Comments on Using Existing Data for the Endocrine Screening Testing Lorenz Rhomberg, PhD Principal Gradient ISRTP 2009 Endocrine Workshop

Tiers Tier 1 SCREENING Tier 2 TESTING Determine whether substances may interact with the Endocrine System (EAT) Tier 2 TESTING Determine whether substances cause adverse effects Information for HazID (and QRA) WoE Triggers ??

From: U.S. Environmental Protection Agency, Office of Prevention, Pesticides, and Toxic Substances, Office of Science Coordination and Policy. TECHNICAL REVIEW DOCUMENT for ENDOCRINE DISRUPTOR SCREENING PROGRAM (EDSP): PROPOSED TIER 1 SCREENING BATTERY. March 7, 2008.

Validation INTERNAL VALIDITY (Reliability – Rigor, Reproducibility among Laboratories) EXTERNAL VALIDITY (Relevance – meaningful and useful for a particular purpose)

Purposes “Technical” – measure/detect a particular material event or activity e.g., ability to bind to ER Assay-for-assay swap, technically equivalent Validation?

Purposes “Technical” “Functional” – measure/detect/characterize a force, process, or action e.g., interaction with androgen signaling Assays that address the same system and functioning (albeit in a somewhat different way) Equivalent in ability to detect “interaction with endocrine system” False negatives?

Purposes “Technical” “Functional” “Dispositional” – enable the motivating decision e.g., enable the conditional triggering of Tier 2 testing What are triggers? WoE considerations?

Purposes “Technical” “Functional” “Dispositional” “Final” – address the ultimate question e.g., Tier 2 test already done What are Tier 2 tests? What would substitute? Can one (should one) obviate screening?

Thank you for the opportunity to present these ideas