Subchronic exposure to four organic UV filters disrupted thyroid endocrine and neuronal systems in zebrafish: Insights into underlying toxicological mechanisms at different life stages

Abstract

Organic ultraviolet filters (OUVFs) are widely used in cosmetics and sunscreen to protect skin and products. While certain OUVFs, such as benzophenone-3 (BP-3), have been shown to disrupt thyroid hormone (TH) system, the endocrine-disrupting and neurotoxic potential of many commonly used OUVFs remains poorly understood. In this study, we chose four frequently used OUVFs: avobenzone (AVB), BP-3, octyl methoxycinnamate (OMC), and octocrylene (OC), and examined their effects on thyroid and neuronal systems in juvenile (30-day exposure following fertilization) and adult male fish (> 6 months old, 21-day exposure). In both juvenile and adult fish, exposure to OUVFs increased TH levels, accompanied by a significant upregulation of genes involved in TH synthesis and bioconversion (i.e., tshr, nis, tg, and/or dio2). In adult fish, the ugt1ab and/or sult1st5 genes were generally upregulated in the liver, compensating for elevated TH levels. In juvenile zebrafish, OUVF exposure induced hypoactivity and anxiety-like behaviors, which were accompanied by alteration of the genes related to neurogenesis (i.e., mbp or gap43) and synaptogenesis (i.e., syn2a, syt1a, and/or stxbp1b). Notably, the anxiety-related marker gene, cfos, was significantly upregulated in both juvenile and adult male zebrafish. The observed neurobehavioral changes appear to be independent of TH disruption. Given the widespread human exposure to OUVFs and conserved biological pathways between zebrafish and humans, these findings have important public health implications and warrant further investigations in human populations.

Keywords: Behavior; Endocrine disruption; Neurotoxicity; Organic UV filters; Thyroid hormone; Zebrafish.