Bioaccessibilities of metal(loid)s and organic contaminants in particulates measured in simulated human lung fluids: A critical review

Particle-bound pollutants can pose a health risk to humans. Inhalation exposure evaluated by total contaminant concentrations significantly overestimates the potential risk. To assess the risk more accurately, bioavailability, which is the fraction that enters into the systemic circulation, should be considered. Researchers have replaced bioavailability by bioaccessibility due to the rapid and cost-efficient measurement for the latter, especially for assessment by oral ingestion. However, contaminants in particulates have different behavior when inhaled than when orally ingested. Some of the contaminants are exhaled along with exhalation, and others are deposited in the lung with the particulates. In addition, a fraction of the contaminants is released into the lung fluid and absorbed by the lung, and another fraction enters systemic circulation under the action of cell phagocytosis on particulates. Even if the release fraction, i.e., release bioaccessibility, is considered, the measurement faces many challenges. The present study highlights the factors influencing release bioaccessibility and the incorporation of inhalation bioaccessibility into the risk assessment of inhaled contaminants. Currently, there are three types of extraction techniques for simulated human lung fluids, including simple chemical solutions, sequential extraction techniques, and physiologically based techniques. The last technique generally uses three kinds of solution: Gamble’s solution, Hatch’s solution, and artificial lysosomal fluid, which are the most widely used physiologically based simulated human lung fluids. External factors such as simulated lung fluid composition, pH, extraction time, and sorption sinks can affect release bioaccessibility, whereas particle size and contaminant properties are important internal factors. Overall, release bioaccessibility is less used than bioaccessibility considering the deposition fraction when assessing the risk of contaminants in inhaled particulates. The release bioaccessibility measurement poses two main challenges: developing a unified, accurate, stable, simple, and systematic biologically based method, and validating the method through in-vivo assays.