PFOS Concentrations Research Articles

Epidemic-specific association of maternal exposure to per- and polyfluoroalkyl substances (PFAS) and their components with maternal glucose metabolism: A cross-sectional analysis in a birth cohort from Hong Kong

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased risk of gestational diabetes mellitus (GDM) and may affect glucose metabolisms during pregnancy. We examined the associations between maternal PFAS exposure and maternal glucose metabolisms and GDM risk among 1601 mothers who joined the Hyperglycaemia-and-Adverse-Pregnancy-Outcome (HAPO) Study in Hong Kong in 2001–2006. All mothers underwent a 75 g-oral-glucose-tolerance test at 24–32 weeks of gestation. We measured serum concentrations of six PFAS biomarkers using high-performance liquid-chromatography-coupled-with-tandem-mass-spectrometry (LC-MS-MS). We fitted conventional and advanced models (quantile-g-computation [qgcomp] and Bayesian-kernel machine regression [BKMR]) to assess the associations of individual and a mixture of PFAS with glycaemic traits. Subgroup analyses were performed based on the enrollment period by the severe-acute-respiratory-syndrome (SARS) epidemic periods in Hong Kong between March 2003 and May 2004. PFOS and PFOA were the main components of PFAS mixture among 1601 pregnant women in the Hong Kong HAPO study, with significantly higher median PFOS concentrations (19.09 ng/mL), compared to Chinese pregnant women (9.40 ng/mL) and US women (5.27 ng/mL). Maternal exposure to PFAS mixture was associated with higher HbA1c in the qgcomp (β = 0.04, 95 % CI: 0.01–0.06) model. We did not observe significant associations of PFAS mixture with fasting plasma glucose (PG), 1-h and 2-h PG in either model, except for 2-h PG in the qgcmop model (β = 0.074, 95 % CI: 0.01–0.15). PFOS was the primary contributor to the overall positive effects on HbA1c. Epidemic-specific analyses showed specific associations between PFAS exposure and the odds of GDM in the pre-SARS epidemic period. The median concentration of PFOS was highest during the peri-SARS epidemic (21.2 [14.5–43.6] ng/mL) compared with the pre-SARS (12.3 [9.2–19.9] ng/mL) and post-SARS (20.3 [14.2–46.3] ng/mL) epidemic periods. Potential interactions and exposure-response relationships between PFOA and PFNA with elevated HbA1c were observed in the peri-SARS period in BKMR model. Maternal exposure to PFAS mixture was associated with altered glucose metabolism during pregnancy. SARS epidemic-specific associations call for further studies on its long-term adverse health effects, especially potential modified associations by lifestyle changes during the COVID-19 pandemic.

An investigation of 3M Cordova, IL production worker's per- and polyfluoroalkyl substances biomonitoring results and mortality experience

Per- and polyfluoroalkyl substances (PFAS) are a wide-ranging group of chemicals that have been used in a variety of polymer and surfactant applications. While 3M Cordova, Illinois was not one of 3M's primary manufacturing facilities for the legacy long-chain PFAS (PFOS, PFOA, PFHxS), it has been a major manufacturing site for short-chain PFAS (compounds that are or may degrade to PFBS or PFBA). The purpose of this research focused on: 1) an analysis of biomonitoring data of employees and retirees, and 2) an analysis of the cohort mortality of workers from 1970 to 2018. Employees had higher PFBS and PFBA serum concentrations than the retirees, while retirees had higher concentrations for PFOS, PFOA, and PFHxS. Compared to the 2017–2018 NHANES data, employees’ PFOS and PFHxS concentrations in 2022 were two-fold higher, with PFOA levels comparable. These NHANES data did not include serum PFBS or PFBA. Cross-sectional trends of PFOS and PFOA levels from 1997 to 2022 showed PFOS declined from 151 ng/mL to 10.4 ng/mL. Similarly, PFOA decreased from 100 ng/mL to 1.5 ng/mL. A longitudinal analysis of 48 participants with measurements in both 2006 and 2022 showed concentrations decreased by 74% for PFOS and 90% for PFOA. In the mortality study, 1707 employees who worked 1 day or longer were followed for an average of 25.6 years and had 143 (8%) deaths. There were no significantly elevated risks for any specific cause of death, regardless of latency period (0 or 15 years). While no specific PFAS exposures were examined, worker mortality experience (1970–2018) was analyzed by major departments representing primary work areas. Employees and retirees at the Cordova facility continue to have elevated PFOS and PFHxS serum concentrations compared to the general population, however, their legacy PFAS concentrations have declined over time, consistent with the estimated serum elimination half-lives of these PFAS in humans assuming nominal ambient exposures. For PFBS and PFBA, the results indicated no long-term accumulation in the blood likely due to their short serum elimination half-lives. After nearly 50 years of follow-up, this Cordova workforce showed no increased risk of mortality from cancer or any other specific cause of death.

Concentrations of 45 Per- and Polyfluoroalkyl Substances in North American River Otters (Lontra canadensis) from West Virginia, USA.

North American river otters (Lontra canadensis) are top predators in riverine ecosystems and are vulnerable to per- and polyfluoroalkyl substance (PFAS) exposure. Little is known about the magnitude of exposure and tissue distribution of PFAS in river otters. We measured 45 PFAS in various tissues of 42 river otters collected from several watersheds in the state of West Virginia, USA. The median concentrations of ∑All (sum concentration of 45 PFAS) varied among tissues in the following decreasing order: liver (931 ng/g wet weight) > bile > pancreas > lung > kidney > blood > brain > muscle. Perfluoroalkylsulfonates (PFSAs) were the predominant compounds accounting for 58-75% of the total concentrations, followed by perfluoroalkyl carboxylates (PFCAs; 21-35%). 8:2 fluorotelomer sulfonate (8:2 FTS), 10:2 FTS, and 6:2 chlorinated polyfluoroalkyl ether sulfonate were frequently found in the liver (50-90%) and bile (96-100%), whereas hexafluoropropylene oxide dimer acid (HFPO-DA) was rarely found. The hepatic concentrations of ∑All in river otters collected downstream of a fluoropolymer production facility located along the Ohio River were 2-fold higher than those in other watersheds. The median whole body burden of ∑All was calculated to be 1580 μg. PFOS and perfluorooctanoic acid (PFOA) concentrations in whole blood of some river otters exceeded the human toxicity reference values, which warrant further studies.

Transport and dispersion of PFOA and PFOS in the Black Sea

A 3-D transport and dispersion model was applied to study the recent past and future dynamics of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) concentrations in the Black Sea for the 2016–2030 period. The modelled surface concentrations show a distinct seasonal behaviour, shaped by winter to spring convective mixing. A significant increasing long-term trend in PFOS concentrations is established, with concentrations in water layers 200 m below the surface increasing at 4–8% per year. Driving mechanisms for PFOA and PFOS transport and accumulation in the subsurface and deeper layers are the cooling of the surface water in winter and the transport of water masses from the North Western Shelf (NWS) of the Black Sea. A simulated 50% phase-out of PFOA and PFOS from 2020 to 2030 shows a 21% reduction in PFOA, while PFOS continues to increase.

Plasmonic synergism in tailored metal–carbon interfaces for real-time single molecular level sniffing of PFOS and PFOA

Generating plasmonic hot-spots through engineering of nanoscale interfaces offers exciting opportunities towards point-of-care analytical detection. The mutual trade-off between ultra-high sensitivity, specificity and reliability are major drawbacks for practical applicability with real-time samples. Fundamentally these originate from low photonic mode density, high ohmic losses, temporally fluctuating and chemically indistinguishable nature of electromagnetic hot-spots. This work describes synergism of metallic plasmons from tailored interfaces of Ag-Au nanoalloys with conical nanocavities of nanocarbon florets (NCF), leading to strong metal-dielectric interfacial coupling. Such, Ag-Au-NCF nanohybrid delivers an unprecedented 1517-fold enhancement in surface-plasmon coupled directed emission (SPCE) of Rhodamine B (RhB) leading to robust (relative standard deviation, RSD < 10 %) single-molecular-level detection of spectroscopically-silent perfluoroalkyl substances (PFAS). The limit-of-detection demonstrated (PFOS = 0.005 ppt) is one-thousand times better than WHO recommendation and surpasses all existing reports. The specific cation–anion interactions between RhB and PFAS are substantiated through density functional calculations that concur with experimental findings. Finally, the emission from this SPCE platform can be visually tracked through a smartphone camera over wide range of PFOS concentrations (0.005–5000000 ppt) in water samples (lake, river, tap, drinking and ocean) and blood-plasma, offering transformative opportunities in analytical sciences.

PFOS and F–53B disrupted inner cell mass development in mouse preimplantation embryo

Perfluorooctane sulfonic acid (PFOS) is a perfluoroalkyl and polyfluoroalkyl substance (PFAS) widely used in daily life. As its toxicity was confirmed, it has been gradually substituted by F–53B (chlorinated polyfluoroalkyl sulfonates, Cl-PFESAs) in China. PFOS exposure during prenatal development may hinder the development of preimplantation embryos, as indicated by recent epidemiological research and in vivo assays. However, the embryotoxicity data for F–53B are scarce. Furthermore, knowledge about the toxicity of F–53B and PFOS exposure to internal follicular fluid concentrations on early preimplantation embryo development remains limited. In this study, internal exposure concentrations of PFOS (10 nM) and F–53B (2 nM) in human follicular fluid were chosen to study the effects of PFAS on early mouse preimplantation embryo development. We found that both PFOS and F–53B treated zygotes exhibited higher ROS activity in 8-cell embryos but not in 2-cell stage embryos. PFOS and F–53B significantly affected the proportion and aggregation of the inner cell mass (ICM) in the blastocyst, but not the total cell number. Mouse embryonic stem cells (mESCs, isolated from the ICM) and embryoid body (EB) assays were employed to assess the toxicity of PFOS and F–53B on the development and differentiation of embryonic pluripotent cells. These results suggested that mESCs exhibited more DNA damage and abnormal germ layer differentiation after brief exposure to PFOS or F–53B. Finally, RNA-sequencing revealed that PFOS and F–53B exposure affected mESCs biosynthetic processes and chromatin-nucleosome assembly. Our results indicate that F–53B has potential risks as an alternative to PFOS, which disrupts ICM development and differentiation.

Method Validation for Quantification of PFOS and PFOA in Human Plasma and a Pilot Study in Blood Donors from Thai Red Cross Society.

Information regarding per- and polyfluorinated substances concentrations in biological samples from the Thai population was still lacking. A sensitive bioanalytical method was developed and validated for the quantification of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) levels in human plasma. Simple protein precipitation and LC-MS/MS techniques were used with stable isotope internal standards of 13C8-PFOS and 13C8-PFOA. The validated method followed the ICH bioanalytical validation guideline, and the results showed good accuracy, precision, and reproducibility. The validated analytical method was then applied to determine PFOS and PFOA concentrations in 50 human plasma samples from the National Blood Center, Thai Red Cross Society. The concentrations were found to be in ranges of <0.91-6.27 ng/mL for PFOS and <0.49-2.72 ng/mL for PFOA. PFOS was also measured separately for its isomers, and the geometric means of the linear isomer (L-PFOS) and branched isomer (br-PFOS) in plasma samples were at 1.85 and 0.41 ng/mL, respectively. Both PFOS and PFOA concentrations were lower in comparison to previous reports from other countries. The present study showed the application of our reliable method to determine PFOS and PFOA in biological samples in order to monitor the human exposure of both chemicals in Thailand.

Per- and polyfluoroalkyl substances (PFAS) in little penguins and associations with urbanisation and health parameters

Per- and Polyfluoroalkyl substances (PFAS) are increasingly detected in wildlife and present concerning and unknown health risks. While there is a growing body of literature describing PFAS in seabird species, knowledge from temperate Southern Hemisphere regions is lacking. Little penguins (Eudyptula minor) can nest and forage within heavily urbanised coastal environments and hence may be at risk of exposure to pollutants. We analysed scat contaminated nesting soils (n = 50) from 17 colonies in lutruwita/Tasmania for 16 PFAS, plasma samples (n = 45) from nine colonies, and three eggs for 49 PFAS. We detected 14 PFAS across the sample types, with perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) most commonly detected. Mean concentration of PFOS in plasma was 2.56 ± 4.3 ng/mL (<LOD–22.3), soil was 2.92 ± 5.39 μg/kg (<LOD–29.8) and eggs were 11.89 ± 11.30 μg/kg (0.27–22.84). Mean concentration of PFHxS in plasma was 0.9 ± 0.84 ng/mL (<LOD–5.6), soil was 11.4 ± 39.18 μg/kg (<LOD–213.3) and eggs were 0.27 ± 0.11 μg/kg (<LOD–0.38). Urbanisation of breeding sites was positively associated with PFOS and PFHxS concentrations in soils and blood. Phenology appeared to be an important predictor of PFHxS load, with moulting birds having lower levels compared to non-moulting birds. We investigated PFAS associations with health parameters and found that haematocrit and total plasma proteins in females were negatively associated with PFOS and positively associated in males. The number of erythrocytic nuclear abnormalities in males was positively associated with PFOS. Findings are the first to document the presence of PFAS in this resident seabird nesting and foraging close to anthropogenically modified habitats. We demonstrate that even in low concentrations, PFAS may have detectable relationships with penguin health. Ongoing research is needed to investigate foraging ecology and trophic bioaccumulation pathways, as well as understand sublethal consequences from exposure.

Associations of Prenatal Per- and Polyfluoroalkyl Substance (PFAS) Exposures with Offspring Adiposity and Body Composition at 16-20 Years of Age: Project Viva.

Findings on the associations between prenatal PFAS exposures and offspring adiposity are inconsistent. Whether such associations may extend to adolescence is especially understudied. We investigated associations of prenatal PFAS exposures with offspring adiposity and body composition at 16-20 years of age. We studied 545 mother-child pairs in the prospective prebirth cohort Project Viva (Boston, Massachusetts). We measured six PFAS (PFOA, PFOS, PFNA, PFHxS, EtFOSAA, and MeFOSAA) in maternal early pregnancy (, range: 5.7-19.6 wk) plasma samples. At the late adolescence visit ( y, range: 15.9-20.0 y), we obtained anthropometric measures and assessed body composition using bioelectrical impedance analysis and dual-energy X-ray absorptiometry. We examined associations of individual PFAS with obesity [i.e., age- and sex-specific body mass index (BMI) percentile] and adiposity and body composition using multivariable Poisson and linear regression models, respectively. We assessed PFAS mixture effects using Bayesian kernel machine regression (BKMR) and quantile g-computation. We used fractional-polynomial models to assess BMI trajectories (at 3-20 years of age) by prenatal PFAS levels. Thirteen percent () of the children had obesity in late adolescence. After multivariable adjustment, higher prenatal PFAS concentrations were associated with higher obesity risk [e.g., 1.59 (95% CI: 1.19, 2.12), 1.24 (95% CI: 0.98, 1.57), and 1.49 (95% CI: 1.11, 1.99) times the obesity risk per doubling of PFOS, PFOA, and PFNA, respectively]. BKMR showed an interaction between PFOA and PFOS, where the positive association between PFOS and obesity was stronger when PFOA levels were lower. Each quartile increment of the PFAS mixture was associated with 1.52 (95% CI: 1.03, 2.25) times the obesity risk and 0.52 (95% CI: , 1.06) higher BMI. Children with higher prenatal PFOS, EtFOSAA, and MeFOSAA concentrations had higher rates of BMI increase starting from 9-11 years of age. Prenatal PFAS exposures may have obesogenic effects into late adolescence. https://doi.org/10.1289/EHP12597.

Prenatal exposure to Per- and polyfluoroalkyl substances and adiposity measures of children at 4 and 6 years: A prospective birth cohort in China

There is growing evidence that prenatal exposure to Per- and polyfluoroalkyl substances (PFAS) was associated with childhood obesity, but evidence on multiple adiposity measures including arm circumference (AC), and waist circumference (WC) among Chinese children is limited. We investigated the associations of prenatal exposure to PFAS with adiposity measures of children at 4 and 6 years of age in the Shanghai-Minhang Birth Cohort Study. A total of 573 mother-child pairs with maternal PFAS concentrations and at least one measurement of adiposity measures of children were included in the present study. Eleven PFAS were assessed in maternal fasting blood samples. Information on children's weight, height, AC, and WC was collected at follow-ups. Weight for age Z score (WAZ), body mass index for age Z score (BMIz), and children overweight were calculated based on the World Health Organization Child Growth Standards. Multivariate linear regression, Poisson regression with robust error variance, and Bayesian Kernel Machine Regression (BKMR) models were used to examine the associations of prenatal exposure to PFAS with children's adiposity measures. Eight PFAS with detection rates above 85 % were included in the analyses. In the multivariate linear regression models, maternal PFNA concentrations were associated with a greater AC (β = 0.29, 95 % Confidence Interval (CI): 0.04–0.55) in 4-year-old children and with an increase in WAZ (β = 0.26, 95 % CI: 0.06–0.46), BMIz (β = 0.31, 95 % CI: 0.09–0.53), AC (β = 0.49, 95 % CI: 0.08–0.90), and WC (β = 1.47, 95 % CI: 0.41–2.52) in 6-year-old children. We also observed the associations of maternal concentrations of PFOS, PFNA, PFUdA, and PFTrDA with the increased risk of children overweight in 6-year-old children. BKMR models further supported the findings from multivariate linear regression and Poisson regression models, and identified PFNA as the most important contributor. Moreover, the associations described above were generally more pronounced in girls. In conclusion, prenatal exposure to PFAS was associated with an increased risk of children's adiposity with a sex-specific manner, and PFNA contributed most to the associations after controlling for the effect of co-exposure to other PFAS compounds, especially among girls at 6 years of age.

Hepatic concentrations of per- and polyfluoroalkyl substances (PFAS) in dolphins from south-east Australia: Highest reported globally

Per- and polyfluoroalkyl substances (PFAS) concentrations were investigated in hepatic tissue of four dolphin species stranded along the south-east coast of Australia between 2006 and 2021; Burrunan dolphin (Tursiops australis), common bottlenose dolphin (Tursiops truncatus), Indo-Pacific bottlenose dolphin (Tursiops aduncus), and short-beaked common dolphin (Delphinus delphis). Two Burrunan dolphin populations represented in the dataset have the highest reported global population concentrations of ∑25PFAS (Port Phillip Bay median 9750 ng/g ww, n = 3, and Gippsland Lakes median 3560 ng/g ww, n = 8), which were 50–100 times higher than the other species reported here; common bottlenose dolphin (50 ng/g ww, n = 9), Indo-Pacific bottlenose dolphin (80 ng/g ww, n = 1), and short-beaked common dolphin (61 ng/g ww, n = 12). Also included in the results is the highest reported individual ∑25PFAS (19,500 ng/g ww) and PFOS (18,700 ng/g ww) concentrations, at almost 30 % higher than any other Cetacea reported globally.Perfluorooctane sulfonate (PFOS) was above method reporting limits for all samples (range; 5.3–18,700 ng/g ww), and constituted the highest contribution to overall ∑PFAS burdens with between 47 % and 99 % of the profile across the dataset. The concentrations of PFOS exceed published tentative critical concentrations (677–775 ng/g) in 42 % of all dolphins and 90 % of the critically endangered Burrunan dolphin.This research reports for the first time novel and emerging PFASs such as 6:2 Cl-PFESA, PFMPA, PFEECH and FBSA in marine mammals of the southern hemisphere, with high detection rates across the dataset. It is the first study to show the occurrence of PFAS in the tissues of multiple species of Cetacea from the Australasian region, demonstrating high global concentrations for inshore dolphins. Finally, it provides key baseline knowledge to the potential exposure and bioaccumulation of PFAS compounds within the coastal environment of south-east Australia.

A new mechanistic insight into the association between environmental perfluorooctane sulfonic acid (PFOS) exposure and attention deficit and hyperactivity disorder (ADHD)-like behavior

Perfluorooctane sulfonic acid (PFOS) is one of the main residual environmental pollutants that threaten human health. PFOS exposure is positively correlated with the prevalence of attention deficit hyperactivity disorder (ADHD); however, the underlying mechanism is unknown. Given that dopamine (DA) is a crucial target for PFOS and that its dysfunction is a key role in ADHD development, it is speculated that PFOS exposure contributes to the occurrence of ADHD to some extent by disrupting DA homeostasis. To establish the relationship between PFOS exposure, DA dysfunction, and ADHD-like behavior, adult zebrafish were exposed to PFOS for 21 days using PFOS concentrations in the serum of patients with ADHD as the reference exposure dose. Results showed that PFOS caused ADHD-like behaviors, with the presence of the slightly elevated percentage of time spent in movement and prolonged time spent in reaching the target zone in the T-maze. Hyperactivity and cognitive ability impairment were more severe with increasing PFOS concentrations. Further investigation showed that PFOS exposure resulted in a decrease in the DA content, accompanied by a decrease in the number of dopaminergic neurons and a disturbance in the transcription profiles of genes associated with the dopaminergic system. Treatment with Ritalin effectively alleviated PFOS-induced ADHD-like behavior and restored DA levels, number of dopaminergic neurons, and expression of DA metabolism-related genes, suggesting that PFOS exposure induced ADHD-like behavior by triggering DA secretion disorder. This study enriches our understanding of the pathogenic mechanisms underlying ADHD development and emphasizes the importance of focusing on the health risks pertaining to environmental exposure.

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.

Associations between prenatal exposure to per- and polyfluoroalkyl substances and wheezing and asthma symptoms in 4-year-old children: The Japan Environment and Children's Study

The effects of early-life exposure to per- and polyfluoroalkyl substances (PFAS) on the onset of asthma in children have been unclear. We examined the association between prenatal PFAS exposure and wheezing and asthma symptoms among 4-year-old children in a total of 17,856 mother-child pairs from the Japan Environment and Children's Study. Maternal first-trimester serum concentrations of six PFAS were used for the exposure assessment. We defined “wheeze ever,” “current wheeze,” “current symptoms of severe asthma,” and “asthma ever” at the age of 4 years by the responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and “doctor-diagnosed asthma” by the response to a corresponding question. Multivariate logistic regression models were used to examine exposure-outcome associations. Our findings revealed that doubling of the PFOA concentration was associated with a reduced occurrence of “wheeze ever,” yielding an adjusted odds ratio of 0.94 (95% CI: 0.90–0.98). Also, doubling in the concentrations of PFOA and PFHxS was associated with a decreased prevalence of “asthma ever,” with adjusted odds ratios of 0.94 (95% CI: 0.88–1.00) and 0.95 (95% CI: 0.90–0.99), respectively. However, these associations were not significant after applying the Bonferroni correction. The estimated exposure-response curves were nearly linear with a subtle or flat slope. When stratified by the child's sex or the mother's history of asthma, most of the estimated confidence intervals were overlapped between each pair of strata. Regional stratification analysis indicated low-to-moderate heterogeneity in 12 exposure-outcome pairs and moderate-to-high heterogeneity in 9 out of the 30 examined pairs. This study found no clear associations between prenatal PFAS exposure and the prevalence of wheezing and asthma among children at the age of 4 years.

Toxicity assessment of perfluorooctanesulfonic acid (PFOS) on a spontaneous plant, velvetleaf (Abutilon theophrasti), via metabolomics

Spontaneous plants often play important ecological roles in terrestrial environments, but impacts of contaminants on spontaneous plants are seldom investigated. Per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanesulfonic acid (PFOS) are ubiquitous in rural and urban soils. In this study, we assessed the effects of PFOS on a spontaneous plant, velvetleaf (Abutilon theophrasti), using endpoints such as plant growth, stress defense, PFOS uptake, and elemental and metabolite profile. We observed stunted growth in plants grown in PFOS-contaminated soils, with PFOS accumulating in their shoots by up to 3000 times more than the control plants. The other endpoints (decreased chlorophyll a synthesis, elevated oxidative stress, reduced shoot Mg concentration, and reduced biomass production) also explained the stunted growth of velvetleaf exposed to elevated PFOS concentrations. We found that 56 metabolites involved in 13 metabolic pathways were dysregulated. The synthesis of important antioxidants such as ascorbic acid, hydroxycinnamic acids (coumaric, caffeic, ferulic, and sinapic acids), and tocopherols decreased, resulting in loss of plant's defense to stress. PFOS also reduced the levels of growth-related and stress-coping metabolites including squalene, serotonin, noradrenalin, putrescine, and indole-3-propionic acid, which further corroborated the restricted growth of velvetleaf exposed to elevated PFOS. These findings provide insights on phytotoxicity of PFOS to velvetleaf, a resilient terrestrial spontaneous plant.

Extracellular Vesicles altered by a Per- and Polyfluoroalkyl Substance Mixture: In Vitro Dose-Dependent Release, Chemical Content, and MicroRNA Signatures involved in Liver Health.

Per- and polyfluoroalkyl substances (PFAS) have emerged as high priority contaminants due to their ubiquity and pervasiveness in the environment. Numerous PFAS co-occur across sources of drinking water, including areas of North Carolina (NC) with some detected concentrations above the Environmental Protection Agency's health advisory levels. While evidence demonstrates PFAS exposure induces harmful effects in the liver, the involvement of extracellular vesicles (EVs) as potential mediators of these effects has yet to be evaluated. This study set out to evaluate the hypothesis that PFAS mixtures induce dose-dependent release of EVs from liver cells, with exposures causing differential loading of microRNAs (miRNAs) and PFAS chemical signatures. To test this hypothesis, a defined PFAS mixture was prioritized utilizing data collected by the NC PFAS Testing Network. This mixture contained three substances, PFOS, PFOA, and PFHxA, selected based upon co-occurrence patterns and the inclusion of both short-chain (PFHxA) and long-chain (PFOA and PFOS) substances. HepG2 liver cells were exposed to equimolar PFAS, and secreted EVs were isolated from conditioned media and characterized for count and molecular content. Exposures induced a dose-dependent release of EVs carrying miRNAs that were differentially loaded upon exposure. These altered miRNA signatures were predicted to target mRNA pathways involved in hepatic fibrosis and cancer. Chemical concentrations of PFOS, PFOA, and PFHxA were also detected in both parent HepG2 cells and their released EVs, specifically within a 15-fold range after normalizing for protein content. This study therefore established EVs as novel biological responders and measurable endpoints for evaluating PFAS-induced toxicity.

Pressure of different level PFOS on aerobic granule sludge: Insights on performance, AGS structure, community succession, and microbial interaction responses

Perfluorooctane sulfonic acid (PFOS) has received much attention due to its potential environmental risks. However, the response of aerobic granular sludge (AGS) to PFOS exposure, particularly the microbial interactions, remains unclear. In this study, we investigated the particle structure of AGS, pollutant removal performance, community succession, and microbial interaction in the AGS system under different PFOS concentrations (0.1 and 1 mg/L). The mass balance showed that PFOS was mainly removed by adsorption with a removal rate of >85 %. PFOS caused some particles to break up and decreased the average particle size from 3.37 mm to 2.64 mm. It also significantly decreased the total nitrogen and total phosphorus removal rates, which was consistent with the deterioration of microbial activity, such as denitrification rate (25 % inhibition), phosphorus uptake rate (73.19 % inhibition), and phosphorus release rate (73.33 % inhibition). PFOS promoted the secretion of extracellular polymer (EPS) in AGS, especially proteins, leading to poor particle hydrophobicity. The network analysis illustrated that PFOS slowed down the information transfer between microorganisms, and increased the competition between them, which may be responsible for the deterioration of the system performance. Connections related to rare species accounted for >75 % of the network, suggesting that rare species have an indispensable role in community information exchange. In addition, rare species acted as seed banks for microorganisms, and under PFOS stress, they transformed into keystone species, which could contribute to system stabilization. This study provides new insights into the effects of PFOS on microbial interactions in AGS systems and the roles of rare species in the AGS microbial community.

Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

OR06-04 Environmental Pollutants Perfluoroalkyl Acids Potently Stimulated Aldosterone Biosynthesis

Abstract Disclosure: B. Caroccia: None. T.M. Seccia: None. G. Pallafacchina: None. M. Piazza: None. I. Caputo: None. R. Rizzuto: None. G. Rossi: None. A large environmental contamination of drinking water by perfluoroalkyl substances (PFAS) markedly increased by 8-fold the plasma levels of pentadecafluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in a Northern Italy population with that shows a high prevalence of arterial hypertension and cardiovascular disease. As the link between PFAS and arterial hypertension is unknown, we investigated if they could enhance the biosynthesis of aldosterone, the main mineralocorticoid hormone that has pressor effects. We exposed human adrenocortical carcinoma HAC15 cells to 1 µM or 10 µM concentration of PFOA and PFOS, alone or in combination, for 24, 48 or 72 hours and we measured changes in cell viability, aldosterone synthase (CYP11B2) mRNA, cell and mitochondrial reactive oxygen species (ROS), and aldosterone production in the absence or presence of the superoxide scavenger tempol. Experiments were also performed in the presence of 10 or 100 nM Ang II. We found that PFAS increased CYP11B2 mRNA by 3-fold and aldosterone secretion and mitochondrial ROS production by 2-fold over controls (p &amp;lt; 0.01 for all). PFAS also enhanced the effects of the aldosterone secretagogue Ang II on CYP11B2 mRNA and aldosterone secretion: 10 nM or 100 nM Ang II increased CYP11B2 mRNA by 12- and 52-fold, respectively, compared to vehicle (p &amp;lt; 0.001). Moreover, 1 µM PFAS potentiated the effect of 10 nM or 100 nM Ang II on CYP11B2 gene expression by 30- and 80-fold, respectively (p &amp;lt; 0.001). As the ROS scavenger tempol, which decreased ROS, significantly blunted the CYP11B2 gene expression induced by either PFAS alone, or by concomitant exposure to Ang II and PFAS, the effect of PFAS likely occurs via increased ROS generation. These results indicate that at concentrations mimicking those found in human plasma of exposed individuals, PFAS exert a prooxidant effect and act as potent disruptors of human adrenocortical cell function, thus implicating them as causative factors of human arterial hypertension due to aldosteronism. Presentation: Thursday, June 15, 2023

Combustion of high-calorific industrial waste in conventional brick kilns: An emerging source of PFAS emissions to agricultural soils

The brick kilns in the South Asian region are widely documented to partially combust high-calorific waste components of synthetic-industrial origin, which contain hazardous constituents, including per- and polyfluoroalkyl substances (PFAS). Correspondingly, these establishments are necessarily built on agricultural land to easily acquire clay by excavating soil horizons, thus making cultivation soils vulnerable to PFAS contaminations. In this pioneering study, the occurrence, distribution profile, traceability and human health risk exposure to forty-four legacy and novel PFAS homologues, including two ultrashort-chain (C2-C3) PFAS, were investigated in agricultural soils around thirty-two conventional brick kilns across three districts of Pakistan. ⅀44PFAS concentrations ranged from 14.3 to 465 ng/g (median: 28.2 ng/g), which were 2 to 70 folds higher than those in background soils, and slightly higher than those reported in agricultural soils in the global literature. The highest occurrence was observed for PFAS alternatives, i.e., 6:2 fluorotelomer sulfonate (6:2 FTSA) (40 %) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) (4.5 %). A significant positive correlation (p < 0.01) was observed among the concentrations of short-chain perfluoroalkyl acids (C4-C7) and novel PFOS substitutes, implying their origin from common sources. Furthermore, ultrashort-chain and short-chain perfluorocarboxylic acids (PFCA) (89 %) and perfluorosulfonic acids (PFSA) (63 %) dominated over long-chain's PFCA (11 %) and PFSA (37 %), respectively. The estimated daily intake to children exposed in surrounding inhabited communities, at 95th percentile concentrations was found to be approaching the European tolerable daily intake limit of 0.63 ng/kg bw/day. Therefore, the brick manufacturing industry is identified as a novel source of PFAS in the adjacent environment and for residents. This suggests the need for further investigations to elucidate the origin of emerging contaminants in the waste streams of the region to safeguard ecological integrity.