Tracing thyroid hormone-disrupting compounds: database compilation and structure-activity evaluation for an effect-directed analysis of sediment

Abstract

A variety of anthropogenic compounds has been found to be capable of disrupting the endocrine systems of organisms, in laboratory studies as well as in wildlife. The most widely described endpoint is estrogenicity, but other hormonal disturbances, e.g., thyroid hormone disruption, are gaining more and more attention. Here, we present a review and chemical characterization, using principal component analysis, of organic compounds that have been tested for their capacity to bind competitively to the thyroid hormone transport protein transthyretin (TTR). The database contains 250 individual compounds and technical mixtures, of which 144 compounds are defined as TTR binders. Almost one third of these compounds (n = 52) were even more potent than the natural hormone thyroxine (T4). The database was used as a tool to assist in the identification of thyroid hormone-disrupting compounds (THDCs) in an effect-directed analysis (EDA) study of a sediment sample. Two compounds could be confirmed to contribute to the detected TTR-binding potency in the sediment sample, i.e., triclosan and nonylphenol technical mixture. They constituted less than 1 % of the TTR-binding potency of the unfractionated extract. The low rate of explained activity may be attributed to the challenges related to identification of unknown contaminants in combination with the limited knowledge about THDCs in general. This study demonstrates the need for databases containing compound-specific toxicological properties. In the framework of EDA, such a database could be used to assist in the identification and confirmation of causative compounds focusing on thyroid hormone disruption.Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-015-8736-9) contains supplementary material, which is available to authorized users.

Cats’ Internal Exposure to Selected Brominated Flame Retardants and Organochlorines Correlated to House Dust and Cat Food

“…Both compounds have a potency to bind to the transport protein for thyroxin and thereby disrupt the thyroid hormone balance, implicating a possible health effect on the cats. 35 PCP has been reported at high concentrations in pet cat samples from Japan, Pakistan, and UK, 38,39,42 but in this study, the concentrations are only one-fifth of these concentrations. In the past, PCP was used to preserve wood, but it may also be formed through the metabolism of HCB.…”

“…22 Thyroid hormone disrupting compounds (THDCs) with a binding potency to TTR has recently been reviewed. 35 The majority of the TTR binding chemicals were aromatic, halogenated, and hydroxylated compounds. These compounds are typical metabolites of BFRs as well as products of organochlorines regulated under Stockholm Convention: polychlorinated biphenyls (PCBs) and organochlorine pesticides such as 1,1-bis(4,4′-dichlorodiphenyl)-2,2,2-trichloroethane (4,4′-DDT), 1,1-bis(4,4′-dichlorodiphenyl)-2,2-dichloroethene (4,4′-DDE), hexachlorobenzene (HCB), and pentachlorophenol (PCP).…”

In Silico Approach To Identify Potential Thyroid Hormone Disruptors among Currently Known Dust Contaminants and Their Metabolites

“…25 Only binding data to human TTR were 101 considered since human exposure is the focus of this study. By this means, we also avoid 102 species-related variation, as this is an important aspect due to variable binding efficiency 103 between species, e.g.…”

Identifying potential endocrine disruptors among industrial chemicals and their metabolites – development and evaluation of in silico tools

“…The A data consisted of the inhibitory concentration fom 25% or 50% of the response induced by the synthetic androgen metribolone (R1881) in harvested Chinese Hamster Ovary (CHO) cells, as collected by Jensen et al (2011). The T data comprised of competitive binding (IC 50 ) to human transthyretin using radiolabelled thyroxine (Weiss et al, 2015). This assay was recently listed as a recommended tier one testing assay (Murk et al, 2013).…”