Removing critical gaps in chemical test methods by developing new assays for the identification of thyroid hormone system-disrupting chemicals—the athena project

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

Removing Critical Gaps in Chemical Test Methods by Developing New Assays for the Identification of Thyroid Hormone System-Disrupting Chemicals—The ATHENA Project

Copyright © 2020 by the authors. 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.EU Horizon 2020 programme, grant number 82516

Cardiovascular actions of dogfish Urotensin I in the dogfish, Scyliorhinus canicula.

A synthetic replicate of dogfish urotensin I (U-I), a 41-amino-acid residue peptide isolated from an extract of the caudal spinal cord region of the European spotted dogfish Scyliorhinus canicula was prepared in order to study its cardiovascular actions in the species of origin. Bolus intraarterial injections of dogfish U-I (0.3-30 nmol/kg body wt) into the celiac artery of unanesthetized dogfish produced a transient fall in arterial blood pressure (P &lt; 0.05 in the dose range 1-3 nmol/kg) followed by a sustained and dose-dependent rise in pressure (P &lt; 0.05 in the dose range 1-30 nmol/kg). The maximum depressor response (to 3 nmol/kg) was 0.25 +/- 0.08 kPa and the maximum presser response (to 30 nmol/kg) was 1.08 +/- 0.09 kPa. There was no significant effect on heart rate at any dose tested. Pretreatment of the animals with the alpha-adrenergic receptor antagonist phentolamine significantly (P &lt; 0.05) attenuated the presser response to injections of dogfish U-I (1 nmol/kg and 10 mol/kg), demonstrating that the effects of the peptide are mediated, at least in part, through release of catecholamines. The data suggest that U-I, released together with potent presser peptide urotensin II from the caudal neurosecretory system, may play a physiological role in cardiovascular regulation in elasmobranchs. (C) 1998 Academic Press.</p

Cardiovascular actions of dogfish Urotensin I in the dogfish, Scyliorhinus canicula.

A synthetic replicate of dogfish urotensin I (U-I), a 41-amino-acid residue peptide isolated from an extract of the caudal spinal cord region of the European spotted dogfish Scyliorhinus canicula was prepared in order to study its cardiovascular actions in the species of origin. Bolus intraarterial injections of dogfish U-I (0.3-30 nmol/kg body wt) into the celiac artery of unanesthetized dogfish produced a transient fall in arterial blood pressure (P &lt; 0.05 in the dose range 1-3 nmol/kg) followed by a sustained and dose-dependent rise in pressure (P &lt; 0.05 in the dose range 1-30 nmol/kg). The maximum depressor response (to 3 nmol/kg) was 0.25 +/- 0.08 kPa and the maximum presser response (to 30 nmol/kg) was 1.08 +/- 0.09 kPa. There was no significant effect on heart rate at any dose tested. Pretreatment of the animals with the alpha-adrenergic receptor antagonist phentolamine significantly (P &lt; 0.05) attenuated the presser response to injections of dogfish U-I (1 nmol/kg and 10 mol/kg), demonstrating that the effects of the peptide are mediated, at least in part, through release of catecholamines. The data suggest that U-I, released together with potent presser peptide urotensin II from the caudal neurosecretory system, may play a physiological role in cardiovascular regulation in elasmobranchs. (C) 1998 Academic Press.</p