In contrast to the existence of standardized methods to assess metal bioaccessibility via the gastrointestinal route, there are no widely-accepted, established in vitro testing protocols to measure elemental solubility in the human lung. This may be attributed, in part, to the difficulty associated with simulating the lung's complex in vivo conditions. The purpose of this review is two-fold: (1) to determine how the bioaccessibility of metals associated with ambient particulate matter (PM) in the human lung has been assessed in the literature, and (2) examine the suitability and biological relevance of applied methods for the measurement of metal bioaccessibility employed to date. The review revealed that limited attention has been paid to the development and application of biologically-relevant in vitro methods to measure elemental solubility in ambient PM as a proxy for bioaccessibility in the human lung. Few studies (n=14) used synthetic lung fluids to simulate in vivo conditions, with only half extracting samples at a biologically-relevant temperature of 37°C. There was limited evidence suggesting that the use of water is less effective as a leaching agent compared to simulated lung fluids. In sum, this scoping review highlights a critical need to develop standardized methods for the systematic assessment of elemental bioaccessibility via the respiratory route. Priority should be placed on the validation of biologically-relevant methods, including the use of leaching agents and extraction parameters used, which allow for testing to be conducted in a reliable, yet cost efficient, manner.
Keywords: Airborne particulate matter; Bioaccessibility; In vitro methods; Metals; Simulated lung fluids.
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