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Environmental Factor, January 2012

Casey presents at international meeting in Hungary

By Debbie McCarley and Cathy Sprankle

Warren Casey, Ph.D. received his NIH Merit Award from NIEHS/NTP Director Linda Birnbaum, Ph.D.

Casey, left, received his NIH Merit Award from NIEHS/NTP Director Linda Birnbaum, Ph.D. (Photo courtesy of Steve McCaw)

Warren Casey, Ph.D., deputy director of the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), (http://iccvam.niehs.nih.gov/)  participated in an expert meeting in Budapest, Hungary, Nov. 30-Dec. 2, 2011. Casey discussed in vitro methods for identifying endocrine disruptors (EDs), substances that might interfere with normal hormone function.

Casey presented updates on NICEATM–ICCVAM ED-related activities at the Ninth Meeting of the Validation Management Group for Non-Animal Testing, sponsored by the Organisation for Economic Co-operation and Development (OECD). (http://www.oecd.org/) 

Casey’s presentations focused primarily on an in vitro method proposed for identifying EDs that interfere with normal estrogen function. This method, the BG1Luc estrogen receptor (ER) transcriptional activation (TA) test method, also known as the LUMI-CELL®ER assay, uses human ovarian cancer cells to identify substances that might act as ER agonists or antagonists, to stimulate or inhibit estrogenic activity.

NICEATM-sponsored validation

NICEATM sponsored an international validation study of the BG1Luc ER TA test method in 2010, and convened an international independent scientific peer review panel to evaluate the study results earlier this year. The peer review was sponsored by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), an interagency committee of the U.S. government administered by NICEATM.

ICCVAM final test method recommendations are provided in the ICCVAM Test Method Evaluation Report: The LUMI-CELL® ER (BG1Luc ER TA) Test Method: An In Vitro Assay for Identifying Human Estrogen Receptor Agonist and Antagonist Activity of Chemicals. These recommendations are the basis for a draft test guideline currently being considered for adoption by the OECD Test Guidelines Programme. If adopted next year, the BG1Luc ER TA test method could then be used internationally as a screening test to identify substances with ER agonist and antagonist activity.

The NICEATM–ICCVAM evaluation of the BG1Luc ER TA test method also supported the development of a performance-based test guideline being considered by OECD. Performance-based test guidelines provide standards by which test methods that assess a similar biological endpoint can be evaluated.

NICEATM and ICCVAM have a commitment to building global partnerships to advance alternatives to animal testing. Participation in events such as the recent OECD meeting is an important part of developing those partnerships.

Concerns about endocrine disruptors

EDs can interfere with the normal function of hormones in the endocrine system. Studies indicating that animal populations exposed to high levels of these substances have an increased incidence of reproductive and developmental abnormalities have raised concerns about the potential human health effects of these substances. While the impact of endocrine disruptors on human health remains poorly defined, these growing concerns have driven international interest in the availability of methods that can provide accurate and timely identification of potential endocrine disruptors.

The NICEATM-sponsored validation study of the BG1Luc ER TA test method included participating laboratories from the U.S., Europe, and Japan. Data from this study were reviewed at a March 2011 independent peer review panel meeting (http://iccvam.niehs.nih.gov/methods/endocrine/PeerPanel11.htm)  sponsored by ICCVAM. The peer review panel agreed with draft ICCVAM recommendations that the BG1Luc ER TA test method was appropriate for use as a screening test to identify substances with ER agonist and antagonist activity.

Final ICCVAM recommendations will be transmitted to federal agencies soon. The draft test guideline currently under consideration by OECD reflects the ICCVAM recommendations.

More information about the NICEATM-sponsored validation study and the ICCVAM evaluation of the BG1Luc ER TA test method is available on the NICEATM–ICCVAM website. (http://iccvam.niehs.nih.gov/methods/endocrine/end_eval.htm) 

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


Casey recognized for work on endocrine disruptors

At the NIEHS Awards Ceremony Dec. 6, Casey received a 2011 National Institutes of Health (NIH) Merit Award (see related story). The award was in recognition of his excellent performance in leading the international validation and interagency evaluation of new testing methods to support the federal government's endocrine disruptor chemical screening program.

Casey joined NIEHS in February 2010, after a number of years at GlaxoSmithKline and its predecessor companies, where he was a senior scientist in discovery and investigative toxicology. He is the author or co-author of 28 publications in peer-reviewed journals and holds three patents.

Casey received his undergraduate degree in biochemistry and his Ph.D. in microbiology from North Carolina State University (NCSU). Casey also serves as an adjunct associate professor in the NCSU Department of Microbiology and is a Diplomate of the American Board of Toxicology.



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