Systematical exploration of the common solvent toxicity at whole organism level by behavioral phenomics in adult zebrafish

Common solvents are frequently used as carriers to dissolve chemicals with a hydrophobic property that is extensively applied in the industrial and biomedical fields. In this study, we aimed to systematically study the sub-chronic effect of ten common solvents at low concentration exposure in adult zebrafish and perform neurobehavioral assessments for mechanistic exploration. After exposed to ten common solvents, including methanol, ethanol (EtOH), dimethyl sulfoxide (DMSO), isopropanol, acetone, polyethylene glycol-400 (PEG-400), glycerol, butanol, pentane, and tetrahydrofuran for continuous 10 day at 0.1% concentration level, adult zebrafish were subjected to perform a serial of behavioral tests, such as novel tank, mirror biting, predator avoidance, social interaction and shoaling. Later, 20 behavioral endpoints obtained from these five tests were transformed into a scoring matrix. Principal component analysis (PCA) and hierarchy clustering were performed to evaluate and compare the zebrafish behavior profiling. By using this phenomic approach, we were able to systematically evaluate the toxicity of the common solvents in zebrafish at a neurobehavioral level for the first time and found each common solvent-induced unique behavioral alteration to produce fingerprint-like patterns in hierarchy clustering and heatmap analysis. Among all tested common solvents, acetone and PEG-400 displayed better biocompatibility and less toxicity since they triggered less behavioral and biochemical alterations while methanol and DMSO caused severe behavior alterations in zebrafish after chronic exposure of these solvents. We conclude the behavioral phenomic approach conducted in this study providing a powerful tool to a systematical exploration of the common solvent toxicity at the whole organism level.