Risk assessment for perfluorooctanoic acid (PFOA) in air, blood serum and water: mortality from liver and kidney disease.

BACKGROUND: Cancer and non-cancer associations have been observed with PFAS (perfluoroalkyl and polyfluoroalkyl) substances in the general population, in populations from locally contaminated environments and in exposed workers. METHODS: A quantitative risk assessment on the PFAS substance perfluorooctanoic acid (PFOA) was conducted for six outcomes using two occupational mortality studies that reported sufficient data to estimate exposure-relationships in relation to serum PFOA levels. Excess lifetime mortality risks were calculated using a life table procedure that applies an exposure response to time-dependent PFOA serum levels for a surviving hypothetical population from ages 20 to 85. Both occupational and general population exposures were described as serum levels, and as air and drinking water concentrations. RESULTS: The estimated occupational inhalation concentrations conferring the benchmark one-per-thousand lifetime risk were 0.21 µg/m3 for chronic kidney disease, 1.0 µg/m3 for kidney cancer and (from the two studies) 0.67 and 1.97 µg/m3 for chronic liver disease. Specific excess lifetime risks estimated in the general population at current PFOA serum levels (~ 1 ng/mL) range 1.5-32 per 100 000 which corresponds to drinking water concentrations of less than 10 ppt. CONCLUSION: Over eight outcome risk estimates, the serum PFOA concentrations conferring 1/1000 occupational lifetime risk ranged 44 to 416 ng/mL corresponding to air concentrations ranging 0.21 to 1.99 µg/m3. The analyses provide a preliminary PFOA quantitative risk assessment for liver and kidney disease mortality which, together with reported assessments for several other end-points, would inform policy on PFAS.

Association between mixed exposure to per- and polyfluoroalkyl substances and metabolic syndrome in Korean adults: Data from the Korean National environmental health survey cycle 4.

AIM: To explore the effect of mixed exposure to per- and polyfluoroalkyl substances (PFAS) on metabolic syndrome (MetS). METHODS: This cross-sectional study used data from the Korean National Environmental Health Survey Cycle 4 (2018-2020). The serum concentrations of five PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], perfluorohexanesulfonic acid, perfluorononanoic acid [PFNA], and perfluorodecanoic acid [PFDeA]) were measured, and the relative potency factor approach was employed for the mixture of PFAS (Cmix) assessment. MetS was diagnosed if the patient satisfied three of five criteria: central obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure (BP), and elevated glycated hemoglobin (HbA1c). Age, sex, smoking, drinking, and exercise status were considered as covariates. The risk of MetS for single and mixed exposure to PFAS was analyzed using binomial regression and Bayesian kernel machine regression (BKMR). RESULTS: A total of 2984 (male:female = 1:1.3; age range, 19-80 years) adults were enrolled. The prevalence of MetS was 45.6%. Each PFAS and Cmix levels were higher in participants with MetS than in those without MetS. Cmix increased the risk of elevated BP and HbA1c, and eventually MetS (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.11-3.60 per log10Cmix; OR = 1.57, 95% CI 1.07-2.31 in the highest quartile of Cmix [Q4] vs. the lowest [Q1]). Sex-specific analyses revealed that the impact of Cmix was valid in females but not in males (Cmix Q4 vs. Q1: OR = 1.01, 95% CI 0.57-1.8 in males; OR = 2.30, 95% CI 1.38-3.84 in females). In the BKMR analysis, mixed exposure to PFAS dose-dependently increased the risk of MetS, particularly in females. Among single exposures, PFNA contributed significantly to the cumulative effect. CONCLUSION: Mixed exposure to PFAS was associated with a higher risk of MetS in females. Further studies on potential health concerns associated with PFAS mixtures are warranted.

Associations between prenatal exposure to per- and polyfluoroalkyl substances and plasma immune molecules in three-year-old children in China.

BACKGROUND: Many studies have reported that prenatal exposure to Per- and Polyfluoroalkyl Substances (PFASs) can disrupt immune function. However, little is known about the effects of PFASs on immune molecules. The study analyzed the association between prenatal exposure to mixed and single PFASs and plasma immune molecules in three-year-old children. METHODS: Ten PFASs were measured in umbilical cord serum, while peripheral blood samples were collected at age three to measure immune molecules. Associations between exposure to individual and combined PFASs and immune molecules were analyzed using Generalized Linear Models and Weighted Quantile Sum (WQS) regression. RESULTS: (1) Interleukin-4 (IL-4) increased by 23.85% (95% CI:2.99,48.94) with each doubling of Perfluorooctanoic Acid (PFOA), and Interleukin-6 (IL-6) increased by 39.07% (95%CI:4.06,85.86) with Perfluorotridecanoic Acid (PFTrDA). Elevated PFOA and Perfluorononanoic Acid (PFNA) were correlated with increases of 34.06% (95% CI: 6.41, 70.28) and 24.41% (95% CI: 0.99, 53.27) in Eotaxin-3, respectively. Additionally, the doubling of Perfluorohexane Sulfonic Acid (PFHxS) was associated with a 9.51% decrease in Periostin (95% CI: -17.84, -0.33). (2) The WQS analysis revealed that mixed PFASs were associated with increased IL-6 (ß = 0.37, 95%CI:0.04,0.69), mainly driven by PFTrDA, PFNA, and 8:2 Chlorinated Perfluoroethyl Sulfonamide (8:2 Cl-PFESA). Moreover, mixed PFASs were linked to an increase in Eotaxin-3 (ß = 0.32, 95% CI: 0.09,0.55), primarily influenced by PFOA, PFTrDA, and Perfluorododecanoic Acid (PFDoDA). CONCLUSIONS: Prenatal PFASs exposure significantly alters the levels of immune molecules in three-year-old children, highlighting the importance of understanding environmental impacts on early immune development.

Examining the impact of polyfluoroalkyl substance exposure on erythrocyte profiles and its related nutrients: Insights from a prospective study on young Taiwanese.

Per- and polyfluoroalkyl substances (PFAS) constitute a group of synthetic chemicals extensively utilized across various commonplace products. PFAS are known to have various toxic effects on human health. The relationship between PFAS exposure and erythrocytes has been a subject of interest in epidemiological research, but so far, only limited cross-sectional studies have investigated. Additionally, the role of erythrocyte related nutrition indicators on PFAS-induced changes in erythrograms has not been explored. To fill these knowledge gaps, we launched a longitudinal study over a decade, tracking 502 adolescents and young adults aged 12 to 30 from the YOung TAiwanese Cohort (YOTA). Our analysis encompassed 11 types of plasma PFAS, as well as erythrograms and serum levels of ferritin, transferrin saturation, vitamin B12, and folate. Our examination unveiled positive associations between specific average levels of PFAS compounds, including linear perfluorooctanoic acid (PFOA), branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), and transferrin saturation. Furthermore, linear PFOA and both linear and branched PFOS were negatively correlated with vitamin B12 levels. Specifically, we observed that the average linear PFOA demonstrated positive correlations with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while average PFNA also exhibited positive associations with hemoglobin (Hb) and hematocrit (Hct) in a multiple linear regression model. Subsequent analysis revealed noteworthy interactions between vitamin B12 and PFNA, as well as folate and PFNA, in the context of their impact on Hb, Hct, and PFNA relationships. Additionally, an interaction with transferrin saturation was identified in the correlation between Hct and PFNA. These findings suggest a plausible link between PFAS exposure and erythrograms among young populations, underscoring the potential involvement of iron status, vitamin B12, and folate in this association. Further studies are imperative to elucidate the precise effects of PFAS on erythrocyte in human subjects.

Mitochondrial DNA copy number mediated the associations between perfluoroalkyl substances and breast cancer incidence: A prospective case-cohort study.

Epidemiologic studies have reported the relationships between perfluoroalkyl substances (PFASs) and breast cancer incidence, yet the underlying mechanisms are not well understood. This study aimed to elucidate the mediation role of mitochondrial DNA copy number (mtDNAcn) in the relationships between PFASs exposure and breast cancer risk. We conducted a case-cohort study within the Dongfeng-Tongji cohort, involving 226 incident breast cancer cases and a random sub-cohort (n = 990). Their plasma concentrations of six PFASs [including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanoic acid (PFHpA), perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)], and peripheral blood levels of mtDNAcn, were detected at baseline by using ultraperformance liquid chromatography-tandem mass spectrometry and quantitative real-time PCR, respectively. Linear regression and Barlow-weighted Cox models were employed separately to assess the relationships of mtDNAcn with PFASs and breast cancer risk. Mediation analysis was further conducted to quantify the mediating effects of mtDNAcn on PFAS-breast cancer relationships. We observed increased blood mtDNAcn levels among participants with the highest PFNA and PFHpA exposure [Q4 vs. Q1, ß(95%CI) = 0.092(0.022, 0.162) and 0.091(0.022, 0.160), respectively], while no significant associations were observed of PFOA, PFDA, PFOS, or PFHxS with mtDNAcn. Compared to participants within the lowest quartile subgroup of mtDNAcn, those with the highest mtDNAcn levels exhibited a significantly increased risk of breast cancer and postmenopausal breast cancer [Q4 vs. Q1, HR(95%CI) = 3.34(1.80, 6.20) and 3.71(1.89, 7.31)]. Furthermore, mtDNAcn could mediate 14.6 % of the PFHpA-breast cancer relationship [Indirect effect, HR(95%CI) = 1.02(1.00, 1.05)]. Our study unveiled the relationships of PFNA and the short-chain PFHpA with mtDNAcn and the mediation role of mtDNAcn in the PFHpA-breast cancer association. These findings provided insights into the potential biological mechanisms linking PFASs to breast cancer risk.

Machine learning predicts the serum PFOA and PFOS levels in pregnant women: Enhancement of fatty acid status on model performance.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has received considerable attention, particularly in pregnant women because of their dramatic changes in physiological status and dietary patterns. Predicting internal PFAS exposure in pregnant women, based on external and relevant parameters, has not been investigated. Here, machine learning (ML) models were developed to predict the serum concentrations of PFOA and PFOS in a large population of 588 pregnant participants. Dietary exposure characteristics, demographic parameters, and in particular, serum fatty acid (FA) data were used for the model development. The fitting results showed that the inclusion of FAs as covariates significantly improved the performance of the ML models, with the random forest (RF) model having the best predictive performance for PFOA (R2 = 0.33, MAE = 1.51 ng/mL, and RMSE = 1.89 ng/mL) and PFOS (R2 = 0.12, MAE = 2.65 ng/mL, and RMSE = 3.37 ng/mL). The feature importance analysis revealed that serum FAs greatly affected PFOA concentration in the pregnant women, with saturated FAs being associated with decreased PFOA levels and unsaturated FAs with increased levels. Comparison with one-compartment pharmacokinetic model further demonstrated the advantage of the ML models in predicting PFAS exposure in pregnant women. Our models correlate for the first time blood chemical concentrations with human FA status using ML, introducing a novel perspective on predicting PFAS levels in pregnant women. This study provides valuable insights concerning internal exposure of PFASs generated from external exposure, and contributes to risk assessment and management in pregnant populations.

Quantifying levels of per- and polyfluoroalkyl Substances (PFAS) in water and serum after contamination from agricultural biosolid application.

The National Academies of Sciences, Engineering, and Medicine recommends per- and polyfluoroalkyl substance (PFAS) blood testing for patients with risk of elevated exposure, and the Agency for Toxic Substances and Disease Registry (ATSDR) suggests PFAS blood testing based on exposure. Barriers to PFAS blood testing include cost, access to labs, and evolving laboratory methods. We quantify water and serum PFAS levels among a highly-exposed cohort in an area with groundwater contaminated by historical agricultural biosolid application. We compare the gold standard PFAS serum test with a commercial test and results from a one-compartment toxicokinetic model. Participants were adults (n = 30) whose household (n = 19) water had levels of the sum of six PFAS > 500 ng/L. Serum PFAS were measured using liquid chromatography-tandem mass spectrometry. Demographic and water consumption data were collected via telephone. Serum PFAS results from the commercial test were accessed via medical record. Statistical analysis included descriptive statistics and bivariate plots of serum levels. Perfluorohexanoic acid, perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorobutanesulfonic acid, perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were detected in 19 wells, and PFHpA, PFOA, PFNA, perfluorodecanoic acid, perfluoroundecanoic acid, PFHxS, and PFOS were detected in at least 19 participants' serum. In well water, PFOA and PFOS levels had geometric means (GMs) of 1749 ng/L (geometric standard deviation [GSD] 2.4) and 887 ng/L (GSD 19.7), respectively. In serum, PFOA and PFOS had GMs of 116.2 µg/L (GSD 13.5) and 58.3 µg/L (GSD 13.8), respectively. Our results are comparable with and had a wider mix of PFAS than other high-exposure cohorts. There was good agreement between the commercial and gold standard tests for PFOA, PFNA, and PFHxS, and mixed agreement between the gold standard test and modeled predictions, suggesting water-based toxicokinetic models of serum PFAS may be inadequate for assessing exposure in this population.

High-throughput, low-cost quantification of 11 therapeutic antibodies using caprylic acid precipitation and LC-MS/MS.

BACKGROUND: Therapeutic drug monitoring of treatment with therapeutic antibodies is hampered by the application of a wide range of different methods in the quantification of serum levels. LC-MS based methods could significantly improve comparability of results from different laboratories, but such methods are often considered complicated and costly. We developed a method for LC-MS/MS based quantification of 11 therapeutic antibodies concomitantly measured in a single run, with emphasis on simplicity in sample preparation and low cost. RESULTS: After a single-step sample purification using caprylic acid precipitation to remove interfering proteins, the sample underwent proteolysis followed by LC-MS/MS analysis. Infliximab is used as internal standard for sample preparation while isotope-labeled signature peptides identified for each analyte are internal standards for the LC-MS/MS normalization. The method was validated according to recognized guidelines, and pipetting steps can be performed by automated liquid handling systems. The total precision of the method ranged between 2.7 and 7.3 % (5.1 % average) across the quantification range of 4-256 µg/ml for all 11 drugs, with an average accuracy of 96.3 %. Matrix effects were xamined in 55 individual patient samples instead of the recommended 6, and 147 individual patient samples were screened for interfering compounds. SIGNIFICANCE AND NOVELTY: Our method for simultaneous quantification of 11 t-mAb in human serum allows an unprecedented integration of robustness, speed and reduced complexity, which could pave the way for uniform use in research projects and clinical settings alike. In addition, the first LC-MS protocol for signature peptide-based quantification of durvalumab is described. This high throughput method can be readily adapted to a drug panel of choice.

Association of diet with per- and polyfluoroalkyl substances in plasma and human milk in the New Hampshire Birth Cohort Study.

Per- and polyfluoroalkyl substances (PFAS) are related to various adverse health outcomes, and food is a common source of PFAS exposure. Dietary sources of PFAS have not been adequately explored among U.S. pregnant individuals. We examined associations of dietary factors during pregnancy with PFAS concentrations in maternal plasma and human milk in the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in maternal plasma collected at ∼28 gestational weeks and human milk collected at ∼6 postpartum weeks. Sociodemographic, lifestyle and reproductive factors were collected from prenatal questionnaires and diet from food frequency questionnaires at ∼28 gestational weeks. We used adaptive elastic net (AENET) to identify important dietary variables for PFAS concentrations. We used multivariable linear regression to assess associations of dietary variables selected by AENET models with PFAS concentrations. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, as well as gestational week of blood sample collection (plasma PFAS), postpartum week of milk sample collection (milk PFAS), and enrollment year. A higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. For example, every 1 standard deviation (SD) servings/day increase in egg intake during pregnancy was associated with 4.4 % (95 % CI: 0.6, 8.4), 3.3 % (0.1, 6.7), and 10.3 % (5.6, 15.2) higher plasma PFOS, PFOA, and PFDA concentrations respectively. Similarly, every 1 SD servings/day increase in white rice intake during pregnancy was associated with 7.5 % (95 % CI: -0.2, 15.8) and 12.4 % (4.8, 20.5) greater milk PFOS and PFOA concentrations, respectively. Our study suggests that certain dietary factors during pregnancy may contribute to higher PFAS concentrations in maternal plasma and human milk, which could inform interventions to reduce PFAS exposure for both birthing people and offspring.

PFAS and their association with the increased risk of cardiovascular disease in postmenopausal women.

Cardiovascular diseases (CVDs) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence CVD risk. Per- and polyfluoroalkyl substances (PFASs) are a class of highly fluorinated chemicals used in household consumer and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorobutanesulfonic acid in postmenopausal women from our previously established CVD study. We used liquid chromatography with tandem mass spectrometry, supported by machine learning approaches, and the detection and quantification of serum metabolites and proteins. Here, we show that PFOS can be a good predictor of coronary artery disease, whereas PFOA can be an intermediate predictor of coronary microvascular disease. We also found that the PFAS levels in our study are significantly associated with inflammation-related proteins. Our findings may provide new insight into the potential mechanisms underlying the PFAS-induced risk of CVDs in this population. This study shows that exposure to PFOA and PFOS is associated with an increased risk of cardiovascular disease in postmenopausal women. PFOS and PFOA levels correlate with amino acids and proteins related to inflammation. These circulating biomarkers contribute to the etiology of CVD and potentially implicate a mechanistic relationship between PFAS exposure and increased risk of cardiovascular events in this population.

Human biomonitoring follow-up study on PFOA contamination and investigation of possible influencing factors on PFOA exposure in a German population originally exposed to emissions from a fluoropolymer production plant.

BACKGROUND: In the past, perfluorooctanoic acid (PFOA) was produced and applied as an emulsifier in a fluoropolymer production plant in the Altötting district, southern Bavaria (Germany). This chemical was released directly into the environment, resulting in the contamination of the local drinking water. During a human biomonitoring (HBM) survey in 2018, increased median PFOA blood serum levels, compared to a normally exposed control group with no known source of PFOA exposure from Munich, Germany, were detected in the resident population (23.18 µg/l in the general population, 20.71 µg/l in the children's group). The follow-up study aimed to investigate whether purification of the drinking water as the main PFOA exposure source has been successful in reducing internal PFOA exposure and to estimate the association of internal PFOA exposure with possible influencing factors. METHODS: Only individuals who had already participated in the HBM study in 2018 were included. For the determination of the PFOA serum concentration, 5 ml of blood was drawn from each participating person. Blood samples were collected in the period from June to August 2022. Furthermore, information on sociodemographic characteristics, health status, dietary behaviour and other lifestyle factors were collected by means of a self-administered questionnaire. To examine the association of PFOA blood serum levels with possible influencing factors, such as age, gender and consumption of fish and game meat, a logistic regression model with a PFOA value > 10 µg/l as outcome was used. RESULTS: A total of 764 individuals participated in the follow-up study in 2022. Analyses were performed separately for the general population (n = 559), women of reproductive age (15-49 years old) (n = 120), and children under 12 years old (n = 30). Median PFOA blood levels have decreased by 56.9% in the general population, by 59.8% in the group of women of reproductive age and by 73.4% in the group of children under 12 years old. In the general population, a higher probability of a PFOA value > 10 µg/l was found for those aged 40-59 years (Odds ratio (OR) = 2.33 (95%CI: 1.23 to 4.43, p = 0.01) and those aged 60 years and older (OR = 5.32, 95%CI: 2.78 to 10.19, p < 0.001). CONCLUSIONS: In all study groups, the median PFOA serum levels decreased as expected after a half-life of four years, which confirms that contamination via drinking water has ceased. Furthermore, our study identified age as a significant predictor of internal PFOA exposure, while no influence was found for the consumption of fish and game meat. Further investigations are needed to quantify in a more detailed way the influence of dietary habits on PFOA exposure.

Per- and polyfluoroalkyl substances (PFAS) and fetal growth: A nation-wide register-based study on PFAS in drinking water.

BACKGROUND: There is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth. OBJECTIVES: We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA). MATERIALS AND METHODS: We included all births in Sweden during 2012-2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of ß coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture. RESULTS: Among the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01-1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight. DISCUSSIONS: We observed an association of the sum of PFAS4 - especially PFOS - with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.

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.

Associations of per- and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones.

BACKGROUND/AIMS: Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development. METHODS: In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp). RESULTS: Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: -0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: -5.7; 95%CI: -10.3, -0.8, and %Δ: -4.1; 95%CI: -7.6, -0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: -5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: -7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: -9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: -17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: -16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: -3.7, 20.9). CONCLUSION: PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings.

Per- and polyfluoroalkyl substances (PFAS) in senior care facilities and older adult residents.

Per- and polyfluoroalkyl substances (PFAS) are fluorinated organic compounds used in a variety of consumer products and industrial applications that persist in the environment, bioaccumulate in biological tissues, and can have adverse effects on human health, especially in vulnerable populations. In this study, we focused on PFAS exposures in residents of senior care facilities. To investigate relationships between indoor, personal, and internal PFAS exposures, we analyzed 19 PFAS in matched samples of dust collected from the residents' bedrooms, and wristbands and serum collected from the residents. The median ∑PFAS concentrations (the sum of all PFAS detected in the samples) measured in dust, wristbands, and serum were 120 ng/g, 0.05 ng/g, and 4.0 ng/mL, respectively. The most abundant compounds in serum were linear- and branched-perfluorooctane sulfonic acid (L-PFOS and B-PFOS, respectively) at medians of 1.7 ng/mL and 0.83 ng/mL, respectively, followed by the linear perfluorooctanoic acid (L-PFOA) found at a median concentration of 0.59 ng/mL. Overall, these three PFAS comprised 80 % of the serum ∑PFAS concentrations. A similar pattern was observed in dust with L-PFOS and L-PFOA found as the most abundant PFAS (median concentrations of 13 and 7.8 ng/g, respectively), with the overall contribution of 50 % to the ∑PFAS concentration. Only L-PFOA was found in wristbands at a median concentration of 0.02 ng/g. Significant correlations were found between the concentrations of several PFAS in dust and serum, and in dust and wristbands, suggesting that the indoor environment could be a significant contributor to the personal and internal PFAS exposures in seniors. Our findings demonstrate that residents of assisted living facilities are widely exposed to PFAS, with several PFAS found in blood of each study participant and in the assisted living environment.

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.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with hypertensive disorders of pregnancy in the Atlanta African American Maternal-Child cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans. METHODS: Participants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use. RESULTS: The geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy. CONCLUSIONS: In this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population.

Associations between serum perfluoroalkyl and polyfluoroalkyl concentrations and diabetes mellitus in the Korean general population: Insights from the Korean National Environmental Health Survey 2018-2020.

AIMS: Recent epidemiologic research has examined the relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and diabetes mellitus with inconclusive findings. In this cross-sectional study, we aimed to explore the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population as well as the combined effects of exposure to mixed PFAS compounds. METHODS: We analyzed data from participants aged ≥19 years enrolled in the Korean National Environmental Health Survey Cycle 4 (2018-2020). Individuals diagnosed with diabetes were excluded to minimize potential bias. We identified cases of pre-diagnostic diabetes based on the HbA1c level ≥6.5% and prediabetes as HbA1c levels of 5.7-6.49%. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were quantified using high-performance liquid chromatography-tandem mass spectrometry. Survey-weighted logistic regression models were used to assess the relationships between PFAS levels and diabetes risk, adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) was used to investigate the combined effects of exposure to mixed PFAS compounds. RESULTS: In the study population excluding participants with diagnosed diabetes (n = 2709), the prevalence of pre-diagnostic diabetes and prediabetes was 4.8% and 30.1%, respectively. Significant positive associations were found between serum PFHxS and PFOS quartiles and pre-diagnostic diabetes risk. Likewise, among those without diagnosed or pre-diagnostic diabetes (n = 2579), the highest quartiles of PFDeA, PFHxS, and PFOS and the overall PFAS level were associated with an increased risk of prediabetes compared with the lowest quartiles. BKMR analysis revealed a significant positive association between overall serum PFAS level and prediabetes risk, which was most marked for PFOS. CONCLUSIONS: These findings highlight the potential health implications of PFAS exposure and prediabetes risk. Further research is needed to validate these associations and identify potential mechanistic pathways.