Research In the USEPA

Janet Keough, Ph.D. Associate Director for Science

U.S. EPA/Office of Research and Development, National Health and Environmental Effects Research Laboratory

Mid-Continent Ecology Division- Duluth

US Environmental Protection AgencyOffice of Research and Development

National Environmental Policy Act of 1969 (NEPA); 42 U.S.C. 4321-4347

Chemical Safety Information, Site Security and Fuels Regulatory Relief Act Public Clean Air Act (CAA); 42 U.S.C. s/s 7401 et seq. (1970)

Clean Water Act (CWA); 33 U.S.C. ss/1251 et seq. (1977)

Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA or Superfund) 42 U.S.C. s/s 9601 et seq. (1980)

Emergency Planning & Community Right-To-Know Act (EPCRA); 42 U.S.C.

Endangered Species Act (ESA); 7 U.S.C. 136;16 U.S.C. 460 et seq. (1973)

Federal Insecticide, Fungicide and Rodenticide Act (FIFRA); 7 U.S.C. s/s 135 et seq. (1972)

Federal Food, Drug, and Cosmetic Act (FFDCA) 21 U.S.C. 301 et seq.

Food Quality Protection Act (FQPA) Public Law 104-170, Aug. 3, 1996

Freedom of Information Act (FOIA); U.S.C. s/s 552 (1966)

Occupational Safety and Health Act (OSHA); 29 U.S.C. 651 et seq. (1970)

Oil Pollution Act of 1990 (OPA); 33 U.S.C. 2702 to 2761

Pollution Prevention Act (PPA); 42 U.S.C. 13101 and 13102, s/s et seq. (1990)

Resource Conservation and Recovery Act (RCRA); 42 U.S.C. s/s 321 et seq. (1976)

Safe Drinking Water Act (SDWA); 42 U.S.C. s/s 300f et seq. (1974)

Superfund Amendments and Reauthorization Act (SARA); 42 U.S.C.9601 et seq. (1986)

Toxic Substances Control Act (TSCA); 15 U.S.C. s/s 2601 et seq. (1976)

National Laws with EPA Oversight

Today’s issues are broad in scope, deep in complexity and widespread

in their impacts.

Nick D. Kim

http://lab-initio.com/index.html

21st Century Environmental Challenges

• On climate change: Unless we act dramatically and quickly, science tells us our climate and our way of life are literally in jeopardy. – John Kerry, Secretary of State

• Nitrogen and phosphorus are leading causes of water pollution across the nation, threatening surface water quality and drinking water supplies. – US EPA

• Only a few hundred of the many thousands of chemicals in use in the US have been tested for safety.

– US EPA

• America’s critical infrastructure for drinking water and waste water systems received a grade of D, and may soon fail to meet society’s needs.

– Am Soc Civil Engineers

5

“Science is and has always been the backbone of the

EPA’s decision-making.”

Gina McCarthy - EPA AdministratorNovember, 2013

Science to Support EPA’s Mission

Program Offices(Air, Water, Waste, Chemicals)

Office of Research and Development

National Decisions

Scientific Foundation

Regional OfficesPrimary Interface

with States

Implementation

EPA Mission:Protect Human Health and the

Environment

• Policies• Regulations

• Congressional mandates

7

Provide science and technology to support EPA’s mission of protecting human health and the environment.

Mission for Research & Development

Bristol Bay, Alaska

GulfOil

Spill

8

ORD Research Facilities

Newport, OR

Las Vegas, NV

Duluth, MN

Ada, OK

Gulf Breeze, FL

Athens, GA

Chapel Hill, NC

Grosse Ile, MI

Narragansett, RI

Washington, DCCincinnati, OH

RTP, NC

Corvallis, OR

Edison, NJ

9

Air, Climate & Energy

Safe & SustainableWater Resources

Sustainable & Healthy Communities

Chemical Safety for Sustainability

Human Health Risk Assessment

Homeland Security

ORD Research Programs

10

Mid-Continent Ecology Division

Duluth, MN

Grosse Ile, MI

USEPA Mid-Continent Ecology DivisionResearch to Answer Agency Programs

High Priority Agency Problems

Ecosystem Resil ience &

Sustainability

PredictiveEcotoxicology

Drivers of Research for EPA’s Mid-Continent Ecology Division

National Drivers:FIFRA Pesticides Risk Assessments

FQPA Pesticides and Personal Use Chemicals RACWA Chemicals in Water, Integrity of Waters of the US

TSCA Chemicals in Industry RA

Regional Drivers:Great Lakes Water Quality Agreement

Great Lakes Restoration InitiativeRegional WQ Criteria

Regional Water Quality MonitoringState Environmental Issues

Addressing EPA’s National Research Priorities Within the Great Lakes Region

USEPA Mid-Continent Ecology DivisionResearch to Answer Agency Programs

High Priority Agency Problems

Ecosystem Resilience &

Sustainability

PredictiveEcotoxicology

Predicting Chemical Toxicitywith Limited Data

Identify “normal” biological pathways whose perturbation results in adverse responses to chemicals

Determine chemical characteristics that enable them to perturb these pathways

Develop mechanism-based approaches to measure these characteristics In silico (computational) methods (e.g., QSAR) In vitro (e.g., HTP) toxicity pathway assays Short-term in vivo tests with pathway-specific endpoints (including

suites of genomic measures)

Translate these mechanistic data into transparent depictions of potential risk/hazard

A Paradigm Shift in Risk Assessment

Molecularinitiating event

Key events or predictiverelationships spanning

levels of biological organization

Adverse outcomerelevant to

risk assessment

QSAR, read acrossIn vitro, HTS

Biomarkers‘Omics’

Predictive Toxicology

Toxicant Macro-MolecularInteractions

Cellular Responses

OrganResponses

IndividualResponses

PopulationResponses

Adverse Outcome Pathway

AOPs Provide an Organization and Communication Framework

Molecularinitiating event

Key events or predictiverelationships spanning

levels of biological organization

Adverse outcomerelevant to

risk assessment

19

ChemicalPropertyProfile

Receptor/Ligand

InteractionDNA Binding

Protein Oxidation

Gene Activation

Protein Production

Altered SignalingProtein

Depletion

Altered PhysiologyDisrupted

HomeostasisAltered Tissue Developmentor Function

LethalityImpaired

DevelopmentImpaired

ReproductionCancer

ToxicantMacro-Molecular

InteractionsCellular

ResponsesOrgan

ResponsesIndividual

Responses

Structure

Recruitment

Extinction

PopulationResponses

Adverse Outcome Pathway

AOPs Provide an Organization and Communication Framework

Molecularinitiating event

Key events or predictiverelationships spanning

levels of biological organization

Adverse outcomerelevant to

risk assessment

20

ChemicalPropertyProfile

Receptor/LigandInteraction

DNA BindingProtein Oxidation

Gene ActivationProtein ProductionAltered SignalingProtein Depletion

Altered PhysiologyDisrupted

HomeostasisAltered Tissue Developmentor Function

LethalityImpaired

DevelopmentImpaired

ReproductionCancer

Toxicant Macro-MolecularInteractions

Cellular Responses

OrganResponses

IndividualResponses

Structure

Recruitment

Extinction

PopulationResponses

Adverse Outcome Pathway

CN

NN

Aromatase inhibition

8

0

2

4

6

E2

(ng/

ml)

*

*

0

10

20

Vtg

(mg/

ml)

*

* *Control 2 10 50

Fadrozole (µg/l)

8

0

2

4

6

E2

(ng/

ml)

*

*

0

10

20

Vtg

(mg/

ml)

*

* *Control 2 10 50

Fadrozole (µg/l)

-20 -18 -16-14-12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20Exposure (d)

0

2

4

6

8

10

(Tho

usan

ds)

Cum

ulat

ive

Num

ber o

f Egg

s

Control21050

Fadrozole (ug/L)

***

-20 -18 -16-14-12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20Exposure (d)

0

2

4

6

8

10

(Tho

usan

ds)

Cum

ulat

ive

Num

ber o

f Egg

s

Control21050

Fadrozole (ug/L)

***

Reduced E2, Vtg synthesis

Impaired vitellogenesis Reduced fecundity

AOPs Provide an Organization and Communication Framework

Molecularinitiating event

Key events or predictiverelationships spanning

levels of biological organization

Adverse outcomerelevant to

risk assessment

21

ChemicalSubcellular

TargetCells

EffectedAdverse Outcome

PeripheralTissue/Organ

Ex: MethimazoleTPO Enzyme

Inhibition

ThyroidFollicular Cells T4 Synthesis

Serum T4

Systemic T4 Insufficiency

ArrestedAmphibian

Metamorphosis

SNH

NCH3

T4 Release

Molecular InitiatingEvent

Circulating TH Status Altered MorphologyTPO Enzyme Inhibition Thyroid Histology

AOP Discovery: Thyroid Peroxidase Inhibition Adverse Outcome Pathway

USING CROWD-SOURCINGAND WIKI TECHNOLOGY TOGATHER AOP RESEARCHRESULTS AND KNOWLEDGEFOR A BROAD SPECTROM OFADVERSE PATHWAYS

AOP-KBHub

Shared chemical, biological and toxicological ontologies

Third party Applicationsand plugins

AOP Xplorer

Visualize attribute networks to discover

& explore AOPs in a broader

context

Effectopedia

Detailed development of structured & computational

AOPs

AOP Wiki

Collaborative development of AOP

descriptions & evidence

Intermediate Effects DB

Chemical-related AOP components in a regulatory

context

AOP Knowledgebase (AOP-KB)

The AOP-KB project is an OECD initiative, which is executed as a close collaboration between the European Commission's

Joint Research Centre (JRC), the US Environmental Protection Agency (EPA), and the US Army Engineer Research

& Development Center (ERDC).

Data needed for development

ScreeningRead Across

Environmental Surveillance

Prioritization, Integrated Approaches to Testing and

Assessment

Quantitative Risk AssessmentsExposure Reconstruction

Domains of Applicability

Cost and time required for development

Uncertainties for Prediction/extrapolation

•New chemicals (PMN)•Pesticide inerts•Replacements•Green chemistry

•TSCA

•Pesticides•HPV•WQ Standards

•FIFRA•CWA

•Current use•High economic value•Cost benefit•Criminal enforcement actions

•Social-economic-environmental

Examples

Balancing Breadth and Depth of AOPs

Pathway-Based Approaches to Effects-Based Monitoring in the Great Lakes

Chemical monitoring strategies are effective only for chemicals whose hazards are well understood and for which sensitive analytical methods are available.

Which chemicals in the environment should concern us?

Biological effects monitoring can be a powerful complement to chemical monitoring:

• To detect exposure to chemicals for which analytical methods are unavailable or impractical.

• To provide insight into the potential biological consequences of those exposures.

NEED: Develop practical effects-based approaches for monitoring chemicals of emerging concern (e.g., with currently unknown hazard or exposure potentials) in the Great Lakes.

Pathway-Based Approaches to Effects-Based Monitoring in the Great Lakes

APPROACH:

• Caged fish studies conducted at 32 locations spread across 5 Great Lakes AOCs

• Complementary in vitro bioassay analyses (EPA), analytical chemistry (FWS), and feral fish histology/biomarkers (USGS).

•St. Louis River/ Duluth Harbor

•Lower Green Bay/ Fox River

•Milwaukee Estuary •Detroit River

•Maumee River

Sequence Alignment to Predict Across Species Susceptibility(SeqAPASS)

Predict Relative Intrinsic Susceptibility

• Intrinsic susceptibility: the vulnerability of an organism to chemical insult due to its inherent biological composition– Receptor/enzyme (protein) available for the chemical to act upon

• Relative: based on comparisons to a query protein– Molecular target conservation is one component of multiple determinants

of species susceptibility

Strategic Automated Approach for Assessing Protein Similarity among Taxa

Level 1

Level 2

Level 3

Developed with both researchers and risk assessors in mind

Level 1 SeqAPASS Results

More likely to be susceptible Less likely

to be susceptible

Acetylcholinesterase Inhibition

USEPA Mid-Continent Ecology DivisionResearch to Answer Agency Programs

High Priority Agency Problems

Ecosystem Resilience &

Sustainability

PredictiveEcotox icology

Prospectus for the Near FutureGreat Lakes Water Quality Agreement : Coupling Land with Watersheds and Nearshore Zones

What sustains the integrity of land-water systems across the coastal mosaic?

• An array of aquatic habitats that are linked to and influenced by watersheds and offshore zones

• Complex hydrology & connectivity• Understanding linkages is essential for effective monitoring, assessment, and

management

Watershed

Offshore

The coastal mosaic:

SensorsCTD

Fluorometer(calibrated to Chl a)

TransmissometerLaser Optical Plankton Counter

(Zooplankton >150 µm)NO3

Along-shoreline towing survey strategy

Evolved to be along constant depth contour

High-resolution data along 500 to 1000 km of shoreline

Courtesy of Kelly and Yurista

y = 0.35x + 0.46R² = 0.37, n= 51

y = 0.45x + 0.69R² = 0.57, n= 62

0.0

0.5

1.0

1.5

2.0

2.5

0 0.5 1 1.5 2 2.5

Tow

-bas

edin

tegr

ated

wat

er co

lum

n av

erag

esfo

r bot

tom

dep

th a

nd sa

me

segm

ents

hed

(Ln(

Chla

), µg

/L)

August

September

Spatially Balanced Probability Survey- 45 stations in each lake

- 0-30 m depth and <5 km from shore

AGRICULTURE METRIC)

National Coastal Condition AssessmentA comprehensive, efficient, and powerful style of point sampling

EPA-OW included US Great Lakes

GLEI projectDanz et al. 2005, 2007

Kelly, Bartsch, Vinson, Yurista, Yule et al. In prep)

Statistical Confidence ModelingNomograph for Whole Lake Estimates as a Function of Effort

(ordered subsets of sample size n, using 2011 design results)

Integrated Coastal Observing Systems for Large Lakes

High-resolution tow “census”

along 20-m depth contour

Probabilistic surveyNational Coastal

Condition Assessment

Basin-wide watershed stressor

characterization

Nokomis 3-5 September 2014

Nokomis 12-17 September 2014

Initial testing of EPA’s AUV (Slocum glider)

in Lake Superior

Development of tools for monitoring the Great Lakes: Autonomous Underwater Vehicles (AUVs)

Cooperative effort of GLNPO, MED and

UMN-Duluth (Drs. Jay Austin and Laura

Fiorentino post doc)

Nokomis 25 Sep – 6 Oct(out and back)

Ecosystem Forecasting Models toPredict Response to Pollution Management

The Heartland Feeds the Gulf of Mexico

41

EPACOM

dissolved oxygen

sediment

zooplankton

carbon cycle

phytoplankton

CMAQ loads

dissolved and detrital carbon

phosphorus

nitrogen

silicon

nutrient cycle

• 20 state variables• nitrogen

– NO3, NH4

– DON, LON, RON

• phosphorus– SRP, DOP, LOP,

ROP

• silicon – SA, SU

• carbon– DOC, LOC, ROC

• 2 phytoplankton• 1 zooplankton

Gulf of Mexico Dissolved Oxygen Model

Office of Research and Development

Model Predicted (map) versus Observed (squares) Dissolved Oxygen in the Gulf of Mexico

Three Overlapping Phases in the History of the EPA

1) Command and Control

2) Risk assessment / Risk management

3) Sustainability

Sustainability

“… to create and maintain conditions, under which humans and nature can exist in productive harmony, that permit fulfilling the social, economic, and other requirements of present and future generations.”

- NEPA 1969, NAS 2011

45

Environment

EconomySocial Systems

Area of Concern (AOC) RemediationPromotes Sustainability

Fishing Related EconomyLand and Property ValuesWaterfront AmenitiesEco-TourismBoating

Drinking Water Quality Contaminant Remediation

Brownfield redevelopment

Wastewater Treatment

Science Education

Environmental Justice

Tribal culture (wild rice,Fish consumption)

Water Contact Sports

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Partnerships– EPA ORD, Region 5 , Great Lakes National Program

Office, Brownfields Redevelopment Program, Great Lakes Legacy Program, Great Lakes Restoration Initiative, Superfund

– NOAA Sea Grant and National Estuarine Reserve Research Program

– Center for Disease Control Agency for Toxic Substances and Disease Registry

– State Natural Resources management agencies– Community and non-profit organizations for the

restoration and redevelopment of Great Lakes AOCs

The benefits of contaminated sediment remediation, habitat restoration, and water quality protection to Great Lakes coastal

communities

Ecosystems (nature)

Biophysical structuree.g., habitat

Functione.g., nutrient cycling

Human wellbeing

Socio-cultural benefitse.g., food, recreation

Economic valuee.g., green GDP

Ecosystem services link nature to human wellbeing

Ecosystem services

e.g., fish populations,clean water, clean air

Natural walleyepopulations

Recreational fishingSpawning habitat

in Upper St. Louis River

Ecosystem structure Ecosystem service Human Benefit

Case Study: Remediation-to-Restoration-toRevitalization of the St Louis River Area of Concern

Based on Sierszen et al. (2012). A Review of selected ecosystem services provided by coastal wetlands of the Laurentian Great Lakes. Aquatic Ecosystem Health and Management

Ecosystem Services of Great Lakes Coastal Wetlands

Ecosystem Service Indicator Societal

ImportanceSpatial

DistributionInformationAvailability

WildlifePopulation densities, habitat

quality, and harvest for select bird, amphibian and reptile species

High but variable

Widespread but variable by species

High but variable by

species

Fisheries Population densities & age structure, habitat quality for select

speciesVery High Widespread High

Water Quality Nutrient concentrations and cycling, sedimentation, DO regime Very High Widespread High

Plant crops Wild rice population extents and harvest

Low but culturally specific

Localized Limited

Climate Regulation

C sequestration – lacking indicators Unknown Unknown Lacking

Coastal Protections Wetland extend and distribution High Localized Limited

51

Mapping Ecosystem Services and Benefits Remediation – Restoration – Revitalization

All have spatial properties

Location, Location, Location!

Using hydroacoustic and field vegetation surveys to assess whether biota is constrained by the availability and quality of habitat.

Higher quality habitat associated with dense aquatic vegetation.

Lower quality fish and bird habitat in harbor associated with sparse aquatic vegetation.

Using water P and N concentrations and sediment denitrification rates to estimate nutrient processing in an AOC.

nutri

ents

(ug

L-1)

0

50

100

150

200

250

300

DE

A (u

g N

day

-1)

0

20000

40000

60000

80000

River

TP NOx Base Denitrification

nutri

ents

(ug

L-1)

0

50

100

150

200

250

300

DE

A (u

g N

day

-1)

0

20000

40000

60000

80000

Bay

Base Denitrification

NOxTP

nutri

ents

(ug

L-1)

0

50

100

150

200

250

300

DE

A (u

g N

day

-1)

0

20000

40000

60000

80000

Harbor

TP NOx Base Denitrification

Offshore systems can contribute excess nitrate to coastal systems.

Using socioeconomic data to see whether property value relate to the proximity of contaminated sites.High value waterfront parcels (highlighted) can be found relatively close to Superfund and Brownfield sites ( ).

St Louis River EstuaryRestoration-to-Revitalization for Shore Fishing –

An Ecosystem Service Benefit

St Louis River EstuaryStacked Ecosystem Goods and Services (EGS)

Thanks!

http://lab-initio.com