The medical value of mosquitoes attracted researchers worldwide to search for a valuable way to control such
serious insects. The continuous development of resistance against chemical insecticides pushed toward looking
for novel and promising compounds against mosquitoes. In this study, the toxicity and physio-developmental
effects of 10–30 nm spherical zinc oxide nanoparticles (ZnONPs) in aqueous suspension was addressed against
the first larval instar of Culex pipiens mosquito. The calculated value of LC50 was about 0.892 g/L while the sub
lethal concentration LC20 recorded about 0.246 g/L. Larvae treated with ZnONPs suffered reduced growth rate,
longer developmental period and malformations in the breathing tube. Furthermore, the treated larvae showed
clear abnormal appearance of the gastric caeca and midgut epithelia under transmission electron microscope
(TEM). These abnormalities appeared as condensation of the nuclear chromatin, abnormal shape or absence of
microvilli, highly increased amount of smooth endoplasmic reticulum in the cytoplasm and appearance of
numerous vacuoles. Additionally, ZnONPs interfered with several biochemical pathways such as induction of
oxidative stress which appeared in the form of increased levels of hydrogen peroxide and inability to activate the
detoxifying enzymes alkaline phosphatase (ALP), catalase and glutathione peroxidase (GPX). On the contrary,
the activity of the antioxidant enzyme superoxide dismutase (SOD) increased in treated larvae. Furthermore,
LC20 and LC50 of ZnONPs inhibited the growth rate of the larval gut fauna in vitro. These results clearly show that ZnONPs target several tissues leading to serious alteration in the physiological and developmental processes in C. pipiens mosquito larvae.