Toxicomorphomics and toxicokinetics of quinalphos on embryonic development of zebrafish (Danio rerio) and its binding affinity towards hatching enzyme, ZHE1.

This study outlines the toxic effects of Quinalphos (QP), an organophosphrous insecticide on the development of zebrafish (Danio rerio) embryos, with special emphasis on toxicomorphomics and toxicokinetics of target enzyme, AChE. A range of concentrations was used to elucidate the median lethal concentration (LC50) of Quinalphos. Furthermore, embryos were exposed to two sub-lethal concentrations LC10 (0.66mg/L) and LC20 (1.12mg/L) along with a median lethal concentration (3.0mg/L) for 96h. Several morphological aberrations like lordosis, kyphosis, scoliosis, heart edema, breaks in the neuronal tube and underdeveloped facial parts were noticed, which were of concentration and time dependent. The QP has adequately hindered hatching process during the course of exposure which was upheld by the in silico docking studies with hatching enzyme, ZHE1. The length of hatchlings at 96h in LC50 concentration was significantly reduced to 47% compared to control. A significant pericardial effusion (5 to 16 fold) was observed in >90% of LC50 treated groups. Morphological changes in heart lead to the bradycardia, which ultimately leading to heart failure in some cases. The swimming behavior was significantly diminished in relation to the inhibition of AChE levels. From the in vitro kinetic studies, the kinetic constants Km, Vmax and inhibitory concentration Ki (4.45×10-5M) was determined which supported the competitive nature of QP.