Screening methods for thyroid hormone disruptors.
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.
DeVito
M
M
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Biegel
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Brouwer
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A
Brown
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S
Brucker-Davis
F
F
Cheek
A O
AO
Christensen
R
R
Colborn
T
T
Cooke
P
P
Crissman
J
J
Crofton
K
K
Doerge
D
D
Gray
E
E
Hauser
P
P
Hurley
P
P
Kohn
M
M
Lazar
J
J
McMaster
S
S
McClain
M
M
McConnell
E
E
Meier
C
C
Miller
R
R
Tietge
J
J
Tyl
R
R
D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008403:Mass Screening; D009929:Organ Size / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D013974:Thyroxine / Q000037:antagonists & inhibitors*; D014284:Triiodothyronine / Q000037:antagonists & inhibitors*
D013956:Antithyroid Agents; D014284:Triiodothyronine; D013974:Thyroxine