One size does not fit all in thyroid disruption: distinct thyroid hormone profiles and adverse outcomes after developmental exposure to PTU (propylthiouracil), DE-71 (brominated flame retardant) and OMC (octyl methoxycinnamate)

Correct thyroid hormone economy is crucial for mammalian brain development. In humans, even mild, non-clinical hypothyroxinemia during pregnancy has been linked to reduced IQ and increased risk of neurobehavioral disorders in the offspring. Several groups of environmental chemicals can interfere with thyroid hormone economy, which raises concern about their potential to disrupt human brain development. Here, we tested how developmental exposure to three thyroid-disrupting chemicals with differing mechanisms of action could affect thyroid hormone economy and cause adverse outcomes. We exposed 104 pregnant Sprague Dawley rats from gestational day (GD) 7 to postnatal day (PD) 22 to either corn oil (vehicle control), the anti-thyroid drug PTU (1 or 2.5 mg/kg/day), the UV-filter OMC (375 or 500 mg/kg/day) or a commercial mixture of brominated flame retardants DE-71 (20 or 40 mg/kg/day). Serum hormones (T3, T4 and TSH), body-, and organ weights were measured in dams and offspring at different times during the study. Our results showed that the three different compounds showed a distinct pattern of effects on liver, thyroid and brain, which seemed closely related to their primary mechanism of action. PTU exposure increased thyroid gland weight, DE-71 caused liver weight increases whereas reductions in brain weights were seen in OMC exposed offspring. The three compounds also caused very different effects on thyroid hormone economy and the hormone effect patterns varied in dams and offspring over the time course of the study. Thus, in developmental toxicity studies it is important to assess thyroid hormone economy at several time points throughout the study, in order to obtain better understand the chemically induced changes and to best protect humans from the adverse effects of thyroid hormone disruption. Future studies should focus on elucidating the origin of the different effect patterns and link them to possible adverse effects on the developing brain.