Quantitative Identification and Prioritization of Combined Effects of Multiple Endocrine Disrupting Compound Exposure on Oxidative Stress

Limited epidemiological evidence has discussed the synergistic effects of exposure to multiple pollutants and their resultant combined toxicity, such as oxidative stress damage. This study quantitatively identified and prioritized the combined exposure effects of 91 environmental pollutants on oxidative stress, including metals, hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), phthalate esters metabolites (mPAEs), and per-and polyfluoroalkyl substances (PFASs). Results showed the total exposure concentration of metals (899.68µgL-1) was greater than mPAEs (402.00µgL-1), followed by OH-PAHs (25.63µgL-1) and PFASs (10.36µgL-1). Higher levels of metals, mPAEs, and PFASs, both as individual exposure and as pollutant mixture, were significantly associated with the elevated oxidative stress. In terms of contribution weight, mPAEs and metals exposure had the strongest positive impact on oxidative damage. Significant interactive effects between metals and mPAEs, as well as between mPAEs and PFASs, on exposure and oxidative damage were innovatively observed. The benchmark dose estimation values of OH-PAHs increased in 8-hydroxy-2′-deoxyguanosine, 8-dihydroguanine and malondialdehyde levels by 10%, and PFASs increased in o,o′-dityrosine level by 10%, were the lowest, suggesting that OH-PAHs and PFASs could have lower safety margin levels for oxidative damage than other pollutants. This study is the first to provide a synergistic and quantitative comparison of oxidative stress resulting from simultaneous exposure to multiple pollutants.