@article{phelps_connors_ferrero_dewitt_yoder_2024, title={Per- and polyfluoroalkyl substances alter innate immune function: evidence and data gaps}, volume={21}, ISSN={1547-691X 1547-6901}, url={http://dx.doi.org/10.1080/1547691X.2024.2343362}, DOI={10.1080/1547691X.2024.2343362}, abstractNote={Per- and polyfluoroalkyl substances (PFASs) are a large class of compounds used in a variety of processes and consumer products. Their unique chemical properties make them ubiquitous and persistent environmental contaminants while also making them economically viable and socially convenient. To date, several reviews have been published to synthesize information regarding the immunotoxic effects of PFASs on the adaptive immune system. However, these reviews often do not include data on the impact of these compounds on innate immunity. Here, current literature is reviewed to identify and incorporate data regarding the effects of PFASs on innate immunity in humans, experimental models, and wildlife. Known mechanisms by which PFASs modulate innate immune function are also reviewed, including disruption of cell signaling, metabolism, and tissue-level effects. For PFASs where innate immune data are available, results are equivocal, raising additional questions about common mechanisms or pathways of toxicity, but highlighting that the innate immune system within several species can be perturbed by exposure to PFASs. Recommendations are provided for future research to inform hazard identification, risk assessment, and risk management practices for PFASs to protect the immune systems of exposed organisms as well as environmental health.}, number={1}, journal={Journal of Immunotoxicology}, publisher={Informa UK Limited}, author={Phelps, Drake W. and Connors, Ashley M. and Ferrero, Giuliano and DeWitt, Jamie C. and Yoder, Jeffrey A.}, year={2024}, month={May} }
 @article{bline_dewitt_kwiatkowski_pelch_reade_varshavsky_2024, title={Public Health Risks of PFAS-Related Immunotoxicity Are Real}, ISSN={["2196-5412"]}, DOI={10.1007/s40572-024-00441-y}, abstractNote={Abstract
              Purpose of Review
              The discovery of per- and polyfluoroalkyl substances (PFAS) in the environment and humans worldwide has ignited scientific research, government inquiry, and public concern over numerous adverse health effects associated with PFAS exposure. In this review, we discuss the use of PFAS immunotoxicity data in regulatory and clinical decision-making contexts and question whether recent efforts adequately account for PFAS immunotoxicity in public health decision-making.
            
              Recent Findings
              Government and academic reviews confirm the strongest human evidence for PFAS immunotoxicity is reduced antibody production in response to vaccinations, particularly for tetanus and diphtheria. However, recent events, such as the economic analysis supporting the proposed national primary drinking water regulations and clinical monitoring recommendations, indicate a failure to adequately incorporate these data into regulatory and clinical decisions.
            
              Summary
              To be more protective of public health, we recommend using all relevant immunotoxicity data to inform current and future PFAS-related chemical risk assessment and regulation. Biological measures of immune system effects, such as reduced antibody levels in response to vaccination, should be used as valid and informative markers of health outcomes and risks associated with PFAS exposure. Routine toxicity testing should be expanded to include immunotoxicity evaluations in adult and developing organisms. In addition, clinical recommendations for PFAS-exposed individuals and communities should be revisited and strengthened to provide guidance on incorporating immune system monitoring and other actions that can be taken to protect against adverse health outcomes.
            }, journal={CURRENT ENVIRONMENTAL HEALTH REPORTS}, author={Bline, Abigail P. and Dewitt, Jamie C. and Kwiatkowski, Carol F. and Pelch, Katherine E. and Reade, Anna and Varshavsky, Julia R.}, year={2024}, month={Mar} }
 @article{wallis_kotlarz_knappe_collier_lea_reif_mccord_strynar_dewitt_hoppin_2023, title={Estimation of the Half-Lives of Recently Detected Per- and Polyfluorinated Alkyl Ethers in an Exposed Community}, volume={57}, ISSN={["1520-5851"]}, url={https://doi.org/10.1021/acs.est.2c08241}, DOI={10.1021/acs.est.2c08241}, abstractNote={To estimate half-lives for novel fluoroethers, the GenX Exposure Study obtained two serum measurements for per- and polyfluoroalkyl substances (PFAS) for 44 participants of age 12-86 years from North Carolina, collected 5 and 11 months after fluoroether discharges into the drinking water source were controlled. The estimated half-lives for these compounds were 127 days (95% confidence interval (95% CI) = 86, 243 days) for perfluorotetraoxadecanoic acid (PFO4DA), 296 days for Nafion byproduct 2 (95% CI = 176, 924 days), and 379 days (95% CI = 199, 3870 days) for perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA). Using these estimates and the literature values, a model was built that predicted PFAS half-lives using structural properties. Three chemical properties predicted 55% of the variance of PFAS half-lives based on 15 PFAS. A model with only molecular weight predicted 69% of the variance. Some properties can predict the half-lives of PFAS, but a deeper understanding is needed. These fluoroethers had biological half-lives longer than published half-lives for PFHxA and PFHpA (30-60 days) but shorter than those for PFOA and PFOS (800-1200 days). These are the first and possibly only estimates of human elimination half-lives of these fluoroethers.}, number={41}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Wallis, Dylan J. and Kotlarz, Nadine and Knappe, Detlef R. U. and Collier, David N. and Lea, C. Suzanne and Reif, David and McCord, James and Strynar, Mark and DeWitt, Jamie C. and Hoppin, Jane A.}, year={2023}, month={Oct}, pages={15348–15355} }
 @article{cuffney_wilkie_kotlarz_knappe_lea_collier_dewitt_hoppin_2023, title={Factors associated with per- and polyfluoroalkyl substances (PFAS) serum concentrations in residents of New Hanover County, North Carolina: The GenX exposure study}, volume={237}, ISSN={["1096-0953"]}, url={https://doi.org/10.1016/j.envres.2023.117020}, DOI={10.1016/j.envres.2023.117020}, abstractNote={In 2017, people living in New Hanover County, North Carolina, learned that for ∼40 years they were unknowingly exposed to per- and polyfluoroalkyl substances (PFAS) through drinking water sourced by the Cape Fear River. Using data from the GenX Exposure Study, which measured serum PFAS levels in county residents, we aimed to understand questionnaire-measured factors associated with serum PFAS levels. Because most residents were served by the same municipal water source, we focused on surrogate factors of drinking water exposure that may contribute to variability in PFAS levels. Our analysis included 335 participants aged 6 and older. We included seven chemicals detected in ≥75% of the study population: four well-studied perfluoroalkyl acids (PFOA, PFOS, PFNA, PFHxS) and three understudied fluoroethers (Nafion byproduct 2, PFO4DA, PFO5DoA). For each PFAS, we evaluated associations of variables with serum PFAS levels adjusting for key demographic characteristics. Additionally, we developed predictive models for each PFAS. We used years of residence in the lower Cape Fear Region as a surrogate for water consumption. Duration of drinking water exposure was associated with higher serum levels of all seven PFAS. Drinking municipal water treated by home filters or other sources of water (non-city) were associated with lower PFAS concentrations for all seven PFAS compared to drinking municipal water without additional filtration. Males had higher levels of well-studied PFAS, but there was no difference for fluoroethers. For six PFAS, the predictive models explained ≥30% of the variance in serum PFAS levels. While some factors were significantly associated with levels of individual PFAS, their relative importance to overall prediction was low, such as microwave popcorn consumption. Consistently, water consumption-related variables were important for both the association and predictive investigations. These analyses provide additional evidence that drinking water is a primary source for serum PFAS concentrations among New Hanover County residents.}, journal={ENVIRONMENTAL RESEARCH}, author={Cuffney, Michael and Wilkie, Adrien A. and Kotlarz, Nadine and Knappe, Detlef and Lea, C. Suzanne and Collier, David N. and Dewitt, Jamie and Hoppin, Jane A.}, year={2023}, month={Nov} }
 @article{phelps_palekar_conley_ferrero_driggers_linder_kullman_reif_sheats_dewitt_et al._2023, title={Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst}, volume={20}, ISSN={["1547-6901"]}, url={https://doi.org/10.1080/1547691X.2023.2176953}, DOI={10.1080/1547691X.2023.2176953}, abstractNote={Abstract Per- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.}, number={1}, journal={JOURNAL OF IMMUNOTOXICOLOGY}, author={Phelps, Drake W. and Palekar, Anika I. and Conley, Haleigh E. and Ferrero, Giuliano and Driggers, Jacob H. and Linder, Keith E. and Kullman, Seth W. and Reif, David M. and Sheats, M. Katie and DeWitt, Jamie C. and et al.}, year={2023}, month={Dec} }
 @article{arnold_blum_branyan_bruton_carignan_cortopassi_datta_dewitt_doherty_halden_et al._2023, title={Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern}, ISSN={["1520-5851"]}, DOI={10.1021/acs.est.2c08244}, abstractNote={Quaternary ammonium compounds (QACs), a large class of chemicals that includes high production volume substances, have been used for decades as antimicrobials, preservatives, and antistatic agents and for other functions in cleaning, disinfecting, personal care products, and durable consumer goods. QAC use has accelerated in response to the COVID-19 pandemic and the banning of 19 antimicrobials from several personal care products by the US Food and Drug Administration in 2016. Studies conducted before and after the onset of the pandemic indicate increased human exposure to QACs. Environmental releases of these chemicals have also increased. Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal. This work presents a critical review of the literature and scientific perspective developed by a multidisciplinary, multi-institutional team of authors from academia, governmental, and nonprofit organizations. The review evaluates currently available information on the ecological and human health profile of QACs and identifies multiple areas of potential concern. Adverse ecological effects include acute and chronic toxicity to susceptible aquatic organisms, with concentrations of some QACs approaching levels of concern. Suspected or known adverse health outcomes include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs’ role in antimicrobial resistance has also been demonstrated. In the US regulatory system, how a QAC is managed depends on how it is used, for example in pesticides or personal care products. This can result in the same QACs receiving different degrees of scrutiny depending on the use and the agency regulating it. Further, the US Environmental Protection Agency’s current method of grouping QACs based on structure, first proposed in 1988, is insufficient to address the wide range of QAC chemistries, potential toxicities, and exposure scenarios. Consequently, exposures to common mixtures of QACs and from multiple sources remain largely unassessed. Some restrictions on the use of QACs have been implemented in the US and elsewhere, primarily focused on personal care products. Assessing the risks posed by QACs is hampered by their vast structural diversity and a lack of quantitative data on exposure and toxicity for the majority of these compounds. This review identifies important data gaps and provides research and policy recommendations for preserving the utility of QAC chemistries while also seeking to limit adverse environmental and human health effects.}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Arnold, William A. . and Blum, Arlene and Branyan, Jennifer and Bruton, Thomas A. . and Carignan, Courtney C. and Cortopassi, Gino and Datta, Sandipan and DeWitt, Jamie and Doherty, Anne-Cooper and Halden, Rolf U. and et al.}, year={2023}, month={May} }
 @article{kotlarz_mccord_collier_lea_strynar_lindstrom_wilkie_islam_matney_tarte_et al._2020, title={Measurement of Novel, Drinking Water-Associated PFAS in Blood from Adults and Children in Wilmington, North Carolina}, volume={128}, ISSN={["1552-9924"]}, DOI={10.1289/EHP6837}, abstractNote={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 and PFO4DA were detected in >99% 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 34% for Nafion byproduct 2 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 23% to participants’ summed PFAS (median: 25.0 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. https://doi.org/10.1289/EHP6837}, number={7}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Kotlarz, Nadine and McCord, James and Collier, David and Lea, C. Suzanne and Strynar, Mark and Lindstrom, Andrew B. and Wilkie, Adrien A. and Islam, Jessica Y. and Matney, Katelyn and Tarte, Phillip and et al.}, year={2020}, month={Jul} }
 @article{kwiatkowski_andrews_birnbaum_bruton_dewitt_knappe_maffini_miller_pelch_reade_et al._2020, title={Scientific Basis for Managing PFAS as a Chemical Class}, volume={7}, ISSN={["2328-8930"]}, url={https://doi.org/10.1021/acs.estlett.0c00255}, DOI={10.1021/acs.estlett.0c00255}, abstractNote={This commentary presents a scientific basis for managing as one chemical class the thousands of chemicals known as PFAS (per- and polyfluoroalkyl substances). The class includes perfluoroalkyl acids, perfluoroalkylether acids, and their precursors; fluoropolymers and perfluoropolyethers; and other PFAS. The basis for the class approach is presented in relation to their physicochemical, environmental, and toxicological properties. Specifically, the high persistence, accumulation potential, and/or hazards (known and potential) of PFAS studied to date warrant treating all PFAS as a single class. Examples are provided of how some PFAS are being regulated and how some businesses are avoiding all PFAS in their products and purchasing decisions. We conclude with options for how governments and industry can apply the class-based approach, emphasizing the importance of eliminating non-essential uses of PFAS, and further developing safer alternatives and methods to remove existing PFAS from the environment.}, number={8}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS}, publisher={American Chemical Society (ACS)}, author={Kwiatkowski, Carol F. and Andrews, David Q. and Birnbaum, Linda S. and Bruton, Thomas A. and DeWitt, Jamie C. and Knappe, Detlef R. U. and Maffini, Maricel V and Miller, Mark F. and Pelch, Katherine E. and Reade, Anna and et al.}, year={2020}, month={Aug}, pages={532–543} }