Endocrine disruption of thyroid hormone system - in vitro assessment of several modes of action of chemicals and environmental samples

The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These gaps put the public at risk and risk assessors in a difficult position. Decisions about the status of chemicals as thyroid hormone system disruptors currently are based on inadequate toxicity data. The ATHENA project (Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies) has been conceived to address these gaps. The project will develop new test methods for the disruption of thyroid hormone transport across biological barriers such as the blood–brain and blood–placenta barriers. It will also devise methods for the disruption of the downstream effects on the brain. ATHENA will deliver a testing strategy based on those elements of the thyroid hormone system that, when disrupted, could have the greatest impact on diminished or enhanced thyroid hormone action and therefore should be targeted through effective testing. To further enhance the impact of the ATHENA test method developments, the project will develop concepts for better international collaboration and development in the area of thyroid hormone system disruptor identification and regulation.

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In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors.

iScience ◽

10.1016/j.isci.2021.102957 ◽

2021 ◽

pp. 102957

Author(s):

Yanis Zekri ◽

Laure Dall Agnol ◽

Frédéric Flamant

Keyword(s):

Thyroid Hormone ◽

Nuclear Receptors ◽

Capacity To Act ◽

In Vitro Assessment

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In vitro assessment of the capacity of pesticides to act as agonists/antagonists of the thyroid hormone nuclear receptors

10.1101/2020.12.21.423731 ◽

2020 ◽

Author(s):

Yanis Zekri ◽

Laure Dall Agnol ◽

Frédéric Flamant ◽

Romain Guyot

Keyword(s):

Thyroid Hormone ◽

Nuclear Receptors ◽

Transcriptome Analysis ◽

Cellular Response ◽

In Vitro Tests ◽

Neural Cells ◽

Hormone Signaling ◽

Neurodevelopmental Toxicity ◽

In Vitro Assessment

SummarySeveral in vitro tests, including transcriptome analysis of neural cells, were performed to assess the capacity of 33 pesticides to act as thyroid hormone disruptors (THD). Although some pesticides elicit a cellular response, which interferes with thyroid hormone signaling, we found no evidence that they can act as receptor agonists or antagonists. We conclude that the nuclear receptors of thyroid hormone are not common targets of THD, and that pesticide neurodevelopmental toxicity is not explained by a general alteration of neural cell response to thyroid hormone.

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