Download Executive Summary: Bioanalytical Tools to Analyse Hormonal

Review of endocrine assays Executive summary Much of the work on endocrine disruption from exposure to environmental contaminants has been carried out on the estrogenic axis. In the last decade substantial effort has been put into the development of bioassays to assess the estrogenicity of various waters including drinking water, ground water, surface water and wastewater. But the endocrine system is not simply about estrogenic activity, and several other hormonal systems (such as androgens, progestagens, glucocorticoids, retinoids, thyroid etc) play a crucial role in the maintenance of homeostasis, sexual development, metabolism, growth and behaviour. Substantially less information is available on those other endocrine endpoints, although it is becoming clear that these pathways can also be disrupted by exposure to environmental contaminants. Methods that rely on biological activity are finding increasing utility as screening tools, because the chemical nature of the endocrine disrupting sample may be unknown and/or difficult to quantify/identify, and the biological method may be the best (or only) indicator of biological activity. This is particularly true for those less‐studied endocrine endpoints, where the causative chemical(s) is/are often unknown. This project continues and expands on previous GWRC efforts to develop and validate methods to measure estrogenic activity in water to include a range of substantially less well‐studied endocrine endpoints. Focussing on androgens, steroidogenesis, progestagens, glucocorticoids, thyroid hormone, PPAR and retinoid acid receptors, the reports provides information on: •
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Production, function and molecular and cellular mode of action of the different hormones, Overview of chemicals identified as EDCs for each particular endpoint, Review of in vitro methods currently available for each endpoint, Current status of interassay comparisons and interlaboratory validations, Reported activity in environmental waters, and An expert evaluation of the different in vitro methods currently available. The main conclusions of the report are that: 1. Androgenic and (to a lesser extent) progestagenic activity have undergone sound inter‐
laboratory and inter‐assay validation with model compounds. While these comparisons did not test water samples, water data from other publications is available and a meta‐analysis of all available literature would provide a broad understanding of the suitability of each assay to water testing. 2. It is possible to measure interference with steroidogenesis (and an in vitro assay has been carefully validated), but it can be difficult to interpret unless there is significant toxicity. As such, this endpoint may require further basic science before it can be meaningfully applied to water testing. 3. Several bioassays are available to measure thyroid activity, but it is unclear how relevant each assay is to water monitoring. Different assays measure thyroid interference at a different level, and this endpoint would greatly benefit from a methodical inter‐assay comparison to determine the suitability of these assays to test thyroid activity in water. 4. Little is known about glucocorticoid, retinoid X receptor (RXR) and peroxisome proliferator‐
activated receptor (PPAR) activity in water. These endpoints have been identified as high Page | 5 GWRC (2012) priority by a recent OECD review on endocrine disruption. It is important to understand the likely exposure from water for these endocrine endpoints that have a clear causal link to metabolism and obesity. 5. Finally, most assays have been applied patchily to measure endocrine activity in wastewater. There is little information on non‐estrogenic endocrine activity in other waters, including drinking, surface and ground water. Page | 6