# Presentation: 869744

## The EDMVS’Draft Work Plan

- Presentation to the EDMVS,
- June 5, 2002

##  Purpose of  Today’s WorkPlan 

- Show progress of EDSP
- Provide the status of each assay
- Project what’s next

## Tier I Screening Battery recommended for consideration by EDSTAC 

- Steroidogenesis
- Pubertal - female
- Fish Screen
-         aka short term fish  reproduction
- Amphibian Metamorphosis
- Estrogen / Androgen receptor binding
- Hershberger
- Uterotrophic

## Alternative Assays recommended for consideration by EDSTAC 

- Tier I
- Aromatase
- Pubertal male
- Adult 14 –day intact male
- Tier ?
- In Utero through Lactation

## Tier II Assays recommended for consideration by EDSTAC

- Mammalian 2-generation
- Avian 2-gen. Reproduction
- Amphibian Development and Repro.
- Invertebrate (Mysid) Lifecycle
- Fish Lifecycle

## Tier I Assays

## Steroidogenesis

-         _**Milestone **_**                      **_**Current Status**_
**DRP/Protocol                    ******** June 02**
**Prevalidation**
**      ****-sectional testes**
**          ****optimization                 Today &Aug 03**
**       ****-cell based (H295R)        In ORD Lab**
**Validation**
**      ****-multi-chemical                 to lab Aug 03**
**      ****-inter-lab                            to lab Aug 03**
**   ********June 03 = complete, date presented to EDMVS **

## Pubertals – m&f

-             _**Milestone**__** **_**                                 **
**DRP equivalent**
**Prevalidation **
**	****-Single Dose Study**
**	****-Multi-chemical & multi-dose          Protocols**
**	****-Multi-chemical & multi-dose Studies**
**           ****data to EDMVS Aug 03**
**	****-Restricted Feeding Study****	**
**Validation (inter-lab)****	**** **

_**Current Status**_
******  ****Dec 01**
****** ****Dec 01**
****** ****Dec 01**
**In lab ******
****** ****July 02**
**To lab Aug 03**

## Fish Screen

-         _**Milestones**_**                                   **_**Current Status**_** **
**DRP/Protocol                                       ******** Mar 02 **
**Prevalidation**
**	****   ****-ShortTerm  Fish Repro. in FHM    ******** Mar 02 **
**       ****-Short term fish repro. In **
**              ****FHM w/multi-chemicals              In lab ********	**
**	****  ****- Comparative Study Plans:              ******** Mar 02**
**    ****	****   ****-Comparative Studies:                  To EDMVS Aug 03**
**	****	****Vitellogenin Methods ****(FHM,**
**                  ****Medaka, Zebrafish)****                           In lab ******
**	****	****Fathead Minnow Assays                 In lab ********       **
**Validation (inter-lab)                 depends on OECD**

## Amphibian Metamorphosis

-            _**Milestone**_**                                **_**Current Status**_
- DRP/Protocol                           July 02
- Pre-validation
-        prometamorphosis
-          - transferable  protocol      proj. Dec 03
-           -protocol demonstration   proj. Dec 04
-           -optimization studies              TBD
- Validation (inter-lab OECD)          TBD
-      Proj = projected completion date

## ER / AR binding

**	****ICCVAM**
- Scientific Expert Panel’s           May 2002
-           retrospective validation
- EDMVS briefed by ICCVAM     July 2002
- Expert Panel  Final Report       Sept 2002
- EDSP: AR in lab (preval)      Aug 02 –Sept 03
- EDSP: ER in lab (valid)         May 02 – May 04

## Aromatase

-      _**Milestones **_**                                 **_**Current Status **_
**DRP / Protocol                               ******** Mar 02**
**Prevalidation**
**      ****-placental microsomal assay    Today & Aug 03**
**       ****compare bovine, human, porcine**
**	****  ****-cell based assay                        Today & Aug 03**
**      ****-comparison: microsomal &**
**           ****recombinant & multi chem    Today & Aug 03**
**	**
**Validation (inter-lab)                       to lab Sept 03**

## In Utero   Lactation

**        **_**Milestone**__ _                         _**Current Status**_
**DRP                                  ********Dec 02**
**	**** ****-****Protocol review                    ********Mar 02**** **
**Prevalidation **
**	**** ****-****Protocol Demo                  report  due 8/03**
**      ****-Multi-chem study                       TBD**
**Validation (inter-lab)****	****     ****TBD**

## Tier II Assays

## Mammalian 2-generation

-       _Milestone _                     _Current Status_
- DRP/Protocol                            --
- Prevalidation
- 	 **One-gen. Ext. Protocol           ******** Dec 02**
**	****  ****Propylthiouracil Study           ********  July 02**
**	****  ****One-gen Ext. study                 Tomorrow**
- Validation (inter-lab)              TBD

## Avian 2-gen. Reproduction

-      _Milestone _                         _Current Status_
**DRP/Protocol                     ******** Fall 03**
**Prevalidation**
**    ****-Avian Dosing Study Plan        ******** Mar 02**
**     ****-Avian Dose Study                        in lab**
**	**** ****-Protocol demo                             future**
**Validation ****(inter-lab OECD)****     **** future**

## Amphibian Dev. & Repro. 

-      _Milestones _                 _Current Status_
- DRP/Protocol                  proj. Dec 04
- Prevalidation
-        -transferable protocol      future
-        -multi-chem study            future
- Validation (inter-lab)            future

## Mysid Lifecycle 

-      _Milestones _                   _Current Status_
- DRP/Protocol                     July 02
- Prevalidation
-       -transferable protocol     Proj. Dec 03
-       -multi-chem study               future
- Validation (inter-lab OECD)   future

## Fish Lifecycle

-         _Milestones _                 _Current Status_
- DRP/Protocol                     Dec** **02
- Prevalidation
-        -protocol demo                  future
-        -multi-chem study              future
- Validation (inter-lab OECD)  future

## August 19-21, (22?) 2003 

- Fish Screen
-     -Comparative FHM assays
-     -comparative vitellogenin **Medaka,**
**          ****Zebrafish, FHM**
**     ****-OECD Phase 1A**
- Aromatase
- Steroidogenesis
- Pubertals male and female
- Strain / Species Discussion

## Oct 2003

- Avian DRP
- In Utero through lactation
-         protocol demonstration results
-      (Teleconference is an option)

## Spring 2004

**Amphibian Dev. & Repro. DRP (Tier II)**
**Avian Dosing Study**
**Amphibian Screen transferable protocol**
**Fish Screen multi-chemical results**
**Fish Screen Phase 1B (OECD)  **

## Slide 23