Aerosol Toxicokinetics: A Framework for Unraveling Toxicological Dynamics from Air to the Body

Exposure to atmospheric aerosols threatens human health and is yet to be effectively addressed globally. Aerosol toxicity strongly depends upon components whose chemical profiles and concentrations can constantly evolve throughout atmospheric transformation, inhalation, distribution, metabolism, and excretion. Despite the abundant studies on aerosol components and their toxic effects, the dynamics in component concentrations and related biological effects from air to the body remain unclear. Here, we propose a conceptual toxicokinetic framework to mathematically deduce the bioavailable concentration from the changing bulk concentration of aerosol constituents in the atmosphere. The biological effects of single or multiple components are further predicted via toxicodynamic modeling according to their bioavailable concentrations. Atmospheric concentrations of toxic composition can in turn be regulated by risk-based guidelines, aiming to alleviate <i>in vivo</i> toxic effects. This perspective demonstrates how serial toxicokinetic-toxicodynamic equations bridge the knowledge gap between ambient aerosols and associated toxic effects in human bodies. The prediction from an inhalation perspective also allows connecting with the exposomes from aggregate exposure pathways. We call for the development of the model validity and integrate quantitative adverse outcome pathways to apply for exposure-disease modeling, providing novel insights into air quality policymaking and public health management.