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Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies

Project description

Novel tests to identify chemicals that disrupt thyroid hormone delivery to the embryo

Endocrine-disrupting chemicals (EDCs) are abundant. They are found in plastics, pesticides and flame retardants, leaking into the environment and food chain and accumulating in the human body. EDCs can disrupt the function of hormonal systems by mimicking hormones or blocking their normal action in the body. During the first few weeks of gestation, the foetus is unable to produce thyroid hormone and relies on maternal supply. It is known that EDCs in the maternal system can decrease circulating thyroid hormone, changing the levels that reach the foetus and resulting in a negative outcome. The EU-funded ATHENA project aims to develop new test methods to identify the EDCs that disrupt thyroid hormone delivery to the embryo, damaging brain development in utero.

Objective

The ATHENA consortium aims to mobilise the scientific progress made in recent years to close critical gaps left open in test methods for thyroid hormone axis disrupting-chemicals. We will develop new methods for incorporation into existing OECD test guidelines that can capture the consequences of maternal thyroid hormone deficiency on the developing brain, due to disruption of delivery of thyroid hormones to the foetus. To make this possible, we will establish new endpoints for identifying down-stream effects on the developing brain in foetal and post-natal life. We will provide new test methods for chemicals that interfere with the delivery of thyroid hormones to the foetus and the adult brain across physiological barriers such as the placenta, the blood brain barrier and the blood brain cerebrospinal fluid barrier. We will also develop QSARs for the screening of large compound libraries and methods for capturing disruption of the local supply of thyroid hormone by inhibition of deiodinases, dehalogenases and cell membrane transporters. Based on the construction of AOP networks for adverse neurodevelopmental effects, we will deliver a comprehensive testing strategy that can protect from chemicals that have the potential to harm brain development in foetal life and adulthood by disrupting the availability of thyroid hormones. Finally, ATHENA will conceive strategies for the international harmonisation of screening, testing and hazard identification for thyroid hormone axis disrupting chemicals. ATHENA comprises world-leading endocrinologists, experts in endocrine disruption and experts in modelling brain function ex vivo who collectively will deliver a step change in thyroid disruptor testing.

Call for proposal

H2020-SC1-BHC-2018-2020

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Sub call

H2020-SC1-2018-Single-Stage-RTD

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Coordinator

BRUNEL UNIVERSITY LONDON
Net EU contribution
€ 1 154 313,75
Address
Kingston lane
UB8 3PH Uxbridge
United Kingdom

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Region
London Outer London — West and North West Harrow and Hillingdon
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Participants (11)