The Belgian Society of Toxicology and Ecotoxicology (BelTox) will organize the 54th Congress of the European Societies of Toxicology (EUROTOX 2018) from 2 to 5 September, 2018, in Brussels. Besides three universities, Brussels hosts many stakeholders in toxicological sciences such as the EU institutions, ILSI Europe, ECETOC, and numerous industry trade associations.
We are pleased to be presenting our poster at Eurotox 2018, poster number #852.
In vitro approaches to risk assess chemical mediated changes in thyroid function.The hypothalamic-pituitary-thyroid axis (HPT axis) is conserved across vertebrate evolution. Perturbation of thyroid hormone homeostasis (THH) can lead to adverse effects in thyroid function affecting growth, metabolism and cognitive function. In utero, appropriate thyroid hormone concentrations are absolutely required for normal nervous system development. Chemical disruption of THH can occur via a number of mechanisms, including increased hepatic thyroid hormone clearance, inhibition of iodide transport into the thyroid (sodium/iodide symporter), inhibition of iodide oxidation (thyroid peroxidase (TPO)) and inhibition of thyroid hormone deiodination (deiodinases). To understand the effect of chemicals on these functions the following assays are utilised. 1. in vitro primary hepatic thyroid hormone metabolism (multiple species), 2. thyroid peroxidase inhibition (multiple species), 3. deiodinase inhibition (rat and human), 4. sodium/iodide symporter inhibition (rat). Rat sodium iodide symporter inhibition and rat and human deiodinase 1,2 and 3 inhibition assays are currently being validated. Here we report the validation of in vitro rat, dog, pig and human TPO inhibition and in vitro primary hepatocyte metabolism of thyroxine (T4). In concurrence with the literature, TPO inhibition by 6-propyl-2-thiouracil (PTU) shows broad sensitivity across the species tested. in rat (IC502.2 µM ) Dog (IC5017.7 µM ) pig (IC507.6 µM) and human (IC5050.9 µM ). T4 metabolism by primary cultures of human and rat hepatocytes show a consistent dose response induction (approximately 2 fold over vehicle control) in response to reference item administration. These assays form part of an in vitro screen used to generate data to understand chemical endocrine disruption hazard.
View full poster Thyroid Function Poster.