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Environmental Factor, January 2013

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Casey meets with international experts to assess endocrine disruptor testing

By Debbie McCarley and Cathy Sprankle

Warren Casey, Ph.D.

Casey is one of several scientists from NIEHS research divisions who are striving for a better understanding of endocrine disruption. (Photo courtesy of Steve McCaw)

NTP scientist Warren Casey, Ph.D., participated in two expert meetings in November 2012 that considered in vitro methods for detecting substances that might interfere with normal hormone function. Casey is acting director of the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).

Casey attended the annual meeting of the Validation Management Group for Non-animal Testing (VMG-NA) Nov. 29-30. He also attended the first meeting of the Thyroid Scoping Effort Expert Group (TSEEG) Nov. 28. Both meetings were sponsored by the Organisation for Economic Co-operation and Development (OECD) and took place at OECD Headquarters in Paris.

NICEATM is committed to building global partnerships to advance alternatives to animal testing. Participation in events such as the recent OECD meetings is an important part of developing those partnerships.

Concerns about endocrine disruptors spur test method development

Endocrine disruptors are substances that interfere with the normal function of hormones in the endocrine system. Studies have shown that animals exposed to these substances exhibit reproductive and developmental abnormalities. These studies have raised concerns that such substances might have similar effects in humans, and a growing body of research supports this hypothesis. Thus, test methods are needed that can provide accurate and timely identification of potential endocrine disruptors.

NICEATM coordinated an international validation study of the BG1 Luc estrogen receptor (ER) transactivation (TA) assays, which identify substances with the potential to induce or inhibit activity of the estrogen receptor. The BG1 Luc ER TA test methods gained international acceptance when the OECD adopted a test guideline describing them in October 2012.

The November VMG-NA meeting considered additional methods currently under evaluation for this purpose by the U.S. Environmental Protection Agency (EPA) and groups in Europe and Japan. Casey serves on the study management teams for these projects. He commented on their progress and addressed questions about selection of reference chemicals and evaluation methods.

Another topic considered at the November meeting was the development of medium and high throughput screening methods for endocrine disruptors. Casey presented recent work performed by the Tox21 (1MB) consortium on the adaptation of the BG1 Luc ER TA methods to a high throughput platform, which was one of several case studies discussed at the meeting.

Group established to evaluate status of thyroid assays

Participants of the newly established TSEEG gathered in an effort to identify available assays for the detection of potential thyroid disruptors and assess their suitability for regulatory use or potential future test guideline development.

The thyroid gland regulates energy use in the body and affects the body’s response to other hormones. It is another potential target of endocrine disruptors. In the past, the thyroid system has received less attention than the estrogen system, in regard to the development of test methods. Establishment of the TSEEG was recommended by the VMG-NA to address this important need. The expert group is chaired by Kevin Crofton, Ph.D., of the EPA National Center for Computational Toxicology.

Recommendations from this meeting will be submitted to the national coordinators of the OECD Test Guidelines Programme, who will consider it at their meeting later this spring. Approval of the recommendations will provide direction for future development of test methods to identify potential thyroid disruptors.

(Debbie McCarley is a special assistant to William Stokes, D.V.M. Cathy Sprankle is a communications specialist with ILS Inc., support contractor for NICEATM.)

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