# Presentation: 720946

## ORD:  Scientific and Technological Support for the Agency’s EDSP

**Ralph L. Cooper**
**Chief, Endocrinology Branch**
**Reproductive Toxicology Division**
**National Health and Environmental Effects Research Laboratory**
**Office of Research and Development**
**U.S. Environmental Protection Agency**
**August 21, 2007**

## ORD will develop protocols that the Agency will validate and use in implementing its mandated screening and testing program.  
ORD scientist will also provide scientific expertise through the transfer of the protocols and their validation.  
This is a “problem-driven” research area.  The Agency needs this research in order to implement its Congressionally mandated EDSP.

**ORD will develop protocols that the Agency will validate and use in implementing its mandated screening and testing program.  **
**ORD scientist will also provide scientific expertise through the transfer of the protocols and their validation.  **
**This is a “problem-driven” research area.  The Agency needs this research in order to implement its Congressionally mandated EDSP****.**

## Linkage and Timeline for APGs to Meet Long Term Goal 3

**Linkage and Timeline for APGs to Meet Long Term Goal 3**

**FY01**

**FY04**

**FY05**

**FY07**

**FY08**

**FY09**

**FY10**

**FY11**

**FY12**

**Develop **

**standardized **

**protocols for **

**testing **

**chemicals for **

**their potential **

**endocrine**

**mediated **

**effects to **

**meet FQPA **

**requirements**

**Support EPA’s Screening and Testing Program**

**FY02**

**FY03**

**Shading denotes APG**
**Appears in multiple LTGs**

**Evaluate **
**existing testing guidelines for their adequacy to evaluate endocrine mediated effects**** **

**Develop**
**Standardized**
**Protocols for**
**Screening**
**chemicals for **
**their potential **
**endocrine **
**mediated**
**effects  to**
**meet FQPA**
**requirements**

**Develop **
**standardized**
**protocols for**
**testing**
**chemicals for **
**their potential **
**endocrine**
**mediated**
**effects to mee**
**FQPA**
**requirements**

**Identify key**
**risk**
**assessment**
**issues and **
**develop **
**guidance for**
**assessing**
**endocrine**
**disruptors**

- Provide at least 1
**Computational mode**
**For assessing**
**Endocrine disrptor**
**compounds **

**FY06**

## Background/Chronology

**ORD has long history with identifying and evaluating EDCs.**
**Predates FQPA & SDWA.**
**EDSTAC FACA provided guidance to EPA in 1998 on structure of the program**
**NHEERL EDC Implementation Plans (2000, revised 2004),   Focus Area A**
**Examination of Estrogen, Androgen, Thyroid & HPG**

## Background/Chronology

**Endocrine Disruptors Screening Program (OSCP)**
**Priority setting, Tier 1 Screening, Tier 2 Testing.**
**Organizing and participation in numerous workshops on Screening and Testing ( National & International**
**EDMVS , EDMVAC, BOSC , PART and recommendations Incorporated.**
**Assisting with final validation of protocols**

## EDSP Validation:  Primary Contributors

**Validation of **
**Assays**

**Office of Science, **
**Coordination and Policy (OSCP)**

**Endocrine Disruptors **
**Advisory Committees**
**(EDSTAC, EDMVS, EDMVAC)**

**Organization for Economic**
**Cooperation and Development **
**(OECD)**

**Interagency Coordinating **
**Committee for the Validation **
**of Alternative Methods**
**(ICCVAM)**

**Office of Research**
**and Development**
**(ORD)**

**Contractor**

## Framework

**Initial Sorting**
**Priority Setting**
**Screening (Tier 1)**
**Identifies substances for further testing**
**E,A,T and HPG**
**In vitro and in vivo assays**
**Testing (Tier 2**
**Identifies adverse effects and establishes dose-response relationship for hazard assessment**
**Multigenerational studies covering a broad range of taxa.**

## Status:  Tier 1 In Vitro Assays 12/04

| In vitro | Protocol | DRP | Pre Validation | ISR | Peer Review |
| --- | --- | --- | --- | --- | --- |
| ER (rat cytosol)  * | ● | ● | O |   |  |
| hER binding OECD, a | ● | ● | O |  |  |
| AR (rat cytosol) *  | ● | ● | ● |  |  |
| hAR binding OECD, a *  | O |  |  |  |  |
| Steroidogenesis |  |  |  |  |  |
|   -rat sliced testes | ● | ● | O |  |  |
|   -H295 OECD, a | ● | O |   |  |  |
| Aromatase-a
placental/recombinant | ● | ● | ● |  |  |

**Status:  Tier 1 *****In Vitro***** Assays 12/04**

**a  Alternate**

**●** **ORD**

- ●   **Collaborative Effort**

**O ** **In Progress**

***  APM EDC-3-411**

***  APM EDC-3-411**

**DRP = Detailed Review Paper**

**ISR = Integrated Summary Report **

## Status:  Tier 1 In Vitro Assays 8/07

| In vitro | Protocol | DRP | Pre Validation | ISR | Peer Review |
| --- | --- | --- | --- | --- | --- |
| ER (rat cytosol)  * | ● | ● | O | O |  |
| hER binding OECD, a | ● | ● | ● |   |  |
| AR (rat cytosol) *  | ● | ● | ● | O | 12-07 |
| hAR binding OECD, a *  | ● | O |  |  |  |
| Steroidogenesis |  |  |  |  |  |
|   -rat sliced testes | ● | ● | HOLD |  |  |
|   -H295 OECD, a | ● | ● |  O |  | 2008  |
| Aromatase-a
placental/recombinant | ● | ● | ● | O | 12-07 |

**a  Alternate**

**●** **ORD**

- ●   **Collaborative Effort**

**O ** **In Progress**

***  APM EDC-3-411**

***  APM EDC-3-411**

**DRP = Detailed Review Paper**

**ISR = Integrated Summary Report **

**Status:  Tier 1 *****In Vitro***** Assays 8/07**

## Status:  Tier 1 In Vivo Assays 12/04

| In vitro | Protocol | DRP | Pre Validation | ISR | Peer Review |
| --- | --- | --- | --- | --- | --- |
| Hershberger OECD, * | O | ● | ● | O |  |
| Uterotrophic OECD  | O | O | O | O |  |
| Pubertal Female | ● | ● | O |  |  |
| Pubertal Malea | ● | ● | O |  |  |
| Frog MetamorphOECD | ● | O | O |  |  |
| Fish ScreenOECD | ● | O | O |  |  |

**Status:  Tier 1 *****In Vivo***** Assays 12/04**

**a  alternate**

- ● **ORD**

- ● **Collaborative Effort**

**O** **In Progress**

**O Exclusive OECD effort**

***  ORD Lead Lab**

**DRP = Detailed Review Paper**

**ISR = Integrated Summary Report **

## Status:  Tier 1 In Vivo Assays 8/07

| In vitro | Protocol | DRP | Pre Validation | ISR | Peer Review |
| --- | --- | --- | --- | --- | --- |
| Hershberger OECD, * | ● | ● | ● | ● | ● |
| Uterotrophic OECD  | O | O | O | O | O |
| Pubertal Female | ● | ● | ● | O |  12/07 |
| Pubertal Malea | ● | ● | ● | O | 12/07 |
| Frog MetamorphOECD | ● | ● | O | O | 12/07 |
| Fish ScreenOECD | ● | ● | ● | O | 12/07 |

**a  alternate**

- ● **ORD**

- ● **Collaborative Effort**

**O** **In Progress**

**O Exclusive OECD effort**

***  ORD Lead Lab**

**DRP = Detailed Review Paper**

**ISR = Integrated Summary Report **

## Status:  Tier 2 Assays 12/04

| In vitro | Protocol | DRP | Demo | Guidance Document | Peer Review  |
| --- | --- | --- | --- | --- | --- |
| Mammalian Extended 1 generationOECD | O | O |  |  |   |
| Avian 2 Generation OECD | O |   |  |  |  |
| AmphibianOECD
Development Repro * | O |  |  |  |   |
| Fish 2 GenerationOECD * | O |   |  |  |  |
| Mysid LifecycleOECD | ● | ● | O | O |  |
| In Utero/Lactational | ● | ● |  |  |   |

- ● **ORD**

- ● **Collaborative Effort**

**O** **In Progress**

***  ****ORD Lead Lab**

**DRP = Detailed Review Paper**

**ISR = Integrated Summary Report **

**Status:  Tier 2 Assays 12/04**

## Status:  Tier 2 Assays 8/07

| In vitro | Protocol | DRP | Demo | Guidance Document | Peer
Review |
| --- | --- | --- | --- | --- | --- |
| Mammalian Extended 1 generation OECD | ● | ● | O | O | 2008 (summer) |
| Avian 2 Generation OECD | ● | ● |  |  |  |
| AmphibianOECD
Development Repro * | O | O | O |  |   |
| Fish 2 GenerationOECD * | O | O |  |  |  |
| Mysid 2 Generation OECD | ● | ● | O |  |  |
| In Utero/Lactational ●
 | ● | ● |  |  |   |

**● ****ORD**** **

**● ****Collaborative Effort**

**O In Progress**

***  ORD Lead Lab**

**DRP = Detailed Review Paper**

**ISR = Integrated Summary Report **

**●  ****SAP, 1/07**

**Status:  Tier 2 Assays 8/07**

## FutureAgency wide, National & International Activities

**ORD Investigators will continue to be active in:**** **
**Consultation on protocol validation**
**Writing ISRs, assist with Peer Review**
**Tier 2 protocol standardization**
**Several species**
**Consultation on Screening Battery**
**Evaluation of new high throughput protocols/batteries**
**Prioritizing chemicals**