Insights into the Endocrine Disrupting Activity of Emerging Non-Phthalate Alternate Plasticizers against Thyroid Hormone Receptor

[helvella]

We have seen a fair amount of discussion about the impact of Endocrine Disrupting Chemicals (EDC) on the thyroid gland and on the utilisation of thyroid hormones.

This paper reports that at least some candidates to replace phthalates (a known group of EDCs) are even worse!

Toxics.2022 May; 10(5): 263.

Published online 2022 May 19. doi: 10.3390/toxics10050263

PMCID: PMC9145736

PMID: 35622676

Insights into the Endocrine Disrupting Activity of Emerging Non-Phthalate Alternate Plasticizers against Thyroid Hormone Receptor: A Structural Perspective

Torki A. Zughaibi,1,2 Ishfaq Ahmad Sheikh,1,2,* and Mohd Amin Beg1,2

Miguel Machado Santos, Academic Editor

Abstract

Many endocrine-disrupting chemicals (EDCs) have a ubiquitous presence in our environment due to anthropogenic activity. These EDCs can disrupt hormone signaling in the human and animal body systems including the very important hypothalamic-pituitary-thyroid (HPT) axis causing adverse health effects. Thyroxine (T4) and triiodothyronine (T3) are hormones of the HPT axis which are essential for regulation of metabolism, heart rate, body temperature, growth, development, etc. In this study, potential endocrine-disrupting activity of the most common phthalate plasticizer, DEHP, and emerging non-phthalate alternate plasticizers, DINCH, ATBC, and DEHA against thyroid hormone receptor (TRα) were characterized. The structural binding characterization of indicated ligands was performed against the TRα ligand binding site employing Schrodinger’s induced fit docking (IFD) approach. The molecular simulations of interactions of the ligands against the residues lining a TRα binding pocket, including bonding interactions, binding energy, docking score, and IFD score were analyzed. In addition, the structural binding characterization of TRα native ligand, T3, was also done for comparative analysis. The results revealed that all ligands were placed stably in the TRα ligand-binding pocket. The binding energy values were highest for DINCH, followed by ATBC, and were higher than the values estimated for TRα native ligand, T3, whereas the values for DEHA and DEHP were similar and comparable to that of T3. This study suggested that all the indicated plasticizers have the potential for thyroid hormone disruption with two alternate plasticizers, DINCH and ATBC, exhibiting higher potential for thyroid dysfunction compared to DEHA and DEHP.

Keywords: endocrine disruption, alternate plasticizers, structural binding characterization, thyroid hormone receptor, thyroid dysfunction

This paper is freely accessible here:

ncbi.nlm.nih.gov/pmc/articl...

jimh111

[jimh111]

Thanks, I didn't get the Alert but came across this anyway.

These ECDs are a real problem because their effects do not surface until they have been used for years. This is because current testing consists of feeding them to rodents and measuring TSH (to detect effects on hormone activity) and total T4 (to see if they reduce thyroidal output). The harmless substances will be approved and most harmful ones banned before they reach production. The problem is a few will have local effects that do not affect TSH or T4. This is usually because they have little or no effect on the TRβ2 receptor which is mainly expressed in the pituitary and little elsewhere. Since these EDCs don't affect the pituitary affected individuals have normal TSH, fT3 and fT4 and so are told they are not hypothyroid. These individuals need supraphysiological doses of thyhroid hormone to overcome the resistance caused by the EDC.

I won't bother reading this paper, it looks very heavy going. The important point is the TRα1 receptor is affected. This receptor is widely expressed in the body, especially the brain. It's role in the pituitary is very minor so any effect on this T3 receptor will not show up in blood tests. In affected individuals TSH, fT3, fT4 are unlikely to change, blood tests will be normal and they will not be diagnosed.

This is a problem recognised by the WHO and UN Environment Programme who have called for better testing including including using markers of tissue hormone activity in their 'State of the Science' document unep.org/resources/report/s... . I'm not aware of any progress on this. This link gives a simple introduction to EDCs youtu.be/ibfAF66JzFE(Not working as expected?) .