Detecting Indirect Thyroid Disrupting Chemicals (TDC) In Vitro
Rat-Specific Induction for T4 Metabolism
Chemicals that disrupt thyroid function can act directly on the pathways involved in thyroid hormone (TH) synthesis in the thyroid or indirectly by affecting how thyroid hormones, such as thyroxine (T4) and triiodothyronine (T3), are metabolized in the liver. Chemicals that activate CAR/PXR nuclear receptors in the liver may increase T4 catabolism by inducing Cytochrome P450 (CYP) phase I and phase II enzymes in the liver.
Rats are at greater risk than humans for the development of chemically induced thyroid tumors, in part due to species differences in TH conjugation rates and nuclear receptor sensitives to xenobiotics. In addition, there are higher serum concentrations of thyroxine binding globulin (TBG) in humans compared to rats.
The LifeNet Health Solution
The species differences in CAR/PXR-mediated changes in T4 serum concentrations is important as it suggests an adverse event in the rate may or may not have relevance to human safety. To properly test chemicals for their potential to disrupt thyroid function thyroid function by activation of CAR/PXR-controlled hepatic metabolism of T4, it is important to utilize rat and human liver models that closely mimic the in vivo compound-induced perturbations in TH clearance mechanisms and enable cross-species translation.
The LifeNet Health TruVivo 2D+ hepatic system provides both rat and human species options in order for this comparison to be performed.
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