Untargeted Metabolomics Associated with Behavioral and Toxicological Studies Yield Insights into the Impact of 2,6-Dichloro-3-hydroxy-1,4-benzoquinone Disinfection By-Product on Zebrafish Larvae

Abstract

The disinfection by-product 2,6-dichloro-3-hydroxy-1,4-benzoquinone (2,6-DCBQ-OH) is a halobenzoquinone that emerges after chlorination. Therefore, it will inevitably come into contact with aquatic organisms. The aim of this study was to investigate the effect of 2,6-DCBQ-OH on zebrafish embryos. The dose-dependent toxicity was recorded, and the LC50 value was found to be 186 μg/L. Toxicity was accompanied with morphological, developmental, and behavioral abnormalities, and metabolic alterations. The association of phenotypic alterations with metabolic alterations was investigated through metabolomic study. In the control group, 25 metabolic pathways were identified, and 10 of them remained unaffected upon exposure to the halobenzoquinone. The upregulation of the glutathione pathway suggested that 2,6-DCBQ-OH can cause oxidative stress. In addition, the upregulation of the β-alanine metabolism pathway may be associated with the observed reduced swimming activity observed. Likewise, the downregulation of pathways associated with glycerophospholipids and butyrate can result in endocrine disruption, ineffective regulation of weight and body composition, and glucose homeostasis. The fatty acid elongation and synthesis of essential amino acids are downregulated, which can be associated with insufficient organogenesis at early life stages. In conclusion, exposure of zebrafish to 2,6-DCBQ-OH results in dysregulation and metabolic collapse of the organism, which ultimately result in developmental, morphological, behavioral, and other abnormalities.