Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals

Journal of Hazardous Materials

et al. 2014

h i g h l i g h t s• Yeast bioassays were used to evaluate the TR disrupting activities of the sediments.• The organic extracts showed TR antagonistic activities.• The elutriates also significantly antagonized the TR.• The causes of toxicity in the elutriates appear to be partly related to the heavy metals. a r t i c l e i n f o a b s t r a c tIn the present study, yeast bioassays were used to evaluate and characterize the thyroid receptor (TR) disrupting activities of the organic extracts and elutriates of the sediments from the Guanting Reservoir, Beijing, China. An accelerated solvent extraction was used to separate the organic extracts, which were subjected to a yeast bioassay. The organic extracts could affect thyroid hormone signaling by decreasing the binding of the thyroid hormone. The TR antagonistic activity equivalents (TEQ bio ) referring to amiodarone hydrochloride were calculated and the observed TEQ bio-organic extracts ranged from 25.4 ± 3.7 to 176.9 ± 18.0 g/g. Elutriate toxicity tests using the modified yeast bioassay revealed that the elutriates also significantly antagonized the TR, with the TEQ bio-elutriates ranging from N.D. to 7.8 ± 0.8 g/L. To characterize the toxic compounds, elutriates were extracted by using a C18 cartridge or treated with ethylenediaminetetraacetic acid (EDTA, 30 mg/L). The results suggested that the addition of EDTA eliminated over 74.3% of the total effects, and the chemical analysis revealed that heavy metals, some of which exhibited TR disrupting potency, for example Zn and Cd, were detectable with higher concentrations in the elutriates. Thus, the cause(s) of toxicity in the elutriate appear to be partly related to the heavy metals.

Section: Introductionmentioning

confidence: 99%

Thyroid hormone disrupting activities of sediment from the Guanting Reservoir, Beijing, China

Journal of Hazardous Materials

et al. 2014

“…The bioassay, particularly the in vitro assay, could be an effective supplementary method for the primary screening of thyroid-disrupting activities due to its ease of manipulation and ability to process large number of samples quickly and inexpensively (Murk et al 2013;Shi et al 2011;Gaido et al 1997). Unfortunately, these bioassays often require water-sample pretreatment, which not only remove interference from the matrix but also eliminates some TDCs in the tested water samples.…”

Section: Discussionmentioning

confidence: 99%

“…Thyroid hormones (THs) participate in several important physiological processes, including the regulation of energy metabolism, growth, and differentiation and the development and maintenance of brain function (Murk et al 2013). Thus, maintaining normal thyroid function is essential for psychological and physiological well-being (Boas et al 2012).…”

mentioning

confidence: 99%

Identification of Thyroid-Receptor Antagonists in Water from the Guanting Reservoir, Beijing, China

Arch Environ Contam Toxicol

Han

et al. 2014

Thyroid hormone (TH) has long been known to be essential for normal brain development in both humans and animals, and increasing evidence suggests that environmental components may disrupt TH signaling. In the present study, two-hybrid yeast bioassay and chemical analysis were used to evaluate and identify thyroid-receptor (TR) disruptors in water from the Guanting Reservoir, Beijing, China. Modified yeast bioassay showed that the water samples could affect TH signaling. The bioassay-derived amiodarone hydrochloride equivalents ranged from 33.8 ± 3.3 to 308.5 ± 31.8 lg/L. Solid-phase extraction was used to separate the organic extracts, which were subjected to bioassay and chemical analysis. The organic extracts significantly antagonized the TR, which accounted for [86.0 % of the total effects. Thus, organic extracts may play a major role in the TR-disruption activity of the water. Phenols, organochlorine pesticides, and phthalate esters were detected in the organic extracts. Chemical analysis and toxic-equivalent calculation showed that a major cause of the TR antagonism of the water was dibutyl phthalate (80.1 to 122.7 %).

“…Several studies based on in vitro and in vivo assays have revealed that heavy metals, such as cadmium (Cd), mercury (Hg), and zinc (Zn), act as potential EDCs by activating estrogen receptor (ER) and modulating the estrogenic activity of endogenous hormones (Denier et al 2009;Isidori et al 2010;Ali et al 2010). However, the endocrine disruption induced by chemicals is not restricted to the sex hormone system but also includes thyroid hormone (TH) disruption (Murk et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Thyroid hormones participate in several important physiological processes, including the regulation of energy metabolism, growth and differentiation, and the development and maintenance of brain function (Murk et al 2013). However, increasing evidence from animal and in vitro studies indicates that the thyroid is vulnerable to endocrine-disrupting effects (Boas et al 2012).…”

Section: Introductionmentioning

confidence: 99%

T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc

Liu

et al. 2016

Environ Sci Pollut Res

In the present study, a two-hybrid yeast bioassay and a T-screen were used to screen for the thyroid receptor (TR)-disrupting activity of select metallic compounds (CdCl 2 , ZnCl 2 , HgCl 2 , CuSO 4 , MnSO 4 , and MgSO 4 ). The results reveal that none of the tested metallic compounds showed TRagonistic activity, whereas ZnCl 2 , HgCl 2 , and CdCl 2 demonstrated TR antagonism. For the yeast assay, the dose-response relationship of these metallic compounds was established, and the concentrations producing 20 % of the maximum effect of ZnCl 2 , HgCl 2 , and CdCl 2 were 9.1 × 10 −5 , 3.2 × 10 −6 , and 1.2 × 10 −6 mol/L, respectively. The T-screen also supported the finding that ZnCl 2 , HgCl 2 , and CdCl 2 decreased the cell proliferation at concentrations ranging from 10 −6 to 10 −4 mol/ L. Furthermore, the thyroid-disrupting activity of metallic compounds in environmental water samples collected from the Guanting Reservoir, Beijing, China was evaluated. Solid-phase extraction was used to separate the organic extracts, and a modified two-hybrid yeast bioassay revealed that the metallic compounds in the water samples could affect thyroid hormone-induced signaling by decreasing the binding of the thyroid hormone. The addition of ethylenediaminetetraacetic acid (30 mg/L) could eliminate the effects. Thus, the cause(s) of the thyroid toxicity in the water samples appeared to be partly related to the metallic compounds.