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Michael DeVito,¹ Lisa Biegel,² Abraham Brouwer,³ Scott Brown,⁴ Franciose Brucker-Davis,⁵ Ann Oliver Cheek,⁶ Russ Christensen,⁷ Theo Colborn,⁵ Paul Cooke,⁸ James Crissman,⁹ Kevin Crofton,¹ Dan Doerge,¹⁰ Earl Gray,¹ Peter Hauser,¹¹ Pamela Hurley,¹² Michael Kohn,¹³ Jozef Lazar,¹¹ Suzanne McMaster,¹ Michael McClain,¹⁴ Eugene McConnell,¹⁵ Christoph Meier,¹⁶ Ronald Miller,⁹ Joseph Tietge,¹ and Rochelle Tyl¹⁷

¹National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 USA
²Haskell Laboratory for Industrial Medicine, Newark, DE 19714 USA
³Department of Toxicology, Wageningen Agricultural University, Wageningen, The Netherlands
⁴National Water Resource Institute, Burlington, Ontario, Canada
⁵World Wildlife Fund, Washington, DC 20037 USA
⁶Center for Bioenvironmental Research, Tulane Medical Center, New Orleans, LA 70112 USA
⁷Bayer Corporation Agriculture Division of Toxicology, Stillwell, KS 66085 USA
⁸College of Veterinary Medicine, University of Illinois, Urbana, IL 61802 USA
⁹The Dow Chemical Company, Midland, MI 48674 USA
¹⁰National Center for Toxicological Research, Jefferson, AR 72079 USA
¹¹Psychiatry Services, Baltimore VA Medical Center, Baltimore, MD 21201 USA
¹²Office of Pesticide Prevention and Toxic Substances, U.S. Environmental Protection Agency, Washington, DC 20460 USA
¹³National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA
¹⁴Hoffmann-LaRoche Inc., Preclinical Development Administration, Nutley, NJ 07110 USA
¹⁵ Raleigh, NC 27613 USA
¹⁶Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA
¹⁷Research Triangle Institute, Research Triangle Park, NC 27709 USA

Abstract

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund ; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors ; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful ; however, this method requires validation and standardization prior to use as a broad-based screen. Key words: developmental toxicity, endocrine disruptors, neurobehavioral toxicity, screens, thyroid hormone, thyroid hormone receptors. Environ Health Perspect 107:407-415 (1999) . [Online 8 April 1999]

http://ehpnet1.niehs.nih.gov/docs/1999/107p407-415devito/ abstract.html

Address correspondence to M. DeVito, U.S. EPA (MD-74) , Research Triangle Park, NC 27711 USA.

This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Approval does not signify that the contents necessarily reflect the view and policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

We thank the many people involved in helping conduct the workshop and prepare the report, especially J. Gaye (Duke University) . In addition, the authors would like to thank M. Santostefano and B. Slezak for reviewing earlier drafts of this document.

Received 6 November 1998 ; accepted 28 January 1999.