Developmental toxicity and thyroid hormone-disrupting effects of acetyl tributyl citrate in zebrafish and Japanese medaka

Chemical pollution from plasticizers in water environments is a serious environmental problem worldwide. Phthalate plasticizers have potential endocrine-disrupting effects in vertebrates. In this study, the effects of a non-phthalate acetyl tributyl citrate (ATBC) plasticizer on endocrine hormone activity (according to thyroid-related gene expression) and the developmental toxicity of ATBC were determined in zebrafish (Danio rerio) and Japanese medaka (Oryzias latipes) embryos. ATBC exposure increased the mortality of zebrafish and Japanese medaka at concentrations of 443.05 and 1,937.41 μg/L, respectively. Body curvature, edema, and growth inhibition were also observed after ATBC exposure in both species. Importantly, both species exhibited suppressed thyroid-related gene mRNA expression after ATBC exposure. ATBC exposure significantly suppressed the expression of thyroid-stimulating hormone beta subunit (tshβ), iodothyronine deiodinase 1 (dio1), dio2, and thyroid hormone receptor alpha (trα) in zebrafish. In Japanese medaka, ATBC exposure suppressed the mRNA expression of dio2, trα, and trβ but not tshβ and dio1. In summary, ATBC exposure inhibited thyroid-related gene expression and led to improper swim bladder inflation in the test species. This is the first report of a non-phthalate ATBC plasticizer inducing abnormal embryo development and disrupting thyroid hormone activity in fish.