A Systematic Review of Environmentally Persistent Free Radical (EPFR) Formation, Characteristics, and Health Effects: Are There Sufficient Data for Risk Assessment?

Environmentally persistent free radicals (EPFRs) are stable free radicals formed on particulate matter (PM) through processes such as combustion and pyrolysis. These free radicals are generated on transition metal oxide surfaces in the presence of aromatic precursors. Exposure to EPFRs occurs primarily via inhalation of PM deriving from combustion, traffic, industrial activities, and both indoor and outdoor burning. Other environmental factors that might generate EPFRs are radon, electronic and tobacco cigarettes. EPFRs exhibit unexpectedly long half-lives, ranging from several weeks to, in some cases, several years. EPFRs may be carbon-centered, oxygen-centered or mixed, identified by g-values exhibited in electron paramagnetic resonance analysis. The radicals undergo redox cycling within aqueous solutions and in biological tissues/fluids triggering production of reactive oxygen species (ROS), comprised primarily of hydroxyl, superoxide, and peroxyl radicals. The stability of EPFRs, their association with PM2.5, and their ability to generate ROS may pose significant concerns for human health. To determine whether there are sufficient data for risk assessment, recent advances were examined in the following important aspects of EPFR research: (1) atmospheric chemistry, (2) human exposures, (3) animal toxicity, and (4) epidemiology. Our review found insufficient epidemiological and exposure studies; however, toxicological data in animals suggested that EPFR inhalation contributes to cardiovascular, respiratory, and metabolic diseases. Although EPFRs are not currently surveyed by a regulatory monitoring system, data indicate their widespread presence in the environment and their potential to initiate/exacerbate diseases.