[Progress in the metabolic and biotransformation of polycyclic aromatic hydrocarbons and their derivatives in humans].

Polycyclic aromatic hydrocarbons （PAHs） are organic compounds produced primarily through the incomplete combustion of coal， petroleum， and other carbon-based materials. These compounds are environmentally ubiquitous and have attracted widespread attention because they are significantly biologically toxic and have far-reaching implications for public health and societal wellbeing. Consequently， developing a comprehensive understanding of how PAHs and their derivatives metabolically biotransform in the human body is critical for devising precise preventive strategies and targeted health interventions. PAHs and their derivatives metabolically transform in a complex process involving a broad variety of enzymes and pathways， and are usually divided into three distinct phases. Phase I encompasses oxidative， reductive， and hydrolytic reactions that are primarily catalyzed by cytochrome P450 （CYP） enzymes. These processes produce intermediates such as monohydroxyls， diols， diol-epoxides， and quinones， some of which （e.g.， diol-epoxides） form covalent DNA adducts， thereby contributing to their toxicities. Phase Ⅱ involves conjugation reactions， such as glucuronidation， sulfation， and glutathionylation， which enhance the water solubilities of the metabolites and facilitate their elimination. These detoxified metabolites are actively transported and excreted bile or urine in phase Ⅲ， which effectively minimizes internal PAH exposure and prevents accumulation. Metabolites generated at various stages of PAH metabolism serve as crucial biomarkers for assessing human exposure levels. For example， urinary monohydroxy PAH metabolites （e.g.， 1-hydroxypyrene） have been widely adopted as reliable biomarkers for characterizing PAH exposure. However， owing to their structural diversity， PAHs metabolize via considerably different mechanisms to afford a variety of products， which highlights the need to differentiate individual PAHs and their derivatives in order to precisely assess exposure and evaluate nuanced health risks. Understanding the time-dose-effect relationships of PAH metabolites provides another major PAH-biomonitoring challenge. Investigating these dynamics is essential for revealing the cumulative and long-term health effects associated with exposure to multiple PAHs and their derivatives. Moreover， such studies provide scientific bases for formulating personalized and refined health-protection strategies. For instance， exploring how individual susceptibility， such as genetic polymorphisms in CYP enzymes or conjugation pathways， affects PAH metabolism is expected to significantly improve risk stratification and targeted interventions. PAH exposure is associated with significant health risks because they are associated with a range of diseases， including lung， pancreatic， and gastrointestinal cancers， as well as respiratory and cardiovascular diseases. The pervasive environmental presence of PAHs further complicates exposure scenarios， necessitating the comprehensive monitoring of various populations and environmental contexts. In addition to individual exposure， population-scale studies are expected to inform public health policies and regulatory actions aimed at reducing PAH exposure， particularly in vulnerable populations. This review concisely summarizes the metabolic pathways and product categories associated with four types of PAHs： parent， nitroxylated， oxidized， and alkylated. It emphasizes recent advances in our understanding of parent PAH metabolism in humans， focusing on their implications for exposure characterization， health risk assessment， source tracing， and regulatory decision-making. This paper aims to provide a scientific foundation for the advancement of human biomonitoring efforts and the development of evidence-based public health interventions tailored to reduce the burden of PAH exposure by addressing the complexities of PAH metabolism.