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Overview of USEPA’s Endocrine Disruptors Research Program

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Overview of USEPA’s Endocrine Disruptors Research Program. Elaine Z. Francis, Ph.D. National Program Director Pesticides and Toxics Research Program Environmental Technology Council January 26, 2006 [email protected]. Outline. What are Endocrine Disruptors? Examples of EPA’s research - PowerPoint PPT Presentation
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Overview of USEPA’s Endocrine Disruptors Research Program Elaine Z. Francis, Ph.D. National Program Director Pesticides and Toxics Research Program Environmental Technology Council January 26, 2006 [email protected]
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Page 1: Overview of USEPA’s Endocrine Disruptors Research Program

Overview of USEPA’s Endocrine Disruptors

Research Program

Overview of USEPA’s Endocrine Disruptors

Research Program

Elaine Z. Francis, Ph.D.

National Program DirectorPesticides and Toxics Research Program

Environmental Technology CouncilJanuary 26, 2006

[email protected]

Elaine Z. Francis, Ph.D.

National Program DirectorPesticides and Toxics Research Program

Environmental Technology CouncilJanuary 26, 2006

[email protected]

Page 2: Overview of USEPA’s Endocrine Disruptors Research Program

OutlineOutline

• What are Endocrine Disruptors?

• Examples of EPA’s research

• Collaborations

• Future directions and where ETC can provide support

Page 3: Overview of USEPA’s Endocrine Disruptors Research Program

What Are Endocrine Disruptors?What Are Endocrine Disruptors?

Page 4: Overview of USEPA’s Endocrine Disruptors Research Program

Endocrine SystemEndocrine System

• Plays a key role in the development, growth, reproduction and behavior of humans and wildlife Glands - organs that secrete hormones Hormones - chemical messengers

released into the bloodstream Receptors - cellular components that

interact with hormones

• Plays a key role in the development, growth, reproduction and behavior of humans and wildlife Glands - organs that secrete hormones Hormones - chemical messengers

released into the bloodstream Receptors - cellular components that

interact with hormones

Page 5: Overview of USEPA’s Endocrine Disruptors Research Program

What is an Endocrine Disruptor?

What is an Endocrine Disruptor?

• An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations.

(IPCS/WHO, 2002)

Page 6: Overview of USEPA’s Endocrine Disruptors Research Program

Effluents

Flame Retardants

Fungicides

Herbicides

Insecticides

Metals

Pharmaceuticals

Phenols

Plasticizers

PAHs

Soy Products

Surfactants

WWTP, pulp and paper mills, CAFOs

PBDEs

Vinclozolin

Atrazine

Methoxychlor

Tributyltin

Ethinyl Estradiol

Bisphenol A

Phthalates

PCBs, dioxin

Genistein

Alkylphenol

Ethoxylates

Some Classes of Known or Suspected EDCs

Some Classes of Known or Suspected EDCs

Page 7: Overview of USEPA’s Endocrine Disruptors Research Program

Purported Adverse Effects: Wildlife

Purported Adverse Effects: Wildlife

• Eggshell thinning in bird populations due to DDT• Abnormal reproductive development in alligators in Lake

Apopka, Florida following pesticide spill• Nearly complete mortality of young Lake Ontario trout from

exposure to dioxin-like compounds• Simultaneous presence of both male and female reproductive

organs (imposex) in mollusks exposed to alkyltins• Synthesis in male fish living near sewage outfalls of a

hormonally regulated protein (vitellogenin) normally found only in female fish

• Birth defects in Lake Michigan birds exposed to PCBs and other chemicals

• Eggshell thinning in bird populations due to DDT• Abnormal reproductive development in alligators in Lake

Apopka, Florida following pesticide spill• Nearly complete mortality of young Lake Ontario trout from

exposure to dioxin-like compounds• Simultaneous presence of both male and female reproductive

organs (imposex) in mollusks exposed to alkyltins• Synthesis in male fish living near sewage outfalls of a

hormonally regulated protein (vitellogenin) normally found only in female fish

• Birth defects in Lake Michigan birds exposed to PCBs and other chemicals

Page 8: Overview of USEPA’s Endocrine Disruptors Research Program

Androgens in the Environment: Effects of Pulp Mill Effluent on Fish

Androgens in the Environment: Effects of Pulp Mill Effluent on Fish

Courtesy of Lou Guillette, UF

ExposedBuckeye Plant, Fenhalloway River, FL

Mosquitofish

Page 9: Overview of USEPA’s Endocrine Disruptors Research Program

Purported Adverse Effects: Humans

Purported Adverse Effects: Humans

• Reproductive tract cancers and abnormalities in offspring of women who used DES during pregnancy

• Neurodevelopmental problems in children exposed prenatally to PCBs

• Exposure to high levels of PBBs prenatally and via breast milk may lead to early onset of puberty in girls

• Speculation regarding the declines in male reproductive health

• Speculation regarding increases in certain cancers (breast, prostate, testicular) that may have endocrine-related basis

Page 10: Overview of USEPA’s Endocrine Disruptors Research Program

• Evidence suggests that environmental exposure to man-made chemicals that mimic hormones may cause adverse health effects in human and wildlife populations

• Chemicals of concern (i.e., pesticides, industrial, contaminants of drinking water) are EPA’s responsibility (e.g., TSCA, FIFRA, FQPA, SDWAA)

• FQPA and SDWAA requirements to develop and implement a screening and testing program

• In spite of how much we know, there are still many scientific uncertainties in our knowledge of endocrine disruptors nature of effects (e.g., developmental/reproductive, cancer, neurobehavioral) extent of the problem (e.g., declining wildlife populations) dose-response relationships (e.g., which chemicals, what levels of exposure,

shape of dose-response curve)

Why is the USEPA concerned about EDCs?

Why is the USEPA concerned about EDCs?

Page 11: Overview of USEPA’s Endocrine Disruptors Research Program

Examples of EPA’s Research on Endocrine Disruptors

Examples of EPA’s Research on Endocrine Disruptors

Page 12: Overview of USEPA’s Endocrine Disruptors Research Program

Updated NHEERL

Implementation Plan

Program Review

by BOSC

Page 13: Overview of USEPA’s Endocrine Disruptors Research Program

Diverse Nature of Research Program - Unique Among Research Organizations

Diverse Nature of Research Program - Unique Among Research Organizations

• Multi-disciplinary set of research areas for both human health and wildlife – cuts across the risk assessment/risk management paradigm

• Research partners – bring diverse talents to address a science question• Across divisions within a lab • Across National Labs • With scientists from academia, other federal agencies, industry

• Research approaches• Computational, field, lab• Molecular to whole organisms• Invertebrates to humans• Biological, analytical, engineering

Page 14: Overview of USEPA’s Endocrine Disruptors Research Program

Multi-Year Plan (2000-2012):

Long-Term Goals

Multi-Year Plan (2000-2012):

Long-Term Goals• Provide a better understanding of the

science underlying the effects, exposure, assessment, and management of endocrine disruptors

• Determine the extent of the impact of endocrine disruptors on humans, wildlife, and the environment

• Support EPA’s screening and testing program

Page 15: Overview of USEPA’s Endocrine Disruptors Research Program

• Better understanding of science

– What are the dose-response relationships?

– Needed extrapolation tools?

– Effects of multiple EDCs?

– Management of unreasonable risks?

– Risk assessment approaches?

• Determining the extent of the problem

– What effects are occurring in human and wildlife populations?

– Exposure determinations?

– What chemical classes are responsible?

– Major sources and fates?

• Supporting EPA’s screening and testing program

– Adequacy of testing guidelines?

Scope of EPA’s EDCs Research Program: Key Questions Aligned

Under Long Term Goals

Scope of EPA’s EDCs Research Program: Key Questions Aligned

Under Long Term Goals

Page 16: Overview of USEPA’s Endocrine Disruptors Research Program

• Determining classes of chemicals that act as EDCs and their potencies (Anti)androgens, (anti)estrogens, antithyroids

• Investigating mode of action of certain EDCs Results of studies on atrazine and vinclozolin were critical to improving

the Agency’s risk assessments and setting tolerances Pioneering research on androgens/anti-androgens Thyroid hormone homeostasis as a target for environmental chemicals

• Studying approaches to cumulative risk to EDCs

• Determining the dose-response curves for EDCs at environmentally relevant concentrations

Examples of Research - LTG 1Examples of Research - LTG 1

Page 17: Overview of USEPA’s Endocrine Disruptors Research Program

• Studying the impact of developmental exposures in the short term and later in life Characterizing cellular and

molecular mechanisms of abnormal reproductive development

• Effects of methoxychlor and vinclozolin during testis development and subsequent impact on male fertility – transgenerational epigenetic effects

Examples of Research – LTG 1Examples of Research – LTG 1

Anway et al. 2005. Science 308:1466-9

Page 18: Overview of USEPA’s Endocrine Disruptors Research Program

• Examining the ability to extrapolate across species

Wilson et al., 2004. Environ Sci Technol 38(23):6314-21

Examples of Research – LTG 1Examples of Research – LTG 1

Page 19: Overview of USEPA’s Endocrine Disruptors Research Program

Examples of Research – LTG 1Examples of Research – LTG 1

• Identifying major sources of EDCs entering the environment, focusing on: wastewater treatment plants drinking water treatment plants concentrated animal feeding

operations contaminated sediments sources of combustion

• Developing tools to minimize exposures to EDCs

Page 20: Overview of USEPA’s Endocrine Disruptors Research Program

• Paper Mill Effluents Identified androgenic compounds and

masculinization of female fish

• Drinking Water Determining performance Analytical methods development – steroids and alkylphenols

• CAFOs High levels of estrogens found in swine lagoons Androgenic activity found in run-off from cattle farms Characterized impact of exposures on current aquatic organisms and

estimated future population-level effects Developing analytical methods

Examples of Research – LTG 2Examples of Research – LTG 2

Page 21: Overview of USEPA’s Endocrine Disruptors Research Program

Examples of Research – LTG 2 Wastewater TreatmentExamples of Research – LTG 2 Wastewater Treatment

• Source Characterization National Effluent Study (NERL/NRMRL) OW Influent/Effluent Survey (OW/NRMRL/NERL) Effluent and Receiving Waters studies (ORSANCO/NERL/NRMRL -

Ohio R., Wheeling and ALCOSAN) Fate of APs in land-applied biosolids

• Determining Performance Fate in pilot scale municipal treatment Biodegradation of alkylphenols and hormones under WWTP and

sediment redox conditions Full-scale wastewater treatment On-site treatment (septic, constructed wetlands)

Page 22: Overview of USEPA’s Endocrine Disruptors Research Program

Wastewater Treatment (cont’d)Wastewater Treatment (cont’d)

• Methods to determine performance GC/MS for steroid hormones, APs - effluent, raw,

biosolids HPLC for long-chain APs Adaptation of fish estrogenicity assay LC/MS/MS for (de)conjugated hormones

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Page 23: Overview of USEPA’s Endocrine Disruptors Research Program

• Determining the magnitude of adverse impacts on wildlife Evidence that EDCs are affecting wildlife at individual level Evidence that EDC effects in individuals are causing

population-level effects What tools are needed to provide linkage between

population level effects and diagnostic evidence of EDC impacts

Examples of Research – LTG 2 Examples of Research – LTG 2

Page 24: Overview of USEPA’s Endocrine Disruptors Research Program

• Determining the magnitude of adverse impacts of EDCs on human health Supporting 12 epidemiology studies

across federal agencies• Swan et al. 2005 reported decrease in

AGD in male infants with prenatal phthalate exposure

• Exposure to high levels of PBBs prenatally and via breast milk may impact puberty in girls

• Conducted large scale exposure studies to assess exposures of children to environmental chemicals, including some suspected EDCs

Examples of Research – LTG 2Examples of Research – LTG 2

Page 25: Overview of USEPA’s Endocrine Disruptors Research Program

Assays Under Development Under LTG 3: Supporting Agency’s Screening and Testing Program

Assays Under Development Under LTG 3: Supporting Agency’s Screening and Testing Program

In utero/lactation -tier ? aa

Fish lifecycle

Mysid Lifecycle

Amphibian dev, repro

Avian 2-gen

Mammalian 2-gen

T2 - In vivo

Fish screen

Frog metamorphosis

Pubertal (male)

Pubertal (female)

Uterotrophic

Hershberger

T1 - In vivo

- H295R aa

Steroidogenesis

- rat sliced testes

- recombinant aa

Aromatase - placenta

hrAR binding aa

AR (rat cytosol)

hrER binding aa

ER (rat cytosol)

T1 - In vitro

aa alternate

Page 26: Overview of USEPA’s Endocrine Disruptors Research Program

Coordinating Research Across US Federal Agencies and Collaborating InternationallyCoordinating Research Across US Federal Agencies and Collaborating Internationally

• Endocrine Disruptors Interagency Working Group –1995-2000; 2003-

• Provided support for Administrator for G-8 Environmental Ministers Meetings

• Chaired IPCS/WHO/OECD Steering Committee Developed Global Endocrine Disruptors Research Inventory Developed a “Global State of the Science” report (WHO, 2002)

• Collaborate with EU, Japan, World Health Organization, Global Water Research Coalition

• Participate on OECD work groups

• Exploring establishing Global Endocrine Disruptors Working Group

Page 27: Overview of USEPA’s Endocrine Disruptors Research Program

What’s in the Future?What’s in the Future?

• Taking into consideration recommendations by external scientific panel at Program Review

• Continuing to develop new methods/tools and applying them to environmentally relevant issues

• Interest in expanding our partnerships and collaborations

Page 28: Overview of USEPA’s Endocrine Disruptors Research Program

PPCPs in the NewsPPCPs in the News

Page 29: Overview of USEPA’s Endocrine Disruptors Research Program

How ETC Can Support EDCs Research

How ETC Can Support EDCs Research

• Evaluate innovative treatment technologies for managing CAFO wastes, domestic wastes managed on-site, tertiary treatment technologies for managing domestic and industrial wastes commonly disposed of through wastewater treatment systems ETC could facilitate collaborations between industry and

EPA to develop new and innovative risk management strategies for CAFOs, on-site WWT, water reuse

ETC could bring technology-based systems to the low tech CAFO and WWT management strategies

ETC could help identify economic and incentive based strategies to influence more active development of innovative treatment technologies

Page 30: Overview of USEPA’s Endocrine Disruptors Research Program

SummarySummary

• There is global concern regarding exposures to some environmental agents that interfere with endocrine systems

• USEPA is collaborating with other US federal agencies and other countries on screening and testing and research programs

• USEPA’s research is providing immediate results in developing assays for implementation in the screening and testing program

• USEPA’s long-term research program on EDCs focuses on the most critical uncertainties in determining whether humans and wildlife populations are being impacted by levels of EDCs in the environment, in identifying the sources of those exposures, and approaches to reduce/prevent them

• ETC can help identify and broker technology solutions


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