Section 6.3:

Interpretation and Application: IBER

Patience Browne

Exposure Assessment Coordination and Policy Division

Office of Science Coordination and Policy

Office of Chemical Safety and Pollution Prevention

Slide 1 of 20
Presentation Roadmap

Androgen Receptor 

Bioactivity

Introduction

Estrogen Receptor 

Bioactivity

Exposure

Toxicokinetics/Dosimetry

Integrated Bioactivity 

Exposure Ranking

Future Directions

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Major Points of the Section

 Computational tools discussed in previous 

sections have been peer-reviewed by SAP and for 

publication

 Models with continue to be refined as more data 

become available

 Approach for including high throughput and 

computational methods in EDSP framework

 Identifying chemicals with lower exposurebioactivity ratios, allows EPA to efficiently use 

resources

 Multicentury project becomes multiyear

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 3 of 20
Introduction

 Over the past several years, EPA has initiated a stepwise scientific review of computational tools and 

defined specific applications in EDSP

• January 2013 SAP meeting “Prioritizing the Universe of 

Endocrine Disruptor Screening Program (EDSP) Chemicals 

Using Computational Toxicology Tools”: 

– The approach presented is appropriate for prioritizing the EDSP 

chemical inventory to identify chemicals based on ER 

interactions.

• July 2014 SAP “New High Throughput Methods to 

Estimate Chemical Exposure”:

– SEEM framework represents quality science adequate for testing 

or validating predictions using conservative ‘worst-case’ 

scenarios.

– HTE be used simultaneously with HTP bioactivity for screening

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 4 of 20
Objectives: IBER

 Before using the IBER approach in the EDSP 

framework, EPA is reviewing the scientific 

strengths and limitations of the approach

1. Prioritize chemicals for further EDSP screening 

and testing based on rank of ER bioactivity and 

estimated exposure

2. Prioritize chemicals for further EDSP screening 

and testing based on rank of AR bioactivity and 

estimated exposure

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Bioactivity

ToxCast

Exposure

ExpoCast

HTTK Integrated Bioactivity

Exposure Ranking

(IBER)

Prioritization

Screening

Some or All

EDSP Tier 1 Assays

Testing Some or All

EDSP Tier 2 Assays

Proposed Methodological Approach

Figure 6.2

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Bioactivity

ToxCast

Exposure

ExpoCast

HTTK Integrated Bioactivity

Exposure Ranking

(IBER)

Prioritization

Screening

Some or All

EDSP Tier 1 Assays

Testing Some or All

EDSP Tier 2 Assays

CompTox

CompTox

CompTox

Proposed Methodological Approach

Figure 6.2

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Estrogen Agonist Bioactivity

Figure 2.16

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Androgen Antagonist Bioactivity

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Proposed Method

Bioactivity

ToxCast

Exposure

ExpoCast

HTTK Integrated Bioactivity

Exposure Ranking

(IBER)

Prioritization

Screening

Some or All

EDSP Tier 1 Assays

Testing Some or All

EDSP Tier 2 Assays

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 10 of 20
Integrated Bioactivity Exposure Ranking

Figure 1.3

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Integrated ER Bioactivity Exposure Ranking

EC = 4.96 X 10-3

ER = 0 

Dimethyl phthalate Pyridaben

ER = 4.09X10-5

EC= 8.15x10-6

2-Phenylphenol

ER = 0.12 

EC = 6.96X10-4

ER = 2.26 

Vinclozolin

ER = 39.7 

EC = 4.95 X 10-6

Cyproconazole

EC = 1.7 X 10-8

Figure 1.3

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IBER >1 X 106IBER >1 X 106IBER >1 X 106IBER = 2.1 X 103

IBER = 4.8
IBER for ER

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IBER for AR

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Chemical Space

EDSP Universe

L1

L2

TK

1855

185

1444

~10,000

49

56

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Integrated Bioactivity Exposure Ranking

Slide 16 of 20
Integrated Bioactivity Exposure Ranking

Slide 17 of 20
Slide 18 of 20

Integrated Bioactivity Exposure Ranking
Advantages of IBER

 Models will continue to be revised and 

improved as more data are available

• Provides predictions for thousands of chemicals

 Allows resources to be focused on chemicals 

more likely to have endocrine effects

• List 1 chemicals have limited estrogen and/or 

androgen receptor-mediated bioactivity 

• Prioritizes chemicals based on bioactivity and 

exposure

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 19 of 20
Revisiting Objectives: IBER

 Before using the IBER approach in the EDSP 

framework, EPA is reviewing the scientific 

strengths and limitations of the approach

1. Prioritize chemicals for further EDSP screening and 

testing based on rank of ER bioactivity and 

estimated exposure

2. Prioritize chemicals for further EDSP screening and 

testing based on rank of AR bioactivity and 

estimated exposure

– List 1: 4 ER & 4 AR chemicals < 106

– List 2: 0 ER & 2 AR chemicals < 106

– Universe: 58 ER & 55 AR chemicals < 106

FIFRA SAP: Integrated Bioactivity Exposure Ranking Dec 2-5, 2014 Slide 20 of 20