Increased adverse effects during metabolic transformation of short-chain chlorinated paraffins by cytochrome P450: A theoretical insight into 1-chlorodecane

Short-chain chlorinated paraffins (SCCPs), frequently detected in human tissues or organs, can result in threat to human health by disturbing normal metabolism. However, their metabolism mechanisms and fates are largely unclear. Therefore, to better understand the impacts of SCCPs and their metabolites on the human health, the metabolic mechanism and kinetics of SCCPs by cytochrome P450 enzymes (CYPs) were explored using density functional theory employed 1-chlorodecane as a model SCCPs. The results show that 1-chlorodecane could be readily metabolized by CYPs, and the rate constant reaches up 42.3 s−1 in human body. Dechlorination of 1-chlorodecane is unlikely to occur and hydroxylation is dominated via H-abstraction pathways, especially from the intermediate C atom of 1-chlorodecane. The toxicity assessments suggest that the two metabolites, 10-chloro-decan-5-ol and 1-chlorodecanol could exhibit higher bioaccumulation, carcinogenicity and more serious damage on cardiovascular system after the metabolism of 1-chlorodecane. To our knowledge, this is the first study from the viewpoint of theoretical analysis to explore the metabolism of typical SCCPs in human body. It may provide deep insight into the metabolic transformation mechanism of SCCPs and cause the concerns about the adverse effects of their metabolites in human body.