Citation:

Gray, E. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of Experience to Improve Screening and Testing for Endocrine Active Chemicals##. Swiss Society of ALTEX (ed.), ALTEX. Society ALTEX Edition, Kuesnacht, Switzerland, (1):63-78, (2014).

Impact/Purpose:

This workshop summary paper describes the presentations at a workshop reviewing last 15 years worth of data using the EDSP Endocrine Screening Program assays and evaluating their performance and limitations of the assays and recommendations for interpretation of the data and the results of the battery as a whole. As it represents the opinions of several different authors, only the section written by Dr Gray is reviewed and being cleared herein. PLEASE EXPEDITE THIS CLEARANCE AS THE ARTICLE MAY BE IN THE JOURNAL ONLINE VERY QUICKLY AS IT IS NOT BEING PEER-REVIEWED SINCE IT IS A WORKSHOP SUMMARY

Description:

This product is a brief description of the oral presentation given by Dr LE Gray Jr at the meeting for the T4 workshop report-Lessons learned, challenges, ansd opportunities: The U.S. Endocrine Disruptor Scrrening Program published in the journal ALTEX, edited by the Swiss Society ALTEX Edition, is the official journal of CAAT (the Johns Hopkins Center for Alternatives to Animal Testing), EUSAAT (the European Society for Alternatives to Animal Testing), t4, the Transatlantic Think Tank for Toxicology (Baltimore, Utrecht, Konstanz), and the Doerenkamp chairs in Germany, India, The Netherlands, Switzerland, and USA. Dr. Earl Gray (EPA) in a presentation titled “A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of Experience to Improve Screening and Testing for Endocrine Active Chemicals” discussed an alternative logic-based decision-tree strategy for staging the EDSP Tier 1 screening assays (Ankley and Gray, 2013). The strategy involves utilizing two in vivo assays (i.e., FSTRA and the male rat pubertal assay) as “Gatekeepers”. Using this proposed framework, if both assays yield negative results for potential endocrine activity, then a chemical would be considered a low priority for further endocrine evaluation and additional Tier 1 assays would not be conducted. Conversely, if the “Gatekeeper” assays detected any positive results then additional specific Tier 1 assays would be conducted on a case-by-case basis, depending upon the specific estrogen (E), androgen (A), or thyroid (T) signals observed in the two “Gatekeeper” assays. This proposed alternative EDSP screening strategy was coined “Tier 0.5” by participants. Dr. Gray also discussed the potential value of incorporating a possible “Tier 1.5” screening strategy in lieu of moving directly to Tier 2 for chemicals with positive Tier 1 results. He noted that the current challenges in interpreting Tier 1 data, concern over extensive animal use and significant cost of Tier 2 testing assays are compelling reasons for the potential implementation and use of this alternative screening approach. Briefly, Tier 1.5 could be conducted following Tier 1 screening, and utilize additional or refined in vitro or short-term in vivo assays to confirm equivocal Tier 1 screening results, or explore potential effects and modes of action in more detail prior to the selection and initiation of extensive Tier 2 testing. He also cautioned against using pubertal male and female rat data to classify chemicals as potential EDs where the dosage levels produced overt toxicity or exceeded the MTD since reductions in terminal body weights greater than 10% of control are clearly associated with reductions in several E, A and T-regulated endpoints (Laws et al., 2007) . Dr Gray also noted that some of the endpoints sensitive to E and A are not included in multigenerational assays. These specific endpoints could be added on a case-by case basis as indicated by the EDSP screening data. In addition, for some effects the multigenerational assays don’t examine a sufficient number of animals to detect the NOAEL accurately (Blystone et al., 2010).

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