Developmental and cardiac toxicity assessment of Ethyl 3-(N-butylacetamido) propanoate (EBAAP) in zebrafish embryos.

ABSTRACT

Ethyl 3-(N-butylacetamido) propanoate (EBAAP) is one of the most widely used mosquito repellents worldwide, and is also commonly used to produce cosmetics. Residues have recently been detected in surface and groundwater in many countries, and their potential to harm the environment is unknown. Therefore, more studies are needed to fully assess the toxicity of EBAAP. This is the first investigation into the developmental toxicity and cardiotoxicity of EBAAP on zebrafish embryos. EBAAP was toxic to zebrafish, with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). EBAAP exposure also reduced body length, slowed the yolk absorption rate, induced spinal curvature and pericardial edema, decreased heart rate, promoted linear lengthening of the heart, and diminished cardiac pumping ability. The expression of heart developmental-related genes (nkx2.5, myh6, tbx5a, vmhc, gata4, tbx2b) was dysregulated, intracellular oxidative stress increased significantly, the activities of catalase (CAT) and superoxide dismutase (SOD) decreased, and malondialdehyde (MDA) content increased significantly. The expression of apoptosis-related genes (bax/bcl2, p53, caspase9, caspase3) was significantly upregulated. In conclusion, EBAAP induced abnormal morphology and heart defects during the early stages of zebrafish embryo development by potentially inducing the generation and accumulation of reactive oxygen species (ROS) in vivo and activating the oxidative stress response. These events dysregulate the expression of several genes and activate endogenous apoptosis pathways, eventually leading to developmental disorders and heart defects.