Individual Perfluoroalkyl Substances Research Articles

Early life poly- and perfluoroalkyl substance levels and adiposity in the first 2 years of life.

Poly- and perfluoroalkyl substances (PFASs) are nondegradable, man-made chemicals. They accumulate in humans with potential harmful effects, especially in susceptible periods of human development, such as the first months of life. We found that, in our cohort, exclusively breastfed (EBF) infants had 3 times higher PFAS plasma levels compared with exclusively formula-fed (EFF) infants at the age of 3 months. Thus, PFASs could potentially reduce the health benefits of breastfeeding. We investigated the associations between PFAS levels at the age of 3 months and accelerated gain in fat mass during the first 6 months of life, body composition at 2 years, and whether these associations differ between EBF and EFF infants. In 372 healthy term-born infants, we longitudinally assessed anthropometrics, body composition (by air-displacement plethysmography and dual-energy X-ray absorptiometry), and visceral and subcutaneous fat (by abdominal ultrasound) until the age of 2 years. The plasma levels of 5 individual PFASs were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry at the age of 3 months. We studied associations between PFAS levels and outcomes using multiple regression analyses. Higher early life plasma perfluorooctanoic acid and total PFAS levels were associated with an accelerated gain in fat mass percentage [FM%; >0.67 SD score (SDS)] during the first 6 months of life. Higher early life PFAS levels were associated with lower fat-free mass (FFM) SDS at the age of 2 years, but not with total FM% SDS at 2 years. Furthermore, we found opposite effects of PFAS levels (negative) and exclusive breastfeeding (positive) at the age of 3 months on FFM SDS at 2 years. Higher PFAS levels in early life are associated with accelerated gains in FM% during the first 6 months of life and with lower FFM SDS at the age of 2 years, which have been associated with an unfavorable body composition and metabolic profile later in life. Our findings warrant further research with longer follow-up times.

Prenatal exposure to poly- and perfluoroalkyl substances and postpartum depression in women with twin pregnancies

BackgroundWomen with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. ObjectiveTo estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. MethodsOur study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. ResultsUsing quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. ConclusionsThe first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.

Occurrence, mass loading, and post-control temporal trend of legacy perfluoroalkyl substances (PFASs) in the middle and lower Yangtze River

Present study focused on per- and polyfluoroalkyl substances (PFASs) occurrence in dry and wet seasons in the middle and lower Yangtze River (YZR) and changing temporal trends after years of control. Results revealed that perfluorooctanoic acid (PFOA) was 75 % of total PFAS concentrations (∑11PFASs). ∑11PFASs were ranged 0.20–28.49 ng/L and 1.17–112.84 μg/kg in water and sediment. The logKoc of perfluoroalkyl carboxylic acids was positive with the carbon chain length (p < 0.05, r2 = 0.78). A meta-analysis of results from 16 peer-reviewed publications about PFASs in the YZR showed that fluorochemical industries strongly influenced the high PFAS levels in the detected scenes. PFOA was still the primary pollutant. Individual PFAS in the lower reach was higher than those in the middle reach. The mass loading of PFASs imported into the sea was 10.80 t/y. This study will help develop effective approaches for controlling emerging pollutants in the YZR.

Prenatal Exposure to Poly- and Perfluoroalkyl Substances (2009-2014) and Vaccine Antibody Titers of Measles, Mumps, Rubella, and Varicella in Children Four to Eight Years Old from the Healthy Start Cohort.

Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations. We estimated associations between prenatal PFAS exposure and child antibody titers for measles, mumps, rubella (MMR), and varicella after immunization. We measured serum antibody titers of 145 children (4-8 y old) enrolled in the Healthy Start cohort in Colorado, whose mothers had PFAS quantified mid-pregnancy (2009-2014). We used linear and logistic regression models to assess the relationship between five PFAS detected in of mothers and continuous or non-high-censored ("low") antibody titers and quantile g-computation to evaluate the overall effect of the PFAS mixture. Median concentrations of individual PFAS were at or below the median reported among females in the United States. After receiving two vaccine doses, seropositive levels of antibodies were detected among most (93%-100%) children. Each log-unit increase in perfluorononanoate was associated with 2.09 [95% confidence interval (CI): 1.13, 3.87] times higher odds of a low measles titer, and each log-unit increase in perfluorooctanoate was associated with 2.46 (95% CI: 1.28, 4.75) times higher odds of a low mumps titer. Odds ratios for all other PFAS were elevated, but CIs included the null. Each quartile increase in the PFAS mixture was associated with 1.35 (95% CI: 0.80, 2.26) times higher odds of a low measles titer and 1.44 (95% CI: 0.78, 2.64) times higher odds of a low mumps titer. No significant associations were observed between PFAS and varicella or rubella antibodies. In stratified analyses, associations were negative among female children, except for perfluorohexane sulfonate and varicella, whereas they were positive among males. Some prenatal PFAS were associated with lower antibody titers among fully immunized children. The potential for immunotoxic effects of PFAS requires further investigation in a larger study, because exposure is ubiquitous globally. https://doi.org/10.1289/EHP12863.

Perfluoroalkyl substances in umbilical cord blood and blood pressure in offspring: a prospective cohort study

BackgroundHumans are widely exposed to perfluoroalkyl substances (PFAS), which have been found to be associated with various adverse birth outcomes. As blood pressure (BP) is an important parameter reflecting cardiovascular health in early life, it is necessary to investigate the association of PFAS exposure during early lifetime and BP in childhood. Therefore, we investigated the potential association between PFAS levels in umbilical cord blood and BP of the offspring at 4 years of age in a prospective cohort study.MethodsPFAS in umbilical cord blood samples after birth were measured with high-performance liquid chromatography/tandem mass spectrometry in the Shanghai Birth Cohort. BP was measured at 4 years of age in the offspring. Multiple linear regression model was used to investigate the association between individual PFAS level and BP of the offspring. Bayesian kernel machine regression (BKMR) was used to analyze the relationship between the PFAS mixture and BP of the offspring, while weighted quantile sum (WQS) regression was utilized for sensitivity analysis.ResultsA total of 129 mother-child pairs were included in our analysis. In multiple linear regressions, we observed that long-chain PFAS, mainly including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUA), was negatively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP). BKMR showed that an increase in umbilical cord blood PFAS mixture levels was significantly associated with a decrease in SBP, DBP and MAP [Estimated differences (SD): -0.433 (0.161); -0.437 (0.176); -0.382 (0.179), respectively]. The most important component in the association with SBP, DBP, and MAP was PFUA. PFDoA was found to be positively associated with SBP, DBP and MAP in both models. Sensitivity analysis with WQS regression showed consistent results.ConclusionOur findings suggested that umbilical blood PFAS exposure was negatively associated with BP in offspring at 4 years of age, including SBP, DBP, and MAP.

SAT445 Exposure To Perfluoroalkyl Substances At Preconception In Association With Metabolic Phenotype In Women From Singapore

Abstract Disclosure: N.J. Cohen: None. M. Yao: None. V. Midya: None. S. India-Aldana: None. S.S. Andra: None. S. Narasimhan: None. A.K. Meher: None. M. Arora: None. J.K. Chan: None. S.Y. Chan: None. Y. Kway: None. N. Michael: None. S.A. Sadanathan: None. J.G. Eriksson: None. S.S. Velan: None. T.K. Hian: None. Y. Oulhote: None. J. Huang: None. D. Valvi: None. Background and Aim: Exposure to perfluoroalkyl substances (PFAS) may result in adverse metabolic health outcomes, but few studies have focused on preconception PFAS exposures and metabolic dysregulation which could impact pregnancy. We assessed cross-sectional and prospective associations between preconception PFAS concentrations and glucose regulation, insulin sensitivity, and magnetic resonance imaging (MRI) based adiposity measures in a Singaporean cohort of women who were actively attempting to conceive. Methods: Our analyses included 384 participants from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), from which 126 underwent abdominal MRI at preconception. 15 different PFAS in preconception plasma samples were measured, and metabolic measures were cross-sectionally assessed at preconception (waist-to-height ratio [WHtR], 2-hour oral glucose tolerance test [OGTT] indices, and MRI-based measures of abdominal adiposity and liver fat), and prospectively at 24-28 weeks of gestation (2-hour OGTT indices). We used linear regression models to assess associations between individual PFAS and metabolic phenotype at preconception and pregnancy. In addition, we used Bayesian weighted quantile sum (BWQS) regression to assess the joint associations of the PFAS mixture with study outcomes. Results: We observed negative associations between perfluorononanoic acid (PFNA) concentrations and visceral adipose tissue (VAT; log2-transformed) volume (β per doubling of PFNA=-0.12 cm3, 95% CI -0.24, 0.00) and log2-transformed liver fat percentage (β=-0.28%, 95% CI -0.52, -0.04). Inverse associations were observed between the individual PFAS and most mid-pregnancy OGTT indices and insulin resistance, but were not statistically significant. Associations were not statistically significant for all preconception OGTT indices. Conclusions: We did not find strong evidence for an association between preconception PFAS concentrations and prenatal metabolic outcomes in young women in Singapore. Cross-sectional analyses indicated reduced adiposity in VAT volume and liver fat percentage with increasing PFAS concentration, which requires further investigation in prospective, more diverse, and larger studies. Presentation: Saturday, June 17, 2023

In utero exposure to poly- and perfluoroalkyl substances and children respiratory health in the three first years of life

BackgroundPoly- and perfluoroalkyl substances (PFAS) are used in a wide range of products. Experimental studies suggested impaired lung development and pro-inflammatory response following exposure to some PFAS. We aimed to assess the associations between prenatal exposure to PFAS and children respiratory health. MethodsThe study is based on 433 mother-child pairs. 26 PFAS were measured in maternal serum collected during pregnancy. Lung function parameters were measured at 2 months using tidal breathing flow-volume loops and multiple-breath nitrogen washout and at 36 months using oscillometry. Incidence of respiratory health diseases (asthma, wheeze, bronchitis, bronchiolitis) in the first 36 months of life was assessed by repeated questionnaires. A cluster-based analysis was applied to identify prenatal PFAS exposure patterns. Adjusted linear and logistic regressions were performed to assess the associations between PFAS exposure patterns as well as individual PFAS, and each respiratory health parameter. ResultsWe excluded 13 PFAS due to low quantification (<5%). Relying on the 13 remaining PFAS, we identified three exposure clusters, characterized by low (N = 163), medium (N = 236) and high (N = 51) pregnancy PFAS concentrations. Compared to children belonging to the low exposure group, children in the moderate exposure group had higher reactance at 7 Hz (X7) and lower frequency dependence of resistance between 7 Hz and 19 Hz (R7-19) at 36 months, suggesting better lung function. No association of any exposure metric was detected with respiratory diseases in the first 3 years of life. ConclusionsOur study relying on both mixture and uni-pollutant analyses, does not provide evidence for a deleterious effect of prenatal PFAS exposure on respiratory health at an early age.

Prenatal exposure to legacy PFAS and neurodevelopment in preschool-aged Canadian children: The MIREC cohort

BackgroundExposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. ObjectiveTo quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex. MethodsWe measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics. ResultsGeometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10–2.50), 4.97 (3.20–6.20) and 1.09 (0.67–1.60) μg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p < .01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = −2.80, 95% CI: −4.92, −0.68; PFOS: B = −2.64, 95% CI: −4.77, −0.52; PFHxS: B = −2.92, 95% CI: −4.72, −1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = −3.16, 95% CI: −4.90, −1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: −0.99, 2.26). No significant associations were found for EF in either males or females. ConclusionsHigher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific.

Prenatal exposure to perfluoroalkyl substances and child intelligence quotient: Evidence from the Shanghai birth cohort

Background and aimEpidemiological evidence on the association between prenatal exposure to Perfluoroalkyl substances (PFAS) and child cognition remains unclear. Thus, we aimed to investigate whether prenatal exposure to PFAS is associated with intelligence quotient (IQ) in offspring. MethodThis study population included 2031 mother-child pairs in the Shanghai Birth Cohort (SBC) enrolled during 2013–2016. Ten PFAS were measured by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in maternal plasma samples collected in early gestation between 9 and 16 weeks of gestation. Child IQ was assessed using the Wechsler Preschool and Primary Scales of Intelligence-Fourth Edition (WPPSI-IV) at 4 years of age. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into tertiles) and child IQ. A quantile g-computation approach was used to evaluate the joint and independent effects of PFAS on IQ. We also examined whether the associations varied by child sex. ResultsWe found no significant associations between ln-transformed nine individual PFAS and child full scale IQ (FSIQ) or subscale IQ after adjusting for potential confounders. The observed associations were not modified by child sex. PFAS in tertiles showed the same pattern. Results from quantile g-computation showed that PFAS mixture was not associated with child IQ; perfluorobutane sulfonate was negatively associated with FSIQ (β, −0.81; 95 % CI: −1.55, −0.07), and perfluorooctane sulfonate was also associated with lower fluid reasoning index scores (β, −1.61; 95 % CI: −3.07, −0.16) while adjusting for the other PFAS. ConclusionPFAS mixture during early pregnancy was not associated with child IQ. For certain individual PFAS, there were inverse associations with FSIQ or subscale IQ. Considering the evidence is still inconsistent, further research is needed to confirm or refute these results in other populations and to elucidate the potential neurotoxicology of PFAS.

Perfluoroalkyl substances (PFASs) in aquatic products from the Yellow-Bohai Sea coasts, China: Concentrations and profiles across species and regions

Perfluoroalkyl substances (PFASs) are emerging contaminants capable of harming human health, primarily via ingesting aquatic products. The current study monitored a survey of 23 PFASs in 1049 aquatic products from the coasts of the Yellow-Bohai Sea in China to comprehensively investigate the concentrations and distributions of PFASs. PFOA, PFOS, PFNA, PFOSA, and PFUdA were more predominantly and frequently detected than other PFASs in all samples, dominating PFAS patterns in aquatic products. The mean levels of ∑PFASs in different species followed the order: marine shellfish > marine crustaceans > fish > cephalopods > sea cucumber. Profiles of PFASs differ between species, suggesting species-specific accumulation plays a role. Various aquatic species are potential environmental bioindicators that signal individual PFAS contamination. For instance, clams can act as a potential PFOA bioindicator. High ∑PFAS levels in some sites (such as Binzhou, Dongying, Cangzhou, and Weifang) could be attributed to industrial activities involving fluoropolymer manufacture. The differences between PFAS concentrations and profiles in aquatic products across the study regions have been proposed as PFAS fingerprints of the Yellow-Bohai Sea coasts. Analyses of principal components and Spearman correlations indicated that the precursor biodegradation possibly contribute to C8–C10 PFCAs in the study samples. This study reported a wide presence of PFASs in different species of aquatic products across the Yellow-Bohai Sea coasts. The potential health risks that PFASs pose in certain species (such as marine shellfish and marine crustaceans) should not be neglected.

Association between early-childhood exposure to perfluoroalkyl substances and ADHD symptoms: A prospective cohort study

There is evidence that exposure to perfluoroalkyl substances (PFAS) is associated with attention-deficit/hyperactivity disorder (ADHD) symptoms. Previous studies have focused on prenatal exposure to PFAS, and only few studies have examined the associations of early-childhood exposure, especially at low exposure levels. This study explored the association between early-childhood exposure to PFAS and ADHD symptoms later in childhood. In 521 children, we measured the serum levels of six PFAS in peripheral blood at the ages of 2 and 4 years, including perfluorooctanoate (PFOA), perfluornonanoicacid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonate (PFOS). The ADHD Rating Scale IV (ARS) was utilized to measure ADHD traits at 8 years of age. We explored the relationship between PFAS and ARS scores using Poisson regression models after adjusting for potential confounders. Levels of exposure to individual PFAS and the summed value were divided into quartiles to examine possible nonlinear relationships. All six PFAS exhibited inverted U-shaped curves. Children in the 2nd and 3rd quartile levels of each PFAS showed higher ARS scores than those in the1st quartile level. Below the 3rd quartile of the summed levels of six PFAS (ΣPFAS), a doubling of the ΣPFAS was associated with an 20.0 % (95 % CI: 9.5 %, 31.5 %) increase in ADHD scores. However, at the age of 4 years, none of the evaluated PFAS exhibited linear or nonlinear associations with the ARS scores. Thus, school-aged children may be vulnerable to the neurotoxic effects of exposure to PFAS at age 2 that contribute to ADHD, particularly at low to mid-levels.

Exposure to serum perfluoroalkyl substances and biomarkers of liver function: The Korean national environmental health survey 2015–2017

BackgroundExposure to perfluoroalkyl substances (PFAS) may increase the risk of liver disease by disrupting cholesterol and lipid synthesis/metabolism, leading to higher liver-enzyme concentrations. However, most studies assessing association between PFAS and liver enzymes focused on individual PFAS. Moreover, PFAS concentrations differ based on sex and obesity status, and it remains unclear whether these factors affect associations with liver function. Therefore, we examined the association between exposure to both individual and combined PFAS and liver-function biomarkers and assessed sex and obesity as effect modifiers in Korean adults. MethodsWe measured serum concentrations of the five most abundant PFAS (PFOA, PFOS, PFHxS, PFDA, PFNA) and three liver enzymes (alanine transaminase [ALT], aspartate aminotransferase [AST], γ-glutamyl transferase [GGT]) in 1404 adults from the Korean National Environmental Health Survey Cycle 3, 2015–2017. We used linear regression to evaluate associations between individual PFAS and liver-function biomarkers, assessing sex and obesity as possible effect modifiers, and performed Bayesian kernel machine regression and quantile g-computation to evaluate the overall effect of PFAS mixture on biomarkers of liver function. ResultsAmong 1404 Korean adults, all five PFAS were detected. Geometric mean concentration was highest for PFOS (16.11 μg/L), followed by PFOA (5.83 μg/L), PFHxS (2.21 μg/L), PFNA (2.03 μg/L), and PFDA (1.06 μg/L). In multivariable linear regression, all PFAS were positively associated with ALT, AST, and GGT; 2-fold increase in each PFAS was associated with 3.4–8.6% higher ALT, 2.4–4.6% higher AST, and 4.6–11.1% higher GGT (all p < 0.05). Positive associations for PFOA, PFDA, and PFNA with AST were stronger in men, and positive associations for PFOS with ALT and GGT were stronger in women. Compared to obese participants, nonobese participants had higher average percent changes in each enzyme, particularly GGT, when individual PFAS concentration doubled. Additionally, increased exposure to PFAS mixtures was associated with higher ALT, AST, and GGT. In quantile g-computations, simultaneous quartile increase in all PFAS was significantly associated with 6.9% (95%CI: 3.7, 10.2) higher ALT, 4.5% (95%CI: 2.4, 6.6) higher AST, and 8.3% (95%CI: 3.7, 13.1) higher GGT levels, on average. ConclusionsExposure to individual and combined PFAS is associated with higher liver enzymes in Korean adults, providing additional evidence for the association between PFAS exposure and risk of liver disease.

Exposure to perfluoroalkyl substances and women's fertility outcomes in a Singaporean population-based preconception cohort

ObjectivesExperimental models have demonstrated a link between exposure to perfluoroalkyl substances (PFAS) and decreased fertility and fecundability; however, human studies are scarce. We assessed the associations between preconception plasma PFAS concentrations and fertility outcomes in women. MethodsIn a case-control study nested within the population-based Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), we measured PFAS in plasma collected in 2015–2017 from 382 women of reproductive age trying to conceive. Using Cox proportional hazards regression (fecundability ratios [FRs]) and logistic regression (odds ratios [ORs]) models, we assessed the associations of individual PFAS with time-to-pregnancy (TTP), and the likelihoods of clinical pregnancy and live birth, respectively, over one year of follow-up, adjusting for analytical batch, age, education, ethnicity, and parity. We used Bayesian weighted quantile sum (BWQS) regression to assess the associations of the PFAS mixture with fertility outcomes. ResultsWe found a 5–10 % reduction in fecundability per quartile increase of exposure to individual PFAS (FRs [95 % CIs] for clinical pregnancy = 0.90 [0.82, 0.98] for PFDA; 0.88 [0.79, 0.99] for PFOS; 0.95 [0.86, 1.06] for PFOA; 0.92 [0.84, 1.00] for PFHpA). We observed similar decreased odds of clinical pregnancy (ORs [95 % CIs] = 0.74 [0.56, 0.98] for PFDA; 0.76 [0.53, 1.09] for PFOS; 0.83 [0.59, 1.17] for PFOA; 0.92 [0.70, 1.22] for PFHpA) and live birth per quartile increases of individual PFAS and the PFAS mixture (ORs [95 % CIs] = 0.61 [0.37, 1.02] for clinical pregnancy, and 0.66 [0.40, 1.07] for live birth). Within the PFAS mixture, PFDA followed by PFOS, PFOA, and PFHpA were the biggest contributors to these associations. We found no evidence of association for PFHxS, PFNA, and PFHpS and the fertility outcomes examined. ConclusionsHigher PFAS exposures may be associated with decreased fertility in women. The potential impact of ubiquitous PFAS exposures on infertility mechanisms requires further investigation.

Bone mass density following developmental exposures to perfluoroalkyl substances (PFAS): a longitudinal cohort study

BackgroundEnvironmental exposures to industrial chemicals, including perfluoroalkyl substances (PFAS), may play a role in bone development and future risk of osteoporosis. However, as prospective evidence is limited, the role of developmental PFAS exposures in bone density changes in childhood is unclear. The objective of this study was to estimate associations between serum-PFAS concentrations measured in infancy and early childhood and areal bone mineral density (aBMD) measured at age 9 years in a birth cohort of children from the Faroe Islands.MethodsWe prospectively measured concentrations of five PFAS in cord serum and serum collected at 18 months, 5 years and 9 years, and conducted whole-body DXA scans at the 9-year clinical visit. Our study included 366 mother-child pairs with DXA scans and at least one PFAS measurement. We estimated covariate-adjusted associations of individual PFAS concentrations with age-, sex- and height-adjusted aBMD z-scores using multivariable regression models and applied formal mediation analysis to estimate the possible impact of by several measures of body composition. We also evaluated whether associations were modified by child sex.ResultsWe found PFAS exposures in childhood to be negatively associated with aBMD z-scores, with the strongest association seen for perfluorononanoic acid (PFNA) at age 5 years. A doubling in age-5 PFNA was associated with a 0.15 decrease in aBMD z-score (95% CI: − 0.26, − 0.039). The PFNA-aBMD association was significantly stronger in males than females, although effect modification by sex was not significant for other PFAS exposures. Results from the mediation analysis suggested that any potential associations between aBMD and 18-month PFAS concentrations may be mediated by total body fat and BMI, although most estimated total effects for PFAS exposures at age 18 months were non-significant. PFAS exposures at age 9 were not associated with age-9 aBMD z-scores.ConclusionsThe PFAS-aBMD associations identified in this and previous studies suggest that bone may be a target tissue for PFAS. Pediatric bone density has been demonstrated to strongly track through young adulthood and possibly beyond; therefore, these prospective results may have important public health implications.

Association of maternal perfluoroalkyl substance exposure with postpartum haemorrhage in Guangxi, China

Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide, and it may be caused by environmental endocrine disruptors. Prenatal exposure to perfluoroalkyl substances (PFASs) in women has been linked to pregnancy disorders and adverse birth outcomes, but no data are available on the relationship between PFAS exposure during pregnancy and postpartum haemorrhage. This study aimed to explore the associations of maternal PFAS exposure with the postpartum haemorrhage risk and total blood loss. A total of 1496 mother-infant pairs in the Guangxi Zhuang birth cohort were included between June 2015 and May 2018. The concentration of PFASs in serum was detected using ultrahigh liquid chromatography-tandem mass spectrometry. Multiple binomial regression and linear regression models were used to analyse individual PFAS exposures. The mixture of PFASs was analysed using Bayesian Kernel Machine Regression (BKMR). In single substance exposure models, exposure to perfluorohexanesulfonic acid (PFHxS) increased the risk of postpartum haemorrhage (OR: 3.42, 95 % CI: 1.45, 8.07), while exposure to perfluorododecanoic acid (PFDoA) was inversely associated with the risk of postpartum haemorrhage (OR: 0.42, 95 % CI: 0.22, 0.80). The concentrations of perfluoroundecanoic acid (PFUnA) (β: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (β: 0.05, 95 % CI: 0.40, 88.95) exposure were positively correlated with the amount of postpartum haemorrhage; this result occurred only in the absence of covariate adjustment. In BKMR models, the risk of postpartum haemorrhage increased with increasing exposure to a PFAS mixture. In conclusion, our study suggested that maternal serum PFAS exposure during pregnancy was associated with the risk of postpartum haemorrhage.

Evaluating the Distribution of Perfluoroalkyl Substances in Rice Paddy Lysimeter with an Andosol.

The properties of potential emerging persistent contaminants, perfluoroalkyl substances (PFAS), in an andosol rice paddy lysimeter were analyzed to determine their mobility and leaching behavior regarding carbon chain length and functional groups. For this purpose, simulated contaminated water (ΣPFAS = 1,185,719 ng/L) was used in the lysimeter. The results showed that PFAS distribution in the paddy soil lysimeter was influenced by the migration of these substances into irrigation water and their adsorption into the soil. PFHxS (C6) and PFOS (C8), which are the main components of the simulated contaminated water, were mostly captured in the soil layers of the low-humic andosol layer (0–35 cm). PFAS distribution may depend on soil properties, such as total carbon (TC) content. Compared with perfluoroalkane sulfonic acids (PFSAs), the distribution of perfluoroalkyl carboxylic acids (PFCAs) in soil showed significant variation. The remaining PFCAs were distributed across all layers of the lysimeter, except for the longer-chain PFCAs. Moreover, the PFSA distribution was directly correlated with the carbon chain number, whereby longer- and shorter-chain PFSAs accumulated in the top and bottom soil layers, respectively. This study provides detailed information on the distribution, leaching, uptake, and accumulation of individual PFAS in andosol paddy fields in Japan.

Associations of single and multiple perfluoroalkyl substances exposure with folate among adolescents in NHANES 2007–2010

BackgroundThe accumulation of perfluoroalkyl substances (PFAS) in human body has raised concerns about the potential health impacts on children and adolescents. However, no study has evaluated the associations of PFAS exposure with folate concentrations among adolescents. MethodsIn the present study, we mainly used three statistical approaches, namely multiple linear regression, Bayesian Kernel Machine Regression (BKMR), and quantile-based g-computation (Q-gcomp) models, to evaluate associations of individual PFAS and their mixtures with serum and red blood cell (RBC) folate concentrations in a sample of 721 adolescents from the NHANES 2007–2010. ResultsIn multiple linear regression models, for per unit increase in ln-transformed perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) concentrations, RBC folate concentrations decreased by 72.4 (95% confidence interval (CI): −112.7, −32.2), 58.3 (95% CI: −115.0, −1.6), 60.7 (95% CI: −107.5, −13.8), and 76.5 (95% CI: −119.0, −33.9) nmol/L, respectively. A similar significant inverse association was also observed between ln-transformed PFDA and serum folate. BKMR models further confirmed inverse associations of serum PFOS and PFDA with RBC folate, and serum PFDA with serum folate. However, the inverse associations of PFOA and PFNA with RBC folate shown in multiple linear regression model were not observed or less evident in BKMR analyses. We observed interactions of PFOA with PFOS, PFNA, and PFDA on RBC folate in BKMR models, with the negative slopes for PFOS, PFNA, and PFDA increased when PFOA concentration increased from the 10th percentile to the 90th percentile. Both BKMR and Q-gcomp models suggested that the mixtures of five PFAS showed inverse overall associations with RBC folate concentration. ConclusionsThe present study revealed that adolescent exposure to PFAS might affect serum and RBC folate concentrations.

Chlorinated Polyfluorinated Ether Sulfonates and Thyroid Hormone Levels in Adults: Isomers of C8 Health Project in China.

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (μIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

The relationship between multiple perfluoroalkyl substances and cardiorespiratory fitness in male adolescents.

Exposure to perfluoroalkyl substances (PFASs) is associated with a number of adverse health outcomes. However, the relationship between mixed and individual PFAS exposure and cardiorespiratory fitness (CRF) in adolescents remains unclear. We used cross-sectional data from 491 teenagers (aged 13-19years) from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) and examined the association between mixed PFAS exposure and CRF via weighted quantile sum (WQS) regression. Maximal oxygen consumption (VO2max) was used to evaluate CRF. Multivariate linear regression was performed to investigate the relationship between each PFAS and VO2max as well as the relationship between PFAS exposure and the inflammation parameters and blood lipid content. Mediation analyses were performed to investigate possible explanations of the risk of low CRF due to PFAS exposure. The results showed that for males, mixed PFAS exposure was negatively related to VO2max (beta = - 0.80, 95% CI: - 1.53 to - 0.10, P = 0.028) and that of the PFASs, perfluorononanoic acid (PFNA) had the greatest influence on VO2max. In the individual PFAS analysis, PFNA was negatively related to VO2max in male adolescents (beta = - 1.49, 95% CI: - 2.65 to - 0.32, P = 0.013). Additionally, significant relationships among serum PFNA levels and total cholesterol and the white blood cell (WBC) count were found. Mediation analyses revealed that WBC count accounted for 24.18% of the variation between PFNA level and CRF. The present results provide epidemiological evidence that exposure to PFASs, mainly PFNA, is negatively associated with CRF, possibly via alterations in WBC count.

Abstract 12258: Associations Between Serum Perfluoroalkyl Substances and Vascular Function

Introduction: Perfluoroalkyl substances (PFA)s are ubiquitous synthetic organic compounds used in packaging, flame retardants and stain resistant fabric. The use of older, long-chain, persistent PFAs in the U.S. has been phased out due to cardiometabolic health effects and replaced with short-chain, less persistent, alternative PFAs for which little data on cardiotoxicity exists. We evaluated the relationships between serum PFAs and noninvasive measures of vascular function by carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART). Methods: We measured 14 serum PFAs using hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients without CVD from an urban medical center. Using medical records and questionnaires, we collected demographic and clinical data; and measured PWV and BART using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. Results: Of the 14 measured PFAs, 10 were detectable in &gt;50% of samples, and were included for analysis. Each standard deviation increase in perfluroheptanoic acid (PFHpA) was associated with -0.17 (-0.34, -0.002) decrease in log BART. The weighted index of PFAs in mixture 1 (Table) was significantly and inversely associated with log BART; each tertile increase in the weighted index of mixture 1 was associated with a -0.29 (-0.52, -0.06) decrease in log BART, with PFHpA having the greatest weight (0.73) in the mixture. In contrast, neither individual PFAs nor PFA mixtures were associated with PWV. Conclusions: Increasing concentrations of a new, short-chain PFA, PFHpA, are associated with impaired vascular function among outpatients without CVD. Our findings contribute evidence of potential adverse cardiovascular effects of currently used PFAs.