PFAS Exposure Research Articles

Metabolic and phenotypic changes induced by PFAS exposure in two human hepatocyte cell models

PFAS are ubiquitous industrial chemicals with known adverse health effects, particularly on the liver. The liver, being a vital metabolic organ, is susceptible to PFAS-induced metabolic dysregulation, leading to conditions such as hepatotoxicity and metabolic disturbances. In this study, we investigated the phenotypic and metabolic responses of PFAS exposure using two hepatocyte models, HepG2 (male cell line) and HepaRG (female cell line), aiming to define phenotypic alterations, and metabolic disturbances at the metabolite and pathway levels. The PFAS mixture composition was selected based on epidemiological data, covering a broad concentration spectrum observed in diverse human populations. Phenotypic profiling by Cell Painting assay disclosed predominant effects of PFAS exposure on mitochondrial structure and function in both cell models as well as effects on F-actin, Golgi apparatus, and plasma membrane-associated measures. We employed comprehensive metabolic characterization using liquid chromatography combined with high-resolution mass spectrometry (LC-HRMS). We observed dose-dependent changes in the metabolic profiles, particularly in lipid, steroid, amino acid and sugar and carbohydrate metabolism in both cells as well as in cell media, with HepaRG cell line showing a stronger metabolic response. In cells, most of the bile acids, acylcarnitines and free fatty acids showed downregulation, while medium-chain fatty acids and carnosine were upregulated, while the cell media showed different response especially in relation to the bile acids in HepaRG cell media. Importantly, we observed also nonmonotonic response for several phenotypic features and metabolites. On the pathway level, PFAS exposure was also associated with pathways indicating oxidative stress and inflammatory responses. Taken together, our findings on PFAS-induced phenotypic and metabolic disruptions in hepatocytes shed light on potential mechanisms contributing to the broader comprehension of PFAS-related health risks.

Multimedia distribution and release characteristics of emerging PFAS in wastewater treatment plants in Tianjin, China

Legacy and emerging PFAS in the air, wastewater, and sludge from two wastewater treatment plants (WWTPs) in Tianjin were investigated in this study. The semi-quantified nontarget PFAS accounted for up to 99 % of ƩPFAS in the gas phase, and aqueous film-forming foam (AFFF)-related PFAS were predominant in wastewater (up to 2250 ng/L, 79 % of ƩPFAS) and sludge (up to 4690 ng/g, 95 % of ƩPFAS). Furthermore, field-derived air particle-gas, air-wastewater, and wastewater particle-wastewater distribution coefficients of emerging PFAS are characterized, which have rarely been reported. The emerging substitute p-perfluorous nonenoxybenzenesulfonate (OBS) and AFFF-related cationic and zwitterionic PFAS show a stronger tendency to partition into particle phase in air and wastewater than perfluorooctane sulfonic acid (PFOS). The estimated total PFAS emissions from the effluent and sludge of WWTP A were 202 kg/y and 351 kg/y, respectively. While the target PFAS only accounted for 20–33 % of the total emissions, suggesting a significant underestimation of environmental releases of the nontarget PFAS and unknown perfluoroalkyl acid precursors through the wastewater and sludge disposal. Overall, this study highlights the importance of comprehensive monitoring and understanding the behavior of legacy and emerging PFAS in wastewater systems, and fills a critical gap in our understanding of PFAS exposure.

Non-Targeted PFAS Suspect Screening and Quantification of Drinking Water Samples Collected through Community Engaged Research in North Carolina's Cape Fear River Basin.

A community engaged research (CER) approach was used to provide an exposure assessment of poly- and perfluorinated (PFAS) compounds in North Carolina residential drinking water. Working in concert with community partners, who acted as liaisons to local residents, samples were collected by North Carolina residents from three different locations along the Cape Fear River basin: upper, middle, and lower areas of the river. Residents collected either drinking water samples from their homes or recreational water samples from near their residence that were then submitted by the community partners for PFAS analysis. All samples were processed using weak anion exchange (WAX) solid phase extraction and analyzed using a non-targeted suspect screening approach as well as a quantitative approach that included a panel of 45 PFAS analytes, several of which are specific to chemical industries near the collection site locations. The non-targeted approach, which utilized a suspect screening list (obtained from EPA CompTox database) identified several PFAS compounds at a level two confidence rating (Schymanski scale); compounds identified included a fluorinated insecticide, a fluorinated herbicide, a PFAS used in polymer chemistry, and another that is used in battery production. Notably, at several locations, PFOA (39.8 ng/L) and PFOS (205.3 ng/L) were at levels that exceeded the mandatory EPA maximum contaminant level (MCL) of 4 ng/L. Additionally, several sites had detectable levels of PFAS that are unique to a local chemical manufacturer. These findings were communicated back to the community partners who then disseminated this information to the local residents to help empower and aid in making decisions for reducing their PFAS exposure.

Abstract 830: Michigan cancer and research on the environment study (MI-CARES) cohort: Baseline methods and participant characteristics

Abstract Michigan has a long history of adverse environmental exposures, many of which are still ongoing, like the Flint water crisis, extreme air pollution burden, and widespread PFAS exposure. Michigan is also home to a diverse population of Latinx, Black, White, and Middle Eastern/North African (MENA) Americans. Because minority populations are underrepresented in environment and cancer research despite being at greater risk of being exposed to environmental hazards and having worse cancer outcomes, Michigan is uniquely positioned for studying the associations between environmental exposures and cancer risk. In June 2022, the Michigan Cancer and Research on the Environment Study (MI-CARES) began recruitment with a goal of establishing a cohort of over 100,000 Michiganders to examine these associations. Any Michigander aged 18-49 is eligible to enroll in MI-CARES. By focusing on this age range, we will capture exposures during important windows of susceptibility prior to the onset of most cancers.While recruitment is open to all state-wide, efforts are focused on six environmental injustice hotspots, identified using the MiEJScreen tool, a relative summary score capturing pollution burden and population vulnerability: the metro areas of Kalamazoo, Grand Rapids, Flint, Lansing, Detroit, and Bay City-Saginaw.MI-CARES will enroll equal numbers of Black, Latinx, MENA, and White participants. To support participation in diverse communities, study materials are available in Arabic, English, and Spanish. MI-CARES has employed a multifaceted community engagement strategy and is recruiting from these communities directly and with the help of community partners. An incentive of $10 is also provided to participants who successfully complete the questionnaire.To democratize participation, MI-CARES enrollment can be completely remote, but in-person and paper-based enrollment is available. Enrollment includes a baseline questionnaire, consent for data linkage, and annual follow-up surveys. Participants are also asked to provide saliva and blood spot samples via a mailed at-home biospecimen collection kit. Biospecimens will be analyzed for environmental exposures like heavy metals and for intermediate cancer markers including inflammation, cellular aging, immune function, and altered metabolism. Participant data will be linked to neighborhood-level exposure databases, administrative databases like cancer registries and death indices, and to the Michigan Neonatal Biobank. More than 4,000 Michiganders have enrolled in MI-CARES. Data on initial cohort members including environmental exposure history and demographic characteristics will be presented. MI-CARES is part of the Cohorts for Environmental Exposures and Cancer Risk (CEECR) consortium, which is funded by the National Cancer Institute and the National Institute for Environmental Health Sciences. Citation Format: Lilah Khoja, Maxwell Salvatore, Minh Tung Phung, Isabella De Sa, Heatherlun Uphold, Justin Colacino, Alison M. Mondul, Bhramar Mukherjee, Dana Dolinoy, Celeste Leigh Pearce. Michigan cancer and research on the environment study (MI-CARES) cohort: Baseline methods and participant characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 830.

Predictors of Serum Per- and Polyfluoroalkyl Substances Concentrations among U.S. Couples Attending a Fertility Clinic.

Previous studies have examined the predictors of PFAS concentrations among pregnant women and children. However, no study has explored the predictors of preconception PFAS concentrations among couples in the United States. This study included 572 females and 279 males (249 couples) who attended a U.S. fertility clinic between 2005 and 2019. Questionnaire information on demographics, reproductive history, and lifestyles and serum samples quantified for PFAS concentrations were collected at study enrollment. We examined the PFAS distribution and correlation within couples. We used Ridge regressions to predict the serum concentration of each PFAS in females and males using data of (1) socio-demographic and reproductive history, (2) diet, (3) behavioral factors, and (4) all factors included in (1) to (3) after accounting for temporal exposure trends. We used general linear models for univariate association of each factor with the PFAS concentration. We found moderate to high correlations for PFAS concentrations within couples. Among all examined factors, diet explained more of the variation in PFAS concentrations (1-48%), while behavioral factors explained the least (0-4%). Individuals reporting White race, with a higher body mass index, and nulliparous women had higher PFAS concentrations than others. Fish and shellfish consumption was positively associated with PFAS concentrations among both females and males, while intake of beans (females), peas (male), kale (females), and tortilla (both) was inversely associated with PFAS concentrations. Our findings provide important data for identifying sources of couples' PFAS exposure and informing interventions to reduce PFAS exposure in the preconception period.

PFAS alters placental arterial vasculature in term human placentae: A prospective pregnancy cohort study

IntroductionPerfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function. ObjectivesThe objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes. MethodsUsing data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image. ResultsIn both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (β = −0.23, 95% CI: −0.41, −0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (β = −0.19, 95% CI: −0.34, −0.051). There were no reliable differences in effect by fetal sex. DiscussionThe findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks.

PFAS exposure and female fertility in animals.

PFAS exposure and female fertility in animals.

PFAS Modulate Osmotic Signaling Independent of Gravimetric Changes in the Rat Uterus.

Various PFAS have been identified as potential endocrine-disrupting chemicals due to estrogen receptor activation, impacts on puberty timing, or impacts on hormonally sensitive endpoints in fish. This study screened multiple PFAS in the rat uterotrophic assay to determine potential estrogenic effects on the uterus with PFAS exposure. This study also explored PFAS-dependent uterine signaling with an osmotic stress mRNA gene expression array. Briefly, Sprague-Dawley rats (26-39 days old) were ovariectomized, and uterine tissue was allowed to regress for a 3-week period of recovery. Animals were then exposed daily via oral gavage to PFAS for 4 days, and then uterine weight was determined. In contrast to the positive control estrogens, the PFAS tested (4:2, 6:2, and 8:2FTOH; perfluorooctanesulfonamide (PFOSA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), nafion byproduct 2 (NBP2), 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8-diol) and 1H,1H,10H,10H-perfluorodecane-1,10-diol (FC10-diol)) caused no significant changes in the uterine weight. Hormonally active compounds can act as carcinogens, and because earlier rodent work has demonstrated that chronic PFOA exposure is associated with increased risk of uterine cancer, uterine mRNA gene expression was explored with an osmotic stress RT-qPCR array. PFAS exposure significantly upregulated multiple genes across the array, with PFOSA being the compound most similar to the reference estrogens (estradiol benzoate and ethinyl estradiol) in its expression pattern. Also, across all PFAS, pathway analysis revealed that the paxillin pathway, a pathway important in tumor suppressor gene SHP-2 signaling, was significantly upregulated with PFAS exposure. These results demonstrate that in vitro estrogen screens or impacts in fish may show different responses from direct impacts on mammalian uterine weight as assessed with the uterotrophic assay. This study also builds out new mechanisms that may contribute to understanding of carcinogenic changes seen in the uterus after PFAS exposure.

PFASs in Cerebrospinal Fluids and Blood-CSF Barrier Permeability in Patients with Cognitive Impairment.

Attention has been drawn to the associations between PFASs and human cognitive decline. However, knowledge on the occurrence and permeability of PFASs in the brains of patients with cognitive impairment has not been reported. Here, we determined 30 PFASs in paired sera and cerebrospinal fluids (CSFs) from patients with cognitive impairment (n = 41) and controls without cognitive decline (n = 18). We revealed similar serum PFAS levels but different CSF PFAS levels, with lower CSF PFOA (median: 0.125 vs 0.303 ng/mL, p < 0.05), yet higher CSF PFOS (0.100 vs 0.052 ng/mL, p < 0.05) in patients than in controls. Blood-brain transfer rates also showed lower RCSF/Serum values for PFOA and higher RCSF/Serum values for PFOS in patients, implying potential heterogeneous associations with cognitive function. The RCSF/Serum values for C4-C14 perfluoroalkyl carboxylates exhibited a U-shape trend with increasing chain length. Logistic regression analyses demonstrated that CSF PFOS levels were linked to the heightened risk of cognitive impairment [odds ratio: 3.22 (1.18-11.8)] but not for serum PFOS. Toxicity inference results based on the Comparative Toxicogenomics Database suggested that PFOS in CSF may have a greater potential to impair human cognition than other PFASs. Our results contribute to a better understanding of brain PFAS exposure and its potential impact on cognitive function.

Ultrashort pfas: a review of the topic.

Ultrashort perfluoroalkyl substances (UsPFAS), characterized by carbon chain lengths of 2 to 4 atoms, represent a distinct subgroup within the broader PFAS class of chemicals. Despite their lower molecular weight, ultrashort PFAS have gained significant attention due to their widespread presence. This article provides a comprehensive review of the topic. We analyzed 33 articles published between 2017 and 2024 found on Pubmed using "ultrashort PFAS" as keyword. We compared: 1- environmental matrices in which ultrashort PFAS were found, 2- different distribution patterns, 3- degradation pathways, to better understand whether they may resemble longer-chain PFAS, which are known for their bioaccumulation and persistence as "forever chemicals". The occurrence of ultrashort PFAS has been documented in different environmental matrices (including surface waters, waste waters, precipitations, sediments, soils, and also human serum and urine) indicating widespread environmental exposure. Advanced analytical techniques, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS), have enabled the sensitive detection and quantification of these compounds at trace levels. Studies keep finding new ultrashort PFAS and have focused on elucidating their sources and fate pathways to better understand their behavior in natural systems. The toxicity of ultrashort PFAS remains an area of active in-vestigation. While less is known about their health effects, studies suggest potential adverse impacts on organisms and ecosystems. This underscores the importance of continued research to assess the eco-logical consequences of ultrashort PFAS exposure and bring up risk management strategies.

Guided optimization of ToxPi model weights using a Semi-Automated approach

The Toxicological Prioritization Index (ToxPi) is a visual analysis and decision support tool for dimension reduction and visualization of high throughput, multi-dimensional feature data. ToxPi was originally developed for assessing the relative toxicity of multiple chemicals or stressors by synthesizing complex toxicological data to provide a single comprehensive view of the potential health effects. It continues to be used for profiling chemicals and has since been applied to other types of “sample” entities, including geospatial (e.g. county-level Covid-19 risk and sites of historical PFAS exposure) and other profiling applications. For any set of features (data collected on a set of sample entities), ToxPi integrates the data into a set of weighted slices that provide a visual profile and a score metric for comparison. This scoring system is highly dependent on user-provided feature weights, yet users often lack knowledge of how to define these feature weights. Common methods for predicting feature weights are generally unusable due to inappropriate statistical assumptions and lack of global distributional expectation. However, users often have an inherent understanding of expected results for a small subset of samples. For example, in chemical toxicity, prior knowledge can often place subsets of chemicals into categories of low, moderate or high toxicity (reference chemicals). Ordinal regression can be used to predict weights based on these response levels that are applicable to the entire feature set, analogous to using positive and negative controls to contextualize an empirical distribution. We propose a semi-supervised method utilizing ordinal regression to predict a set of feature weights that produces the best fit for the known response (“reference”) data and subsequently fine-tunes the weights via a customized genetic algorithm. We conduct a simulation study to show when this method can improve the results of ordinal regression, allowing for accurate feature weight prediction and sample ranking in scenarios with minimal response data. To ground-truth the guided weight optimization, we test this method on published data to build a ToxPi model for comparison against expert-knowledge-driven weight assignments.

PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice.

Multiple factors can contribute to sub-fecundity, including genetics, lifestyle, and environmental contaminants. PFASs are characterized as "forever chemicals" due to their ubiquitous contamination and their persistence in the environment, wildlife, and humans. Numerous studies have demonstrated that PFAS exposure adversely affects multiple bodily functions, including liver metabolism and gonadal function. It is unclear, however, how the disruption of hepatic fatty acid metabolism affects testicular function. In this study, male mice were administered 0.3 and 3 μg/g body weight of PFOS for 21 days. Our data showed that PFOS exposure caused hepatic steatosis, as evidenced by significant increases in triglyceride levels, expression of ATP-citrate lyase, and fatty acid synthase, as well as fasting insulin levels. PFOS perturbed the expression levels of hepatokines, of which fibroblast growth factor-21 (Fgf-21), leukocyte cell-derived chemotaxin-2 (Lect-2), and retinol-binding protein-4 (Rbp-4) were significantly reduced, whereas angiopoietin-like 4 (Angptl4) was noticeably increased. While Rbp-4 and Fgf-21 are known to contribute to spermatogenesis and testosterone synthesis. In PFOS-exposed groups, testicular ATP, and testosterone decreased significantly with a significant increase in the expression of peroxisome proliferator-activated receptor-coactivator 1α. Mass spectrophotometry imaging revealed the localization of PFOS in testes, along with significant increases in fatty acid metabolites. These included arachidonic acid, dihomo-α-linolenic acid, dihomo-γ-linolenic acid, oxidized ceramide, diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, which are associated with inflammation and post-testicular causes of infertility. This study revealed potential links between PFOS-elicited changes in hepatic metabolism and their impacts on testicular biology. This study provides insights into alternative targets elicited by PFOS that can be used to develop diagnostic and therapeutic strategies for improving testicular dysfunction.

Per- and poly-fluoroalkyl substances in commercial organic eggs via fishmeal in feed

Chicken eggs can be a significant source of human PFAS exposure. A survey of PFAS in commercial eggs from larger farms across Denmark showed the absence or low contents of PFAS in free-range and barn eggs. However, organic eggs from eight farms collected in September 2022 had a similar profile of nine PFASs with a predominance of odd over even carbon length PFCAs. Farm 11–13 e.g. had egg yolk ng/g concentrations of PFOA 0.07 ± 0.02; PFNA 0.37 ± 0.04; PFDA 0.13 ± 0.00; PFUnDA 0.22 ± 0.04; PFDoDA 0.06 ± 0.02; PFTrDA 0.15 ± 0.04; PFTeDA 0.02 ± 0.02; PFHxS 0.10 ± 0.04; PFOS 2.62 ± 0.11. Normalised to PFOS, the relative sum of other PFAS showed no difference between the eight organic egg samples, but significant differences between mean individual PFASs (p = 1.4E-25), reflecting a similar profile. The PFAS found in two fishmeal samples with the same origin as the fishmeal used for the organic feed production, could account for the contents in the eggs via estimated transfer from the feed. Furthermore, the estimated transfer from concentration in feed to concentration in egg increased with the carbon length of the PFCA. Exposure (95th percentile) of ∑4PFAS (PFOA, PFNA, PFHxS, PFOS) solely from consumption of 311 g ∼ 5–6 organic eggs/week was for children 4–9 years 10.4 ng/kg bw, i.e. a significant exceedance of the tolerable weekly intake of 4.4 ng/kg bw established by the European Food Safety Authority. Based on the PFAS exposures from organic egg consumption, the organic egg producers decided voluntarily to cease adding fishmeal to the feed. Since the feed-to-egg half-lives are ≤1 week for PFOA, PFOS, and PFHxS, the removal of fishmeal as a feed ingredient should eliminate PFAS after 1–2 months. This was demonstrated in analyses of ten organic egg samples collected by the authorities without PFAS in eight and with 0.1 and 0.4 ng/g ∑4PFAS in two samples.

Exposure to Perfluoroalkyl Substances and Hyperlipidemia Among Adults: Data From NHANES 2017-2018.

The present study aims to explore the relationship between perfluoroalkyl substances (PFAS) exposure and hyperlipidemia using data from the National Health and Nutrition Examination Survey. A total of 1600 subjects were included in the analysis, and nine kinds of PFAS were measured. Multivariate logistic regression analysis was performed to explore the association between serum PFAS and hyperlipidemia. Compared with the lowest quartile of perfluoromethylheptane sulfonic acid isomers (Sm-PFOS), the percentage change for hyperlipidemia was 57% and 41% in the third and highest quartile of PFOS. The positive association between Sm-PFOS and hyperlipidemia remained significant in population younger than 60 years, and the odds ratio for hyperlipidemia in fourth quartile of Sm-PFOS was 1.81. These findings indicated that serum Sm-PFOS was independently associated with a higher risk for hyperlipidemia. The epidemiological study warrants further study to elucidate the causal relationship between them.

PFAS Exposure in a Community with a Former Paper Mill: Source Apportionment and Relative Exposure via Drinking Water and Diet

PFAS Exposure in a Community with a Former Paper Mill: Source Apportionment and Relative Exposure via Drinking Water and Diet

PFAS exposure and changes in the extracellular microRNA profile in a cohort of adolescents undergoing bariatric surgery

PFAS exposure and changes in the extracellular microRNA profile in a cohort of adolescents undergoing bariatric surgery

Longitudinal effects of PFAS exposure on insulin sensitivity and β-cell function among women with gestational diabetes mellitus history

Longitudinal effects of PFAS exposure on insulin sensitivity and β-cell function among women with gestational diabetes mellitus history

S01-03: PFAS exposure among European teenagers included in the HBM4EU-Aligned studies and its relationship with reproductive hormone and Kisspeptin levels

S01-03: PFAS exposure among European teenagers included in the HBM4EU-Aligned studies and its relationship with reproductive hormone and Kisspeptin levels

PFAS and Phthalate/DINCH Exposure in Association with Age at Menarche in Teenagers of the HBM4EU Aligned Studies.

Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent. We studied the association between PFAS and phthalate/DINCH exposure and age at menarche using data of 514 teenagers (12 to 18 years) from four aligned studies of the Human Biomonitoring for Europe initiative (HBM4EU): Riksmaten Adolescents 2016-2017 (Sweden), PCB cohort (follow-up; Slovakia), GerES V-sub (Germany), and FLEHS IV (Belgium). PFAS concentrations were measured in blood, and phthalate/DINCH concentrations in urine. We assessed the role of each individual pollutant within the context of the others, by using different multi-pollutant approaches, adjusting for age, age- and sex-standardized body mass index z-score and household educational level. Exposure to di(2-ethylhexyl) phthalate (DEHP), especially mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), was associated with an earlier age at menarche, with estimates per interquartile fold change in 5OH-MEHP ranging from -0.34 to -0.12 years in the different models. Findings from this study indicated associations between age at menarche and some specific EDCs at concentrations detected in the general European population, but due to the study design (menarche onset preceded the chemical measurements), caution is needed in the interpretation of causality.

Associations between PFAS concentrations and the oxidative status in a free-living songbird (Parus major) near a fluorochemical facility

For the past 7 decades, PFAS have been used in many different products and applications, which has led to a widespread contamination of these compounds. Nevertheless at present, little is known about the effects of these compounds on avian wildlife. Therefore, this study investigated associations between PFAS concentrations in the plasma and the oxidative status (i.e. non-enzymatic antioxidants and biomarkers of oxidative stress) in great tits at two sites near a fluorochemical manufacturing facility. Different PFAS were detected in the blood plasma with a mean ΣPFAS of 16062 pg/μL at the site closest to the facility. The PFAS profile in the plasma consisted mainly of PFOS, PFOA, PFDA and PFDoDA, where concentrations were higher for these compounds at the site closest to the plant. Our results show a clear link between PFAS and the antioxidant status of the birds; total antioxidant capacity and peroxidase activity were higher near the plant site, while the glutaredoxin activity was higher further away. Additionally, positive associations were found between PFDoDA and glutathione-S-transferase activity, between PFOS and glutathione-S-transferase activity, between PFDA and peroxidase activity, and between PFOS and peroxidase activity. Lastly, a negative association was found between plasma PFDA concentrations and the total polyphenol content. Interestingly, malondialdehyde levels did not differ between sites, suggesting lipid peroxidation was not affected. Although our results suggest that great tits with elevated PFAS concentrations did not suffer oxidative damage, the antioxidant defence responses were significantly triggered by PFAS exposure. This implies that the great tits have managed to defend themselves against the possible oxidative damage coming from PFAS contamination, although the upregulated antioxidant defences may have fitness costs. Further, experiments are needed to investigate the specific mechanisms by which PFAS induce oxidative stress in avian species.