摘要:Background: From 1980 to 2017, a fluorochemical manufacturing facility discharged wastewater containing poorly understood per- and polyfluoroalkyl substances (PFAS) to the Cape Fear River, the primary drinking water source for Wilmington, North Carolina, residents. Those PFAS included several fluoroethers including HFPO-DA also known as GenX. Little is known about the bioaccumulation potential of these fluoroethers. Objective: We determined levels of fluoroethers and legacy PFAS in serum samples from Wilmington residents. Methods: In November 2017 and May 2018, we enrolled 344 Wilmington residents ≥ 6 years of age into the GenX Exposure Study and collected blood samples. Repeated blood samples were collected from 44 participants 6 months after enrollment. We analyzed serum for 10 fluoroethers and 10 legacy PFAS using liquid chromatography–high-resolution mass spectrometry. Results: Participants’ ages ranged from 6 to 86 y, and they lived in the lower Cape Fear Region for 20 y on average (standard deviation: 16 y). Six fluoroethers were detected in serum; Nafion by-product 2, PFO4DA, and PFO5DoA were detected in > 85 % of participants. PFO3OA and NVHOS were infrequently detected. Hydro-EVE was present in a subset of samples, but we could not quantify it. GenX was not detected above our analytical method reporting limit ( 2 ng / mL ). In participants with repeated samples, the median decrease in fluoroether levels ranged from 28% for PFO5DoA to 65% for PFO4DA in 6 months due to wastewater discharge control. Four legacy PFAS (PFHxS, PFOA, PFOS, PFNA) were detected in most ( ≥ 97 % ) participants; these levels were higher than U.S. national levels for the 2015–2016 National Health and Nutrition Examination Survey. The sum concentration of fluoroethers contributed 24% to participants’ total serum PFAS (median: 25.3 ng / mL ). Conclusion: Poorly understood fluoroethers released into the Cape Fear River by a fluorochemical manufacturing facility were detected in blood samples from Wilmington, North Carolina, residents. Health implications of exposure to these novel PFAS have not been well characterized.