다환방향족탄화수소의 인체노출과 위해성평가를 위한 약동학적 고려사항

초록

Polycyclic aromatic hydrocarbons (PAHs) are a complex class of environmental contaminants generated during incomplete combustion and thermal decomposition of organic matter. Human exposure occurs through inhalation, ingestion, dermal contact, smoking, occupational settings, and consumption of heat-processed foods. Although environmental concentrations and estimated intake remain essential starting points for exposure assessment, they do not sufficiently describe absorbed dose, metabolite formation, tissue distribution, or biomarker time courses. Pharmacokinetic and toxicokinetic considerations are critical for interpreting human exposure to polycyclic aromatic hydrocarbons, with key determinants including structural heterogeneity, exposure routes, biomonitoring, and absorption, distribution, metabolism, excretion (ADME) characteristics. Low-molecular-weight compounds such as naphthalene are more volatile and require route-specific interpretation, whereas high-molecular-weight compounds such as benzo[a]pyrene are more strongly associated with particle binding, first-pass metabolism, and bioactivation. Urinary hydroxy metabolites, especially 1-hydroxypyrene, are practical biomarkers, but their interpretation depends on sampling time and compound-specific kinetics. Published human studies show rapid absorption and elimination of naphthalene, fluorene, phenanthrene, and pyrene after oral administration, whereas microdosing studies of benzo[a]pyrene demonstrate extensive metabolism and altered kinetics under mixed-exposure conditions. These findings indicate that urinary biomarkers should be interpreted together with compound-specific pharmacokinetics, sampling time, and metabolite formation rather than as simple concentration markers. PBPK modeling can further link external exposure, biomarker levels, absorbed dose, and target-tissue relevant dose through reverse dosimetry and internal dose estimation. Therefore, integrating biomonitoring, pharmacokinetic parameters, and PBPK modeling provides a practical framework for translating environmental PAH exposure into human-relevant risk assessment.

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