# Lessons Learned, Challenges, & Opportunities: The U.S. Endocrine Disruptor Screening Program

Results of Workshop Held April 23 - 24, 2013 | Research Triangle Park, NC Michael L. Dourson, Toxicology Excellence for Risk Assessment Presented to the Science Advisory Panel, May 21 & 22, 2013

# Alliance for Risk Assessment ( ARA ) Guiding Principles

• Promote science

- based decision making.

• Enhance harmonization and consistency in risk assessments... through an open, transparent, multi

- stakeholder approach.

• Maintain access to risk assessment experts not normally available within an organization.

• Increase the capacity and quality of risk values by...... sharing costs, information, and human resources.

# ARA Steering Committee

• Anita Meyer

--- United States Army Corps of Engineers
• Annette Dietz

--- Oregon Department of Environmental Quality
• Bette Meek

--- University of Ottawa
• Edward Ohanian

--- United States Federal Employee
• Michael Dourson

--- Toxicology Excellence for Risk Assessment ( recused )
• Michael Honeycutt

--- Texas Commission on Environmental Quality
• Ralph Perona

--- Neptune & Company (tribal representative)
• William Hayes

--- State of Indiana

# EDSP Workshop Organizing Committee

• Rick Becker

--- American Chemistry Council
• Susan Borghoff

--- Integrated Laboratory Systems , co - chair
• Warren Casey

--- National Institute of Environmental Health Sciences
• Thomas Hartung

--- Center for Alternatives to Animal Testing, Johns Hopkins University
• Michael Holsapple

--- Battelle
• Daland Juberg

--- Dow AgroSciences , co - chair
• Sue Marty

--- The Dow Chemical Company
• Ellen Mihaich

--- Endocrine Policy Forum (ER 2 )
• Glen Van Der Kraak

--- University of Guelph
• Mike Wade

--- Health Canada
• Kate Willett

--- Humane Society of the United States

# Why would over 240 scientists attend? Giving Back by Sharing Lessons Learned

• Focus
– shared science and experience and identified opportunities to inform future efforts to evaluate endocrine disruption potential.

• Discussed the challenges and lessons learned from conducting the EDSP Tier 1 assays in a regulatory context, and provided suggestions for improvements to Tier 1 screening and for future testing practices.

# Workshop Objectives

• Provide participants with knowledge gained and lessons learned from testing on the initial list of chemicals.

• Identify challenges and best practices in the technical and biological assessment of endocrine modulation.

• Discuss insights on the challenges of integrating and interpreting the data collected from Tier 1 assays.
• Explore insights on biological mechanisms relevant to endocrine modulation and their application in interpretation and decision making.

• Engage perspectives from a range of stakeholders, including academia, government, industry, and NGOs

## Session 1: Performance of the EDSP Tier 1 Screening Assays for Estrogen, Androgen, and Thyroid Pathways

• Focused on 11 Tier 1 assays, highlighting challenges and solutions

• Three experts involved in the conduct of these assays presented their experiences and discussed their ideas for improvements:

– Dr. Colleen Toole ( Ceetox )

– Dr. Leah Zorrilla (ILS, Inc.)

– Dr. Katherine Coady (Dow Chemical Company)

# Session 1: Perspectives

• The Tier 1 results are intended to be used in conjunction with Tier 2 data for risk

- based decision

- making. However, the endpoints in Tier 1 assays are not designed for risk assessment.
• Several technical difficulties were identified for in vitro assays.
• The requirement (and value) for testing at such high concentrations (i.e., biological significance) was questioned.

# Session II: Practical Applications of Tier 1 Data

• Focused on how to apply the current Tier 1 battery results to identify modes of action; and a weight of evidence ( WoE ) assessment for evaluating potential interactions with endocrine pathways.

• Expert Speakers:

– Dr. Earl Gray (U.S. EPA)

– Dr. Sue Marty (Dow Chemical Company)

– Dr. Christopher Borgert (Applied Pharmacology and Toxicology, Inc.)

# Session II: Perspectives

• Development of critical systematic evaluation of existing data prior to implementation of Tier 2 testing in multiple species.

• Tier 1.5 screening strategy.

• The assessment and application of alternative data could be highly relevant to replace Tier 1 assays, provided scientific validation of alternative approaches for regulatory decision

- making.

# Session III: Considerations for Future Endocrine Testing

• Provided perspectives on the future of endocrine screening and the promise of in vitro high

- throughput analyses, toxicity pathways, and prediction models.
• Expert Speakers:

– Dr. David Dix (U.S. EPA)

– Dr. Mel Andersen (The Hamner Institutes for Health Sciences)

– Dr. Thomas Hartung (CAAT, Johns Hopkins)

– Dr. Catherine Willett (Humane Society of the United States)

– Dr. Lisa Ortego (Bayer CropScience )

– Dr. Thaddeus Schug (NIEHS)

# Session III: Perspectives

• Enhanced predictive tools and stringent validation practices are necessary to achieve future regulatory acceptance of molecular pathways for risk assessment.

• Explicit consideration of human and ecological exposure potential would be valuable to aid in prioritization for the EDSP.

• Current collaborations focused at improving exposure assessment and reverse dosimetry screening in HTS assays show promise for developing a risk

- based decision tool.

• Collaboration, coordination, and communication amongst the regulatory community and stakeholders is vital.

# Session IV: Participant Discussion

• In the final session, workshop participants were provided an extended opportunity to discuss their experiences, perspectives, and concerns regarding the future of the EDSP.
• A number of common themes emerged, many discussions focused on Session I

- III Perspectives. Ex:

– Critical review and update to the guidelines

– Biomonitoring for exposure

- based prioritization

– Reduction in number of animals used in testing

– Robust WoE approach using potency and exposure for additional testing

# Session IV: Perspectives

• Two

- assay Gatekeeper approach

– A logic

- based decision

- tree strategy for staging the EDSP Tier 1 screening assays


## • Benefits ALL stakeholders

– Decreases time and cost per chemical

– Reduces number of animals used

– Increases the amount of assessments conducted

# Workshop Summary

• The experience and insight of the practitioners and laboratories conducting the screening provides an unprecedented resource for informing the future.

• This workshop brought together multiple stakeholders in an open forum for the opportunity to review and discuss the scientific challenges and lessons learned from the EDSP.

• Results of the workshop will be useful to inform ongoing and future efforts to determine the endocrine disruption potential of chemicals.

• Final speaker presentations, workshop materials, and workshop report are available at http://tera.org/peer/edsp/

# Over 43 Workshop Sponsors

# Thank you!