Bioaccessibility and Toxicity of Particle-Bound Metals and Polycyclic Aromatic Hydrocarbons: Sources, Respiratory Fate, Mechanisms, and Risk Assessment

Abstract Particulate matter (PM) mass is widely used to estimate health risk, yet particles with similar mass concentrations can produce very different biological effects. Toxicity depends on source, size, atmospheric aging, chemical speciation, and the mixture of compounds carried on particle surfaces. This critical narrative review examines particle-bound metals and polycyclic aromatic hydrocarbons (PAHs), following their pathway from respiratory deposition and bioaccessibility to oxidative stress and toxicity. Metal release varies with element, source, particle size, extraction conditions, and solid-to-liquid ratio, while acidic lysosomal environments often increase dissolution compared with near-neutral extracellular fluids. PAH release is shaped by hydrophobicity, binding to soot, surfactants, proteins, and changes in the respiratory environment during inflammation. Once released, or when particles are taken up by cells, these constituents may contribute to oxidative stress, antioxidant depletion, inflammation, genotoxicity, and vascular injury. Poorly soluble particles can still remain biologically active even when only a small fraction of their chemical content is released. Interactions between metals and organic compounds may be synergistic or antagonistic, further complicating interpretation of complex PM mixtures. Differences in simulated lung fluids, dosimetry, speciation, and biological validation also limit comparisons across studies. We therefore propose a tiered framework integrating PM mass, source, size, speciation, compartment-specific bioaccessibility, oxidative potential, and delivered-dose toxicology. Bioaccessibility should complement, rather than replace, whole-particle testing. Greater consistency and attention to real-world mixtures may improve source prioritization and health-risk interpretation.