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.
Highlights
Both anthropogenic and naturally occurring compounds that are widely spread in the environment have the potential to disrupt the endocrine system of organisms
427 entries representing 250 compounds and technical mixtures were included in the database
All compounds have been tested for their binding potency to TTR, derived from seven different species, human, birds, fishes, and amphibians (Rana catesbeiana and Xenopus laevis, 45 entries)
Summary
Both anthropogenic and naturally occurring compounds that are widely spread in the environment have the potential to disrupt the endocrine system of organisms. It is important to identify thyroid hormone-disrupting compounds (THDCs) and to construct screening methodologies to be included in monitoring programs [2]. In 2006, a review paper on TH disruption assays was published by the Organisation for Economic Co-operation and Development (OECD) [3], and in 2010, it was proposed to establish a thyroid scoping effort group (TSEG) to determine the state of in vitro thyroid assays since 2006. The purpose of the TSEG was to bring relevant in vitro thyroid assays to the attention of OECD member countries and provide recommendations for their development and use [2]. Out of the 18 assays reviewed, the top three of the selected assays focused on TH disruption via transport protein binding [3]. This study recommended using disrupted circulation and transport of TH via the binding to serum transport proteins for the evaluation of the TH-disrupting potency of compounds
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