Blood concentrations of per- and polyfluoroalkyl substances are associated with autoimmune-like effects in American alligators from Wilmington, North Carolina

Abstract

Surface and groundwater of the Cape Fear River basin in central and coastal North Carolina is contaminated with high levels of per- and polyfluoroalkyl substances (PFAS). Elevated levels of PFAS have also been found in blood of fish and wildlife from the Cape Fear River, and in the blood of human populations reliant on contaminated well or surface water from the Cape Fear River basin as a source of drinking water. While the public and environmental health impacts of long-term PFAS exposures are poorly understood, elevated blood concentrations of some PFAS are linked with immunotoxicity and increased incidence of some chronic autoimmune diseases in human populations. The goal of this One Environmental Health study was to evaluate PFAS exposure and biomarkers related to immune health in populations of American alligators (Alligator mississippiensis), a protected and predictive sentinel species of adverse effects caused by persistent toxic pollutants. We found that serum PFAS concentrations in alligator populations from the Cape Fear River were increased compared to a reference population of alligators from the adjoining Lumber River basin. The elevated serum PFAS concentrations in the Cape Fear River alligators were associated with increased innate immune activities, and autoimmune-like phenotypes in this population. In addition to evidence of significantly higher double stranded-DNA binding autoantibodies in adult Cape Fear River alligators, our qRT-PCR analysis found remarkably high induction of Interferon-α signature genes implicated in the pathology of human autoimmune disease. We interpret the association of increased PFAS exposure with disrupted immune functions to suggest that PFAS broadly alters immune activities resulting in autoimmune-like pathology in American alligators. This work substantiates and extends evidence from experimental models and human epidemiology studies showing that some PFAS are immune toxicants.

Domestic Dogs and Horses as Sentinels of Per- and Polyfluoroalkyl Substance Exposure and Associated Health Biomarkers in Gray’s Creek North Carolina

“…Since NBP2 was first identified in the Cape Fear River in 2017 it has been consistently detected in humans and animals that reside in and around this river basin. 14,16,17,44 To our knowledge, this is the first study to report PFAS exposure in horses. The relatively high frequency of detection of NBP2 (64.2%) and the higher geometric mean concentration of NBP2 in horses (0.57 ng/mL) compared to those in dogs (0.12 ng/mL) emphasize the utility of these animals as sentinels of contaminant exposure in the natural environment from a point source.…”

“…20 Nevertheless, recent findings from our lab and others have reported PFOS as the PFAS found at the highest concentrations in wildlife and humans that co-utilize the Cape Fear River, potentially demonstrating high degrees of bioaccumulation for this perfluoroalkyl acid and/or decomposition of polyfluoroalkyl compounds into PFOS as a terminal breakdown product. 16,17,21,22,44 Additional studies are needed to determine if these findings are driven by (1) unidentified sources of PFOS exposure, including dietary sources that may retain PFOS (e.g., fish and vegetation), (2) differences in biological half-lives (PFOS > PFOA) in these species, and/or (3) terminal transformation of longer-chain precursors into PFOS that result in the high concentrations detected in serum. 57−59 In contrast to dogs, horses living in the same area had higher concentrations of NBP2 in their serum and unique, albeit limited, detection of HFPO-DA and PFO5DoDA.…”

“…Methods for the preparation of standard curves, mass spectrometry conditions, and quality controls were identical to those used previously. 16,17 Additional details are also contained in supplemental methods (Supporting Information Document 1).…”

“…The PFAS analyzed were chosen based on compounds that were previously detected in the NC Cape Fear River basin and the availability of appropriate authentic standards. ,,, At the time of analysis, analytical standards were available for 33 PFAS of interest (Table S3). Methods for the preparation of standard curves, mass spectrometry conditions, and quality controls were identical to those used previously. , Additional details are also contained in supplemental methods (Supporting Information Document 1).…”

“…For decades, Fayetteville Works, a fluorochemical manufacturing facility located along the border of Cumberland County in central North Carolina (NC; Figure S1), has discharged PFAS into the surrounding environment through vent stack emissions and direct discharge of process wastewater into the Cape Fear River. − As a result, elevated levels of PFAS are present in residential drinking water and blood samples from fish, wildlife, and humans living near the Cape Fear River. − Owing to concerns regarding the persistence and toxicity of long-chain PFAS, US manufacturers participating in the 2010/2015 perfluorooctanoic acid (PFOA) stewardship program, put forth by the Environmental Protection Agency (EPA), report that they no longer produce PFOA and perfluorooctanesulfonic acid (PFOS) . Consequently, the production and use of shorter-chain alternatives, such as the perfluoroalkyl ether acid (PFEA) hexafluoropropylene oxide dimer acid (HFPO-DA), colloquially known as a GenX chemical, has increased. ,, Recent monitoring efforts have detected PFEAs in thousands of private wells in the eastern half of the state, including many in the Gray’s Creek area of southern Cumberland County NC, with concentrations of HFPO-DA exceeding the EPA’s drinking water health advisory limit of 10 parts per trillion (ppt; Table S1; Figure S2).…”