Identification by Liquid Chromatography–Tandem Mass Spectrometry and Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry of the Contributor to the Thyroid Hormone Receptor Agonist Activity in Effluents from Sewage Treatment Plants

Abstract

3,3′,5-Triiodothyroacetic acid (TRIAC) was identified as a major contributor to the activity of thyroid hormone receptor (TR) agonists in environmental water. TRIAC contributed 60–148% of the TR-agonist activity in effluents from sewage treatment plants (STPs). Meanwhile, the contributions of 3,5,3′-triiodothyronine (T3), 3,3′,5,5′-tetraiodothyronine (T4), and analogues were <1%. TRIAC concentrations in the range of 0.30–4.2 ng/L are likely enough to cause disruption of the thyroid system in living aquatic organisms. The origin of TRIAC in the STP effluents was investigated by analyzing both STP influents and effluents. Relatively high concentrations of T3 and T4 (2.5 and 6.3 ng/L, respectively) were found only in the influents. TRIAC was identified only in the effluents. These findings suggested that T3 and T4 in STP influents were potentially converted into TRIAC during activated sludge treatment or by other means. The evaluation of TRIAC at relevant environmental concentrations by in vivo assays and an appropriate treatment to reduce the TR activity in sewage are needed.

TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs

“…As environmental water could be contaminated with TRIAC, 18 we determined the biological effects of exogenous TRIAC. Comparisons were performed against T3, a main endogenous contributor of TH actions.…”

“…As described in the introduction , the effluent from several sewage treatment plants have been found to contain TRIAC, which suggests that environmental water can be contaminated by TRIAC. 18 In wildlife, malformations were developed not only by T4 and T3 but by exposure to TRIAC. 39 The data we have presented here provides a warning of an adverse risk posed by environmental TRIAC toward the human CNS.…”

“… 14 , 15 , 16 , 17 We determined TRIAC is a main contributor of THR agonist activity in sewage effluents. 18 Importantly, sewage treatment plants can release chemicals into environmental water, which can subsequently be consumed by humans, as well as wildlife. We reemphasize that TRIAC binds to THRs as a ligand and exhibits agonist activity equal to or greater than that of T3.…”

TRIAC disrupts cerebral thyroid hormone action via a negative feedback loop and heterogenous distribution among organs

“…As described in the Introduction, the effluent from several sewage treatment plants have been found to contain TRIAC, which suggests that environmental water can be contaminated by TRIAC (18). In wildlife, malformations were developed not only by T4 and T3 but by exposure to TRIAC (36).…”

“…THR agonist activity in sewage effluent has been determined in multiple countries (14–17). We determined TRIAC is a main contributor of THR agonist activity in sewage effluents (18). Importantly, sewage treatment plants can release chemicals into environmental water, which can subsequently be consumed by humans as well as wildlife.…”