Metabolomic mechanisms of short chain chlorinated paraffins toxicity in rats

Short chain chlorinated paraffins (SCCPs) have received increased interest worldwide since they were added to the list of controlled POPs in Annex A of the Stockholm Convention in 2017. Although many toxicological studies have already shown that SCCPs are hepatotoxic, nephrotoxic, and thyrotoxic to rodents, there have been few studies to date that have characterized changes in the metabolic pathways targeted by SCCPs. In this study, a UPLC-Q-TOF-MS based plasma metabolomics approach was used to investigate the toxicity of SCCPs in rats. Liver and kidney injury occurred rapidly after high-dose SCCP exposure, and the most relevant pathways affected were energy metabolism, amino acid metabolism, glycerophospholipid metabolism, nucleotide metabolism, and vitamin B metabolism. Exposure to SCCPs inhibited the tricarboxylic acid cycle and accelerated degradation. Fluctuating levels of phospholipids and nucleotides may have contributed to the neurotoxicity of SCCPs. In addition, the down regulation of folic acid induced by SCCPs may have led to malformations during the early development of laboratory animals. These results suggested that high exposure levels of SCCPs may have serious health risks and more research is needed to assess the health status of relevant occupational groups.