Unveiling Priority Emerging PFAS in Taihu Lake Using Integrated Nontarget Screening, Target Analysis, and Risk Characterization.

Amidst tightening regulations, the proliferation of next-generation per- and polyfluoroalkyl substances (PFAS) necessitates a deeper understanding of their environmental fate and potential risks. Here, we conducted a comprehensive assessment of PFAS in the water and sediment of Taihu Lake, incorporating both nontarget and target screening, seasonal and geographical variation analysis, and risk prioritization. A total of 58 PFAS from 13 classes were identified, revealing complex PFAS contamination. In addition to short-chain perfluoroalkyl carboxylates (PFCAs) and sulfonates (PFSAs), bis(trifluoromethanesulfonyl)imide (Ntf2) and perfluoro-2,5-dimethyl-3,6-dioxo-heptanoic acid (C7 HFPO-TA) exhibited relatively high concentrations in water, with median values of 21.7 and 5.72 ng/L, respectively. Seasonal and geographical variation analysis revealed elevated levels of C7 HFPO-TA, Ntf2, and perfluorohexanoic acid (PFHxA) in the northeastern areas, suggesting transport via water diversion project. Multicriteria risk prioritization identified four high priority PFAS (Ntf2, C7 HFPO-TA, PFHxA, and perfluorooctanoic acid (PFOA)) in water and two high priority PFAS (hexafluoropropylene oxide dimer acid (HFPO-DA) and PFHxA) in sediment. Overall, this study revealed Ntf2 and C7 HFPO-TA as priority PFAS in Taihu Lake, underscoring the urgent necessity of evaluating risks associated with these emerging PFAS.

Interactions of Potential Endocrine-Disrupting Chemicals with Whole Human Proteome Predicted by AlphaFold2 Using an In Silico Approach.

Binding with proteins is a critical molecular initiating event through which environmental pollutants exert toxic effects in humans. Previous studies have been limited by the availability of three-dimensional (3D) protein structures and have focused on only a small set of environmental contaminants. Using the highly accurate 3D protein structure predicted by AlphaFold2, this study explored over 60 million interactions obtained through molecular docking between 20,503 human proteins and 1251 potential endocrine-disrupting chemicals. A total of 66,613,773 docking results were obtained, 1.2% of which were considered to be high binding, as their docking scores were lower than -7. Monocyte to macrophage differentiation factor 2 (MMD2) was predicted to interact with the highest number of environmental pollutants (526), with polychlorinated biphenyls and polychlorinated dibenzofurans accounting for a significant proportion. Dimension reduction and clustering analysis revealed distinct protein profiles characterized by high binding affinities for perfluoroalkyl and polyfluoroalkyl substances (PFAS), phthalate-like chemicals, and other pollutants, consistent with their uniquely enriched pathways. Further structural analysis indicated that binding pockets with a high proportion of charged amino acid residues, relatively low α-helix content, and high ß-sheet content were more likely to bind to PFAS than others. This study provides insights into the toxicity pathways of various pollutants impacting human health and offers novel perspectives for the establishment and expansion of adverse outcome pathway-based models.

Exposure and potential risks of thirteen endocrine- disrupting chemicals in pharmaceuticals and personal care products for breastfed infants in China.

Ingestion of breast milk represents the primary exposure pathway for endocrine-disrupting chemicals (EDCs) in newborns. To elucidate the associated risks, it is essential to quantify EDC levels in both breast milk and infant urine. This study measured the concentrations of 13 EDCs, including parabens (methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), iso-propyl paraben, butyl paraben, and iso-butyl paraben), bisphenols (bisphenol A (BPA), bisphenol F, bisphenol S, bisphenol AF, and bisphenol Z), triclosan (TCS), and triclocarban, in breast milk and infant urine to assess their potential health effects and endocrine disruption risks. In total, 1 014 breast milk samples were collected from 20 cities across China, along with 144 breast milk samples and 134 urine samples from a mother-infant cohort in Hangzhou. The EDCs were detected using ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry. Endocrine-disrupting potency was evaluated using a predictive method based on EDC affinity for 15 hormone receptor proteins. The toxicological priority index (ToxPi), incorporating population exposure data, was employed to assess health risks associated with exposure to multiple EDCs. Among the 13 EDCs, MP, EP, PP, BPA, and TCS were detected in over 50 % of breast milk samples, with the highest median concentrations observed for MP (0.37 ng/mL), EP (0.29 ng/mL), and BPA (0.17 ng/mL). Across the 20 cities, 0 %-40 % of infants had a hazard index (HI) exceeding 1. Based on affinity prediction analysis and estimated exposure, cumulative endocrine disruption risk intensity was ranked as MP > TCS > BPA > EP > PP. This research highlights the extensive exposure of Chinese infants to EDCs, offering a detailed analysis of their varying endocrine disruption potencies and underscoring the significant health risks associated with EDCs in breast milk.

On-site evaluation of DGT passive sampling for quantitatively measuring per- and polyfluoroalkyl substances in a river-estuary-sea water system.

The passive sampling technique of diffusive gradients in thin-films (DGT) is promising for monitoring emerging contaminants such as per- and polyfluoroalkyl substances (PFAS). It is urgent to evaluate the impacts of salinity and exposure time on DGT sampling before it can be set as a standard method. Herein, DGT sampler based on the binding gel of weak anion exchanger (WAX) resin was deployed in a representative water system of the Xiaoqing river-estuary-sea for representative sampling windows (<1 day to 28 days) with high pH (8.18 ± 0.04 to 8.51 ± 0.17) and wide ranges of salinity (0.95 ± 0.07‰ to 14.37 ± 3.92‰), total dissolved solids (1.20 ± 0.09 g/L to 15.29 ± 3.91 g/L) and dissolved organic matter (2.8-32 mg/L). The results showed that the WAX-DGT sampler exhibited good performance for most target PFAS except for short-chain perfluorocarboxylates (C ≤ 5) in 14 days. When the exposure time was over 14 days, biofouling of the sampler may deflect the mass accumulation of the PFAS in the sampler. Salinity played an important role in the mass binding of PFAS by DGT. The shorter the carbon chain of the compound, the greater the influence of the salinity. PFAS with carboxyl groups had greater affinities for the biofouled membrane filter than those with sulfonic groups. In the river-estuary-sea system, where PFAS concentrations changed dynamically, the temporal resolution of the monitoring strategy has been demonstrated to be more important than spatial resolution. DGT provided a better integral of PFAS exposure than grab sampling in the dynamic water system and offered equivalent sensitivity of grab sampling with exposure time <10 d and greater sensitivity with exposure time ≥10 d. Thus, DGT has the advantage of providing high temporal resolution monitoring. This study provided support for the standardization of the DGT technique.

Associations of Serum Per- and Polyfluoroalkyl Substances with Hyperuricemia in Adults: A Nationwide Cross-Sectional Study.

There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. METHODS: This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. RESULTS: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. CONCLUSIONS: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.

Dietary seafood as a potential modifier in the relationship between per- and polyfluoroalkyl substances (PFASs) burden and prediabetes/diabetes: Insights from a nationally representative cross-sectional study.

While seafood is recognized for its beneficial effects on glycemic control, concerns over elevated levels of per- and polyfluoroalkyl substances (PFASs) may deter individuals from its consumption. This study aims to elucidate the relationship between seafood intake, PFASs exposure, and the odds of diabetes. Drawing from the China National Human Biomonitoring data (2017-2018), we assessed the impact of PFASs on the prevalence of prediabetes and diabetes across 10851 adults, including 5253 individuals (48.1%) reporting seafood consumption. Notably, seafood consumers exhibited PFASs levels nearly double those of non-consumers. Multinomial logistic regression identified significant positive associations between serum PFASs concentrations and prediabetes (T3 vs. T1: ORPFOA: 1.64 [1.08-2.49], ORPFNA: 1.59 [1.19-2.13], ORPFDA: 1.56 [1.13-2.17], ORPFHxS: 1.58 [1.18-2.12], ORPFHpS: 1.73 [1.24-2.43], ORPFOS: 1.51 [1.15-1.96], OR6:2 Cl-PFESA: 1.58 [1.21-2.07]). Significant positive association were also found between PFHpS, PFOS, and diabetes. RCS curves indicated significant non-linear relationships between log-transformed PFOA, PFUnDA, PFOS, 6:2 Cl-PFESA, and FBG levels. Subgroup analyses revealed that seafood consumption significantly mitigated the associations between PFASs burdens and prediabetes/diabetes. These findings suggest a protective role of dietary seafood against the adverse effects of PFASs exposure on glycemic disorders, offering insights for dietary interventions aimed at mitigating diabetes risks associated with PFASs.

Nationwide distribution of perfluoroalkyl ether carboxylic acids in Chinese diets: An emerging concern.

With the phase-out of perfluorooctanoic acid (PFOA) and its replacement by perfluoroalkyl ether carboxylic acids (PFECAs), there is a potential for increased exposure to various new PFECAs among the general population in China. While there are existing studies on dietary exposure to legacy perfluoroalkyl and polyfluoroalkyl substances (PFASs), research on dietary exposure to PFECAs, especially among the general Chinese populace, remains scarce. In the present study, we investigated the distribution of PFECAs in dietary sources from 33 cities across five major regions in China, along with the associated dietary intake. Analysis indicated that aquatic animal samples contained higher concentrations of legacy PFASs compared to those from terrestrial animals and plants. In contrast, PFECAs were found in higher concentrations in plant and terrestrial animal samples. Notably, hexafluoropropylene oxide dimer (HFPO-DA) was identified as the dominant compound in vegetables, cereals, pork, and mutton across the five regions, suggesting widespread dietary exposure. PFECAs constituted the majority of PFAS intake (57 %), with the estimated daily intake (EDI) of HFPO-DA ranging from 2.33 to 3.96 ng/kg bw/day, which corresponds to 0.78-1.32 times the reference dose (RfD) (3.0 ng/kg bw/day) set by the United States Environmental Protection Agency. Given the ubiquity of HFPO-DA and many other PFECAs in the nationwide diet of China, there is an urgent need for further research into these chemicals to establish relevant safety benchmarks or consumption advisory values for the diet.

Impact of Gestational Exposure to Individual and Combined Per- and Polyfluoroalkyl Substances on a Placental Structure and Efficiency: Findings from the Ma'anshan Birth Cohort.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.

Associations between serum per- and polyfluoroalkyl substances and thyroid hormones in Chinese adults: A nationally representative cross-sectional study.

Disruption of thyroid homeostasis has been indicated in human studies on the effects of per- and polyfluoroalkyl substances (PFASs). However, limited research exists on this topic within the general Chinese population. Based on a substantial and representative sample of the Chinese adult population, our study provides insight into how PFASs specifically affect thyroid homeostasis. The study included 10 853 participants, aged 18 years and above, sampled from nationally representative data provided by the China National Human Biomonitoring (CNHBM). Weighted multiple linear regression and restricted cubic spline (RCS) models were used to explore the associations between eight individual PFAS concentrations and total thyroxine (T4), total triiodothyronine (T3), and the T4/T3 ratio. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (qgcomp) were employed to explore the joint and independent effects of PFASs on thyroid homeostasis. Both individual PFASs and PFAS mixtures exhibited a significant inverse association with serum T3 and T4 levels, and displayed a positive association with the T4/T3 ratio. Perfluoroundecanoic acid (PFUnDA) [-0.07 (95 % confidence interval (CI): -0.08, -0.05)] exhibited the largest change in T3 level. PFUnDA also exhibited a higher weight compared to other PFAS compounds in qgcomp models. Additionally, a critical exposure threshold for each PFAS was identified based on nonlinear dose-response associations; beyond these thresholds, the decreases in T3 and T4 levels plateaued. Specifically, for perfluoroheptane sulfonic acid (PFHpS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an initial decline in hormone levels was observed, followed by a slight increase when concentrations surpassed 0.7 ng/mL and 2.5 ng/mL, respectively. Sex-specific effects were more pronounced in females, and significant associations were observed predominantly in younger age groups. These insights contribute to our understanding of how PFAS compounds impact thyroid health and emphasize the need for further research and environmental management measures to address these complexities.

Comprehensive Assessment of Exposure Pathways for Perfluoroalkyl Ether Carboxylic Acids (PFECAs) in Residents Near a Fluorochemical Industrial Park: The Unanticipated Role of Cereal Consumption.

With the replacement of perfluorooctanoic acid (PFOA) with perfluorinated ether carboxylic acids (PFECAs), residents living near fluorochemical industrial parks (FIPs) are exposed to various novel PFECAs. Despite expectations of low accumulation, short-chain PFECAs, such as perfluoro-2-methoxyacetic acid (PFMOAA), previously displayed a considerably high body burden, although the main exposure routes and health risks remain uncertain. Here, we explored the distribution of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in diverse environmental media surrounding a FIP in Shandong Province, China. PFECAs were found at elevated concentrations in all tested matrices, including vegetables, cereals, air, and dust. Among residents, 99.3% of the ∑36PFAS exposure, with a 43.9% contribution from PFECAs, was due to gastrointestinal uptake. Dermal and respiratory exposures were negligible at 0.1 and 0.6%, respectively. The estimated daily intake (EDI) of PFMOAA reached 114.0 ng/kg body weight (bw)/day, ranking first among all detected PFECAs. Cereals emerged as the dominant contributor to PFMOAA body burden, representing over 80% of the overall EDI. The median EDI of hexafluoropropylene oxide dimer acid (HFPO-DA) was 17.9 ng/kg bw/day, markedly higher than the USEPA reference doses (3.0 ng/kg bw/day). The absence of established threshold values for other PFECAs constrains a comprehensive risk assessment.

Association between Serum Per- and Polyfluoroalkyl Substance Levels and Risk of Central and Peripheral Precocious Puberty in Girls.

Concerns about the endocrine-disrupting effects of per- and polyfluoroalkyl substances (PFASs) have raised questions about their potential influence on precocious puberty in girls, which is an emerging concern in some populations. However, epidemiological evidence is lacking. In this study, 882 serum samples were collected from girls with central precocious puberty (CPP, n = 226), peripheral precocious puberty (PPP, n = 316), and healthy controls (n = 340) in 2021 in Shanghai, China. The serum levels of 25 legacy and emerging PFASs and 17 steroids were measured. Results showed that PFAS exposure was positively associated with estradiol levels. Eleven PFASs were significantly or marginally associated with the higher odds of the overall precocious puberty. Across subtypes, PFASs were more clearly associated with PPP, while the associations with CPP were consistent in direction but did not reach statistical significance. These findings were consistent with the assessment of PFAS mixtures using quantile-based g-computation (qgcomp) and Bayesian kernel machine regression, with perfluorobutane sulfonate and 6:2 polyfluorinated ether sulfonate showing the highest contribution to joint effects. Although changes in serum estradiol could arise from various factors, our results suggest that the PFAS exposure may contribute to the increase in estradiol secretion, thereby increasing the risk of precocious puberty, especially PPP. The potential effects of PFASs on precocious puberty warrant further investigation, given the associated complications of public health concern, including psychological distress and increased risk of multiple diseases.

Trophic behaviors of PFOA and its alternatives perfluoroalkyl ether carboxylic acids (PFECAs) in a coastal food web.

With the increasing restrictions and concerns about legacy poly- and perfluoroalkyl substances (PFAS), the production and usage of alternatives, i.e., perfluoroalkyl ether carboxylic acids (PFECAs), have risen recently. However, there is a knowledge gap regarding the bioaccumulation and trophic behaviors of emerging PFECAs in coastal ecosystems. The bioaccumulation and trophodynamics of perfluorooctanoic acid (PFOA) and its substitutes (PFECAs) were investigated in Laizhou Bay, which is located downstream of a fluorochemical industrial park in China. Hexafluoropropylene oxide trimer acid (HFPO-TrA), perfluoro-2-methoxyacetic acid (PFMOAA) and PFOA constituted the dominant compounds in the ecosystem of Laizhou Bay. PFMOAA was dominant in invertebrates, whereas the long-chain PFECAs preferred to accumulate in fishes. The PFAS concentrations in carnivorous invertebrates were higher than those in filter-feeding species. Considering migration behaviors, the ∑PFAS concentrations followed the order oceanodromous fish < diadromous fish < non-migratory fish. The trophic magnification factors (TMFs) of long-chain PFECAs (HFPO-TrA, HFPO-TeA and PFO5DoA) were >1, suggesting trophic magnification potential, while biodilution for short-chain PFECAs (PFMOAA) was observed. The intake of PFOA in seafood may constitute a great threat to human health. More attention should be given to the impact of emerging hazardous PFAS on organisms for the health of ecosystems and human beings.

Design and research of soft-body cavity-type detonation drivers.

According to the high-energy-density movement characteristics of animals during jumping, soft-body cavity-type detonation driver that combines the explosive chemical reaction mechanism of hydrogen and oxygen is designed, in order to control the robot in jump to achieve output optimization. Then, combined with the theoretical values of the detonation dynamic equation and experimental data for the performance parameters, the influences of the mixing ratio of hydrogen (H2) and oxygen (O2), the volume of mixed hydrogen and oxygen in the cavity, and the shape, wall thickness, and area ratio value of the soft-body cavity on the output performance of the detonation driver are analyzed. When gas volume is 20:10 mL, the jump height reaches 2.5 m. In addition, the upper and lower area ratio of cavity is optimized to 2:1, improving the output performance by 21.6% on average. Therefore, the above research results provide reference for the driver structure design of jumping robot.

Emerging and Legacy Perfluoroalkyl Substances in Breastfed Chinese Infants: Renal Clearance, Body Burden, and Implications.

BACKGROUND: Human breast milk is a primary route of exposure to perfluoroalkyl substances (PFAS) in infants. To understand the associated risks, the occurrence of PFAS in human milk and the toxicokinetics of PFAS in infants need to be addressed. OBJECTIVES: We determined levels of emerging and legacy PFAS in human milk and urine samples from Chinese breastfed infants, estimated renal clearance, and predicted infant serum PFAS levels. METHODS: In total, human milk samples were collected from 1,151 lactating mothers in 21 cities in China. In addition, 80 paired infant cord blood and urine samples were obtained from two cities. Nine emerging PFAS and 13 legacy PFAS were analyzed in the samples using ultra high-performance liquid chromatography tandem mass spectrometry. Renal clearance rates (CLrenals) of PFAS were estimated in the paired samples. PFAS serum concentrations in infants (<1 year of age) were predicted using a first-order pharmacokinetic model. RESULTS: All nine emerging PFAS were detected in human milk, with the detection rates of 6:2 Cl-PFESA, PFMOAA, and PFO5DoDA all exceeding 70%. The level of 6:2 Cl-PFESA in human milk (median concentration=13.6 ng/L) ranked third after PFOA (336 ng/L) and PFOS (49.7 ng/L). The estimated daily intake (EDI) values of PFOA and PFOS exceeded the reference dose (RfD) of 20 ng/kg BW per day recommended by the U.S. Environmental Protection Agency in 78% and 17% of breastfed infant samples, respectively. 6:2 Cl-PFESA had the lowest infant CLrenal (0.009mL/kg BW per day), corresponding to the longest estimated half-life of 49 y. The average half-lives of PFMOAA, PFO2HxA, and PFO3OA were 0.221, 0.075, and 0.304 y, respectively. The CLrenals of PFOA, PFNA, and PFDA were slower in infants than in adults. CONCLUSIONS: Our results demonstrate the widespread occurrence of emerging PFAS in human milk in China. The relatively high EDIs and half-lives of emerging PFAS suggest potential health risks of postnatal exposure in newborns. https://doi.org/10.1289/EHP11403.

Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study.

Although previous studies have reported an association between maternal serum perfluoroalkyl substance (PFAS) exposure and gestational diabetes mellitus (GDM) risk, results have been inconsistent. Few studies have focused on the combined effects of emerging and legacy PFASs on glucose homeostasis while humans are always exposed to multiple PFASs simultaneously. Moreover, the potential pathways by which PFAS exposure induces GDM are unclear. A total of 295 GDM cases and 295 controls were enrolled from a prospective cohort of 2700 pregnant women in Shanghai, China. In total, 16 PFASs were determined in maternal spot serum samples in early pregnancy. We used conditional logistic regression, multiple linear regression, and Bayesian kernel machine regression (BKMR) to examine individual and joint effects of PFAS exposure on GDM risk and oral glucose tolerance test outcomes. The mediating effects of maternal serum biochemical parameters, including thyroid and liver function were further assessed. Maternal perfluorooctanoic acid (PFOA) exposure was associated with an increased risk of GDM (odds ratio (OR) = 1.68; 95% confidence interval (95% CI): 1.10, 2.57), consistent with higher concentrations in GDM cases than controls. Based on mediation analysis, an increase in the free triiodothyronine to free thyroxine ratio partially explained the effect of this association. For continuous glycemic outcomes, positive associations were observed between several PFASs and 1-h and 2-h glucose levels. In BKMR, PFAS mixture exposure showed a positive trend with GDM incidence, although the CIs were wide. These associations were more pronounced among women with normal pre-pregnancy body mass index (BMI). Mixed PFAS congeners may affect glucose homeostasis by increasing 1-h glucose levels, with perfluorononanoic acid found to be a main contributor. Exposure to PFASs was associated with increased risk of GDM and disturbance in glucose homeostasis, especially in normal weight women. The PFAS-associated disruption of maternal thyroid function may alter glucose homeostasis.

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption.

The placenta is pivotal for fetal development and maternal-fetal transfer of many substances, including per- and polyfluoroalkyl substances (PFASs). However, the intraplacental distribution of PFASs and their effects on placental vascular function remain unclear. In this study, 302 tetrads of matched subchorionic placenta (fetal-side), parabasal placenta (maternal-side), cord serum, and maternal serum samples were collected from Guangzhou, China. Eighteen emerging and legacy PFASs and five placental vascular biomarkers were measured. Results showed that higher levels of perfluorooctanoic (PFOA), perfluorooctane sulfonic acid (PFOS), and chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) were detected in subchorionic placenta compared to parabasal placenta. There were significant associations of PFASs in the subchorionic placenta, but not in the serum, with placental vascular biomarkers (up to 32.5%) and lower birth size. Birth weight was negatively associated with PFOA (ß: -103.8, 95% CI: -186.3 and -21.32) and 6:2 Cl-PFESA (ß: -80.04, 95% CI: -139.5 and -20.61), primarily in subchorionic placenta. Mediation effects of altered placental angiopoietin-2 and vascular endothelial growth factor receptor-2 were evidenced on associations of adverse birth outcomes with intraplacental PFOS and 8:2 Cl-PFESA, explaining 9.5%-32.5% of the total effect. To the best of our knowledge, this study is the first to report on differential intraplacental distribution of PFASs and placental vascular effects mediating adverse birth outcomes and provides novel insights into the placental plate-specific measurement in PFAS-associated health risk assessment.

Serum per- and polyfluoroalkyl substances and abnormal lipid metabolism: A nationally representative cross-sectional study.

BACKGROUND: The associations of legacy per- and polyfluoroalkyl substances (PFAS) with lipid metabolism are controversial, and there is little information about the impact of emerging PFAS (6:2 Cl-PFESA) on lipid metabolism in China. OBJECTIVES: We aimed to explore the associations of legacy and emerging PFAS with lipid profiles and dyslipidemia in Chinese adults. METHODS: We included 10,855 Chinese participants aged 18 years and above in the China National Human Biomonitoring. The associations of 8 PFAS with 5 lipid profiles and 4 dyslipidemia were investigated using weighted multiple linear regression or weighted logistic regression, and the dose-response associations were investigated using restricted cubic spline model. RESULTS: Among the 8 PFAS, the concentration of PFOS was the highest, with a geometric mean of 5.15 ng/mL, followed by PFOA and 6:2 Cl-PFESA, which were 4.26 and 1.63 ng/mL, respectively. Legacy (PFOA, PFOS, PFUnDA) or emerging (6:2 Cl-PFESA) PFAS were associated with lipid profiles (TC, LDL-C, HDL-C, non HDL-C) and dyslipidemia (high LDL-C, high TC, low HDL-C), and their effects on TC were most obvious. TC concentration increased by 0.595 mmol/L in the highest quartile (Q4) of PFOS when compared with the lowest quartile (Q1), (95 % CI:0.396, 0.794). Restricted cubic spline models showed that PFAS are nonlinearly associated with TC, non HDL-C, LDL-C and HDL-C, and that the lipid concentrations tend to be stable when PFOS and PFOA were > 20 ng/mL well as when the 6:2 Cl-PFESA level was > 10 ng/mL. The positive associations between PFAS mixtures and lipid profiles were also significant. CONCLUSIONS: Single and mixed exposure to PFAS were positively associated with lipid profiles, and China's unique legacy PFAS substitutes (6:2 Cl-PFESA) contributed less to lipid profiles than legacy PFAS. In the future, cohort studies will be needed to confirm our findings.

Associations between per and polyfluoroalkyl ether sulfonic acids and vitamin D biomarker levels in Chinese newborns.

Skeleton develops extremely fast during fetal and neonatal stages; thus, fetuses and newborns exhibit unique vulnerabilities to vitamin D metabolism dysregulation, giving vitamin D's principal role in calcium homeostasis. Previous studies linked legacy per and polyfluoroalkyl ether sulfonic acids (PFAS) with vitamin D biomarker status in adults and children; however, how PFAS, especially emerging CI-PFESAs, influence vitamin D among newborns is unknown. This study focused on the epidemiological linkages between PFAS and vitamin D biomarkers. Eleven PFAS, including legacy PFAS and emerging CI-PFESAs, as well as two vitamin D metabolites [25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3)], were determined in cord sera of 992 newborns from a birth cohort in Wuhan, China. The cord serum levels of 25(OH)D2 and 25(OH)D3 were summed as total 25(OH)D, which is a reliable biomarker of vitamin D status. The associations of separated PFAS with vitamin D biomarker levels were analyzed via multiple linear models, whereas the mixture effect was estimated by utilizing the weighted quantile sum (WQS) regression. We observed that per doubling changes in perfluorotridecanoate (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were associated with a 6.04 to 9.05 % change in total 25(OH)D levels. PFHxS contributed over half of the PFAS mixture effect on total 25(OH)D. Stratified analysis indicated that the associations of certain PFAS with vitamin D biomarkers were more pronounced among boys. The emerging CI-PFESAs were not robustly related to vitamin D biomarker levels. The results suggested that exposure to legacy PFAS might disturb vitamin D status in newborns. Future epidemiological studies are required to confirm the association and to determine healthy implications at a later age.

Association of phthalate exposure with low birth weight in couples conceiving naturally or via assisted reproductive technology in a prospective birth cohort.

BACKGROUND: Few studies have investigated the adverse effects of preconception phthalate (PAE) exposure on birth weight in couples receiving assisted reproductive technology (ART) compared to naturally conceived newborns. OBJECTIVES: We examined the association between parental preconception/prenatal urinary phthalate exposure and low birth weight (LBW) risk in couples who conceived using ART or naturally. METHODS: From the Jiangsu Birth Cohort Study (China), we recruited 544 couples who conceived after infertility treatment and 940 couples who conceived naturally and gave birth to a singleton infant between November 2014 and December 2019. Seventeen metabolites of phthalate and three metabolites of phthalate alternatives were analyzed in parental spot urine samples. Clinical data were collected from medical records. We used generalized linear models, elastic net regression, Bayesian kernel machine regression, and quantile-based g-computation to examine the individual and joint effects of parental phthalate exposure on birth weight and LBW risk ratios (RR). RESULTS: The relationship between parental phthalate exposure and birth weight was consistent between ART and natural conception. Maternal exposure to mono-ethyl phthalate and mono-carboxyisooctyl phthalate was associated with an increased risk of LBW in ART-conceived infants (RR = 1.27; 95 % confidence interval (CI): 1.03, 1.56; and RR = 1.31; 95 % CI: 1.03, 1.67, respectively). In contrast, in the spontaneously conceived infants, higher paternal prenatal concentrations of mono-benzyl phthalate and mono-carboxyisononyl phthalate were associated with a 40 % and 53 % increase in LBW risk, respectively. Exposure to PAE mixtures was associated with LBW in ART-conceived infants, with the effects primarily driven by di-ethyl phthalate, benzylbutyl phthalate, and di-isononyl phthalate metabolites. Sex-specific LBW was observed, with females appearing to be more susceptible than males. CONCLUSIONS: Maternal preconception and paternal prenatal exposure to phthalates were associated with increased risk of LBW in infants. Compared with natural conception, ART-conceived fetuses were more sensitive to PAE mixtures, which requires further attention.