Liquid mosquito repellent induces toxic effects in zebrafish

Mosquitoes serve as vectors for life-threatening parasitic diseases, presenting a continuous threat throughout human history. This has resulted in the extensive utilization of various mosquito repellents, including liquid mosquito repellents (LMRs), roll-ons, and topical creams. While these products demonstrate significant efficacy, the toxicological implications associated with their use are not yet fully understood and continue to be a subject of debate. The analysis conducted using gas chromatography-mass spectrometry (GC-MS) on LMR revealed the presence of 158 distinct compounds, among which were Piperazine 2,5-dimethyl propyl and a range of hydrocarbons. The analysis of network toxicology indicated that 78 of the examined compounds contravened Lipinski's rule of five and exhibited considerable overlap with target genes associated with lung cancer pathways, thereby highlighting potential concerns regarding their carcinogenic properties. The exposure of zebrafish embryos to LMR concentrations between 0.1 and 14 µg/mL resulted in developmental toxicity assays that demonstrated a dose-dependent escalation in mortality rates and the occurrence of morphological abnormalities, such as pericardial edema and skeletal deformities. Behavioral assays demonstrated a marked decrease in locomotor activity at elevated LMR concentrations, indicating potential neurotoxic effects. Biochemical analyses revealed elevated levels of reactive oxygen species (ROS), enhanced lipid peroxidation, and diminished glutathione, which are indicative of oxidative stress. Enzyme activity assays indicated a reduction in superoxide dismutase (SOD) and catalase (CAT) activities, alongside an increase in lactate dehydrogenase (LDH) activity, which suggests the occurrence of cellular damage. Analysis of gene expression demonstrated significant dysregulation in genes associated with oxidative stress (SOD1, CAT), inflammatory markers (TNF-α, IL-1β), apoptotic regulators (p53, bcl2), and neurobiological genes (brain-derived neurotrophic factor, bdnf). The results highlight the possible health hazards linked to LMR exposure, which manifest as developmental, biochemical, and genetic alterations in zebrafish embryos.