Pubertals and One-generation Extension

Overview of questions Does the fire raise significant concerns? Should the EPA bring the pubertal and one-gen extension study designs to EDMVS before moving forward? Should EPA halt prevalidation studies that have been begun in parallel with DRP development, until EDMVS approves the DRPs?

Does the fire raise significant concerns? Is Bisphenol A an issue? Does EDMVS wish to see the final report of the independent review panel? yyes, before moving forward yyes, but go ahead in the meantime yno, the fire is not a significant issue

Fire considerations If fire report is brought to EDMVS yone-gen study will not start Nov. 14 ypubertal array study may not begin in early January

Pubertals Single-dose data Multi-dose ystudy design, chemical & dose selection Multiple-chemical array ystudy design, chemical & dose selection

Pubertal considerations December agenda, unavailability of alternative dates. Extend Dec. meeting? Review time for single-dose data y(not available in soft copy) Study design is currently based on the expert advice of developers of assay (EPA/RTP)

One-generation extension New protocol, never performed Developed by EPA/RTP Reviewed by P. Foster, CIIT Proof-of-concept only; multi-chemical study will be done later

Details: Pubertals (1)

Details: Pubertals (2) Male and female are parallel but separate Potential delay due to recent fire in lab

Upcoming EDMVS meetings: December 2001 Detailed Review Papers yaromatase ysteroidogenesis yin utero through lactation Need for pubertal DRP? Low dose

Upcoming EDMVS meetings: March 2002 Detailed Review Papers on OECD assays yFish reproduction yFish chronic yAvian chronic yInvertebrate yFrog screen and chronic (?) Fish repro screen vs. vitellogenin Dose-setting in validation studies Restricted feeding study protocol

Upcoming EDMVS meetings: June 2002 Pubertal prevalidation ysingle-dose ymultiple-dose yarray of chemicals Mammalian two-gen prevalidation ythyroid study yone-gen extension Steroidogenesis prevalidation Aromatase prevalidation

Questions for discussion tomorrow Is the logic of the plan sound? Are the time estimates reasonable? Is a Mammalian 2-gen DRP needed? Is a Mammalian 2-gen practicality study needed? Should we be concerned about the fire in the lab?