Questions from EPA to the Endocrine Disruptor Methods Validation Advisory Committee (EDMVAC)
April 26-28, 2005
1. Should we proceed with validation or are additional studies necessary before validation can begin? If so, what does the Committee recommend?
Many of the considerations involved in the design and execution of the validation of the uterotrophic assay are similar to other in vivo assay validations. While most of the other in vivo assays are not considering several protocols as they proceed to validation, the question of which experimental conditions to standardize (e.g., strain, feed, bedding, etc.) and the number and nature of the reference chemicals to use has been raised with several assays. Thus, the ultimate conclusions as to the adequacy of the validation of the uterotrophic assay may set a precedent for the remaining EDSP assays as they continue through validation and peer review. The EPA is requesting that the Endocrine Disruptor Methods Validation Advisory Committee (EDMVAC) also examine the issues raised by the peer review and provide their opinion(s) on the adequacy of the validation process.
The fish short term reproduction assay is intended to be used in the Endocrine Disruptor Screening Program Tier 1 screening battery to capture estrogen and androgen active substances and provide presumptive evidence to trigger Tier 2 definitive testing of potential adverse effects.
1. For the fathead minnow, are the available data adequate to demonstrate that the assay is capable of responding to estrogen and androgen active substances? If not, what more is recommended?
2. Primary endpoints considered for inclusion consist of vitellogenin, secondary sex characteristics, gonad histopathology, and fecundity. Should additional endpoints be considered for purposes of screening potential endocrine disrupting substances?
3. Given that the fathead minnow is a species of interest and fecundity is an endpoint of interest, what would constitute a "false positive" in terms of a response observed in the assay and warranting Tier 2 definitive testing? How should "false negatives" be addressed?
4. What additional data are recommended to demonstrate the validity of the screening assay for capturing potential adverse effects and triggering Tier 2 testing?
The amphibian metamorphosis assay is intended to be used in the Endocrine Disruptor Screening Program Tier 1 screening battery to capture thyroid active substances and provide presumptive evidence to trigger Tier 2 definitive of potential adverse effects.
1. Given the planned OECD Phase 2 validation work, what additional data are recommended, if any, to demonstrate the validity of the screening assay for capturing presumptive thyroid active substances and triggering Tier 2 testing?