Exposure to per- and polyfluoroalkyl substance (PFAS) mixtures increases papillary thyroid cancer risk and clinicopathological aggressiveness: Findings from a case-control study and risk assessment.

Environmental exposure to mixtures of per- and polyfluoroalkyl substances in Northeast China: exploring links to nodular goiter and papillary thyroid carcinoma

Prenatal exposure to per- and polyfluoroalkyl substances and maternal and neonatal thyroid function in the Project Viva Cohort: A mixtures approach

Exposure to per and poly-fluoroalkyl substances (PFAS) is suggested to interfere with the central nervous system that may affect mental health. Studies on the relationships between exposure to PFAS mixtures and anxiety in humans are rare. This study aimed to evaluate the associations between single and combined exposure to PFAS and anxiety among adults. Data were extracted from the National Health and Nutrition Examination Survey (NHANES, 2007-2012). Six serum PFAS concentrations were accessed including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), PFOS (perfluorooctanesulfonic acid), PFHxS (perfluorohexane sulfonate), PFDA (perfluorodecanoic acid), Me-PFOSA-AcOH (2-(N-methylperfluorooctanesulfonamide) acetic acid). The anxiety state was defined through the questionnaire responses of the participants. Weighted logistics regression was used to calculate their odds ratio (OR) and corresponding confidence interval (95% CI) that assessed the relationship between PFAS exposure and anxiety. Moreover, Two different statistical methods including quantile-based g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were employed to investigate the overall effects of PFAS mixtures on anxiety. The effects of specific PFAS exposure on anxiety varied by sex. In male participants, one-unit increase in PFDA (OR = 0.62; 95%CI: 0.44, 0.88), PFOA (OR = 0.60; 95%CI: 0.41, 0.87), PFNA (OR = 0.68; 95%CI: 0.46, 0.96) concentrations were inversely linked to anxiety. In female participants, a one-unit increase in PFOA (OR = 1.50; 95%CI: 1.05, 2.14) concentration was associated with anxiety. Analysis of Qgcomp demonstrated that PFAS mixtures were negatively associated with anxiety in males (OR = 0.85; 95%CI: 0.74, 0.99), and were positively associated with anxiety in females(OR = 1.16; 95%CI: 1.01, 1.33). Analysis of BKMR suggested that PFAS mixtures were negatively associated with anxiety in the males, while its associations with anxiety were positive in the females. Although a growing number of studies have focused on the relationship between PFAS and anxiety, most have been performed based on animal observations rather than human populations, and the combined effects of PFAS mixtures on anxiety have not been evaluated. To address these gaps, this study first explored the associations between individual PFAS and PFAS mixture exposures and anxiety among US adults. Using data from the National Health and Nutrition Examination Survey, we demonstrated that co-exposure to a mixture of PFAS was negatively associated with anxiety in males, and its association was contrary in females.

Association between maternal exposure to per- and polyfluoroalkyl substances and serum markers of liver function during pregnancy in China: A mixture-based approach

Invited Perspective: Challenges in Evaluating the Effect of Per- and Polyfluoroalkyl Substance Mixtures on Polycystic Ovarian Syndrome

Effects of gestational exposure to individual and mixed PFASs on maternal liver function: evidence from the Wuxi Birth Cohort, animal studies, and toxicogenomic analyses.

Vol. 128, No. 4 Science SelectionOpen AccessReduced Bone Mineral Density in Children: Another Potential Health Effect of PFASis accompanied byPer- and Polyfluoroalkyl Substance Plasma Concentrations and Bone Mineral Density in Midchildhood: A Cross-Sectional Study (Project Viva, United States) Charles W. Schmidt Charles W. Schmidt Search for more papers by this author Published:20 April 2020CID: 044002https://doi.org/10.1289/EHP6519View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack CitationsCopy LTI LinkHTMLPDF ShareShare onFacebookTwitterLinked InRedditEmail AbstractPer- and polyfluoroalkyl substances (PFAS) are among the most stable industrial compounds ever created.1,2 Used for decades to make nonstick cookware, stain-resistant fabrics, firefighting foam, and other products, they persist indefinitely in the environment and accumulate in the bodies of exposed people.3 A study in adults associated higher PFAS levels in blood with lower bone mineral density, which is a risk factor for osteoporosis.4 Now a study in Environmental Health Perspectives provides new evidence associating the chemicals with lower bone mineral density in children, too.5Bone mass accumulates rapidly during childhood and peaks when individuals reach their late teens and early 20s.6 Therefore, “identifying environmental factors with an influence on bone health during childhood and adolescence can inform preventive interventions with potentially large impacts on fracture risk in later life,” says senior author Abby Fleisch, a pediatric endocrinologist at the Maine Medical Center Research Institute in Portland.Peak bone mineral density in youth strongly predicts an individual’s susceptibility to osteoporosis later in life.8 If evidence bears out that PFAS affects bone mineral density, childhood exposures could have long-term implications for bone health. Image: © iStockphoto/nkbimages.For this study, Fleisch’s team reviewed data from children participating in a long-term study of mothers and their children called Project Viva.7 Sponsored in part by Harvard Medical School, Project Viva recruited just over 2,000 pregnant women between 1999 and 2002 and is still following the mother–child pairs today. Fleisch and her colleagues focused specifically on a subset of 576 children who had undergone bone density scans and provided blood plasma samples for chemical analysis when they were between 6 and 10 years of age. The researchers narrowed their analysis to the six most commonly detected PFAS: summed isomers of perfluorooctanoic acid (PFOA), summed isomers of perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid, N-methyl perfluorooctane sulfonamidoacetic acid, and perfluorononanoic acid. They expressed bone mineral density measures as z-scores normalized for age, sex, race, and height.To generate their results, the authors used linear regression models to see whether lower z-scores (indicating lower bone mineral density) were associated with higher plasma concentrations of individual PFASs. In addition, they used a method called weighted quantile sum (WQS) regression to examine the association of z-scores with the PFAS mixture as a whole.According to the analysis, higher concentrations of each individual PFAS were associated with lower z-scores, with the strongest associations estimated for PFOA, PFOS, and PFDA. A similar association was noted for the PFAS mixture. Specifically, every incremental increase in the WQS index was associated with a corresponding reduction in the z-score for bone mineral density.Most of the children came from relatively high socioeconomic backgrounds and had college-educated mothers. Fleisch acknowledges that could limit the generalizability of the findings to the broader population. She points out that wealthier families may be “more prone to use things that have PFAS, such as carpets and furniture with stain-repellant properties.”Naila Khalil, an associate professor at Wright State University who was not involved in the study, notes, “Researchers tend to focus more on soft-tissue and immune impacts from PFAS exposure. Bone is harder to study, especially in growing children. That makes this paper a robust addition to the limited research on PFAS and its impacts on skeletal health.”Antti Koskela, a physician and researcher who specializes in bone development at the University of Oulu, Finland, points to several strengths of the study. Koskela, who also was not involved in the study, specifically cites the large number of participants, the assessment of a complex PFAS mixture on bone health, and the use of total body dual-energy X-ray absorptiometry for measuring bone density, which is considered the gold standard method. “The data confirm earlier findings and underline concerns about PFAS exposure in children,” he says. “The concern [about potential bone effects] is not just for adults anymore.”Charles W. Schmidt, MS, an award-winning science writer from Portland, ME, writes for Scientific American, Science, Undark, various Nature publications, and many other magazines, research journals, and websites.

<p dir="ltr">Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals, abundantly produced and with a wide range of applications. The partial or full fluorination of alkyl substances with varying functional groups, leads to physicochemical properties that are mainly characterised by persistence and amphiphilicity. While these properties are highly valuable for industrial- and consumer products, they pose major challenges in environmental pollution and health implications. Especially influences on the lipid metabolism have been frequently connected to PFAS exposures, yet lack deeper mechanistic understanding, and were, hence, the main investigated experimental subject of this thesis.</p><p dir="ltr">Regulatory efforts for PFAS have been made in the past and are currently underway. A harmonised approach for the assessment of human health effects, following PFAS exposure is, however, still needed. Dose-response assessment, through benchmark dose (BMD) modelling is the state of the science for hazard characterisation for risk assessment purposes. Specifically, the selection of a critical effect size (CES) - a threshold for adversity - of the assessed effect (response), is important in this context.</p><p dir="ltr">This thesis set out to tackle the outlined challenges in toxicological assessments of PFAS in three main approaches.</p><p dir="ltr">1) Testing contrasting ways to select the CESs in different BMD modelling approaches and assess the outcome metrics for select PFAS case-studies (Study I).</p><p dir="ltr">2) Utilise human cell models to gain insights into PFAS-effects on the human lipid metabolism. This was done by investigating PFAS (single and mixture) exposures and PPARa receptor activation, lipid metabolism-related gene expression and lipid accumulation in Study III. Further, PFAS (single) exposure was investigated with regards to affecting hepatocyte lipidomic profiles in Study II.</p><p dir="ltr">3) Assessing the meaningfulness of comparative relative potency factors (RPFs) for PFAS, through characterisation of RPFs, based on the endpoints in Study III.</p><p dir="ltr">The findings of Study I reveal that the CES choice alters the results of a dose- response assessment significantly for both, frequentist and Bayesian BMD modelling. Further, it became apparent that for the selected case-studies, the Bayesian BMD modelling - paired with flexible, effect-specific CES selection - led to more stable and biologically relevant results, supporting their use in regulatory decision-making.</p><p dir="ltr">Study II unveiled wide-range influences of PFAS exposures on the intracellular (hepatocyte) lipid profile. Legacy PFAS (e.g., PFOS and PFOA), as well as substitute PFAS (e.g., HFPO-DA and ADONA), were shown to have lipid profile-altering properties, with PFOS and PFOA having displayed the largest effects.</p><p dir="ltr">The cell-based assays in Study III confirmed PFAS influences in multiple mechanistic steps of the lipid metabolism. This further underscores the body of evidence for the investigated PFAS and PFAS mixtures to be involved in alterations of important lipid metabolic pathways with likely relevance to cardiovascular diseases and other metabolic conditions. With regards to their relative potencies, PFAS appeared to be endpoint-specific, with no unambiguous pattern of potency.</p><p dir="ltr">This thesis offers an assessment of the BMD methodology in chemical hazard characterisation within the context of assessing the risks from PFAS. Further, multi-endpoint assessment and exposures to single PFAS and PFAS mixtures of human relevance, highlighted the importance of the lipid metabolism as a major target system for PFAS toxicity. The use of RPFs to compare PFAS effects in an endpoint-specific manner, however, needs to be further investigated and a universal approach across endpoints appears to be very challenging.</p><h3>List of scientific papers</h3><p dir="ltr">I. BRUNKEN, L., Vieira Silva, A., & Öberg, M. (2025). Selection of the critical effect size alters hazard characterization - a retrospective analysis of key studies used for risk assessments of PFAS. Frontiers in Toxicology. 7. <a href="https://doi.org/10.3389/ftox.2025.1525089" rel="noreferrer" target="_blank">https://doi.org/10.3389/ftox.2025.1525089</a></p><p dir="ltr">II. Kashobwe, L.#, Sadrabadi, F.#, BRUNKEN, L.#, Coelho, A. C. M. F., Sandanger, T. M., Braeuning, A., Buhrke, T., Öberg, M., Hamers, T., & Leonards, P. E. G. (2024). Legacy and alternative per- and polyfluoroalkyl substances (PFAS) alter the lipid profile of HepaRG cells. Toxicology. 506, 153862. # Equally contributed. <a href="https://doi.org/10.1016/j.tox.2024.153862" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.tox.2024.153862</a></p><p dir="ltr">III. BRUNKEN, L., Vieira Silva, A., & Öberg, M. Relative Potency of PFAS in Human Cell Models: Linking PPARa Activation, Gene Regulation, and Lipid Accumulation. [Manuscript]</p>

<p dir="ltr">Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals, abundantly produced and with a wide range of applications. The partial or full fluorination of alkyl substances with varying functional groups, leads to physicochemical properties that are mainly characterised by persistence and amphiphilicity. While these properties are highly valuable for industrial- and consumer products, they pose major challenges in environmental pollution and health implications. Especially influences on the lipid metabolism have been frequently connected to PFAS exposures, yet lack deeper mechanistic understanding, and were, hence, the main investigated experimental subject of this thesis.</p><p dir="ltr">Regulatory efforts for PFAS have been made in the past and are currently underway. A harmonised approach for the assessment of human health effects, following PFAS exposure is, however, still needed. Dose-response assessment, through benchmark dose (BMD) modelling is the state of the science for hazard characterisation for risk assessment purposes. Specifically, the selection of a critical effect size (CES) - a threshold for adversity - of the assessed effect (response), is important in this context.</p><p dir="ltr">This thesis set out to tackle the outlined challenges in toxicological assessments of PFAS in three main approaches.</p><p dir="ltr">1) Testing contrasting ways to select the CESs in different BMD modelling approaches and assess the outcome metrics for select PFAS case-studies (Study I).</p><p dir="ltr">2) Utilise human cell models to gain insights into PFAS-effects on the human lipid metabolism. This was done by investigating PFAS (single and mixture) exposures and PPARa receptor activation, lipid metabolism-related gene expression and lipid accumulation in Study III. Further, PFAS (single) exposure was investigated with regards to affecting hepatocyte lipidomic profiles in Study II.</p><p dir="ltr">3) Assessing the meaningfulness of comparative relative potency factors (RPFs) for PFAS, through characterisation of RPFs, based on the endpoints in Study III.</p><p dir="ltr">The findings of Study I reveal that the CES choice alters the results of a dose- response assessment significantly for both, frequentist and Bayesian BMD modelling. Further, it became apparent that for the selected case-studies, the Bayesian BMD modelling - paired with flexible, effect-specific CES selection - led to more stable and biologically relevant results, supporting their use in regulatory decision-making.</p><p dir="ltr">Study II unveiled wide-range influences of PFAS exposures on the intracellular (hepatocyte) lipid profile. Legacy PFAS (e.g., PFOS and PFOA), as well as substitute PFAS (e.g., HFPO-DA and ADONA), were shown to have lipid profile-altering properties, with PFOS and PFOA having displayed the largest effects.</p><p dir="ltr">The cell-based assays in Study III confirmed PFAS influences in multiple mechanistic steps of the lipid metabolism. This further underscores the body of evidence for the investigated PFAS and PFAS mixtures to be involved in alterations of important lipid metabolic pathways with likely relevance to cardiovascular diseases and other metabolic conditions. With regards to their relative potencies, PFAS appeared to be endpoint-specific, with no unambiguous pattern of potency.</p><p dir="ltr">This thesis offers an assessment of the BMD methodology in chemical hazard characterisation within the context of assessing the risks from PFAS. Further, multi-endpoint assessment and exposures to single PFAS and PFAS mixtures of human relevance, highlighted the importance of the lipid metabolism as a major target system for PFAS toxicity. The use of RPFs to compare PFAS effects in an endpoint-specific manner, however, needs to be further investigated and a universal approach across endpoints appears to be very challenging.</p><h3>List of scientific papers</h3><p dir="ltr">I. BRUNKEN, L., Vieira Silva, A., & Öberg, M. (2025). Selection of the critical effect size alters hazard characterization - a retrospective analysis of key studies used for risk assessments of PFAS. Frontiers in Toxicology. 7. <a href="https://doi.org/10.3389/ftox.2025.1525089" rel="noreferrer" target="_blank">https://doi.org/10.3389/ftox.2025.1525089</a></p><p dir="ltr">II. Kashobwe, L.#, Sadrabadi, F.#, BRUNKEN, L.#, Coelho, A. C. M. F., Sandanger, T. M., Braeuning, A., Buhrke, T., Öberg, M., Hamers, T., & Leonards, P. E. G. (2024). Legacy and alternative per- and polyfluoroalkyl substances (PFAS) alter the lipid profile of HepaRG cells. Toxicology. 506, 153862. # Equally contributed. <a href="https://doi.org/10.1016/j.tox.2024.153862" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.tox.2024.153862</a></p><p dir="ltr">III. BRUNKEN, L., Vieira Silva, A., & Öberg, M. Relative Potency of PFAS in Human Cell Models: Linking PPARa Activation, Gene Regulation, and Lipid Accumulation. [Manuscript]</p>

The association between prenatal per-and polyfluoroalkyl substance levels and Kawasaki disease among children of up to 4 years of age: A prospective birth cohort of the Japan Environment and Children’s study

BackgroundPrevious research indicates that per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism and neurological function via endocrine pathway interference and neuroinflammation. These effects may impair melatonin secretion and disrupt circadian rhythm regulation, suggesting potential links to sleep health. However, the impact of PFAS exposure on adolescent sleep remains unclear. This study examines the associations between PFAS exposure and sleep health indicators in U.S. adolescents.MethodsData from 838 adolescents who participated in the 2005–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed to investigate the association between PFAS exposure and physician-diagnosed sleep disorders. Eight PFAS compounds were identified. Multivariate logistic regression models, restricted cubic spline (RCS) curves, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were used to assess single, linear, and combined effects on adolescent sleep disorders.ResultsNegative associations were observed between adolescent sleep disorders and three PFAS compounds, specifically perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorononanoic acid (PFNA). RCS analysis revealed a significant linear relationship (P for non-linear > 0.05). The BKMR and WQS models demonstrated a combined effect of PFAS exposure on sleep disorders, with PFOS demonstrating the most substantial contribution (effect size: 0.91). The stratified analysis revealed that PFOS exposure had a greater impact on females [odds ratio (OR): 0.54, 95% confidence interval (CI): 0.33–0.87] than males (OR: 0.50, 95% CI: 0.24–1.01), suggesting sex-specific differences in vulnerability.ConclusionsOur findings indicate a negative correlation between specific PFAS and specific sleep disorders in adolescents, with PFOS being the dominant effect component in the PFAS mixture and stronger effects observed in females. However, due to the cross-sectional nature of the study, a causal relationship cannot be established. These results highlight the potential public health impact of PFAS exposure and the need to further investigate the underlying mechanisms and causal pathways in future longitudinal or experimental studies.

Vol. 129, No. 12 Science SelectionOpen AccessA Measure of Strength: Developmental PFAS Exposures and Bone Mineral Content in Adolescenceis accompanied byAssociations of Maternal Serum Perfluoroalkyl Substances Concentrations with Early Adolescent Bone Mineral Content and Density: The Health Outcomes and Measures of the Environment (HOME) Study Charles W. Schmidt Charles W. Schmidt Search for more papers by this author Published:17 December 2021CID: 124002https://doi.org/10.1289/EHP10551AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail AbstractThe amount of bone mass that accumulates during early childhood and adolescence is a significant factor governing skeletal strength and the risk of osteoporosis in older adults.1,2 Growing evidence suggests developing bone may be damaged by exposures to per- and polyfluoroalkyl substances (PFAS).3 A new study in Environmental Health Perspectives4 associates higher concentrations of PFAS in maternal blood during pregnancy with lower measures of bone strength in adolescent children. The study was led by Jessie Buckley, an associate professor of environmental health and engineering at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.Resistance to bone diseases such as osteoporosis depends on maximizing bone mass during critical growth periods, which include adolescence. A new study reports associations between higher prenatal PFAS exposures and lower measures of bone strength in 12-year-olds, with potential implications for adult bone health. Image: © Sergey Novikov/Shutterstock.Commonly described as “forever chemicals” because they are exceedingly resistant to degradation, PFAS have been used as stain, oil, and water repellents and as surfactants in fire-fighting foam.5 Certain PFAS are being phased out of production, but other novel formulations are being introduced to take their place.6Buckley and colleagues analyzed data collected by the Health Outcomes and Measures of the Environment (HOME) study, which enrolled pregnant women from Cincinnati, Ohio, and the surrounding areas between 2003 and 2006. This ongoing study aims to assess how fetal and early-life chemical exposures affect children’s growth and development.7 The women provided blood samples at 16 and 26 weeks of pregnancy and within a day of their child’s delivery. For the current study, the investigators measured PFAS in one sample per participant, with all three sampling points represented in the study.Buckley’s team analyzed data for 206 children from the HOME cohort who had also undergone dual-energy X-ray absorptiometry bone scans at 12 years of age. These scans measure inorganic bone mineral, which gives the skeleton its strength.8 Using those data, the researchers calculated two bone measurements: bone mineral content (BMC) and bone mineral density (BMD). The team then looked at how BMC and BMD measures varied with maternal blood concentrations of four PFAS: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid.Higher concentrations of PFOA and PFNA individually and of all four PFAS assessed as a mixture were associated with lower z-scores for BMC and BMD in the forearm and hip. The lower z-scores suggest that children with higher PFAS exposures had lower average bone mass compared with individuals of the same age, sex, and ancestry. “The mixture’s relationship with bone outcomes was stronger than the relationship [of any single] PFAS,” Buckley says. “This is important, since in the real world people tend to be exposed to mixtures of different PFAS all at once.”Abby Fleisch, a pediatric endocrinologist at Maine Medical Center in Portland, who was not involved in the research, says the study has several strengths. “It identifies gestation as a possible vulnerable window for PFAS exposures to impact bone health later in life,” she says. Furthermore, prospective data gathered so far have been limited to females, whereas Buckley and colleagues studied both sexes. Indeed, higher maternal PFOA concentrations were generally associated with lower z-scores in males compared with females. However, a key limitation, Buckley says, is that small sample sizes resulting from losses during follow-up made it difficult to assess sex-related differences.Still, the study addresses “important questions regarding prenatal exposure to both individual and mixtures of PFAS,” says Meghan Lynch, an environmental epidemiologist and PFAS expert at Abt Associates, an environmental consulting company headquartered in Rockville, Maryland. “Decreases in BMD in childhood are linked to an increase in fractures and the development of osteoporosis,” she says. “More research is needed to understand if this [association with PFAS] persists and if it is exacerbated by ongoing exposure to PFAS through adolescence and beyond.”Charles W. Schmidt, MS, is an award-winning journalist in Portland, ME, whose work has appeared in Scientific American, Nature, Science, Discover Magazine, Undark, the Washington Post, and many other publications.

Individual and joint associations of exposure to per- and polyfluoroalkyl substances with children's mitochondrial DNA copy number, and modified by estimated glomerular filtration rate.

Prenatal exposure to PFAS, associations with child cognitive ability and modification by maternal Vitamin D status: The MABC study.

BackgroundOxidative stress from excess reactive oxygen species (ROS) is a hypothesized contributor to preterm birth. Per- and polyfluoroalkyl substances (PFAS) exposure is reported to generate ROS in laboratory settings, and is linked to adverse birth outcomes globally. However, to our knowledge, the relationship between PFAS and oxidative stress has not been examined in the context of human pregnancy. ObjectiveTo investigate the associations between prenatal PFAS exposure and oxidative stress biomarkers among pregnant people. MethodsOur analytic sample included 428 participants enrolled in the Illinois Kids Development Study and Chemicals In Our Bodies prospective birth cohorts between 2014 and 2019. Twelve PFAS were measured in second trimester serum. We focused on seven PFAS that were detected in >65 % of participants. Urinary levels of 8-isoprostane-prostaglandin-F2α, prostaglandin-F2α, 2,3-dinor-8-iso-PGF2α, and 2,3-dinor-5,6-dihydro-8-iso-PGF2α were measured in the second and third trimesters as biomarkers of oxidative stress. We fit linear mixed-effects models to estimate individual associations between PFAS and oxidative stress biomarkers. We used quantile g-computation and Bayesian kernel machine regression (BKMR) to assess associations between the PFAS mixture and averaged oxidative stress biomarkers. ResultsLinear mixed-effects models showed that an interquartile range increase in perfluorooctane sulfonic acid (PFOS) was associated with an increase in 8-isoprostane-prostaglandin-F2α (β = 0.10, 95 % confidence interval = 0, 0.20). In both quantile g-computation and BKMR, and across all oxidative stress biomarkers, PFOS contributed the most to the overall mixture effect. The six remaining PFAS were not significantly associated with changes in oxidative stress biomarkers. ConclusionsOur study is the first to investigate the relationship between PFAS exposure and biomarkers of oxidative stress during human pregnancy. We found that PFOS was associated with elevated levels of oxidative stress, which is consistent with prior work in animal models and cell lines. Future research is needed to understand how prenatal PFAS exposure and maternal oxidative stress may affect fetal development.