Developmental toxicity and cardiac effects of butyl benzyl phthalate in zebrafish embryos

Phthalic acid esters (PAEs), commonly called phthalates, have become ubiquitous environment pollutants. Studies have focused on reproductive toxicity, neurotoxicity, teratogenicity, tumourigenesis, and mutagenesis of phthalates. However, relatively little is known about the phthalates effects on the heart. Butyl benzyl phthalate (BBP), a member of PAEs, is classified by the US Environmental Protection Agency as a priority environmental pollutant. We studied the developmental toxicity of BBP, especially its effects on the heart development, in zebrafish (Danio rerio) embryos. Embryos at 4 hr post-fertilization (hpf) were exposed to 0, 0.1, 0.6 and 1.2 mg/L BBP until 72 hpf. BBP caused abnormalities in embryo morphology, including yolk-sac edema, spinal curvature, tail deformity, uninflated swim bladder and cardiac defects. Exposure to 0.6 mg/L BBP significantly increased the malformation rate, caused growth inhibition, increased the cardiac malformation rate as well as the distance between the sinus venosus (SV) and bulbus arteriosus (BA), and reduced the heart rate of embryos. Exposure to 1.2 mg/L BBP significantly affected all endpoints, except survival rate at 24 hpf. To preliminarily elucidate the potential mechanism of heart developmental toxicity caused by BBP, we examined the expression of two genes related to heart development, Nkx2.5 and T-box transcription factor 5, by real-time quantitative PCR. The expression of the two genes was dose-dependently downregulated with BBP. BBP could induce developmental toxicity, with adverse effects on the heart development in zebrafish embryos, and alter the expression of genes related to heart development.