Identification of Hydroxylated Chlorinated Paraffins in Human Serum and Their Potential Metabolic Pathways

Short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) are frequently detected in humans. However, information regarding their metabolites is still very limited. Herein, target analysis and halogenation-guided nontarget and suspect screening were conducted on serum samples using UHPLC-Orbitrap-HRMS. The median concentrations of SCCPs and MCCPs were 7.76 and 4.31 ng/mL, respectively. A series of hydroxylated chlorinated paraffins (OH-CPs) were tentatively identified with an estimated average concentration of 1.80 ng/mL, which was approximately 9.9% of the total SCCPs and MCCPs. A chlorine distribution shift was observed from chlorinated paraffins (CPs) dominated by Cl₆ and Cl₇ to OH-CPs dominated by Cl₅, Cl₆, and Cl₄. In human liver cytochrome P450 (CYP) enzyme incubation assays, the CPs in commercial mixtures were mainly metabolized into OH-CPs with various carbon lengths and chlorine substituents. The results obtained from human serum and <i>in vitro</i> experiments suggested the oxidative metabolism of SCCPs and MCCPs in humans. The metabolic pathways were then comprehensively explored using a CP monomer (1,1,1,3,10,11-hexachloroundecane) incubated with the same CYP enzymes, demonstrating that CPs can be metabolized through successive oxidative dechlorination and direct hydroxylation, with subsequent oxidation to carboxylic acids. Further studies should focus on the long-term toxicity of OH-CPs.