FIFRA Scientific Advisory Panel Meeting

Integrated Bioactivity and Exposure Ranking:

A Computational Approach for the 

Screening of Chemicals in the 

Endocrine Disruptor Screening Program

Arlington, VA

December 2 - 5, 2014

Slide 1 of 7
Presentation Roadmap

Introduction

Estrogen Receptor 

Bioactivity

Androgen Receptor 

Bioactivity

Exposure

Toxicokinetics/Dosimetry

Integrated Bioactivity 

Exposure Ranking

Future Directions

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 2 of 7
Endocrine Disruptor Screening Program (EDSP)

 Established in 1998

 Protection of human health and wildlife

 Includes estrogen, androgen and thyroid pathways

 Approach

• Prioritization based on exposure and bioactivity

• Screening for bioactivity

• Testing for dose-response and adverse effects

Prioritization

Bioactivity/ Exposure

Screening

Bioactivity

Testing 

Dose-Response/Adversity

More chemicals Fewer chemicals

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 3 of 7
EDSP Prioritization, Screening & Testing

Prioritization

Bioactivity/Exposure

Screening

Bioactivity

Testing

DoseResponse/Adversity

Relies on:

• QSARs

• ToxCast/ExpoCast

• Monitoring data

• OSRI

Relies on:

• QSARs

• ToxCast

• EDSP Tier 1 data

• OSRI

Relies on:

• EDSP Tier 2 data

• OSRI

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 4 of 7
http://www.epa.gov/endo/pubs/edsp21_work_plan_summary%20_overview_final.pdf

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 5 of 7
http://www.epa.gov/endo/pubs/EDSP_Comprehesive_Management%20Plan_%20021414_f.pdf

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 6 of 7
Current Status of EPA Prioritization & Screening

 52 List 1 chemicals with complete Tier 1 datasets undergoing weight-of-evidence 

determination of endocrine bioactivity, possible Tier 2 testing

 107 List 2 chemicals being prioritized for EDSP screening using high throughput and 

computational methods

 EDSP universe of chemicals being prioritized for EDSP screening using high 

throughput and computational methods

 FIFRA Scientific Advisory Panel peer reviews

• Prioritizing the Universe of Endocrine Disruptor Screening Program (EDSP) Chemicals Using 

Computational Toxicology Tools (January 2013)

– http://www.regulations.gov (Search under EPA docket number: EPA-HQ-OPP-2012-0818)

• Endocrine Disruptor Screening Program (EDSP) Tier 1 Screening Assays and Battery Performance 

(May 2013)

– http://www.regulations.gov (Search under EPA docket number:EPA-HQ-OPP-2013-0075)

• Endocrine Disruptor Screening Program (EDSP) Tier 2 Ecotoxicity Tests (June 2013)

– http://www.regulations.gov (Search under EPA docket number:EPA-HQ-OPP-2013-0182)

• Weight-of-Evidence: Evaluating Results of EDSP Tier 1 Screening (July 2013)

– http://www.regulations.gov (Search under EPA docket number: EPA-HQ-OPP-2013-0230)

• New High Throughput Methods To Estimate Chemical Exposure (July 2014)

– http://www.regulations.gov (Search under EPA docket number: EPA-HQ-OPP-2014-0331)

• Endocrine Activity and Exposure-based Prioritization and Screening (December 2014)

– http://www.regulations.gov (Search under EPA docket ID: EPA-HQ-OPP-2014-0614)

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 7 of 7