Screening Novel Per- and Polyfluoroalkyl Substances in Human Blood Based on Nontarget Analysis and Underestimated Potential Health Risks.

Nontarget analysis has gained prominence in screening novel perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the environment, yet remaining limited in human biological matrices. In this study, 155 whole blood samples were collected from the general population in Shijiazhuang City, China. By nontarget analysis, 31 legacy and novel PFASs were assigned with the confidence level of 3 or above. For the first time, 11 PFASs were identified in human blood, including C1 and C3 perfluoroalkyl sulfonic acids (PFSAs), C4 ether PFSA, C8 ether perfluoroalkyl carboxylic acid (ether PFCA), C4-5 unsaturated perfluoroalkyl alcohols, C9-10 carboxylic acid-perfluoroalkyl sulfonamides (CA-PFSMs), and C1 perfluoroalkyl sulfonamide. It is surprising that the targeted PFASs were the highest in the suburban population which was impacted by industrial emission, while the novel PFASs identified by nontarget analysis, such as C1 PFSA and C9-11 CA-PFSMs, were the highest in the rural population who often drank contaminated groundwater. Combining the toxicity prediction results of the bioaccumulation potential, lethality to rats, and binding affinity to target proteins, C3 PFSA, C4 and C7 ether PFSAs, and C9-11 CA-PFSMs exhibit great health risks. These findings emphasize the necessity of broadening nontarget analysis in assessing the PFAS exposure risks, particularly in rural populations.