A groundbreaking study has revealed alarmingly high levels of ultrashort-chain per- and polyfluoroalkyl substances (PFAS) in the blood of residents from Wilmington, North Carolina, dating from 2010 through 2016. Traditionally, public attention had been focused primarily on longer-chain PFAS compounds like GenX, a chemical historically linked to contamination of the Cape Fear River Basin. However, this new research draws crucial attention to lesser-studied ultrashort-chain PFAS, particularly perfluoromethoxyacetic acid (PFMOAA) and trifluoroacetic acid (TFA), which were found at unexpectedly high concentrations in nearly every blood sample analyzed.
PFAS are a large class of synthetic chemicals widely used for their water- and stain-resistant properties but are notoriously persistent in the environment and human body. Past assumptions suggested ultrashort-chain PFAS do not bioaccumulate due to their small molecular size and unique chemical structures. Moreover, these chemicals eluded detection because until recently, analytical techniques capable of reliably identifying them in human blood were lacking. Advances in technology now enable researchers to monitor these elusive contaminants with unprecedented precision.
Detlef Knappe, a professor specializing in environmental engineering at North Carolina State University and co-corresponding author of the study, emphasizes that the development of these new targeted analytical methods allowed for the discovery that ultrashort-chain PFAS dominate environmental and biological samples, including human serum. Given Wilmington’s extended exposure history due to upstream industrial pollution from the Fayetteville Works chemical plant, the team revisited archived blood and water specimens for deeper investigation.
Starting in 1980, the Fayetteville Works facility had continuously discharged PFAS compounds into the Cape Fear River, a vital drinking water source for Wilmington residents. Public concern escalated following a 2016 joint study by NC State and the U.S. Environmental Protection Agency, which documented elevated GenX levels in local water supplies. Regulations enacted in 2017 mandated stricter control measures at the Fayetteville Works plant, but chronic exposure had already left a legacy embedded in the community’s biological profiles.
This latest inquiry entailed an extensive examination of 56 individual PFAS compounds within two key sets of samples: drinking water collected from the Cape Fear River in 2017, and 119 anonymized blood serum samples from adults residing around Wilmington, spanning collection years 2010 to 2016. Remarkably, 34 of these PFAS were detectable in at least one serum specimen, with only five chemicals constituting a staggering 85% of the total PFAS burden.
Leading the concentration ranks, PFMOAA accounted for a median concentration of 42 nanograms per milliliter (ng/mL), making up nearly half of the summed PFAS load in blood. TFA followed with 17 ng/mL, succeeded by historically recognized PFOS and PFOA at 14 ng/mL and 6.2 ng/mL respectively, and the short-chain PFPrA at 5.4 ng/mL. Correspondingly, the water samples exhibited overwhelming dominance of TFA which represented 70% of total quantified PFAS at 110,000 nanograms per liter (ng/L), while PFMOAA levels reached 38,000 ng/L.
The concentrations recorded in this study present an unsettling scenario. European drinking water guidelines suggest a safety threshold for TFA at 2,200 ng/L, yet the sample from the Cape Fear River recorded levels exceeding fiftyfold of this benchmark. These data offer a potent retrospective snapshot of contaminant exposure prior to the widespread awareness and regulatory interventions initiated in the mid-2010s.
Jane Hoppin, professor of biological sciences and principal investigator in the GenX Exposure Study, underscores the pivotal nature of these findings. Contrary to previous assumptions that short-chain PFAS carry minimal bioaccumulation risk, the data clearly demonstrate their pervasive presence and high internal concentrations among a general population. This upends conventional toxicological perspectives and underscores the urgency for intensive research into health effects associated with PFMOAA, TFA, and related ultrashort-chain PFAS chemicals.
Furthermore, the current scientific understanding of PFAS toxicity remains inadequate, especially concerning these newly recognized ultrashort-chain compounds. Common toxicological endpoints for longer-chain PFAS often involve liver damage and immunotoxicity, but such foundational knowledge remains nascent for PFMOAA and TFA. This knowledge gap hampers risk assessment and complicates public health response strategies.
The study also produced critical insights on the bioaccumulative behavior of these compounds. The relationship between PFAS chain length and bioaccumulation was reaffirmed, with longer chain lengths and sulfonic acid functional groups exhibiting higher persistence in human serum. Nevertheless, the findings highlight that even ultrashort-chain PFAS, despite their lower expected bioaccumulation potential, reach substantial systemic concentrations driven largely by their extraordinarily high environmental prevalence and exposure levels.
Looking ahead, researchers plan to extend their analytical efforts by incorporating cohorts from the ongoing GenX Exposure Study. This will enable temporal comparisons and facilitate characterization of the pharmacokinetics and toxicodynamics of ultrashort-chain PFAS in exposed populations. Understanding how these compounds persist, accumulate, and possibly impact human physiology over longer timescales remains a critical priority.
In conclusion, this comprehensive investigation challenges entrenched dogma regarding the environmental and human health implications of ultrashort-chain PFAS. The Wilmington case study serves as a pivotal example of how historical industrial discharges, coupled with emerging analytical capabilities, unveil previously hidden dimensions of chemical exposure risk. Its revelations necessitate reconsideration of regulatory frameworks and reinforce the imperative for in-depth toxicological evaluations of all PFAS subclasses, not solely the traditionally studied long-chain variants.
This study was published in the esteemed journal Environmental Science & Technology and was supported by major research grants from the National Institute of Environmental Health Sciences and NC State’s Center for Human Health and the Environment (CHHE). The collaboration also included researchers from the University of North Carolina at Chapel Hill, reflecting an interdisciplinary approach essential for tackling complex environmental health challenges.
Subject of Research: Human tissue samples
Article Title: Historical Blood Serum Samples from Wilmington, North Carolina: The Importance of Ultrashort-Chain Per- and Polyfluoroalkyl Substances
News Publication Date: 27-Oct-2025
Web References: DOI 10.1021/acs.est.5c08146
Keywords
Ultrashort-chain PFAS, perfluoromethoxyacetic acid, trifluoroacetic acid, environmental contamination, bioaccumulation, Cape Fear River, Wilmington North Carolina, PFAS exposure, human serum, toxicology, GenX, drinking water quality
Tags: advancements in PFAS analytical techniquesbioaccumulation concerns of ultrashort-chain PFASCape Fear River contamination historyemerging contaminants in human blood analysisenvironmental engineering research on PFASperfluoromethoxyacetic acid concentrationsPFAS health impacts in North Carolinapublic health implications of PFAS exposuresynthetic chemicals environmental persistencetrifluoroacetic acid detectionultrashort-chain PFAS in Wilmington blood samplesWilmington residents exposure study
