Transcriptomic modifications of the thyroid gland upon exposure to phytosanitary-grade fipronil: Evidence for the activation of compensatory pathways.

Fipronil is a phenylpyrazole insecticide used for the control of a variety of pest for domestic, veterinary and agricultural uses. Fipronil exposure is associated to thyroid disruption in the rat. It increases thyroid hormone (TH) hepatic clearance.

The nuclear receptors pregnane X receptor and constitutive androstane receptor contribute to the impact of fipronil on hepatic gene expression linked to thyroid hormone metabolism.

Fipronil is described as a thyroid disruptor in rat. Based on the hypothesis that this results from a perturbation of hepatic thyroid hormone metabolism, our goal was to investigate the pathways involved in fipronil-induced liver gene expression regulations. First, we performed a microarray screening in the liver of rats treated with fipronil or vehicle.

Is the mechanisms of fipronil-induced thyroid disruption specific of the rat: Re-evaluation of fipronil thyroid toxicity in sheep?

In rat, fipronil treatment increases the elimination of thyroid hormones (TH). Relevance of this mechanism for the risk of fipronil for human health is subject to controversy because of the specificities of adult rat for TH plasma binding properties which often lead to the assumption that rats are more sensitive than human to thyroid disruption. This study aimed at determining if the mechanism of fipronil-induced thyroid disruption is altered in sheep a species more relevant to human from the standpoint of TH plasma binding.

Fipronil-induced disruption of thyroid function in rats is mediated by increased total and free thyroxine clearances concomitantly to increased activity of hepatic enzymes.

Fipronil is a widely used phytosanitary product and insecticide for pets. In the rat, fipronil can disrupt thyroid function by decreasing plasma concentrations of total thyroxine (T4) likely through increased T4 clearance. However, the mechanism of fipronil action on thyroid function remains unclear.