Binary and quaternary mixtures of perfluoroalkyl substances (PFAS) differentially affect the immune response to influenza A virus infection.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic organofluorine compounds that persist indefinitely in the environment and bioaccumulate throughout all trophic levels. Biomonitoring efforts have detected multiple PFAS in the serum of most people. Immune suppression has been among the most consistent effects of exposure to PFAS. PFAS often co-occur as mixtures in the environment, however, few studies have examined immunosuppression of PFAS mixtures or determined whether PFAS exposure affects immune function in the context of infection. In this study, mixtures containing two or four different PFAS and a mouse model of infection with influenza A virus (IAV) were used to assess immunotoxicity of PFAS mixtures. PFAS were administered via the drinking water as either a binary mixture of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) or quaternary mixture of PFOS, PFOA, perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). The results indicated that the binary mixture affected the T-cell response, while the quaternary mixture affected the B-cell response to infection. These findings indicate that the immunomodulatory effects of PFAS mixtures are not simply additive, and that the sensitivity of immune responses to PFAS varies by cell type and mixture. The study also demonstrates the importance of studying adverse health effects of PFAS mixtures.

Childhood PFAS exposure and immunotoxicity: a systematic review and meta-analysis of human studies.

BACKGROUND: Exposure to poly- and perfluoroalkyl substances (PFAS) may affect infant and childhood health through immunosuppression. However, the findings of epidemiological literature examining relationships between prenatal/childhood PFAS exposure and vaccine response and infection in humans are still inconclusive. The aim of this review was to examine the effects of PFAS exposure on vaccine antibody response and infection in humans. METHODS: The MEDLINE/Pubmed database was searched for publications until 1 February 2023 to identify human studies on PFAS exposure and human health. Eligible for inclusion studies had to have an epidemiological study design and must have performed logistic regression analyses of gestational or childhood exposure to PFAS against either antibody levels for pediatric vaccines or the occurrence of children's infectious diseases. Information on baseline exposure to PFAS (in ng/mL), the age of PFAS exposure (gestational or in years), and the outcome was measured, potentially leading to multiple exposure-outcome comparisons within each study was collected. Percentage change and standard errors of antibody titers and occurrence of infectious diseases per doubling of PFAS exposure were calculated, and a quality assessment of each study was performed. RESULTS: Seventeen articles were identified matching the inclusion criteria and were included in the meta-analysis. In general, a small decrease in antibody response and some associations between PFAS exposure and childhood infections were observed. CONCLUSIONS: This meta-analysis summarizes the findings of PFAS effects on infant and childhood immune health. The immunosuppression findings for infections yielded suggestive evidence related to PFAS exposure, particularly PFOS, PFOA, PFHxS, and PFNA but moderate to no evidence regarding antibody titer reduction. SYSTEMATIC REVIEW REGISTRATION: The research protocol of this systematic review is registered and accessible at the Open Science Framework ( https://doi.org/10.17605/OSF.IO/5M2VU ).

The association between endocrine disrupting chemicals and nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle-Ottawa scale, I2 statistics, Begg's test, and Egger's test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I2 > 50 %) and the fixed-effects model ( I2 < 50 %). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95 % CI:1.03-1.34), cadmium (Cd) (OR = 1.37, 95 % CI:1.09-1.72), and bisphenol A (OR = 1.43, 95 % CI:1.24-1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95 % CI:1.17-1.84) and Cd increased the risk of "elevated alanine aminotransferase". On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95 % CI:0.93-1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95 % CI:1.01-3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings.

Per-polyfluoroalkyl substances (PFAS) as thyroid disruptors: is there evidence for multi-transgenerational effects?

INTRODUCTION: The environmental spread of pollutants has led to a persistent exposure of living beings to multiple chemicals, by now become ubiquitous in the surrounding environment. Environmental exposure to these substances has been reported to cause multi- and/or transgenerational health effects. Per- and Polyfluorinated Substances (PFAS) raise great concern, given their known effects both as endocrine disruptors and potential carcinogens. The multi/trans-generational effects of different endocrine disruptors have been investigated by several studies, and harmful effects observed also for PFAS. AREAS COVERED: This review examines the current data on the multi-trans-generational effects of PFAS, with a focus on their impact on the thyroid axis. The aim is to determine if there is evidence of potential multi-trans-generational effects of PFAS on the thyroid and/or if more research is needed. EXPERT OPINION: PFAS exposure impacts thyroid homeostasis and can cross the placental barrier. In addition PFAS have shown multi-transgenerational effects in laboratory experiences and animal models, but thyroid disruptive effects of PFAS were also investigated only in a small number of these studies. Efforts are needed to study the adverse effects of PFAS, as not all PFAS are regulated and removal strategies are still being developed.

Systematic review and meta-analysis of birth weight and perfluorohexane sulfonate exposures: examination of sample timing and study confidence.

We examined the association between mean birth weight (BW) differences and perfluorohexane sulfonate (PFHxS) exposure biomarkers.We fit a random effects model to estimate the overall pooled effect and for different strata based on biomarker sample timing and overall study confidence. We also conducted an analysis to examine the impact of a continuous measure of gestational age sample timing on the overall pooled effect.We detected a -7.9 g (95% CI -15.0 to -0.7; pQ=0.85; I2=0%) BW decrease per ln ng/mL PFHxS increase based on 27 studies. The 11 medium confidence studies (ß=-10.0 g; 95% CI -21.1 to 1.1) showed larger deficits than 12 high (ß=-6.8 g; 95% CI -16.3 to 2.8) and 4 low confidence studies (ß=-1.5 g; 95% CI -51.6 to 48.7). 10 studies with mid-pregnancy to late-pregnancy sampling periods showed smaller deficits (ß=-3.9 g; 95% CI -17.7 to 9.9) than 5 post-partum studies (ß=-28.3 g; 95% CI -69.3 to 12.7) and 12 early sampling studies (ß=-7.6 g; 95% CI -16.2 to 1.1). 6 of 12 studies with the earliest sampling timing showed results closer to the null.Overall, we detected a small but statistically significant BW deficit across 27 studies. We saw comparable BW deficit magnitudes in both the medium and high confidence studies as well as the early pregnancy group. Despite no definitive pattern by sample timing, larger deficits were seen in postpartum studies. We also saw results closer to the null for a subset of studies restricted to the earliest biomarker collection times. Serial pregnancy sampling, improved precision in gestational age estimates and more standardised reporting of sample variation and exposure units in future epidemiologic research may offer a greater understanding of the relationship between PFHxS on BW and any potential impact of pregnancy haemodynamics.

Per- and polyfluoroalkyl substances alter innate immune function: evidence and data gaps.

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.

The perils of poly- and perfluorinated chemicals on the reproductive health of humans, livestock, and wildlife.

Poly- and perfluoroalkyl substances (PFAS) are a prominent class of persistent synthetic compound. The widespread use of these substances in various industrial applications has resulted in their pervasive contamination on a global scale. It is therefore concerning that PFAS have a propensity to accumulate in bodily tissues whereupon they have been linked with a range of adverse health outcomes. Despite this, the true extent of the risk posed by PFAS to humans, domestic animals, and wildlife remains unclear. Addressing these questions requires a multidisciplinary approach, combining the fields of chemistry, biology, and policy to enable meaningful investigation and develop innovative remediation strategies. This article combines the perspectives of chemists, soil scientists, reproductive biologists, and health policy researchers, to contextualise the issue of PFAS contamination and its specific impact on reproductive health. The purpose of this article is to describe the challenges associated with remediating PFAS-contaminated soils and waters and explore the consequences of PFAS contamination on health and reproduction. Furthermore, current actions to promote planetary health and protect ecosystems are presented to instigate positive social change among the scientific community.

Thyroid cancer and endocrine disruptive chemicals: a case-control study on per-fluoroalkyl substances and other persistent organic pollutants.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Association of Combined Per- and Polyfluoroalkyl Substances and Metals with Chronic Kidney Disease.

Background: Exposure to environmental pollutants such as metals and Per- and Polyfluoroalkyl Substances (PFAS) has become common and increasingly associated with a decrease in the estimated Glomerular Filtration Rate (eGFR), which is a marker often used to measure chronic kidney disease (CKD). However, there are limited studies involving the use of both eGFR and the urine albumin creatinine ratio (uACR), which are more comprehensive markers to determine the presence of CKD and the complexity of pollutant exposures and response interactions, especially for combined metals and PFAS, which has not been comprehensively elucidated. Objective: This study aims to assess the individual and combined effects of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), Cadmium (Cd), Mercury (Hg), and Lead (Pb) exposure on CKD using data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018. Methods: We employed the use of bivariate logistic regression and Bayesian Kernel Machine Regression (BKMR) in our analysis of the data. Results: Logistic regression results revealed a positive association between PFOA and CKD. Our BKMR analysis revealed a non-linear and bi-phasic relationship between the metal exposures and CKD. In our univariate exposure-response function plot, Cd and Hg exhibited a U and N-shaped interaction, which indicated a non-linear and non-additive relationship with both low and high exposures associated with CKD. In addition, the bivariate exposure-response function between two exposures in a mixture revealed that Cd had a U-shaped relationship with CKD at different quantiles of Pb, Hg, PFOA, and PFOS, indicating that both low and high levels of Cd is associated with CKD, implying a non-linear and complex biological interaction. Hg's interaction plot demonstrated a N-shaped association across all quantiles of Cd, with the 75th quantile of Pb and the 50th and 75th quantiles of PFOA and PFOS. Furthermore, the PIP results underscored Cd's consistent association with CKD (PIP = 1.000) followed by Hg's (PIP = 0.9984), then PFOA and PFOS with a closely related PIP of 0.7880 and 0.7604, respectively, and finally Pb (PIP = 0.6940), contributing the least among the five environmental pollutants on CKD, though significant. Conclusions: Our findings revealed that exposure to environmental pollutants, particularly Hg and Cd, are associated with CKD. These findings highlight the need for public health interventions and strategies to mitigate the cumulative effect of PFAS and metal exposure and elucidate the significance of utilizing advanced statistical methods and tools to understand the impact of environmental pollutants on human health. Further research is needed to understand the mechanistic pathways of PFAS and metal-induced kidney injury and CKD, and longitudinal studies are required to ascertain the long-term impact of these environmental exposures.

Global quantification of emerging and legacy per- and polyfluoroalkyl substances in indoor dust: Levels, profiles and human exposure.

This study investigated the occurrence and distribution of per- and polyfluoroalkyl substances (PFASs) in house dust samples from six regions across four continents. PFASs were detected in all indoor dust samples, with total median concentrations ranging from 17.3 to 197 ng/g. Among the thirty-one PFAS analytes, eight compounds, including emerging PFASs, exhibited high detection frequencies in house dust from all six locations. The levels of PFASs varied by region, with higher concentrations found in Adelaide (Australia), Tianjin (China), and Carbondale (United States, U.S.). Moreover, PFAS composition profiles also differed among regions. Dust from Australia and the U.S. contained high levels of 6:2 fluorotelomer phosphate ester (6:2 diPAP), while perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were predominant in other regions. Furthermore, our results indicate that socioeconomic factors impact PFAS levels. The assessment of human exposure through dust ingestion and dermal contact indicates that toddlers may experience higher exposure levels than adults. However, the hazard quotients of PFASs for both toddlers and adults were below one, indicating significant health risks are unlikely. Our study highlights the widespread occurrence of PFASs in global indoor dust and the need for continued monitoring and regulation of these chemicals.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk.

Conservative estimates by the World Health Organization suggest that at least a quarter of global cardiovascular diseases are attributable to environmental exposures. Associations between air pollution and cardiovascular risk have garnered the most headlines and are strong, but less attention has been paid to other omnipresent toxicants in our ecosystem. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are man-made chemicals that are extensively used in industrial and consumer products worldwide and in aqueous film-forming foam utilized in firefighting. As such, our exposure to PFAS is essentially ubiquitous. Given the long half-lives of these degradation-resistant chemicals, virtually, all people are carrying a body burden of PFAS. Health concerns related to PFAS are growing such that the National Academies of Sciences, Engineering and Medicine has recommended standards for clinical follow-up of individuals with high PFAS blood levels, including prioritizing screening for dyslipidemia. The link between PFAS and dyslipidemia has been extensively investigated, and evidence for associations is compelling. However, dyslipidemia is not the only cardiovascular risk factor with which PFAS is associated. Here, we review the epidemiological evidence for links between PFAS of concern identified by the National Academies of Sciences, Engineering and Medicine and risk factors for cardiovascular disease, including overweight/obesity, glucose intolerance, hypertension, dyslipidemia, and hyperuricemia. Moreover, we review the potential connections of PFAS with vascular disease and atherosclerosis. While observational data support associations between the National Academies of Sciences, Engineering and Medicine PFAS and selected cardiac risk factors, additional research is needed to establish causation and better understand how exposure to PFAS leads to the development of these conditions.

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.

In utero exposures to perfluoroalkyl substances and the human fetal liver metabolome in Scotland: a cross-sectional study.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances are classed as endocrine disrupting compounds but continue to be used in many products such as firefighting foams, flame retardants, utensil coatings, and waterproofing of food packaging. Perfluoroalkyl exposure aberrantly modulates lipid, metabolite, and bile acid levels, increasing susceptibility to onset and severity of metabolic diseases, such as diabetes and metabolic dysfunction-associated steatotic liver disease. To date, most studies in humans have focused on perfluoroalkyl-exposure effects in adults. In this study we aimed to show if perfluoroalkyls are present in the human fetal liver and if they have metabolic consequences for the human fetus. METHODS: In this cross-sectional study, human fetal livers from elective termination of pregnancies at the Aberdeen Pregnancy Counselling Service, Aberdeen, UK, were analysed by both targeted (bile acids and perfluoroalkyl substances) and combined targeted and untargeted (lipids and polar metabolites) mass spectrometry based metabolomic analyses, as well as with RNA-Seq. Only fetuses from normally progressing pregnancies (determined at ultrasound scan before termination), terminated for non-medical reasons, from women older than 16 years, fluent in English, and between 11 and 21 weeks of gestation were collected. Women exhibiting considerable emotional distress or whose fetuses had anomalies identified at ultrasound scan were excluded. Stringent bioinformatic and statistical methods such as partial correlation network analysis, linear regression, and pathway analysis were applied to this data to investigate the association of perfluoroalkyl exposure with hepatic metabolic pathways. FINDINGS: Fetuses included in this study were collected between Dec 2, 2004, and Oct 27, 2014. 78 fetuses were included in the study: all 78 fetuses were included in the metabolomics analysis (40 female and 38 male) and 57 fetuses were included in the RNA-Seq analysis (28 female and 29 male). Metabolites associated with perfluoroalkyl were identified in the fetal liver and these varied with gestational age. Conjugated bile acids were markedly positively associated with fetal age. 23 amino acids, fatty acids, and sugar derivatives in fetal livers were inversely associated with perfluoroalkyl exposure, and the bile acid glycolithocholic acid was markedly positively associated with all quantified perfluoroalkyl. Furthermore, 7α-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis rate, was strongly positively associated with perfluoroalkyl levels and was detectable as early as gestational week 12. INTERPRETATION: Our study shows direct evidence for the in utero effects of perfluoroalkyl exposure on specific key hepatic products. Our results provide evidence that perfluoroalkyl exposure, with potential future consequences, manifests in the human fetus as early as the first trimester of gestation. Furthermore, the profiles of metabolic changes resemble those observed in perinatal perfluoroalkyl exposures. Such exposures are already linked with susceptibility, initiation, progression, and exacerbation of a wide range of metabolic diseases. FUNDING: UK Medical Research Council, Horizon Europe Program of the European Union, Seventh Framework Programme of the European Union, NHS Grampian Endowments grants, European Partnership for the Assessment of Risks from Chemicals, Swedish Research Council, Formas, Novo Nordisk Foundation, and the Academy of Finland.

Prediagnostic serum concentrations of per- and polyfluoroalkyl substances and risk of papillary thyroid cancer in the Finnish Maternity Cohort.

Human exposure to per- and polyfluoroalkyl substances (PFAS) occurs globally through contaminated food, dust, and drinking water. Studies of PFAS and thyroid cancer have been limited. We conducted a nested case-control study of prediagnostic serum levels of 19 PFAS and papillary thyroid cancer (400 cases, 400 controls) in the Finnish Maternity Cohort (pregnancies 1986-2010; follow-up through 2016), individually matched on sample year and age. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for log2 transformed and categorical exposures, overall and stratified by calendar period, birth cohort, and median age at diagnosis. We adjusted for other PFAS with Spearman correlation rho = 0.3-0.6. Seven PFAS, including perfluoroctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), N-ethyl-perfluorooctane sulfonamidoacetic acid (EtFOSAA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorohexane sulfonic acid (PFHxS) were detected in >50% of women. These PFAS were not associated with risk of thyroid cancer, except for PFHxS, which was inversely associated (OR log2 = 0.82, 95% CI: 0.70-0.97). We observed suggestive but imprecise increased risks associated with PFOA, PFOS, and EtFOSAA for those diagnosed at ages <40 years, whereas associations were null or inverse among those diagnosed at 40+ years (P-interaction: .02, .08, .13, respectively). There was little evidence of other interactions. These results show no clear association between PFAS and papillary thyroid cancer risk. Future work would benefit from evaluation of these relationships among those with higher exposure levels and during periods of early development when the thyroid gland may be more susceptible to environmental harms.

The Association of Hypertension with Perfluoroalkyl and Polyfluoroalkyl Substances.

Perfluoroalkyl and polyfluoroalkyl substance (PFAS) is a large group of fluorinated synthetic chemicals, e.g., perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA). Many epidemiological studies have found that PFAS exposure is associated with hypertension risk, but others possess a different opinion. Overall, the relationship between PFASs and hypertension risk remains controversial. We sought to conduct a systematic review and meta-analysis to clarify the association between PFAS exposure and human risk of hypertension.We conducted a meta-analysis based on population-involving studies published from 1975 to 2023, which we collected from Web of Science, PubMed, and Embase databases. The odds ratio (OR) and standardized mean difference (SMD), with their 95% confidence interval (CI), were used to assess the risk of hypertension with PFAS exposure. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Research publications related to our meta-analysis topic were systematically reviewed.Fourteen studies involving 71,663 participants, in which 26,281 suffered hypertension, met the inclusion criteria. Our analyses suggest that exposure to general PFAS (OR = 1.09, 95% CI = 1.04-1.14) or PFOS (OR = 1.17, 95% CI = 1.05-1.30) is associated with hypertension risk. Specifically, elevated levels of general PFAS (SMD = 0.25, 95% CI = 0.08-0.42), PFHxS (SMD = 0.17, 95% CI = 0.07-0.27), and PFDA (SMD = 0.08, 95% CI = 0.02-0.13) are associated with a high risk of hypertension.Our meta-analysis indicates that PFAS exposure is a risk factor for hypertension, and increased hypertension risk is associated with higher PFAS levels. Further study may eventually provide a better and more comprehensive elucidation of the potential mechanism of this association.

Per- and Poly-fluoroalkyl Substances (PFAS) Exposure and Risk of Kidney, Liver, and Testicular Cancers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Per- and poly-fluoroalkyl substances (PFASs) are a large, complex group of synthetic chemicals humans can be exposed to from occupational or environmental sources. In this systematic review and meta-analysis, we examined the association between PFAS exposure, particularly Perfluorooctanoic Acid (PFOA), and Perfluorooctane Sulfonic Acid (PFOS), and risk of kidney, liver, and testicular cancer. METHODS: We systematically searched PubMed to identify cohort and case-control studies reported after the Monograph of the International Agency for Research on Cancer and the Toxicological Profile of the Agency for Toxic Substances and Disease Registry. We assessed the quality of the studies by using a modified version of the Newcastle-Ottawa Scale (NOS). Forest relative risk (RR) plots were constructed for liver, kidney, and testicular cancer. We conducted stratified analyses by geographic region, study design, quality score, outcome, years of publication, exposure source, and PFAS type. A random-effects model was used to address heterogeneity between studies. RESULTS: Fifteen studies, including ten cohort studies, three case-control studies nested in a cohort, and two case-control studies were included after removing duplicate and irrelevant reports. We found an association between overall PFAS exposure and the risk of kidney cancers (RR=1.18, 95% CI =1.05-1.32; I =52.8%, 11 studies). Also, we showed an association between high-level exposure to PFAS and kidney cancer (RR=1.74, 95% CI =1.23-2.47; p=0.005) and testicular cancer (RR=2.22, 95% CI =1.12-4.39; p=0.057). There was no association with liver cancer. We found no heterogeneity by geographical region, PFAS type, study design, outcome, quality score, year of publication, or exposure source. Only two studies reported results among women. CONCLUSIONS: We detected an association between overall PFAS exposure and kidney cancer and high doses of PFAS with testicular cancer. However, bias and confounding cannot be excluded, precluding a conclusion in terms of causality.

Association between per- and polyfluoroalkyl substances and risk of hypertension: a systematic review and meta-analysis.

Background: Existing evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent. Therefore, we aimed to explore the relationship between PFASs and hypertension through this systematic review and meta-analysis. Methods: We searched PubMed, Embase, and the Web of Science databases for articles published in English that examined the relationship between PFASs and hypertension before 13 August 2022. The random effects model was used to aggregate the evaluation using Stata 15.0 for Windows. We also conducted subgroup analyses by region and hypertension definition. In addition, a sensitivity analysis was carried out to determine the robustness of the findings. Results: The meta-analysis comprised 15 studies in total with 69,949 individuals. The risk of hypertension was substantially and positively correlated with exposure to perfluorooctane sulfonate (PFOS) (OR = 1.31, 95% CI: 1.14, 1.51), perfluorooctanoic acid (PFOA) (OR = 1.16, 95% CI: 1.07, 1.26), and perfluorohexane sulfonate (PFHxS) (OR = 1.04, 95% CI: 1.00, 1.09). However, perfluorononanoic acid (PFNA) exposure and hypertension were not significantly associated (OR = 1.08, 95% CI: 0.99, 1.17). Conclusion: We evaluated the link between PFASs exposure and hypertension and discovered that higher levels of PFOS, PFOA, and PFHxS were correlated with an increased risk of hypertension. However, further high-quality population-based and pathophysiological investigations are required to shed light on the possible mechanism and demonstrate causation because of the considerable variability. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, registration number: CRD 42022358142.

Induction of Posterior Vitreous Detachment Using Perfluorooctane Dissection in a Pediatric Patient.

BACKGROUND AND OBJECTIVE: Inducing a posterior vitreous detachment (PVD) may be challenging, especially in pediatric patients with firm vitreo-retinal adherence. This case report will present an alternative method of PVD induction using adjunctive perfluorooctane (PFO). MATERIALS AND METHODS: An 11-year-old boy underwent scleral buckle placement and 23-gauge pars plana vitrectomy for macula-off retinal detachment. Triamcinolone acetonide was used for vitreous staining. A flexible loop was used to peel the hyaloid membrane from attached retina nasal to the optic nerve. A small hole was created in the posterior hyaloid, and a small PFO bubble was injected under the detached vitreous to further dissect it from the retina and propagate the vitreous detachment anteriorly. The vitrector was used to lift and complete the PVD peripherally. RESULTS: PVD induction was obtained with no iatrogenic retinal breaks or postoperative complications. CONCLUSION: PVD induction using a stepwise PFO approach is a safe and effective alternative to conventional techniques. [Ophthalmic Surg Lasers Imaging Retina 2023;54:543-546.].