Waterborne exposure to avobenzone and octinoxate induces thyroid endocrine disruption in wild-type and thrαa-/- zebrafish larvae

Avobenzone and octinoxate are frequently used as organic ultraviolet filters, and these chemicals are widely detected in water. This study evaluated the potential of avobenzone and octinoxate to disrupt thyroid endocrine system in wild-type and Thyroid Hormone Receptor alpha a knockout (thrαa^-/-) zebrafish embryo/larvae. Following a 120 h exposure to various concentrations of avobenzone and octinoxate, larvae mortality and developmental toxicity in wild-type and thrαa^-/- fish were assessed. Triiodothyronine (T3) and thyroxine (T4) levels as well as transcriptional levels of ten genes associated with the hypothalamus-pituitary-thyroid (HPT) axis were measured in wild-type fish. Significantly lower larvae survival rate in thrαa^-/- fish exposed to ≥3 μM avobenzone and octinoxate suggests that the Thyroid Hormone Receptor plays a crucial role in the toxic effects of avobenzone and octinoxate. A significant increase in the deio2 gene level in avobenzone-exposed zebrafish supports the result of an increased ratio of T3 to T4. Significant decrease of T4 level with upregulation of trh, tshβ, and tshr genes indicates feedback in the hypothalamus and pituitary gland to maintain hormonal homeostasis. Our observation indicates that exposure to avobenzone and octinoxate affects the Thyroid Hormone Receptor and the feedback mechanisms of the HPT axis. CLINICAL TRIALS REGISTRATION: Not applicable.

Avobenzone; Development; Knockout; Octinoxate; Thyroid endocrine disruption; Zebrafish.