Pubertals andOne-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? yes, before moving forward yes, but go ahead in the meantime no, the fire is not a significant issue

Fire considerations

• If fire report is brought to EDMVS one-gen study will not start Nov. 14 pubertal array study may not begin in

early January

Pubertals

• Single-dose data• Multi-dose

study design, chemical & dose selection

• Multiple-chemical array study design, chemical & dose selection

Pubertal considerations

• December agenda, unavailability of alternative dates. Extend Dec. meeting?

• Review time for single-dose data (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 aromatase steroidogenesis in utero through lactation

• Need for pubertal DRP?• Low dose

Upcoming EDMVS meetings:March 2002

• Detailed Review Papers on OECD assays Fish reproduction Fish chronic Avian chronic Invertebrate Frog screen and chronic (?)

• Fish repro screen vs. vitellogenin• Dose-setting in validation studies• Restricted feeding study protocol

Upcoming EDMVS meetings:June 2002

• Pubertal prevalidation single-dose multiple-dose array of chemicals

• Mammalian two-gen prevalidation thyroid study one-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?