US EPA CSS-HERA Board of Scientific Counselors Chemical Safety Subcommittee Meeting US EPA CSS-HERA BOSC Meeting - February 2-5, 2021 * o \ ifl PRO^ ------- Table of Contents Meeting Agenda 2 BOSC Subcommittee Roster 6 Office of Research and Development 12 Office of Research and Development Center Leadership 13 CSS Team Roster 15 CSS NPD Team 15 Assistant Center Directors assigned to CSS 15 HERA Team Roster 16 HERA NPD Team 16 Assistant Center Directors assigned to HERA 16 CSS National Research Program Review Charge Questions 17 HERA National Research Program Review Charge Questions 18 CSS STAR Extramural Research Program 19 CSS Highlights and Notable Accomplishments 21 Appendix A: Chemical Safety for Sustainability Part 1: Chemical Safety for Sustainability Strategic Research Action Plan, 2019 - 2022 Part 2: CSS Scientific Portfolio Overview Part 3: CSS Publications Part 4: CSS Models, databases and tools Appendix B: Human and Environmental Risk Assessment Part 1: Human and Environmental Risk Assessment Strategic Research Action Plan, 2019-2022 (delivery forthcoming) Part 2: HERA Scientific Portfolio Overview Part 3: HERA Publications and Products Appendix C: New Approach Methods Work Plan: Reducing use of animals in chemical testing, U.S. EPA June 2020 Appendix D: Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program, U.S. EPA June 2018 v. 1/19/2021 1 ------- Meeting Agenda US EPA Board of Scientific Counselors Chemical Safety Subcommittee Meeting Chemical Safety for Sustainability (CSS) and Health and Environmental Risk Assessment (HERA) Research Programs February 2-5, 2021 Tuesday February 2,2021 TIME (EST) AGENDA ACTIVITY PRESENTER 12:00 -12:10 Meeting kick off/FACA rules/expectations/logistics Tom Tracy, DFO, OSAPE 12:10-12:15 ORD Welcome Jennifer Orme-Zavaleta, ORD Principal DAA for Science 12:15 -12:25 Subcommittee Chair Opening Remarks and Introductions Katrina Waters, Chair 12:25 -12:45 CSS NAMs Research and Development Portfolio: Connecting the Dots to Relevance and Acceptance Jeff Frithsen, NPD, CSS 12:45 -1:05 HERA Advancing the Science and Practice of Assessments Samantha Jones, NPD, HERA 1:05 -1:20 Translating Strategy into Action: Research Implementation Plans in ORD Jill Franzosa, ACD, CCTE 1:20 -1:50 Evolution of NAMs in EPA: From Research to Application Rusty Thomas, CD, CCTE 1:50 - 2:15 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair 2:15 - 2:30 NAMs Research Introduction with Charge Question Jeff Frithsen, NPD, CSS 2:30-2:45 BREAK & Transition to Virtual Break-out Rooms CSS SESSION 1: CONCURRENT PRESENTATIONS ON NAMS RESEARCH Note: Each research topic will be presented in 25 minutes including time for specific questions. 2:45-4:00 SESSION A: Emerging Approaches to Hazard Testing 1. High Throughput Transcriptomics Logan Everett, CCTE 2. High Throughput Phenotypic Profiling Joshua Harrill, CCTE 3. Metabolic Augmentation in in vitro Systems Chad Deisenroth, CCTE SESSION B: NAMs for Exposure 1. High Throughput Exposure Models (SEEM) John Wambaugh, CCTE 2. High Throughput Toxicokinetic Models and 1 VIVE Barbara Wetmore, CCTE 3. Non-Targeted Analysis Jon Sobus, CCTE SESSION C: NAMs for Ecotoxicological Applications 1. Approaches and Models for Species Extrapolation Carlie LaLone, CCTE 2. Novel in vitro Methods for Ecological Species Brett Blackwell, CCTE 3. High Throughput Transcriptomics: A Multi-Species Approach Kevin Flynn, CCTE SESSION D: System-specific Models and Approaches 1. Respiratory tract models Shaun McCullough, CPHEA 2. Inhalation models Mark Higuchi, CPHEA 3. Neurovascular Unit Modeling and Blood Brain Barrier Function Tom Knudsen, CCTE 4:00-5:00 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair 5:00 ADJOURN v. 1/19/2021 2 ------- Wednesday February 3,2021 TIME (EST) AGENDA ACTIVITY PRESENTER 12:00 -12:10 Public comments Tom Tracy, DFO, OSAPE 12:10-12:15 BOSC Subcommittee Chair Opening Remarks Katrina Waters, Chair CSS SESSION 2: APPLICATIONS OF NAMS TO AGENCY AND STATE PROGRAMS 12:15 -12:30 NAMs Applications Introduction with Charge Question Jeff Frithsen, NPD, CSS 12:30-1:00 OCSPP-TSCA Inventory: Prioritization Proof of Concept Richard Judson, CCTE 1:00 -1:30 Developmental Neurotoxicity (DNT) in vitro Battery as an Alternative to DNT in vivo Guideline Studies Used by OPP Tim Shafer, CCTE 1:30 - 2:00 Chemicals of Emerging Concern: A Prioritization Case Study with Minnesota Department of Health Kristin Isaacs, CCTE 2:00 - 2:30 Application of NAMs and AOPs to Surface Water Surveillance and Monitoring in the Great Lakes (EPA Region 5) and a Western River (EPA Region 8) Dan Villeneuve, CCTE 2:30-2:45 BREAK 2:45-3:15 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair CSS SESSION 3: DEMONSTRATIONS OF TOOLS 3:15-3:30 NAMs Tools Demo Intro with Charge Question Jeff Frithsen, NPD, CSS 3:30-4:00 CompTox Chemicals Dashboard Tony Williams, CCTE 4:00-4:30 SeqAPASS Carlie LaLone, CCTE 4:30-5:00 Factotum: Curation of Exposure-Relevant Public Data Kristin Isaacs, CCTE 5:00-5:30 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair 5:30 ADJOURN v. 1/19/2021 3 ------- Thursday February 4,2021 TIME (EST) AGENDA ACTIVITY PRESENTER 12:00-12:05 Meeting kick off/FACA rules/expectations/logistics Tom Tracy, DFO, OSAPE 12:05-12:15 BOSC Subcommittee Chair Opening Remarks Katrina Waters, Chair 12:15-12:25 Connecting Assessment Needs to HERA Research Samantha Jones, NPD, HERA 12:25-12:35 CPHEA Implementation and Workforce planning Wayne Cascio, CD, CPHEA 12:35-12:50 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair HERA SESSION 1: Applying NAMS to Inform HERA Assessments 12:50-1:00 Applying NAMs to Inform HERA Assessments with Charge Question Luci Lizarraga, CPHEA 1:00-1:20 Advancing Read-across in HERA Luci Lizarraga, CPHEA 1:20-1:40 Filling Metabolism Data Gaps in Read-across Matthew Boyce, CCTE 1:40-2:00 Adverse Outcome Pathway (AOP) Footprinting for Mixtures Jason Lambert, CCTE 2:00-2:40 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair 2:40-2:50 BREAK HERA SESSION 2: Advancing Systematic Review Methods 2:50-3:05 Advancing SR Methods and Tools Intro with Charge Question Kris Thayer, CPHEA 3:05-3:25 Organizing and Evaluating Mechanistic Evidence Catherine Gibbons, CPHEA 3:25-3:45 Automated/Machine Learning approaches Michele Taylor, CPHEA 3:45-4:05 Semantic Ontology Mapping Michelle Angrish, CPHEA 4:05-4:25 PFAS 150 systematic evidence maps Laura Carlson, CPHEA 4:25-5:00 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair 5:00 ADJOURN v. 1/19/2021 4 ------- Friday February 5, 2021 TIME (EST) AGENDA ACTIVITY PRESENTER 12:00-12:05 Meeting kick off/FACA rules/expectations/logistics Tom Tracy, DFO, OSAPE 12:05-12:20 BOSC Subcommittee Chair Opening Remarks Katrina Waters, Chair HERA SESSION 3: Advancing Dose-Response Analyses and Tools 12:20-12:35 Advancing Dose-Response Intro with Charge Question John Vandenberg, CPHEA 12:35-12:55 Multi-path Particle Dosimetry Model Annie Jarabek, CPHEA 12:55-1:15 Bayesian Model Averaging and BMDS 3.2 Allen Davis, CPHEA 1:15-1:35 Approximate Probabilistic Analysis (APROBA) Todd Blessinger, CPHEA 1:35-2:10 BOSC Subcommittee discussion and Qs/As Katrina Waters, Chair CSS-HERA Closing 2:10-2:30 Closing Statements and Responses Samantha Jones, NPD, HERA Jeff Frithsen, NPD, CSS 2:30-5:00 BOSC Subcommittee Deliberations Katrina Waters, Chair 5:00 ADJOURN v. 1/19/2021 5 ------- BOSC Subcommittee Roster Designated Federal Official Tom Tracy Office of Science Advisor, Policy, and Engagement Office of Research and Development U.S. EPA Members Affiliation Expertise Background Division Director, Biological Sciences Research, Pacific Northwest National Laboratory (WA Region 10) Systems biology Pharmacokinetics Molecular biology/genomics Endocrinology Bioinformatics Dr. Waters' expertise and research interests are focused around the analysis and biological interpretation of global gene and protein expression data related to mechanism of action or applied research. In addition, she has several years of experience developing and carrying out molecular and biochemical assays in the laboratory to test hypotheses resulting from microarray experiments. President, Paradox Found LLC (NC Region 4) Computational toxicology/biology High-throughput bioassays Molecular toxicology Pharmacology Systems biology Dr. Stevens' research interests are in the areas of predictive and molecular and investigative toxicology and adverse drug reactions. He has studied the role of gene expression in mechanisms of cell injury for over two decades and was among the first to adopt gene expression analysis to understand mechanisms of toxicity. He was a member of the Board of Directors for Upstate Biotechnology and the Interim Vice President for Research and Development for Argonex Pharmaceuticals. Global Head, Safety Pharmacology, GlaxoSmithKline (PA Region 3) Biology Computational toxicology/biology Emerging materials (nanotechnology) Pharmacokinetics Toxicology Dr. Bahinski has expertise in safety pharmacology, drug discovery and development, cardiac physiology and pharmacology, and electrophysiology. His research includes the development of organ-on-a-chip technology for efficacy, safety, and toxicity evaluation of drugs, biologies, environmental toxins, and nanoparticles, including mechanistic studies and disease models. Dr. Bahinski is currently a member of the Science Board of the U.S. Food and Drug Administration. v.1/19/2021 ------- Affiliation Senior Toxicologist, American Chemistry Council (DC Region 3) Senior Director of Chemical Technology & Innovation and Green Chemistry Program Leader, Pfizer Inc. Worldwide Research and Development (CT Region 1) Sally Kleberg Professor of Environmental Toxicology, Duke University (NC Region 4) Expertise Exposure science Risk assessment Toxicology Chemical risk assessment Green chemistry Life cycle analysis Risk assessment Sustainability Biology Ecology Risk assessment Toxicology Background Dr. Becker's expertise is in toxicology, risk assessment, alternatives to animal testing, prediction models, and method validation. He directs the American Chemistry Council's Long-Range Research Initiative, a research program designed to modernize and improve chemical safety assessments. Dr. Becker is a Diplomate of the American Board of Toxicology and a member of the Society of Toxicology, the American Chemical Society, and the Society for Risk Analysis. Dr. Colberg's research interests are research program evaluation, chemical safety for sustainability, human health risk assessment, green chemistry, and chemical risk assessment and management. At Pfizer, he leads the chemistry technologies efforts to evaluate and develop alliances with external partners to deliver platform technologies suitable for greener and more environmentally sound chemical manufacturing of products. Dr. Di Giulio provides expertise in environmental toxicology, ecotoxicology, and risk assessment. His research interests are the effects, including mechanisms, of environmental pollutants on aquatic organisms and humans, and on interconnections between ecological and human health. Dr. Di Giulio has fifteen years' experience directing both the Superfund Research Center and the University Program in Environmental Health at Duke University (supported by the National Institute of Environmental Health Sciences). In addition, he has eight years' experience as Co-Principal Investigator of Duke's Center for the Environmental Implications of Nanotechnology (supported by the National Science Foundation and U.S. Environmental Protection Agency). v.1/19/2021 7 ------- Name Affiliation Expertise Background Chris Gennings, Ph.D. Research Professor, Icahn School of Medicine at MountSinai (NY Region 2) Information science Human health risk assessment (chemical mixtures risk assessment) Dr. Genning's research interests focus on chemical mixtures risk assessment including developing and implementing statistical techniques useful for estimating risk assessment of exposure to combinations of chemicals; designing economical study designs for mixtures of many chemicals; statistical modeling of pesticide mixtures; and integration of mixtures toxicology and statistics. She is the founding director of a T32 training grant from the National Institute of Environmental Health Sciences (NIEHS) in Environmental Statistics, focused on the integration of mixtures toxicology and statistical methods. Her research has been supported by NIEHS, U.S. Environmental Protection Agency, World Health Organization, National Institute of Child Health and Human Development, and the Health Effects Institute. Dale Johnson, Pharm.D., Ph.D.. DABT President and CEO, Emiliem, Inc.; Adjunct Professor, University of Michigan; Adjunct Professor, University of California, Berkeley (Ml Region 5, CA Region 9) Computational toxicology/biology Pharmacokinetics Risk assessment Dr. Johnson has technical expertise in computational toxicology and quantitative structure-activity relationship (QSAR) modeling. At the University of California, Berkeley, Dr. Johnson's research focuses on predictive toxicology and network pharmacology utilizing computational methodology to analyze chemical- biological interactions, model structure activity relationships, and analyze perturbations in systems biology pathways. Daland Juberg, Ph.D., ATS Human Health Science Policy Leader, Corteva (IN Region 5) Toxicology Exposure science Public health (children's health) Risk assessment Dr. Juberg has expertise in public health, toxicology, children's health, exposure science, risk assessment, sustainability, science policy, and risk communication. He has diverse industrial sector and consulting experiences spanning a number of scientific disciplines that are central to the evaluation and protection of human health and the environment. Dr. Juberg is an active member of the Society of Toxicology and a Fellow of the Academy of Toxicological Sciences. v.1/19/2021 8 ------- Affiliation Assistant Professor, California State University, East Bay (CA Region 9) Professor, University of California, Los Angeles (CA Region 9) Senior Scientist, Environmental Defense Fund (DC Region 3) Expertise Epidemiology Human health risk assessment Public health Risk assessment Toxicology Decision science/analysis/value of information Public health Risk assessment Social science Toxicology Behavioral science (risk communication) Biology Chemical risk assessment Computational toxicology/biology High-throughput bioassays Toxicology Background Dr. Lam has expertise in environmental health, environmental health policy, biostatistics, systematic review, and risk assessment. One key area of her research involves the development, improvement, and implementation of evidence-based systematic review methodology tailored specifically for use in environmental health to inform science-based policy- and decision- making. Her other research interests include advancing quantitative tools in risk assessment as well as the incorporation of high throughput screening approaches to predicting human toxicity. Dr. Lam has previously worked with the U.S. Environmental Protection Agency in the Office of Policy. Mr. Malloy's research interests include the application of science and engineering in regulatory and business settings, including nanotechnology, emerging materials, public health, risk assessment, sustainability, toxicology, law and social science, and decision science. One aspect of his research deals with the value and limits of applying decision analysis to public and private decisions regarding identification and evaluation of safer chemicals. Dr. McPartland works to identify and reduce chemical exposures harmful to human health and the environment. Her work at Environmental Defense Fund includes science, policy, and marketplace-related initiatives. In each of these areas, Dr. McPartland works with diverse groups of stakeholders to determine how improvements can be made to understand and ultimately reduce or eliminate toxic chemical exposures. Dr. McPartland has focused on new computational toxicology methods being developed by the U.S. Environmental Protection Agency to better understand and predict chemical hazard and risk, as well as efforts by the agency to apply systematic review methods in chemical assessment. Principal Scientist, Procter and Gamble Company (OH Region 5) Human health risk assessment Risk assessment Toxicology Dr. Rose has expertise in chemical risk assessment, inhalation toxicology exposure assessments, and the development of threshold of toxicological concern approaches. She has established inhalation exposure modeling approaches for consumer products and integrated these approaches into the industry aggregate exposure framework. Dr. Rose is also the leader of the Inhalation Safety Expert Team at The Proctor and Gamble Company. v.1/19/2021 9 ------- Gina Solomon, M.D., Ponisseril Somasundaran, Ph.D., MS Affiliation Principal Investigator, Public Health Institute; Clinical Professor, University of California, San Francisco (CA Region 9) President, Somasundaran, Inc.; La von Duddleson Krumb Professor, Columbia University (NY Region 2) Expertise Endocrinology Environmental health sciences Public health (children's health) Risk assessment Emerging materials Toxicology Background Dr. Solomon has experience working for a non-governmental organization, hospitals, a research institute, and universities. She addresses technical issues as well as policy. Dr. Solomon's prior work has included research on diesel exhaust and asthma, endocrine disrupting chemicals, pesticides, environmental contaminants in New Orleans after Hurricane Katrina, the health implications of the 2010 Gulf oil spill, and the health effects of climate change. Dr. Somasundaran has expertise in green chemistry, energy, waste water treatment, and nanotoxicity/environmental effects of nanoparticles. He specializes in surface and colloid chemistry. His research has been concerned with a wide spectrum of environmental problems including greener chemistry, enhanced oil recovery, remediation, tar sands, coal cleaning, sludge treatment, waste water treatment, and nanotoxicity. Donna Vorhees. Sc.D. Director of Energy Research, Health Effects Institute; Adjunct Assistant Professor, Boston University (MA Region 1) Exposure science Human health risk assessment Clifford P. Weisel, Ph.D. Professor, Exposure Science, Environmental and Occupational Health Sciences Institute, Rutgers University (NJ Region 2) Exposure science Human health risk assessment Dr. Vorhees specializes in multi-pathway exposure assessment and human health risk assessment of chemicals in indoor and outdoor environments. She has 20 years of consulting experience and has conducted deterministic and probabilistic exposure and risk modeling for chemicals, such as polychlorinated biphenyls, dioxins and furans, petroleum hydrocarbons, volatile organic compounds, and metals (e.g., arsenic, lead, and mercury). Dr. Weisel's research experience includes the determination of biomarkers of exposure, measurement of multiroute exposures to volatile organic compounds and disinfection byproducts in drinking water, exposure to children, the role of air pollution in exacerbation of asthma, exposures within modes of transportation, the sources of pollutants to indoor air and their contribution to personal exposure, and the how exposures affect the lung microbiome. v.1/19/2021 10 ------- Name B Mark Wiesner, Ph.D. Affiliation James B. Duke Professor of Civil and Environmental Engineering, Duke University; Chair, Department of Civil and Environmental Engineering, Duke University; Director, Center for the Environmental Implications of NanoTechnology (CEINT) (NC Region 4) Expertise Emerging materials Background Dr. Wiesner's research interests include membrane processes, nanostructured materials, transport and fate of nanomaterials in the environment, colloidal and interfacial processes, and environmental systems analysis. Dr. Wiesner's research pioneered the application of membrane processes to environmental separations and water treatment. He co-edited and -authored the book Water Treatment Membrane Process, and served as the founding Chair of the American Water Works Association's Membrane Research Committee. He also co-edited and - authored the book Environmental Nanotechnologies. v.1/19/2021 11 ------- Office of Research and Development Within the EPA's Office of Research and Development, the national research programs partner with the ORD centers to carry out the research outlined in the StRAP. Center for Public Health & Environmental Assessment (CPHEA) Provides the science needed to understand the complex interrelationship between people and nature in support of assessments and policy to protect human health and ecological integrity. Center for Computational Toxicology & Exposure (CCTE) CCTE researchers are developing and applying cutting edge innovations in methods to rapidly evaluate chemical toxicity, transport, and exposure to people and environments. Chemical Safety for Sustainability & Health and Environmental Risk Assessment Center for Environmental Measurement & Modeling (CEMM) Provides scientific expertise and leadership in the development and application of complex computational models that provide precise and detailed predictions of the activity of contaminants in the environment. Center for Environmental Solutions & Emergency Response (CESER) Plans, coordinates and conducts an applied, customer-driven, national research and development program to improve decision making by EPA, federal, state, tribal and local agencies, when faced with challenging environmental problems in the built environment. v. 1/19/2021 12 ------- Office of Research and Development Center Leadership Immediate Office of the Assistant Administrator Jennifer Orme-Zavaletta Principal Deputy Assistant Administrator for Science and Science Advisor orme-zavaleta.jennifer@epa.gov Chris Robbins Deputy Assistant Administrator for Management robbins.chris@epa.gov Bruce Rodan Associate Director for Science rodan.bruce@epa.gov Liz Blackburn Chief of Staff blackburn.elizabeth@epa.gov Center for Public Health and Environmental Assessment (CPHEA) Wayne Cascio Director cascio.wayne@epa.gov Samantha Jones Associate Director iones.samantha@epa.gov Kay Holt Deputy Director holt.kay@epa.gov Tim Buckley Associate Director buckley.timothv@epa.gov Kathryn Saterson Research Planning and Implementation Staff Lead saterson.kathrvn@epa.gov Center for Computational Toxicology and Exposure (CCTE) Rusty Thomas Director thomas.russell@epa.gov Annette Guiseppi-Elie Associate Director guiseppi-elie.annette@epa.gov Reeder Sams Deputy Director sams.reeder@epa.gov Monica Linnenbrink Research Planning and Implementation Staff Lead linnenbrink.monica@epa.gov Center for Environmental Measurement and Modeling (CEMM) Tim Watkins Director watkins.tim@epa.gov William Fisher Associate Director fisher.william@epa.gov Alice Gilliland Deputy Director gilliland.alice@epa.gov Gene Stroup RPIS Lead stroup.gene@epa.gov v. 1/19/2021 13 ------- Center for Environmental Solutions and Greg Sayles Director sayles.gregory@epa.gov Kelly Dipolt Deputy Director dipolt.kelly@epa.gov Response(CESER) Tom Speth Associate Director speth.thomas@epa.gov Steve Musson Research Planning and Implementation Staff Lead musson.steve@epa.gov v. 1/19/2021 14 ------- CSS Team Roster CSS NPD Team Jeffrey Frithsen National Program Director frithsen.ieff@epa.gov JoeTietge Principal Associate National Program Director tietge.ioe@epa.gov Heidi Bethel Associate National Program Director bethel.heidi@epa.gov Dayna Gibbons CSS Communications Director gibbons.dayna@epa.gov Kathie Dionisio Associate National Program Director dionisio.kathie@epa.gov James Smith Student Services Contractor smith. iames@epa.gov Scarlett Vandyke Student Services Contractor vandvke.scarlett@epa.gov Assistant Center Directors assigned to CSS Barbara Klieforth Office of Science Advisor, Policy and Engagement (CSS Extramural Research Lead) klieforth.barbara@epa.gov Jill Franzosa Center for Computational Toxicology and Exposure (CCTE) franzosa.iill@epa.gov Scott Jenkins Center for Public Health and Environmental Assessment (CPHEA) jenkins.scott@epa.gov John Kenneke Center for Computational Toxicology and Exposure (CCTE) kenneke.john@epa.gov Darcie Smith Center for Environmental Solutions & Emergency Response (CESER) smith.darcie@epa.gov Tiffany Yelverton Center for Environmental Measurement and Modeling (CEMM) velverton.tiffanv@epa.gov Doug Young Center for Computational Toxicology and Exposure (CCTE) young.douglas@epa.gov v. 1/19/2021 ------- HERA Team Roster HERA NPD Team Samantha Jones National Program Director iones.samantha@epa.gov Ashleigh Williams Student Services Contractor williams.ashleigh@epa.gov Beth Owens Principal Associate National Program Director owens.beth@epa.gov Quinn Weinburger Student Services Contractor weinburger.iaqueline@epa.gov Kelly Widener HERA Communications Director widener.kelly@epa.gov Assistant Center Directors assigned to HERA Beth Owens Center for Public Health and Environmental Assessment (CPHEA) owens.beth@epa.gov Jill Franzosa Center for Computational Toxicology and Exposure (CCTE) franzosa.iill@epa.gov Darcie Smith Center for Environmental Solutions & Emergency Response (CESER) smith.darcie@epa.gov v. 1/19/2021 ------- CSS National Research Program Review Charge Questions Introduction: The February 2021 meeting of the CSS-HERA Subcommittee of the Board of Scientific Counselors (BOSC) will review that portion of the CSS portfolio involved in the development and application of New Approach Methodologies (NAMs). The focus of the review is on the implementation of research and development that was outlined at the strategic level in the CSS Strategic Research Action Plan for FY19-22, as previously reviewed by the BOSC. Charge Question 1 The CSS portfolio advances New Approach Methods (NAMs) across multiple research areas related to chemical evaluation and risk assessment. CSS Session 1 presents selected research activities to highlight NAMs development for hazard evaluation, exposure, ecotoxicology, and human-system models. Please provide specific suggestions or recommendations to improve approaches to advance the development and testing of NAMs conducted under the CSS program. Charge Question 2 A key long-term objective of the CSS program is to increase the pace of chemical assessment through the incorporation of NAMs into decision making by EPA programs and regions and other stakeholders. CSS Session 2 presents examples of NAMs implementation that address specific, articulated needs of Agency partners. Please comment on the extent to which these selected research activities have the appropriate approach, structure, and components to increase confidence in, and to facilitate use of, NAMs in Agency decision making. Charge Question 3 CSS continues to develop and evolve multiple publicly-available data resources, analytical tools, and predictive models to facilitate the dissemination and use of chemical-safety information tailored to meeting specific user's needs. The long-term intent is for these CSS-supported platforms to provide a comprehensive resource to support the needs of our partners. CSS Session 3 presents examples of CSS information resources, models, and tools. Please provide suggestions or recommendations regarding how these CSS products can be improved and best implemented to serve EPA partners and external stakeholders? v. 1/19/2021 17 ------- HERA National Research Program Review Charge Questions Charge Question 1: As NAMs' science advances, risk assessors still encounter many chemicals with little-to-no data that require assessment. Research is required to translate and build confidence in the application of these NAMs in HERA science assessment contexts. Building on the case study examples, please provide suggestions or recommendations on how the planned research can best advance the integration of NAM data streams and approaches in HERA science assessments. [Research Area 3, Output 3.1] Charge Question 2: Incorporating the principles of systematic review into the HERA portfolio of assessment products has been a goal of the HERA program for the last several years. In order to achieve this goal, the HERA program intends to advance the field of systematic review more broadly. Based on the progress to date and currently planned products, what suggestion(s) or recommendation(s) does the Subcommittee offer on HERA's research to advance methods for systematic review? [Research Area 3, Output 3.4] Charge Question 3: Dose-response modeling is a critical step in human health assessment. Existing methods have improved upon older methodologies; however, unresolved issues, uncertainties, and complications remain that require targeted research. HERA has planned research products that will result in dose-response methods that are more precise, robust, and meet varied needs. Noting the examples provided, please comment on the extent to which these planned products address important issues in dose-response modeling for application to risk assessment, and ways this research might be augmented? What suggestion(s) or recommendation(s) does the Subcommittee offer to continue to advance methods in dose-response modeling with an application to risk assessment? [Research Area 3, Output 3.5 and Research Area 4, Output 4.1] v. 1/19/2021 18 ------- CSS STAR Extramural Research Program The Science to Achieve Results (STAR) Program is EPA's primary competitive, peer-reviewed, extramural research program. It funds nationally relevant research, leverages a wide variety of scientific and engineering resources, and provides collaborative access to innovative academics. Requests for Application (RFAs) originate in the EPA Office of Research and Development in cooperation with other Agency offices. The Safer Chemicals Research grants align with the core mission of EPA's Chemical Safety for Sustainability (CSS) National Research Program to make informed and timely decisions concerning potential impacts of environmental chemicals on human health and the environment. A selection of recent Safer Chemicals Research RFAs is included below. Assessment Tools for Biotechnology Products (FY2020 RFA) Awards forthcoming Advancing Toxicokinetics for Efficient and Robust Chemical Evaluations (FY2019 RFA) Integrated blood brain barrier-computational model development to predict doses of concern for compound linked neurotoxicity Purdue University 2020-2023 Measuring Toxicokinetics for Organ-on-Chip Devices Vanderbilt University 2020-2023 Integrating tissue chips, rapid untargeted analytical methods and molecular modeling for toxicokinetic screening of chemicals, their metabolites and mixtures Texas A&M University 2020-2023 Toxicokinetic screening of zebrafish cytochrome P450 enzymes for in vitro-in vivo extrapolation Woods Hole Oceanographic Institution 2020-2023 An in vitro-in silico hybrid approach for high-throughput estimation of trans-barrier permeability for chemical pollutants University of Nevada - Reno 2020-2023 Advancing Actionable Alternatives to Vertebrate Animal Testing for Chemical Safety Assessment (FY2018 RFA) (Focus on New Approach Methodologies (NAMs)) Skeletal Teratogenicity of Industrial and Environmental Chemicals Predicted with Human Pluripotent Stem Cells in Vitro University of California - Riverside 2019-2022 A Neurovascular Unit on Chip for Reducing Animals in Organophosphate Neurotoxicology Vanderbilt University 2019-2022 Instrumenting phenotypic immunological responses to toxicants that threaten human reproduction Vanderbilt University Medical Center 2019-2022 v. 1/19/2021 19 ------- Multiplexed human BrainSphere Developmental Neurotoxicity Test for Six Key Events of Neural Development The Johns Hopkins University 2019-2022 Reducing the reliance on early-life stage testing with relevance to euryhaline fishes: Development and implementation of in-vitro assays predictive of early life stage toxicity and population-level effects in Menidia beryl I in a Louisiana State University, Oregon State University 2019-2022 Systems-Based Research for Evaluating Ecological Impacts of Manufactured Chemicals (FY2014 RFA) Integrated Modeling Approaches to Support Systems-Based Ecological Risk Assessment Harvard University, President and Fellow of Harvard Collee, Washington State University 2015-2018 System Toxicological Approaches to Define Flame Retardant Adverse Outcome Pathways Oregon State University 2015-2019 A Bioenergetics-Based Approach to Understanding and Predicting Individual-to Community-Level Ecological Effects of Manufactured Chemicals Towson University 2015-2020 Development of a larval fish neurobehavior adverse outcome pathway to predict effects of contaminants at the ecosystem level and across multiple ecologically relevant taxa Michigan State University 2015-2021 Linking Biological Scales Across Generations: An Estuarine and Marine Model for Measuring the Ecological Impact of Endocrine Disrupting Compounds Oregon State University 2015-2020 Dynamical Systems Models Based on Energy Budgets for Ecotoxicological Impact Assessment University of California-Santa Barbara 2015-2019 Organotypic Culture Models for Predictive Toxicology Center (FY2013 RFA) (Focus on Organs on a Chip) Human Models for Analysis of Pathways (H MAPs) Center University of Wisconsin Madison 2014-2019 Cardiotoxicity Adverse Outcome Pathway: Organotypic Culture Model and in vitro- to in-vivo Extrapolation for High-throughput Hazard, Dose-response and Variability Assessments Texas A&M University 2015-2021 Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials University of Washington 2014-2020 Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology University of Pittsburgh, Vanderbilt University 2014-2019 Full listing of Safer Chemicals Research grants v. 1/19/2021 20 ------- CSS Highlights and Notable Accomplishments 2019 - Present Top 14 Most Published in Journals Journal Impact # of CSS Title Factor Publications 1. Toxicological Sciences 3.703 32 2. Environmental Toxicology and Chemistry 3.152 25 3. Environmental Science & Technology 7.864 18 4. Science of the Total Environment 6.551 12 5. Computational Toxicology 2.11 11 6. Toxicology in Vitro 2.959 9 7. Environmental Health Perspectives 8.341 8 8. Regulatory Toxicology and Pharmacology 2.652 8 9. Environmental Science: Nano 7.683 7 10. Aquatic Toxicology 4.346 6 11. Analytical and Bioanalytical Chemistry 3.637 6 12. Journal of Exposure Science & Environmental Epidemiology 3.531 6 13. Chemosphere 5.778 6 14. PLoSONE 2.74 6 Total Number of Publications 2019 2020 2021 (as of 1/14/2021) 153 133 13 v. 1/19/2021 21 ------- CSS Publications Receiving External Recognition Society of Toxicology's Best Postdoctoral Publication Award, 2021 Nyffeler J, Willis C, Lougee R, et al. (2020). Bioactivitv screening of environmental chemicals using imaging-based high- throughput phenotypic profiling. Toxicol Appl Pharmacol, 389,114876. American Chemical Society Editor's Choice Award, November 2020 Richard AM, Huang R, Waidyanatha S, et al. (2020). The Tox2110K Compound Library: Collaborative Chemistry Advancing Toxicology. Chem Res Toxicol. The Society of Environmental Toxicology and Chemistry Exceptional Paper Award, June 2020 Villeneuve DL, Coady K, Escher Bl, et al. (2019). High-throughput screening and environmental risk assessment: State of the science and emerging applications. Environ Toxicol Chem, 38(1), 12-26. Computational Toxicology Specialty Section of the Society of Toxicology, Paper of the Year, 2019 Toxicological Sciences Paper of the Year: Honorable Mention, 2019 Wambaugh JF, Hughes MF, Ring CL, et al. (2018). Evaluating In Vitro-ln Vivo Extrapolation of Toxicokinetics. Toxicol Sci, 163(1), 152-169. Best Paper Advancing the Science of Risk Assessment, from the Risk Assessment Specialty Section of the Society of Toxicology, 2018 Phillips KA, Wambaugh JF, Grulke CM, et al. (2017). High-throughput screening of chemicals as functional substitutes using structure-based classification models. Green Chemistry, 19(A), 1063-1074. International Society of Exposure Science Award for Best Journal of Exposure Science and Environmental Epidemiology Paper, 2018 Morgan MK, MacMillan DK, Zehr D, Sobus JR (2018). Pvrethroid insecticides and their environmental degradates in repeated duplicate-diet solid food samples of adults. J Expo Sci Environ Epidemiol, 28, 40-45. Included in the Best of the Journal of Exposure Science and Environmental Epidemiology 2018-2019 Special Collection Sobus JR, Wambaugh JF, Isaacs KK, et al. (2018). Integrating tools for non-targeted analysis research and chemical safety evaluations at the US EPA. J Expo Sci Environ Epidemiol, 28, 411-426. v. 1/19/2021 22 ------- CSS Investigators Receiving External Recognition The Society of Toxicology's Enhancement of Animal Welfare Award, 2021 In recognition of contributions made to the advancement of toxicological science through the development and application of methods that replace, refine, or reduce the need for experimental animals. Dr. Barbara Wetmore Center for Computational Toxicology and Exposure LUSH Prize for Young Investigators, 2020 Supporting initiatives to end or replace animal testing. Project: High-throughput phenotypic profiling of human neural progenitor cells to identify putative modes-of-action of developmental neurotoxicants Dr. Johanna Nyffeler Center for Computational Toxicology and Exposure Presidential Early Career Award for Scientists and Engineers (PECASE) Award, 2019 The highest honor bestowed by the U.S. government on outstanding scientists and engineers beginning their independent careers. Dr. Carlie LaLone Center for Computational Toxicology and Exposure Dr. Jon Sobus Center for Computational Toxicology and Exposure SETAC Presidential Citation for Exemplary Service, 2018 For planning and chairing the SETAC North America Focused Topic Meeting "High Throughput-Screening and Environmental Risk Assessment" Dan Villeneuve Center for Public Health and Environmental Assessment v. 1/19/2021 23 ------- |