Screening methods for thyroid hormone disruptors.

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.

Upstream adverse effects in risk assessment: A model of polychlorinated biphenyls, thyroid hormone disruption and neurological outcomes in humans

“…The American Thyroid Association recommends determination of serum TSH and FT 4 concentrations as the standard measure of thyroid function, so we selected studies that include FT 4 measurements (DeVito et al, 1999). The analysis for total T 4 (TT 4 ) is presented in Supplementary Material.…”

Environmental Thyroid Disruptors and Human Endocrine Health

“…colloid size, quantitative appearance of hypertrophic or hyperplastic effects) (Brucker-Davis, 1998;DeVito et al, 1999). However, TH levels vary with time and age, and then, caution must be taken in the result interpretation.…”

“…Regarding in vivo toxicity assays for TDs, several tests have been proposed evaluating delayed eye-opening, abnormalities in the brain development, increased the sperm counts or the testes weight (DeVito et al, 1999). Perchlorate discharge test is also used as in vivo method for determining thyroid toxicity through TR (Atterwill et al, 1987).…”

“…Expert panel reports reviewed the thyroid toxicological methods (Calamandrei et al, 2006;DeVito et al, 1999;Janosek et al, 2006;). Finally, intra-thyroidal T4 content, gene transcription activity and cellular growth appear to be more sensitive endpoints when assessing the significance of thyroid disruption for various chemicals (Boas et al, 2006).…”

Disruption of Thyroid Hormone Function by Environmental Pollutants

“…For developing tadpoles the hypothalamus controls TSH release via corticotropin-releasing factor (CRF) rather than TRH. 35,36) The present investigations focused on the effects of PCBs, BPA and related compounds, UV filters, BFRs, heavy metals and phthalates ( Fig. 1) on TH homeostasis because these substances have been shown to be biologically active and often mimic TH and cause alterations in TH modulated actions.…”