Abstract:[Background] Organic chlorine pesticides (OCPs) are a class of persistent organic pollutants (POPs) that have been prohibited from many years. It can exist in the environment and organisms for a long time and lead to long-term low-dose exposure of people through food chain amplification, causing several disorders and diseases. At present, the content of OCPs represented by p, p’-DDT in the environment is still high, the toxicity is closely related to cytochrome P450 enzyme (CYP)-mediated biotransformation, but its metabolism in the human body is still not clear. [Objective] This study is proposed to clarify the biological conversion process of p, p’-DDT metabolized by CYP2B6. The result will provide basis for the risk assessment and prevention of DDTs. [Methods] The detection method based on gas chromatography-mass spectrometry (GC-MS/MS) was established to detect DDTS in biological samples. The metabolic model in vitro was established, using recombinant enzyme CYP2B6 and p, p'-DDT. The enzyme activity was calculated by Michaelis-Menten equation and DDT (p, p’-DDT) and metabolites (p, p’-DDE、p, p’-DDD) were analyzed in the samples. Using 8-MOP as enzyme inhibitor to verify the metabolical ability of CYP2B6 on p, p'-DDT. Meanwhile, the metabolic model in vivo was established in SD rat (rat CYP2B1 is homologous enzymes of human CYP2B6), using the tail intravenous injection of p, p’-DDT and CYP2B6 specific chemical inhibitor KR-II. The changes of p, p’-DDT prototypes and metabolites (p, p’-DDE、p, p’-DDD) and the change of enzyme activity were assessed in the serum (0min, 5min, 10min, 20min, 30min) and liver microsomes. [Results] A detection method for DDTs was successfully established and tested. Metabolic experiments in vitro confirmed that p, p’-DDT could metabolized by CYP2B6, and the main metabolite was p, p’-DDE, kinetic parameter Km was 15.12 μM, Vmax was 12.8 nmol/min/nmol P450. Inhibitor 8-MOP significantly inhibited the CYP2B6 activity and metabolites p, p’-DDE content significantly decreased. After CYP2B1 was inhibited, the metabolic enzyme activity was significantly decreased and the serum p, p’-DDE, p, p’-DDD product content was lowered. [Conclusion] CYP2B6 can metabolize p, p’-DDT to produce metabolites dominated by p, p’-DDE, and it should be the dominant enzyme of DDTs in the human body. Considering that CYP2B6 is a high mutant metabolic enzyme. There are differences in the expression and activity of CYP2B6, this study can provide a basis for screening of susceptible populations exposed to DDTs and the optimization of risk assessment.