. These efforts included evaluation of ecological and health endpoints. In addition, this position included oversight of design and development of new methods and models for pollution prediction and prevention of chemical exposures. From November of 2013 to May of 2016, Dr. Barone served as the Deputy Director of the risk assessment division of OPPT in OCSPP. His key responsibilities included overseeing risk assessment activities related to both new chemicals and existing chemicals programs, administrative, and resource functions for the entire division. He served as OPPT’s peer review coordinator. Dr. Barone’s health and ecological assessment activities included leadership on a number of OPPT TSCA risk assessments including TCE, antimony trioxide, methylene chloride, n-methyl-pyrrolidone, 1-bromopropane and several flame retardant assessments. Currently, Dr. Barone is the acting Director of the Office of Science Coordination policy (OSCP) which oversees FACA committees reviewing products from OCSPP and houses the endocrine disruptor screening program. Dr. Barone’s experience in cell biology and development of in vitro methods to address hazard of chemicals is currently being put to use in developing new assessment approaches for assuring the safety of chemicals. He has published over 75 peer reviewed papers, technical reports, and book chapters. Dr. Barone has served on peer review panels for numerous government and nongovernmental funding organizations (e.g., VA, NIH, FDA, DOD and Texas A&M University pilot grants program, Cure Autism Now (CAN) Investigator Initiated Research proposals for Jeffress Research Grant Memorial Trust). He has served on numerous government advisory panels (e.g., National Toxicology Program’s Center for the Evaluation of Risks to Human Reproduction and Member of Interagency Advisory

14

Workgroup on Development and Behavior to National Children’s Study, NTP executive committee, Chemical Toxicity Assessment Workgroup of OSTP).

Kristen L. Beck, Ph.D.

Dr. Beck is a research staff member in the Industrial and Applied Genomics group in the Accelerated Discovery Lab of IBM Research. She has been involved in food-related research for over a decade. She has published contributions in mechanistic studies of omega-3 fatty acids in tumorigenesis as well as composition of primate breast milks. Since joining IBM Research in 2015, she has been an essential member of the Consortium for Sequencing the Food Supply Chain and now serves as the IBM Technical Lead. Her current research focuses on analyzing next generation sequencing data to gain insights about microbial ecology in food ingredients as well as confidently determine the presence of various hazards such as pathogenic organisms, antimicrobial resistance genes, or food fraud. She received a Ph.D. in Biochemistry, Molecular, Cellular, and Developmental Biology with a Designated Emphasis in Biotechnology from the University of California, Davis and a B.S. with honors in Biochemistry and Molecular Biology from the University of Nevada, Reno. She was the recipient of two NIH Doctoral T32 Training Grants in Bimolecular Technology and Molecular and Cellular Biology.

Kim Boekelheide, Ph.D. Kim Boekelheide, Ph.D. (co-chair) is professor of Pathology and Laboratory Medicine at the Brown University School of Medicine. He received his B.A. from Harvard University, and M.D. and Ph.D. from Duke University. His research examines fundamental molecular mechanisms by which environmental and occupational toxicants induce testicular injury. Current projects include the development of novel in vitro approaches to safety assessment, use of xenotransplantation approaches for human-relevant toxicity testing, and the discovery of sperm molecular biomarkers that reflect testicular injury. He is Director of the Brown University Superfund Research Program. His research has been continuously funded by the National Institute of Environmental Health Sciences since 1985, and he has received several awards including a Burroughs Wellcome Toxicology Scholar Award (1994-1999).

Jessie Buckley, Ph.D.

Dr. Buckley is an Assistant Professor of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health. She is an environmental and pediatric/perinatal epidemiologist with interests in exposure assessment, epidemiologic methods, and children’s environmental health. Her research utilizes molecular epidemiology approaches to examine the role of endocrine disruptors in the development of childhood obesity. In addition, Dr. Buckley is interested in novel applications of Bayesian and causal inference methods to estimate the health effects of complex exposure mixtures.

15

Vincent James Cogliano, Ph.D. Dr. Cogliano is a health risk assessment scientist at the U.S. Environmental Protection Agency in Washington DC, responsible for scientific reviews of health hazards of chemicals in the environment. He has led EPA’s IRIS program through a series of changes that have improved its fundamental science and management. Previously, Dr Cogliano served as head of the IARC Monographs programme at the International Agency for Research on Cancer (part of the World Health Organization) in Lyon, France. The IARC Monographs are a series of scientific reviews that identify environmental factors that can increase the risk of human cancer. Dr Cogliano received his PhD from Cornell University. Professional interests include qualitative and quantitative health risk assessment and its application to the protection of public health.

Kevin C. Elliott, Ph.D. Kevin C. Elliott, PhD, is an Associate Professor at Michigan State University with joint appointments in Lyman Briggs College, the Department of Fisheries and Wildlife, and the Department of Philosophy. He received his PhD in History and Philosophy of Science from the University of Notre Dame. His research lies at the intersection of the philosophy of science and practical ethics, with an emphasis on critically examining the ways in which ethical and social values influence science and technology. Much of his work has focused on policy-relevant areas of research on environmental pollution, such as endocrine disruption, nanotoxicology, multiple chemical sensitivity, and hormesis. He has authored more than 50 articles and book chapters and has published two books with Oxford University Press: Is a Little Pollution Good for You? Incorporating Societal Values in Environmental Research (2011) and A Tapestry of Values: An Introduction to Values in Science (2017).

Gary Ginsberg, Ph.D. Gary Ginsberg, Ph.D., is a senior toxicologist for the Connecticut Department of Public Health and a lecturer at the Yale School of Public Health. He serves on a number of national committees including EPA’s Science Advisory Board (2008-present) and the National Academies of Sciences, Engineering, and Medicine’s Biomonitoring committee (2004-2006); EPA Risk Methods committee, which produced Science and Decisions (2006-2008); and Inorganic Arsenic Risk Assessment committee (2012-2015). He also served on EPA’s Children’s Health Protection Advisory Committee (2004-2009) and has been an external reviewer on a number of EPA IRIS documents. Dr. Ginsberg has been called on by other federal agencies to provide reviews including OSHA (silica workplace standard), CPSC (cadmium in children’s jewelry), and FDA (dental amalgam). His risk assessments on fish contaminants, synthetic turf fields, acrylamide, cadmium, and assessments pertaining to risks in children and those with genetic polymorphisms have been published in peer reviewed journals. Dr. Ginsberg co-authored a book for the lay public called “What’s Toxic What’s Not” (Berkeley Books, 2006).

16

Kathryn Guyton, Ph.D.

Dr. Kate Guyton is a Senior Toxicologist at the International Agency for Research on Cancer (IARC), World Health Organization in Lyon, France. She contributes expertise in cancer mechanisms to the IARC Monographs Programme. Prior to joining IARC, she served as a Toxicologist in the Office of Research and Development at the US Environmental Protection Agency (2005-2014). She also has experience, as the Director of Scientific Affairs at CCS Associates (1998-2005), working with the US National Cancer Institute in cancer screening, prevention, treatment and imaging. Dr. Guyton received her BA (cum laude) from Johns Hopkins University, her PhD from the Johns Hopkins Bloomberg School of Public Health, and her postdoctoral training at the US National Institutes of Health. Dr. Guyton has been certified as a Diplomate of the American Board of Toxicology since 1998. She has authored more than 60 scientific articles in her area of expertise.

Norbert E. Kaminski, Ph.D. Norbert E. Kaminski, PhD, is the Director of the MSU Institute for Integrative Toxicology and a Professor in the Department of Pharmacology and Toxicology. Dr. Kaminski is a member of the Society of Toxicology and Immunotoxicology Specialty Section, the American Association of Immunologists and the International Cannabinoid Research Society. He served as President of the SOT from 2014-2015. Dr. Kaminski currently serves on the NIEHS National Advisory Environmental Health Sciences Council, and is on the External Advisory Committee of the Oregon State University Superfund Center Grant. Dr. Kaminski was an Associate Editor for the Journal of Pharmacology and Experimental Therapeutics and was also on the editorial board for Toxicological Sciences, International Immunopharmacology, and Nonlinearity in Biology-Toxicology-Medicine. He has served on various scientific advisory committees including the National Academy of Sciences Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides, the U.S. Environmental Protection Agency Science Advisory Board for the Dioxin Reassessment Review, the Health Effects Task Group for NSF International, and the National Academy of Sciences Committee to review EPA’s Exposure and Human Health Reassessment of TCDD and Related Compounds. Dr. Kaminski served on the Board of Trustees for the International Life Sciences Institute-Health and Environmental Sciences Institute from 2003 to 2012. Dr. Kaminski is a faculty trainer for the NIEHS training grant.

Margaret R. Karagas, Ph.D. Margaret R. Karagas, PhD, conducts epidemiologic studies of human malignancies, in particular non-melanoma and melanoma skin cancers, bladder cancer and large bowel neoplasms. She is examining the effects of exposure to toxic metals in drinking water, exogenous and endogenous female sex steroids and the sources of ionizing and non-ionizing radiation. She is also involved in a regional study to understand the excess

17

mortality rates in bladder cancer in Maine, New Hampshire and Vermont. Her work is interdisciplinary, and her studies consider exposure, biologic markers, genetic susceptibility, tumor characteristics, intermediary endpoints and novel statistical approaches.

Patrick McMullen, Ph.D. Patrick McMullen, PhD, has a keen interest in leveraging high-content biological experiments (gene expression studies, high-throughput screens, imaging, and other sources) into a mechanistic understanding of the underlying biology. His background in molecular biology, engineering and programming has been instrumental in interpreting and communicating complex data problems in diverse applications. He manages a diverse computational biology team that uses modeling and high-content data to deepen our understanding of how chemicals interact with biological systems. His group combines expertise and tools from different disciplines to develop innovative strategies for using large-scale data to solve problems related to chemical and drug safety and efficacy.

Gary Miller, Ph.D. Gary Miller, PhD, completed his doctoral training in Pharmacology and Toxicology and postdoctoral training in Molecular Neuroscience. His research has focused on environmental factors involved in the development of neurodegenerative conditions, such as Parkinson's disease. His laboratory works at the interface of neuroscience and toxicology, using a wide variety of experimental techniques. Dr. Miller is Director of the Emory HERCULES center, an NIEHS-funded center focused on the exposome, the environmental analogue to the genome. He also serves as Director of Emory's NIEHS-funded T32 Training Grant in Environmental Health Sciences and Toxicology. Dr. Miller is a Georgia Research Alliance Distinguished Investigator and received the Acheivement Award from the Society of Toxicology. He currently serves as Editor-in-Chief of Toxicological Sciences, the official journal of the Society of Toxicology.

Chirag Patel, Ph.D. Chirag Patel, PhD, is an Assistant Professor at Harvard Center for Biomedical Informatics within Harvard Medical School. Chirag Patel’s long-term research goal is to make large biomedical datasets clinically useful using the tools of “translational bioinformatics". Specifically, his group addresses problems in human health and disease by developing computational methods to reason over high-throughput genomic and environmental information spanning molecules to populations. Realizing that our genomes are just a small bit of the story in human disease after 8 years in the biotechnology industry writing algorithms for genome sequence platforms, Chirag attended graduate school in biomedical informatics – a discipline that applies advances in computing to drive discovery in biomedicine – at Stanford University. Chirag is now starting his own computational group in translational bioinformatics at the Harvard Department of

18

Biomedical Informatics at Harvard Medical School under early investigator funding from the NIH and NSF. Since 2010, Chirag has published 43 papers in peer-reviewed scientific journals and is an advocate of open science and software to democratize biomedical discovery. Melissa Perry, Sc.D. Melissa Perry, ScD, MHS, (co-chair) is Professor and Chair of the Department of Environmental and Occupational Health in the Milken Institute School of Public Health at the George Washington University (GWU). Before joining GWU, she spent 13 years on the Harvard School of Public Health's Department of Environmental Health faculty. As an environmental and occupational epidemiologist, Dr. Perry’s research focuses on the the health impacts of environmental chemicals with particular focus on reproduction, and on the prevention of occupational injuries and disease. Her lab at GW examines environmental impacts on sperm and male fertility. She is the Chair of the Board of Scientific Counselors for the National Center for Environmental Health/Agency for Toxic Substances and Disease Registry of the Centers for Disease Control and Prevention; a Fellow of the Collegium Ramazzini; and a member of the Technical Advisory Board for the Center for Construction Research and Training (CPWR). She has served as President of the American College of Epidemiology and as a standing member of the National Institute for Occupational Safety and Health study section. She served as an associate editor of the journal Reproductive Toxicology and is an editorial board member of Environmental Health. She received her BA from the University of Vermont, and her MHS and ScD from The Johns Hopkins University School of Hygiene and Public Health.

Reza J. Rasoulpour, Ph.D. Reza J. Rasoulpour, PhD., is the Toxicology and Risk Assessment Leader for North America and Latin America within the Human Health Assessment (HHA) group of Dow AgroSciences (DAS). His current responsibilities include leadership of mammalian toxicologists and human health risk assessors who provide subject matter expertise for DAS crop protection and seeds platforms. Rasoulpour also leads several science strategy projects such as incorporation of toxicogenomics into human health safety assessment, membership on the Crop Protection Technology Steering Committee, membership on the Seeds Science Advocacy Steering Team, science advisor to the Predictive Safety Center, development of the new active mammalian toxicity testing paradigm, and facilitator to the DAS R&D Leadership Team (RDLT). Dr. Rasoulpour joined Dow in 2007 with a focus on developmental and reproductive toxicology. Dr. Rasoulpour’s primary research focus has been in leading the epigenetics and toxicogenomics research programs to accelerate pipeline product development as well as investigative mode-of-action research to characterize molecular mechanisms and their impact to product safety assessment. Dr. Rasoulpour has organized numerous symposia and workshops at the Society of Toxicology meetings, has served as an invited speaker and panelist for scientific sessions at the National Academy of Sciences, ICCA-LRI workshops, ILSI-HESI, ECETOC, Crop Life America, Society for Toxicologic Pathology, and the Teratology Society. To date, he has authored/coauthored 36 peer-reviewed

19

publications to the scientific literature, as well as authored a book chapter on the topic of male reproductive biology. Dr. Rasoulpour earned a B.S. from the University of Connecticut, where he received the title of University Scholar, the university’s highest academic honor. He then embarked on researching reproductive toxicology in the laboratory of Kim Boekelheide and was awarded his Ph.D. from Brown University.

Jonathan Samet, M.D., M.S. Dr. Samet, a pulmonary physician and epidemiologist, is Distinguished Professor and Flora L. Thornton Chair, Department of Preventive Medicine at the University of Southern California Keck School of Medicine and Director of the USC Institute for Global Health. Previously, he was chair of the Department of Epidemiology of the Johns Hopkins Bloomberg School of Public Health. His career has centered on epidemiologic research on threats to public health and using research findings to support policies that protect population health. His research has addressed indoor and outdoor air pollution, smoking, radiation risks, cancer etiology and outcomes, and sleep. He has been involved with numerous committees related to use of scientific evidence in characterizing risks and making decisions, including chairing the Clean Air Scientific Advisory Committee of the U.S. EPA and the FDA’s Tobacco Products Scientific Advisory Committee (TPSAC). For three decades he has authored and edited the reports of the Surgeon General on smoking and health, including serving as Senior Scientific Editor for the 50th Anniversary 2014 report. Dr. Samet received the 2004 Prince Mahidol Award for Global Health awarded by the King of Thailand, the Surgeon General’s Medallion in 1990 and 2006, the Edward Livingston Trudeau Medal from the American Thoracic Society/American Lung Association, the Luther L. Terry Award for Distinguished Career from the American Cancer Society, and the 2016 Fries Prize for Health. He is a member of the National Academy of Medicine and received the David M. Rall Medal for his contributions.

Richard Scheines, Ph.D. My research is on causal discovery, in particular the problem of learning about causation from statistical evidence. The theoretical and computational dimensions of this work have come to be called the TETRAD project, which represents nearly 25 years of collaboration with Clark Glymour, Peter Spirtes and many, many others. Building efficient and practically useful algorithms for causal discovery is as much computer science as philosophy, and thus I have a courtesy appointment in the Machine Learning Department. I have also put a lot of effort into building and researching the effectiveness of educational software, ranging from intelligent proof tutors to virtual causality labs to a full semester course on Causal and Statistical Reasoning. Because of this work I have a courtesy appointment in the Human-Computer Interaction Institute.

20

Martyn Smith, Ph.D.

Martyn Smith is a Professor of Toxicology and Kenneth and Marjorie Kaiser Chair of Cancer Epidemiology in the Division of Environmental Health Sciences in the School of Public Health at the University of California Berkeley. He is also Director of the Superfund Research Center at Berkeley, a position he has held continuously since 1987. He received his Ph.D. in Biochemistry from St. Bartholomew's Hospital in London and did Postdoctoral training in toxicology at the Karolinska Institute in Stockholm. Dr. Smith is a laboratory scientist with expertise in molecular epidemiology, toxicology and genomics, and his research is aimed at finding the causes of chronic diseases, including cancer and diabetes. He currently teaches toxicology and mentors graduate students and postdoctoral scholars in the Molecular Toxicology, Epidemiology and Environmental Health Science programs. Dr. Smith is a Fellow of the American Association for the Advancement of Science. He received the 2010 Children’s Environmental Health Network Award, became an Elected Fellow of the Collegium Ramazzini in 2012, and received the 2014 Alexander Hollaender Award from the Environmental Mutagenesis and Genomics Society.

Philip Stark, Ph.D. Philip B. Stark is Professor of Statistics and Associate Dean of Mathematical and Physical Sciences at the University of California, Berkeley. He studies applications of statistics to a variety of scientific and social problems, inferential methodology, and the foundations of statistics.

Eric Tchetgen Tchetgen, Ph.D. Dr Tchetgen Tchetgen is Professor of Biostatistics and Epidemiologic Methods at Harvard University. His primary area of interest is in semiparametric efficiency theory with application to causal inference and missing data problems. In general, he works on statistical and epidemiologic methods that make efficient use of information in data collected by scientific investigators, while avoiding unnecessary assumptions about the underlying unknown data generating mechanism. Recently, his research has focused on problems related to unmeasured confounding in causal inference for which he has developed novel instrumental variable techniques as well as new negatve control methodology.

Mary Beth Terry, Ph.D. Mary Beth Terry, PhD, focuses her research on breast cancer and in the molecular epidemiology and lifecourse methods of the disease, in particular. She is a cancer epidemiologist with over 15 years of leading studies of breast cancer etiology specifically focused on the role of genetics, epigenetics, and other biomarkers play in modifying the effects of environmental exposures. Dr. Terry currently leads four NIH

21

grants through the National Cancer Institute and the National Institute for Environmental Health Sciences that focus on following cancer risk within family-based cohorts. She is also funded through the Breast Cancer Research Foundation. Dr. Terry has authored or co-authored over 200 scientific publications. Her more recent work studying biomarkers, which can be modified throughout life, supports that selected markers of DNA methylation and other biomarkers are associated with breast cancer risk even within high risk families. Understanding whether biomarkers can help explain risk in higher risk women is important as only a minority of women with a family history of cancer carry the BRCA1 or BRCA2 mutation. Her work also focuses on measuring risk factors for mammographic density, a strong intermediate marker of breast cancer. In addition to her doctorate in epidemiology, Dr. Terry has a Master's degree in economics and previously worked as an econometrician and program evaluator for a number of government-sponsored programs. Dr. Terry teaches introductory and advanced epidemiologic methods at the Mailman School of Public Health.

Paolo Vineis, M.D. Paolo Vineis is professor and chair of Environmental Epidemiology at Imperial College London, School of Public Health. He is a leading researcher in the field of molecular epidemiology and his latest research focuses on examining biomarkers of disease risk, complex exposures, and intermediate markers from -omic platforms in large epidemiological studies. He also studies the effect of climate change on non-communicable diseases. He is Head of the Unit of Molecular and Genetic Epidemiology at the HuGeF Foundation in Torino, Italy. Dr. Vineis is coordinator of the European Commission funded Exposomics and Lifepath (H2020) projects and is a principal investigator or co-investigator of numerous international projects. He has more than 800 publications in journals such as Nature, Science, Nature Genetics, Lancet, and Lancet Oncology. Additionally, he is a member of various international scientific and ethics committees and vice-chair of the Ethics Committee at the International Agency for Research on Cancer. Dr. Vineis received his MD from the University of Torino, Italy (see also https://en.wikipedia.org/wiki/Paolo_Vineis).

Meredith Williams, Ph.D. Meredith Williams joined DTSC in December 2013. She has expertise in research and development, product management, and operations for Fortune 500 technology, consumer product, and chemical companies including Applied Materials and 3M, as well as for a leading environmental institute. After nearly 20 years of corporate work she applied her skills in several positions over seven years at the San Francisco Estuary Institute (SFEI), a nationally-recognized center in support of aquatic resource management. Among other duties, she directed the Environmental Data, Information, and Technology team in developing systems and online tools to facilitate effective, data-driven decision making. In 2013, she served as SFEI's interim Executive Director with responsibilities for strategy implementation,

22

financial planning and reporting, internal communications and overall Institute best practices. Meredith strives for collaborative solutions to complex problems and has a track record of championing interdisciplinary project management approaches. She holds B.S. from Yale University and a Ph.D. in physics from North Carolina State University.

23

For biographies, see Standing Committee Biographies.

Planning Committee Roster

Kim Boekelheide Brown University Weihsueh Chiu Texas A&M University Kristi Pullen Fedinick Natural Resource Defense Council Gary Ginsberg Connecticut Department of Public Health Reza J. Rasoulpour Dow AgroSciences

24

Selected Readings

1. Glass, T. A., Goodman, S. N., Hernán, M. A., & Samet, J. M. (2013). Causal Inference in

Public Health. Annual Review of Public Health, 34, 61–75. http://doi.org/10.1146/annurev-publhealth-031811-124606

2. Freedman, David. From association to causation: some remarks on the history of statistics. Statist. Sci. 14 (1999), no. 3, 243--258. doi:10.1214/ss/1009212409. http://projecteuclid.org/euclid.ss/1009212409.

3. Smith MT, Guyton KZ, Gibbons CF, et al. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis. Environmental Health Perspectives. 2016;124(6):713-721. doi:10.1289/ehp.1509912. http://doi.org/10.1289/ehp.1509912

4. Lipsitch, M., Tchetgen, E. T., & Cohen, T. (2010). Negative Controls: A Tool for Detecting Confounding and Bias in Observational Studies. Epidemiology (Cambridge, Mass.), 21(3), 383–388. http://doi.org/10.1097/EDE.0b013e3181d61eeb

5. Ankley, G. T., Bennett, R. S., Erickson, R. J., Hoff, D. J., Hornung, M. W., Johnson, R. D., Mount, D. R., Nichols, J. W., Russom, C. L., Schmieder, P. K., Serrrano, J. A., Tietge, J. E. and Villeneuve, D. L. (2010), Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment. Environmental Toxicology and Chemistry, 29: 730–741. doi:10.1002/etc.34 http://onlinelibrary.wiley.com/doi/10.1002/etc.2708/abstract

6. National Academies of Sciences, Engineering, and Medicine. 2017. Using 21st Century Science to Improve Risk-Related Evaluations. Washington, DC: The National Academies Press. doi:https://doi.org/10.17226/24635. https://www.nap.edu/read/24635/chapter/1

25

Standing Committee The National Academies’ Standing Committee on Use of Emerging Science for Environmental Health Decisions (ESEHD) examines and discusses issues on the use of new science, tools, and research methodologies for environmental health decisions. Workshops organized by ESEHD provide a public venue for communication among government, industry, environmental groups, and the academic community about scientific discoveries and advances in methods and approaches that can be used in the identification, quantification, and control of environmental impacts on human health. The ESEHD committee is organized under the auspices of Board on Life Sciences and the Board on Environmental Studies and Toxicology of the National Academies, and sponsored by the National Institute of Environmental Health Sciences.

Committee Statement of Task

The Standing Committee will examine, explore, and consider issues on the use of emerging science for environmental health decisions. The Committee will provide a public venue for communication among government, industry, environmental groups, and the academic community about scientific advances in methods and approaches that can be used in the identification, quantification and control of environmental impacts on human health. The topics covered will explore new developments in the life sciences, bioinformatics, modeling, and risk or decision analyses that could be applicable to environmental health decision making. Specifically, the Committee will consider topics that fall within the following four themes : 1) emerging scientific tools or data that may address existing issues in environmental health; 2) emerging areas of science that have not traditionally been applied to environmental health research and issues; 3) current and pressing environmental health issues for which new science, tools, or data may offer new insights, approaches, or solutions; and 4) practical issues facing the environmental health science community as it deals with the emerging science. The Standing Committee will accomplish its task by convening public meetings of invited experts to inform the Committee and the sponsor about key scientific issues relevant to the use of emerging scientific information, knowledge, and approaches in regulation, disease prevention, education and personal choice, and clinical intervention and management of diseases caused and/or modified by environmental factors. Attendees in the public meetings will include members of government, industry, environmental groups, and the academic community. These public meetings will also be made available to a broader audience via the internet, and highlights of the discussions will be included in short workshop summaries prepared by staff. Specific topics will be selected by the Standing Committee after considering input from NIEHS and its federal partners. The Standing Committee itself will not issue reports, but the Committee may develop recommendations for consideration of future studies that would require separate approval and funding. Should the sponsor and Committee agree that particular issues need more detailed treatment in the form of consensus studies or meetings with reports, such projects will be approved separately by the Academies and will follow the usual Committee formation and report review procedures under the Standing Committee's

26

oversight. The cost estimate provides for funding of the Standing Committee activity, including public meetings and short workshop summaries.

27

Standing Committee Roster

Dr. Kim Boekelheide (Co-chair) Professor of Medical Science Director of Superfund Research Brown University Dr. Melissa Perry (Co-chair) Professor and Chair Department of Environmental and Occupational Health Milken Institute School of Public Health The George Washington University Dr. Lesa Aylward Principal Summit Toxicology, LLP Dr. Weihsueh Chiu Professor Department of Veterinary Integrative Biosciences Dr. Kevin Elliott Associate Professor Department of Fisheries and Wildlife Michigan State University Dr. Kristi Pullen Fedinick Staff Scientist Natural Resource Defense Council Dr. Gary Ginsberg Senior Toxicologist Division of Environmental and Occupational Health Assessment Connecticut Department of Public Health Dr. Norbert Kaminski Professor and Director Institute for Integrative Toxicology Michigan State University

Dr. Margaret Karagas James W. Squires Professor and Chair Department of Epidemiology Geisel School of Medicine Dartmouth College Dr. Patrick McMullen Research Investigator ScitoVation Dr. Gary Miller Professor Rollins School of Public Health Emory University Dr. Chirag Patel Assistant Professor Department of Biomedical Informatics Harvard Medical School Dr. Reza J. Rasoulpour Toxicology and Risk Assessment Leader Dow AgroSciences Dr. Joel Schwartz Epidemiologist and Professor Department of Environmental Epidemiology Harvard School of Public Health Dr. Gina M. Solomon Deputy Secretary for Science and Health Office of the Secretary California Environmental Protection Agency EX-OFFICIO MEMBER Dr. William Farland Senior Vice President for Research Colorado State University

28

Standing Committee Member Biographies Kim Boekelheide, Ph.D. (co-chair) is professor of Pathology and Laboratory Medicine at the Brown University School of Medicine. He received his B.A. from Harvard University, and M.D. and Ph.D. from Duke University. His research examines fundamental molecular mechanisms by which environmental and occupational toxicants induce testicular injury. Current projects include the development of novel in vitro approaches to safety assessment, use of xenotransplantation approaches for human-relevant toxicity testing, and the discovery of sperm molecular biomarkers that reflect testicular injury. He is Director of the Brown University Superfund Research Program. His research has been continuously funded by the National Institute of Environmental Health Sciences since 1985, and he has received several awards including a Burroughs Wellcome Toxicology Scholar Award (1994-1999). Melissa Perry, ScD, MHS, (co-chair) is Professor and Chair of the Department of Environmental and Occupational Health in the Milken Institute School of Public Health at the George Washington University (GWU). Before joining GWU, she spent 13 years on the Harvard School of Public Health's Department of Environmental Health faculty. As an environmental and occupational epidemiologist, Dr. Perry’s research focuses on the the health impacts of environmental chemicals with particular focus on reproduction, and on the prevention of occupational injuries and disease. Her lab at GW examines environmental impacts on sperm and male fertility. She is the Chair of the Board of Scientific Counselors for the National Center for Environmental Health/Agency for Toxic Substances and Disease Registry of the Centers for Disease Control and Prevention; a Fellow of the Collegium Ramazzini; and a member of the Technical Advisory Board for the Center for Construction Research and Training (CPWR). She has served as President of the American College of Epidemiology and as a standing member of the National Institute for Occupational Safety and Health study section. She served as an associate editor of the journal Reproductive Toxicology and is an editorial board member of Environmental Health. She received her BA from the University of Vermont, and her MHS and ScD from The Johns Hopkins University School of Hygiene and Public Health. Lesa L. Aylward, Ph.D., is an Honorary Associate Professor with a joint appointment between Queensland Children’s Medical Research Institute and the National Research Center for Environmental Toxicology (Entox) and a Principal at Summit Toxicology, LLP. Dr Aylward’s research interests include the development and application of toxicokinetic models and the use of biomonitoring for tracking exposure to chemicals in the environment, foods, and consumer products. She has published extensively on the development of tools for the interpretation of biomonitoring data in a risk assessment context and the use of biomonitoring as an exposure assessment tool in epidemiological studies. Her current research interests include evaluation of the sources of and factors influencing inter- and intra-individual variation in chemical biomarker concentrations with a focus on the design and implementation of biomonitoring for exposure characterization in epidemiological studies. She has several current collaborations with Entox researchers on the use of human biomonitoring to characterize chemical exposures in the Australian general population and in occupationally exposed groups.

29

Weihsueh Chiu, Ph.D., is a professor in the Department of Veterinary Integrative Biosciences at the Texas A&M University. His research focuses on the development of quantitative, data-driven approaches for understanding and predicting the human health effects of environmental chemicals. Specifically, his research applies computational and statistical methods to transform data into knowledge used to protect public health. He also has an interest in approaches to estimate the variability in individual susceptibility to environmental exposures, so as to better protect sensitive subpopulations. Kevin C. Elliott, PhD, is an Associate Professor at Michigan State University with joint appointments in Lyman Briggs College, the Department of Fisheries and Wildlife, and the Department of Philosophy. He received his PhD in History and Philosophy of Science from the University of Notre Dame. His research lies at the intersection of the philosophy of science and practical ethics, with an emphasis on critically examining the ways in which ethical and social values influence science and technology. Much of his work has focused on policy-relevant areas of research on environmental pollution, such as endocrine disruption, nanotoxicology, multiple chemical sensitivity, and hormesis. He has authored more than 50 articles and book chapters and has published two books with Oxford University Press: Is a Little Pollution Good for You? Incorporating Societal Values in Environmental Research (2011) and A Tapestry of Values: An Introduction to Values in Science (2017). Kristi Pullen Fedinick, Ph.D., is a staff scientist in the Health Program at the Natural Resources Defense Council. Kristi Pullen’s decades-long research career includes experience in molecular, structural, and computational biology; biochemistry; and population health. Prior to joining the Health program, she worked as a scientist for the Environmental Law and Policy Center, where she focused on air and drinking-water quality, science communications, and environmental justice. For NRDC, Pullen has worked primarily on high-throughput technologies, predictive toxicology, and chemical-risk assessments. She holds a bachelor’s degree in biochemistry and molecular biology from the University of Maryland, Baltimore County, and a PhD in molecular and cell biology from the University of California, Berkeley. She was a Robert Wood Johnson Foundation Health and Society Scholar at the Harvard School of Public Health. She is based in Washington, D.C. Gary Ginsberg, Ph.D., is a senior toxicologist for the Connecticut Department of Public Health and a lecturer at the Yale School of Public Health. He serves on a number of national committees including EPA’s Science Advisory Board (2008-present) and the National Academies of Sciences, Engineering, and Medicine’s Biomonitoring committee (2004-2006); EPA Risk Methods committee, which produced Science and Decisions (2006-2008); and Inorganic Arsenic Risk Assessment committee (2012-2015). He also served on EPA’s Children’s Health Protection Advisory Committee (2004-2009) and has been an external reviewer on a number of EPA IRIS documents. Dr. Ginsberg has been called on by other federal agencies to provide reviews including OSHA (silica workplace standard), CPSC (cadmium in children’s jewelry), and FDA (dental amalgam). His risk assessments on fish contaminants, synthetic turf fields, acrylamide, cadmium, and assessments pertaining to risks in children and those with genetic

30

polymorphisms have been published in peer reviewed journals. Dr. Ginsberg co-authored a book for the lay public called “What’s Toxic What’s Not” (Berkeley Books, 2006). Norbert E. Kaminski, PhD, is the Director of the MSU Institute for Integrative Toxicology and a Professor in the Department of Pharmacology and Toxicology. Dr. Kaminski is a member of the Society of Toxicology and Immunotoxicology Specialty Section, the American Association of Immunologists and the International Cannabinoid Research Society. He served as President of the SOT from 2014-2015. Dr. Kaminski currently serves on the NIEHS National Advisory Environmental Health Sciences Council, and is on the External Advisory Committee of the Oregon State University Superfund Center Grant. Dr. Kaminski was an Associate Editor for the Journal of Pharmacology and Experimental Therapeutics and was also on the editorial board for Toxicological Sciences, International Immunopharmacology, and Nonlinearity in Biology-Toxicology-Medicine. He has served on various scientific advisory committees including the National Academy of Sciences Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides, the U.S. Environmental Protection Agency Science Advisory Board for the Dioxin Reassessment Review, the Health Effects Task Group for NSF International, and the National Academy of Sciences Committee to review EPA’s Exposure and Human Health Reassessment of TCDD and Related Compounds. Dr. Kaminski served on the Board of Trustees for the International Life Sciences Institute-Health and Environmental Sciences Institute from 2003 to 2012. Dr. Kaminski is a faculty trainer for the NIEHS training grant. Margaret R. Karagas, PhD, conducts epidemiologic studies of human malignancies, in particular non-melanoma and melanoma skin cancers, bladder cancer and large bowel neoplasms. She is examining the effects of exposure to toxic metals in drinking water, exogenous and endogenous female sex steroids and the sources of ionizing and non-ionizing radiation. She is also involved in a regional study to understand the excess mortality rates in bladder cancer in Maine, New Hampshire and Vermont. Her work is interdisciplinary, and her studies consider exposure, biologic markers, genetic susceptibility, tumor characteristics, intermediary endpoints and novel statistical approaches. Patrick McMullen, PhD, has a keen interest in leveraging high-content biological experiments (gene expression studies, high-throughput screens, imaging, and other sources) into a mechanistic understanding of the underlying biology. His background in molecular biology, engineering and programming has been instrumental in interpreting and communicating complex data problems in diverse applications. He manages a diverse computational biology team that uses modeling and high-content data to deepen our understanding of how chemicals interact with biological systems. His group combines expertise and tools from different disciplines to develop innovative strategies for using large-scale data to solve problems related to chemical and drug safety and efficacy. Gary Miller, PhD, completed his doctoral training in Pharmacology and Toxicology and postdoctoral training in Molecular Neuroscience. His research has focused on environmental factors involved in the development of neurodegenerative conditions, such as Parkinson's disease. His laboratory works at the interface of neuroscience and toxicology, using a wide

31

variety of experimental techniques. Dr. Miller is Director of the Emory HERCULES center, an NIEHS-funded center focused on the exposome, the environmental analogue to the genome. He also serves as Director of Emory's NIEHS-funded T32 Training Grant in Environmental Health Sciences and Toxicology. Dr. Miller is a Georgia Research Alliance Distinguished Investigator and received the Acheivement Award from the Society of Toxicology. He currently serves as Editor-in-Chief of Toxicological Sciences, the official journal of the Society of Toxicology. Chirag Patel, PhD, is an Assistant Professor at Harvard Center for Biomedical Informatics within Harvard Medical School. Chirag Patel’s long-term research goal is to make large biomedical datasets clinically useful using the tools of “translational bioinformatics". Specifically, his group addresses problems in human health and disease by developing computational methods to reason over high-throughput genomic and environmental information spanning molecules to populations. Realizing that our genomes are just a small bit of the story in human disease after 8 years in the biotechnology industry writing algorithms for genome sequence platforms, Chirag attended graduate school in biomedical informatics – a discipline that applies advances in computing to drive discovery in biomedicine – at Stanford University. Chirag is now starting his own computational group in translational bioinformatics at the Harvard Department of Biomedical Informatics at Harvard Medical School under early investigator funding from the NIH and NSF. Since 2010, Chirag has published 43 papers in peer-reviewed scientific journals and is an advocate of open science and software to democratize biomedical discovery. Reza J. Rasoulpour is the Toxicology and Risk Assessment Leader for North America and Latin America within the Human Health Assessment (HHA) group of Dow AgroSciences (DAS). His current responsibilities include leadership of mammalian toxicologists and human health risk assessors who provide subject matter expertise for DAS crop protection and seeds platforms. Rasoulpour also leads several science strategy projects such as incorporation of toxicogenomics into human health safety assessment, membership on the Crop Protection Technology Steering Committee, membership on the Seeds Science Advocacy Steering Team, science advisor to the Predictive Safety Center, development of the new active mammalian toxicity testing paradigm, and facilitator to the DAS R&D Leadership Team (RDLT). Dr. Rasoulpour joined Dow in 2007 with a focus on developmental and reproductive toxicology. Dr. Rasoulpour’s primary research focus has been in leading the epigenetics and toxicogenomics research programs to accelerate pipeline product development as well as investigative mode-of-action research to characterize molecular mechanisms and their impact to product safety assessment. Dr. Rasoulpour has organized numerous symposia and workshops at the Society of Toxicology meetings, has served as an invited speaker and panelist for scientific sessions at the National Academy of Sciences, ICCA-LRI workshops, ILSI-HESI, ECETOC, Crop Life America, Society for Toxicologic Pathology, and the Teratology Society. To date, he has authored/coauthored 36 peer-reviewed publications to the scientific literature, as well as authored a book chapter on the topic of male reproductive biology. Dr. Rasoulpour earned a B.S. from the University of Connecticut, where he received the title of University Scholar, the university’s highest academic honor. He then embarked on researching reproductive toxicology in the laboratory of Kim Boekelheide and was awarded his Ph.D. from Brown University.

32

Joel Schwartz, PhD, is an epidemiologist and Professor of Environmental Epidemiology at Harvard University’s School of Public Health. His research is divided in three main areas; he is interested in epidemiology and looking at the health consequences of exposure to pollutants. To date this has had two focuses: health effects of lead and health effects of air pollutants. He has recently begun work looking at water contamination. He has examined cardiovascular effects of lead exposure in adults, cognitive effects in children, auditory effects in children, and effects of lead on children’s growth. He has also done work on sources of lead exposure, including establishing gasoline lead as the major source of lead exposure in the United States. Dr. Schwartz’ air pollution work has examined both acute and chronic effects of air pollution exposure. Recent research has established that exposure to fine combustion particles in the air at concentrations well below current standards are associated with a range of adverse health effects from increased respiratory symptoms, to increased hospital admissions, to increased deaths. This work has led to a tightening of the U.S. air quality standards. He has also done considerable work on health effects of ozone exposure. Dr. Schwartz is interested in methodological questions regarding the modeling of continuous covariates in epidemiologic studies, both for better covariate control and to more accurately assess the relationship between exposure and response. This has involved regression spline models, nonparametric smoothing, and generalized additive models. He has also been using mixed and hierarchical models to combine this information across studies. Case-crossover techniques have also been introduced for these purposes. Dr. Schwartz has demonstrated the effectiveness of these tools in applications in both lead and air pollution studies. He has also been interested in issues involving time series studies, where the outcomes measures are not independent. This has involved generalized least squares and generalized estimating equation approaches. A third major focus of my research is on the effects of antioxidants on respiratory health. To date this has focused on chronic effects (e.g. relationship between dietary intake and level of pulmonary function or symptoms), but future research will examine their potential to modify acute responses as well. A final area of interest is in the use of cost benefit analysis to make environmental decisions. Dr. Schwartz has developed benefit methodologies for assessing the benefits of lead control, and applied those methodologies to the decision to remove lead from gasoline, and recently, in collaboration with colleagues at the Centers for Disease Control, to a decision to revise their screening recommendations for children. He has also been involved in cost benefit analysis of air pollution control. Dr. Schwartz obtained his PhD in 1980 from Brandeis University. Gina M. Solomon, M.D., M.P.H., is the Deputy Secretary for Science and Health at the California Environmental Protection Agency (CalEPA) and a Clinical Professor of Medicine at the University of California San Francisco (UCSF). Prior to coming to CalEPA in 2012, she was a senior scientist at the Natural Resources Defense Council, the director of the occupational and environmental medicine residency program at UCSF, and the co-director of the UCSF Pediatric Environmental Health Specialty Unit. Dr. Solomon’s work has spanned a wide array of areas, including children’s environmental health, reproductive toxicity, cumulative impacts and evaluating the use of novel data streams to screen chemicals for toxicity. She has also done work in exposure science for air pollutants, pesticides, mold, and metals in soil and on the health effects of

33

climate change. She was involved in the aftermath of Hurricane Katrina, the Gulf oil spill, and the Chevron Richmond explosion and fire, and is currently working to improve refinery process safety in California. Dr. Solomon serves on both the U.S. EPA’s Science Advisory Board and Board of Scientific Counselors, where she co-chairs the Subcommittee on Chemical Safety for Sustainability and Human Health Risk Assessment. She also serves on the NRC’s Board on Environmental Studies in Toxicology and previously served on the Committees on Toxicity Testing in the 21st Century and Exposure Science in the 21st Century, as well as on the National Toxicology Program’s Board of Scientific Counselors. Dr. Solomon received her bachelor’s degree from Brown University, her M.D. from Yale, and did her M.P.H. and her residency and fellowship training in internal medicine and occupational and environmental medicine at Harvard.

34

Notes

35

Notes

36

Notes

37

Notes

38

Notes

39

40