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DEVELOPMENT, STANDARDIZATION AND VALIDATION OF THE MAMMALIAN IN VIVO ASSAYS IN THE PROPOSED TIER I SCREENING BATTERY FOR ENDOCRINE DISRUPTORS
Impact/Purpose:
In response to the Congressional mandate to develop and initiate a screening program to identify chemicals that disrupt endocrine function (Public Law 104-170 and 104-182, August 1996), the Agency produced a report entitled "Endocrine Disruptor Screening Program (EDSP): Proposed Statement of Policy" (Federal Register, 1998). The Tier 1 Screening (T1S) Battery is a major component of the EDSP and includes a series of in vivo and in vitro assays designed to detect chemicals that alter the estrogen, androgen or thyroid systems in humans, fish and wildlife. Prior to implementation, the assays included in the T1S must undergo a rigid validation process to document that the tests are scientifically sound. The general stages of this process include: (1) protocol development; (2) demonstration that each assay achieves its purpose and is reliable, leading to a standardized protocol; (3) demonstration that the standardized protocols can be performed consistently at different laboratories with comparable results; (4) the evaluation of the T1S protocols by an independent scientific peer review; and (5) the selection of the final assays for incorporation into the OECD/FIFRA/TSCA Test Guidelines. The Office of Pollution Prevention and Toxic Substances (OPPTS) is coordinating the validation of the T1S assays, and is working in close liaison with the Interagency Coordinating Committed for the Validation of Alternative Methods (ICCVAM) and the Organization for Economic Co-operation and Development (OECD). The objective of the research activities described here is to assist OPPTS in the development, standardization and validation of the T1S mammalian in vivo assays by (1) identifying scientific and technical questions that should be addressed during the pre-validation process; (2) designing and conducting studies which address and resolve these issues; (3) evaluating data submitted by contract and other laboratories assisting with the validation process; and (4) providing senior scientists as consultants to OPPTS and to serve on national and international advisory boards/committees that are actively involved in the validation process.
Description:
This research directly supports the development, standardization and validation of several Tier 1 screening mammalian in vivo assays. Through the development and use of many of these assays for testing specific hypothesis in their respective research programs, these investigators have extensive knowledge of the usefulness, reliability and caveats of many of these assays. This type of information is critical during the standardization and validation process for the identification of critical issues that should be addressed prior to implementation. Assays included in this research the uterotrophic assay, the Hershberger assay, the assay for the assessment of pubertal development and thyroid function in juvenile rats, the in utero/lactation assay, the two-generation reproductive toxicity assay, and the short-term thyroid screening assay in pubertal female rats.