Disproportionately Higher Contribution of Endotoxin to PM2.5 Bioactivity than Its Mass Share Highlights the Need to Identify Low-Concentration, High-Potency Components

The contribution of microbial components and their sources to the bioactivity of airborne fine particulate matter (PM_2.5) remains unclear. This study validated the concentration-additive mixture effects of ambient PM_2.5 fractions on in vitro interleukin-8 (IL-8) induction, enabling quantification of the role of endotoxin from Gram-negative bacteria in IL-8 induction by PM_2.5 from contrasting environments. Endotoxin consistently contributed to PM_2.5-induced IL-8 at both the coastal site (0.1-10%) and the urban site (0.1-17%), far exceeding its mass fraction in PM_2.5 (<0.0001%). Among reported components, endotoxin demonstrated the highest toxicity-to-mass contribution ratio (10,000:1-100,000:1) due to its high potency. This suggests that reducing PM_2.5 toxicity may not necessarily require a proportional reduction in its mass. The sources of Gram-negative bacteria shifted from predominantly natural origins at the coastal site (natural-to-anthropogenic ratio of 1.6:1) to increasing anthropogenic contributions at the urban site (natural-to-anthropogenic ratio of 0.7:1). These anthropogenic sources, including the built environment, sewage treatment, and humans, fall outside conventional pollution-intensive categories. These findings highlight the importance of identifying high-potency, low-concentration components and their sources. Targeting such components is critical for cost-effective PM_2.5 abatement strategies and achieving significant public health benefits, especially in regions with low-to-moderate PM_2.5 levels.