40 years of exposure and now the “new exposure science”

40 Years of Exposure and NOW the New Exposure Science

Office of Research and Development 2 A little history What is the new exposure science What do we need to do to move it forward

Office of Research and Development 3 40 Years was a long time ago!! Me Computational Methods Visualization Communication

Office of Research and Development 4 My First Foray into Exposure Science The opportunity: Analytical chemistry was for the first time good enough to measure many, many chemicals in the environment The time: 1976 The place: MIT The mentor: Ron Hites The problem: The Delaware River

Office of Research and Development 5 Organic Chemicals in the Delaware River-- Results Hundreds of chemicals identified Naturally occurring, municipal discharge, and industrial chemicals Industrial chemicals were of three types General urban pollution Industrial sources Specific sources Rohm &Haas chlorinated reaction products of pesticide manufacturing Controversy Rohm & Haas Impact final piece of information for replacing the water treatment system in Philadelphia

Office of Research and Development 6 A quick trip though the last 40 years Why is human exposure science so narrow point of contact? Why hasnt it taken a systems approach to the science? The way modern exposure science started explains but it should and is evolving Systems approaches will be key to the future

Office of Research and Development 7 Human Exposure Science in the 80s Humans are at risk to stressors (mostly chemical) because of what they come in contact with Reducing exposure is a way to protect health Many surrogates were used to estimate exposure and dose Ambient monitors Source emissions Simple questionnaire Analytical chemistry was good enough to test hypotheses about surrogates for exposure and determine what was important

Office of Research and Development 8 Seminal Research: TEAM Studies 1979 to 1985 Measured 20 volatile organic chemicals in outdoor air, indoor air, personal air, and drinking water Samples collected daytime and nighttime over 2 seasons Over 600 participants from Elizabeth/Bayonne NJ Contra Costa County, CA Devils Lake, SD Greensboro, NC Participants selected to represent the population in each area Hypotheses: People in most polluted areas should have highest exposure.

Office of Research and Development 9 TEAM Study Findings No matter where you lived Personal exposures > indoor >outdoor Personal concentrations were 5 to 10 times higher than outdoors For many chemicals correlations between outdoor air and personal exposures were poor Conclusions Indoor environments and activities were significantly more important than environmental concentrations

Office of Research and Development 10 Thus began our obsession to understand the Indoor environment, activities, point of contact and Research to improve the estimates for exposure

Office of Research and Development 11 Many Field Studies and Emission Tests Later Tens of thousands of participants in field studies General population Life stages children and elderly susceptibilities Hundreds of materials and products testes Different chemicals PAHs, phthalates, PM, VOCs, aldehydes, pesticides, CO, NO2 Different Matrices water, air, soil, dust, food, wipes, and biological samples Different Settings homes, schools, vehicles, offices, hospitals California, New York, Texas, Virginia, Massachusettes

Office of Research and Development 12 To name a few studies TEAM Nursing Mothers study EPA Indoor Air study CARB VOC Exposure Study CARB PAH and Phthalate Study EPA PTEAM CARB PAH Indoor Air Study CARB Commuter Study SoCAL School Study EPA NHEXAS EPA Agricultural Health Study EPA Brownville Study NYSERDA Exposure to Combustion Products NYSERDA Radon Study Cal Public Heath Trust Emissions Study PM Panel Studies

Office of Research and Development 13 And some Kids Studies Childrens Total Exposure to Persistent Pollutants (CTEPP) First National Environmental Health Survey of Child Care Centers (CCC) American Healthy Home Study (AHHS) Biological and Environmental Monitoring for Pesticide Exposures in Children Living in Jacksonville, Florida (JAX) Agricultural Community Exposure Study (CHAMACOS) Childrens Pesticide Post-Application Exposure Study (CPPAES) Feasibility of Macroactivity Approach to Assess Dermal Exposure (Daycare) Distribution of Chlorpyrifos Following a Crack and Crevice Type Application in the US EPA Indoor Air Quality Test Research House Characterizing Pesticide Residue Transfer Efficiencies (Transfer)

Office of Research and Development 14 The Science (methods and knowledge) was being built Results showed strong influence of the built environment and activities in the environment on exposure Materials Product Use Combustion sources Human activities are critical to exposure The environments we live in The products we use Our contact with chemicals Building construction and operation are important for both ambient and indoor pollutants Understanding was summarized in models both processes and inputs

Office of Research and Development 15 Crucial Impacts Many toxic chemicals were taken out of products and materials PM exposure studies supported the science behind the 1997 PM NAAQS PM at ambient sites can be used to predict personal exposure Studies provided important understanding, data, and models for estimating kids exposure for FQPA Information used to delist certain pesticides for indoor applications

Office of Research and Development 16 Dose at the target Linked Exposure/PBPK Models PBPK/PD Model Tissue metric distributions Biomarker distributions Activity and environmental concentration distributions Exposure pathways lung brain kidney stomach skin liver Exposure Model

Office of Research and Development 17 Internalizing exposure Biologically effective dose Exposure as Part of a Systems Approach for Assessing Risk Linda S. Sheldon1 and Elaine A. Cohen Hubal2 1National Exposure Research Laboratory, and 2National Center for Computational Toxicology, U.S. Environmental Protection Agency, A biomonitoring framework to support exposure and risk assessments Jon R. Sobus, Yu-Mei Tan, Joachim D. Pleil, Linda S. Sheldon National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Adapting concepts from systems biology to develop systems exposure event networks for exposure science research Joachim D. Pleil*, and Linda S. Sheldon National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, The endpoint for exposure is biologically effective dose Integrated models can predict exposure and dose at the target organ, cell, AOP are needed

Office of Research and Development 18 New Exposure Science We were developing Methods, data, and models to understand exposure It was useful and having impact But we needed more, much more And a transformative change was needed

Office of Research and Development 19 It is important. Exposure science provides real world context for describing risk, well-being, and sustainability Complex societal problems and growing demand for information to address Climate change, Security threats, Population pressure Habitat loss, Increases in childhood illness Advances in measurements and computational techniques provide new tools EPA with NIEHS commission an NRC report to provide a transformation for exposure science Used as a catalyst to develop a new science Drivers for a New Exposure Science

Office of Research and Development 20 Changes the perspective on exposure science and how it is conducted Extends beyond the exposure event to the transport and transformation of agents from their source to a dose Is multi-scale and includes multiple stressors across scales of time, space, and biological organization Exposure science must deliver knowledge that is effective, timely, and relevant Provides a Conceptual Systems Framework for exposure science Stresses collaborations within and outside the Federal Government should be developed Concepts in the NRC Report

Office of Research and Development 21 stressors as well as receptors Actions or Events Disasters Climate change Market demands Population growth Policy decisions 1 Health Function Service Societal Demands Dynamic System *Adaptation from NRC Report in red Role of Human Activities NRC Report: Conceptual Systems Framework

Office of Research and Development 22 NRC Vision: Use advanced technologies to move the science forward Methods to track sources, concentrations and receptors at multiple scales Remote sensing Ubiquitous and embedded sensing Biomonitoring Methods and Tools for Analysis Geographic Information Systems Multi-scale exposure modeling Statistical methods and tools for predictive modeling Informatics Information Management Publicly available systems for data sharing Community Engagement and Promoting Public Trust Protecting research volunteers Managing issues of privacy Citizen Science

19952014 and beyond Field/Lab direct measurements Omic/informatics/sensors/ Computational predictive measurements Stand alone empirical models Integrated systems & Predictive models Targeted chemical exposure modeling High through-put exposure modeling Gathering dataMining data New Exposure Science Transition in Research

Office of Research and Development 24 Cool Tools but with a purpose Broaden Scope Increase Pace Improve Accuracy Increase Public Engagement Reduce burden/cost

Office of Research and Development 25 EPA Exposure Summit Goal to understanding the new science, its value to EPA, and what needs to be done to implement Exposure Speed dating on the New Science Sensors for Air Monitoring Ubiquitous Sensing Biomonitoring New Methods to Extend Analytical Space New Data sources Twitter, Nielsen, Apps Rapid computational Exposure Models - computationally lean and linked models All can be found on

Office of Research and Development 26 Ubiquitous Sensing Methods of obtaining information about an object within coming in contact Rapid, cheap, real-time, field-deployable Public engagement Water quality measures such as turbidity, chlorophyll-a, cyanobacteria, etc. Unexpected capabilities: crowd sourcing Low [conc] High [conc] Grand Lake St. Mary in 2010. Satellite derived cyanobacteria indices are consistent with Ohio EPA samples. Ohio EPA sampled for microcystin blooms on June 14 th and concentrations jumped from

Office of Research and Development 27 Applications to Air Pollutants Collaborations with NASA to improve use of satellites for health applications Discover AQ and Tempo Joint research to develop/evaluate air quality parameters using satellite data Provide data for improving fine-scale air quality simulations NASA P-3B NASA King Air EPA, Sate, Local, and temporary Ground sites

Office of Research and Development 28 Untargeted Analysis extends limited analytical space Testing Feasibility of Application to Environmental Samples Chemicals for risk assessment and regulation are often driven by Analytical Space Analytical Space has been gradually increasing for the past 40 years Advanced MSTOF methods have been applied to tens of thousands of chemicals in biological samples We are now applying these methods to environmental samples

Office of Research and Development 29 House-Dust or Water Sample Dust samples (~50) from National Homes Survey TOFMS +/- SCREEN Easier More Difficult Most Difficult Presence of a DB matched peak Presence of a confirmed compound Quantitation of a compound Yes/No Analysis Approaches --ALL ARE POSSIBLE Water -Polar Organic Chemical Integrative Sampler (POCIS)

Office of Research and Development 30 Summary of number of peaks during 45min running by Liquid Chromatography/Time-of-Flight MS

Office of Research and Development 31 Computational Exposure: Integrating Disparate Data Streams and Models to Rapidly Predict Exposure to Chemicals Integrated HT Models Fate and Transport Human Behaviors and Exposure Factors Multiple Scenarios Extensible/Scalable Exposures and Doses Sensitivity and Uncertainty Chemical Functional Use Chemical Functional Use Chemical Structures Chemical Structures Consumer Product Characterization Consumer Product Characterization Consumer Product Use Consumer Product Use Population Characterization Population Characterization Exposure Scenarios/Equations Exposure Scenarios/Equations Composition/ Emission Sources Composition/ Emission Sources Prevalence, Frequency, Amount Prevalence, Frequency, Amount Demographics, Behavior, Physiology Demographics, Behavior, Physiology Population-level Evaluation And Calibration Case Study Evaluation Chemical Properties Chemical Properties QSAR

Office of Research and Development 32 Framework for Computational Exposure 32 Framework requires information on Physical Chemical properties that drives fate and transport methods to predict stochastic decisions that drive human behaviors important for chemical use and exposure Current focus on consumer use chemicals highest human exposure potential

Office of Research and Development 33 SHEDS-HT: Merging Multiple Data Streams to Produce Exposure Predictions for 1000s of Chemicals Exposures By Lifestage

Office of Research and Development 34 Moving the Science Forward

Office of Research and Development 35 Exposure is contact of a stressor at the external boundary of a receptor Exposure Science is the collection and analysis of information to understand the nature of the contact chemical, physical, and biological stressors Exposure is the experience of the environment Includes both human and ecological receptors Must describe the entire environment including both positive and negative stressors Embraces the idea of cumulative impacts Suggests a dynamic system Allow us to grow along the trajectory from Should the Definition be Changed? Risk - Impact of negative stressors Well-being -Impact of positive And negative stressors Sustainability -For current and future generations

Office of Research and Development 36 Fundamental Principles Early findings must be transmitted and retained Importance of indoor environments and products to humans Computational exposure efforts PFOS/PFOA Individual vs. population exposure and riskdifferent goal and different requirements Standards and ontologies preliminary work should be extended Standard methods Air infiltration methods Biomonitoring collection methods ISES COULD PLAY A MAJOR ROLE IN THESE

Office of Research and Development 37 New Science must be evaluated Difficult but needed not just method evaluation but evaluation of the data relative to the intended use Computational Exposure example Identify and acquire multiple data streams traditional or nontraditional; of known or potential value Combine data streams to estimate exposure/dose for large set of chemicals (not one at a time) Evaluate exposure/dose estimates for chemical sets vs. known estimates; Identify key data limitations and sources Iterate process Biomonitoring as an exposure metric

Office of Research and Development 38 Big Data Crucial to Exposure Science especially data on activities However society, in general, is struggling with privacy and accessibility So, what data will be most useful, how can we use it without and identifiers, how do we protect human subjects, how do we apply this data to populations How do we make all data accessible ISES COULD/SHOULD PLAY A MAJOR ROLE IN THIS

Office of Research and Development 39 Exposure Science MUST be Multidisciplinary Human and Eco Exposure Scientist and Toxicologist Air Modelers and Epidemiologist Exposure Science and Life Cycle

Office of Research and Development 40 These are exciting times with many, many new tools that will allow us to do things we have never done before We need to learn how to use them and demonstrate how they can be applied As you move forward BE BOLD, BE INNOVATIVE, BE SMART, COMMUNICATE, COMMUNICATE, COMMUNICATE

Office of Research and Development 41 Nothing presented here was done alone, Many, Many Thanks to all I have collaborated with

40 years of exposure and now the “new exposure science”

Documents

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office of research

new exposure science

years of exposure

human exposure science

seminal research

highest exposure

important slide