Perfluorooctanoate Exposure Research Articles

The Association between Prenatal Per- and Polyfluoroalkyl Substances Exposure and Neurobehavioral Problems in Offspring: A Meta-Analysis.

Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been suggested to be associated with neurobehavioral problems in offspring. However, current epidemiological studies on the association between prenatal PFAS exposure and neurobehavioral problems among offspring, especially attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are inconsistent. Therefore, we aimed to study the relationship between PFAS exposure during pregnancy and ADHD and ASD in offspring based on meta-analyses. Online databases, including PubMed, EMBASE, and Web of Science, were searched comprehensively for eligible studies conducted before July 2021. Eleven studies (up to 8493 participants) were included in this analysis. The pooled results demonstrated that exposure to perfluorooctanoate (PFOA) was positively associated with ADHD in the highest quartile group. Negative associations were observed between perfluorooctane sulfonate (PFOS) and ADHD/ASD, including between perfluorononanoate (PFNA) and ASD. There were no associations found between total PFAS concentration groups and neurobehavioral problems. The trial sequential analyses showed unstable results. Our findings indicated that PFOA and PFOS exposure during pregnancy might be associated with ADHD in offspring and that prenatal PFOS and PFNA exposure might be associated with ASD in offspring. According to the limited evidence obtained for most associations, additional studies are required to validate these findings.

Microcosm experiment to test bacterial responses to perfluorooctanoate exposure

The impact of perfluoroalkyl and polyfluoroalkyl substances on microbial communities is challenging to investigate in situ because of the complexity and dynamics of natural ecosystems. In the present study, four microcosms were established to explore the impact of perfluorooctanoate (PFOA) on bacterial communities in riverine and marine settings. PFOA distribution between the aqueous and sedimentary phases fluctuated in both PFOA-amended and unamended control systems. PFOA was more rapidly partitioned into the sediment in marine than in riverine microcosms. Differences in iron concentration and salinity may influence PFOA exchange between water and sediment. In marine microcosms, the alpha diversity of bacterial communities was significantly correlated to PFOA concentration. PFOA tended to correlate more strongly with bacterial community composition in water than in sediment. At the whole system level, Lefse's analysis indicated Algoriphagus halophilus as biomarkers for PFOA exposure in both riverine and marine systems, and the family Flavobacteriaceae were also more abundant in the exposed systems. In terms of temporal variation (comparison between three time points in the systems), metastat analysis showed great variability of potential PFOA-sensitive bacteria at the genus level. As such, most PFOA-sensitive genera were transitory and variable and existed for a short term in different systems (river, sea, blank, and experiment) and phases. Compared with other PFOA-sensitive genera, we suggest that further research is carried out to explore the use of Limnobacter as a bioindicator for temporal monitoring of PFOA pollution.

The Conundrum of the PFOA human half-life, an international collaboration

The Steering Committee of the Alliance for Risk Assessment (ARA) opened a call for scientists interested in resolving what appeared to be a conundrum in estimating of the half-life of perfluorooctanoate (PFOA) in humans. An Advisory Committee was formed from nominations received and a subsequent invitation led to the development of three small independent working groups to review appropriate information and attempt a resolution. Initial findings were shared among these groups and a conclusion developed from the ensuing discussions.Many human observational studies have estimated the PFOA half-life. Most of these studies note the likely occurrence of unmonitored PFOA exposures, which could inflate values of the estimated PFOA half-life. Also, few of these studies estimated the half-life of PFOA isomers, the branched chains of which likely have shorter half-lives. This could deflate values of the estimated linear PFOA half-life. Fortunately, several studies informed both of these potential problems. The majority opinion of this international collaboration is that the studies striking the best balance in addressing some of these uncertainties indicate the likely central tendency of the human PFOA half-life is less than 2 years. The single best value appears to be the geometric mean (GM) of 1.3 years (Zhang et al., 2013, Table 3), based on a GM = 1.7 years in young females (n = 20) and GM = 1.2 years in males of all ages and older females (n = 66). However, a combined median value from Zhang et al. (2013) of 1.8 years also adds value to this range of central tendency. While the Collaboration found this study to be the least encumbered with unmonitored PFOA exposures and branched isomers, more studies of similar design would be valuable. Also valuable would be clarification around background exposures in other existing studies in case adjustments to half-life estimates are attempted.

Single PFAS and PFAS mixtures affect nuclear receptor- and oxidative stress-related pathways in precision-cut liver slices of Atlantic cod (Gadus morhua)

The aim of the present study was to investigate effects of per- and polyfluoroalkyl substances (PFAS), both single compounds and a mixture of these, using precision-cut liver slices (PCLS) from Atlantic cod (Gadus morhua). PCLS were exposed for 48 h to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) (10, 50 and 100 μM), and three mixtures of these at equimolar concentrations (10, 50 and 100 μM). Transcriptomic responses were assessed using RNA sequencing. Among exposures to single PFAS, PFOS produced the highest number of differentially expressed genes (DEGs) compared to PFOA and PFNA (86, 25 and 31 DEGs, respectively). Exposure to the PFAS mixtures resulted in a markedly higher number of DEGs (841). Clustering analysis revealed that the expression pattern of the PFAS mixtures were more similar to PFOS compared to PFOA and PFNA, suggesting that effects induced by the PFAS mixtures may largely be attributed to PFOS. Pathway analysis showed significant enrichment of pathways related to oxidative stress, cholesterol metabolism and nuclear receptors in PFOS-exposed PCLS. Fewer pathways were significantly enriched following PFOA and PFNA exposure alone. Significantly enriched pathways following mixture exposure included lipid biosynthesis, cancer-related pathways, nuclear receptor pathways and oxidative stress-related pathways such as ferroptosis. The expression of most of the genes within these pathways was increased following PFAS exposure. Analysis of non-additive effects in the 100 μM PFAS mixture highlighted genes involved in the antioxidant response and membrane transport, among others, and the majority of these genes had synergistic expression patterns in the mixture. Nevertheless, 90% of the DEGs following mixture exposure showed additive expression patterns, suggesting additivity to be the major mixture effect. In summary, PFAS exposure promoted effects on cellular processes involved in oxidative stress, nuclear receptor pathways and sterol metabolism in cod PCLS, with the strongest effects observed following PFAS mixture exposure.

Gestational Perfluorooctanoate Exposure and Childhood Metabolome at Age 8 Years

BACKGROUND AND AIM: Gestational exposure to perfluorooctanoate (PFOA) is associated with excess adiposity and increased cardiometabolic risk in children. To identify potential mechanisms underlying these associations, we characterized metabolic alterations and pathways associated with gestational PFOA exposure in 8-year-old children using a metabolome-wide association study (MWAS). METHODS: METHODS: We performed untargeted, high-resolution metabolomic profiling of serum samples collected at age 8-years from 106 children enrolled in the HOME study (Cincinnati, OH) using high-resolution liquid chromatography mass spectrometry (LC-MS). During pregnancy, we quantified PFOA concentrations in serum collected from their mothers using LC-MS methods. Associations between maternal PFOA concentrations during pregnancy and annotated metabolites detected in child serum samples were evaluated using multivariable linear regression adjusted for child age, sex, and race with a false discovery rate 20%. Pathway level changes were determined by characterizing metabolite networks; enriched pathways were determined using Mummichog. RESULTS:Maternal PFOA concentrations during pregnancy (median: 5.2 ng/mL, 25th-75th percentile: 3.6-7.3 ng/mL) were associated with alterations in the child metabolome at age 8 years. Associations that met FDR20% included 203 metabolites, of which 144 were negatively associated with PFOA concentrations. Annotation of metabolites included a range of lipids and dietary factors, while pathway enrichment identified alterations in amino acid metabolism, lipid pathways, oxidative stress, de novo fatty acid biosynthesis and catabolism. CONCLUSIONS:This is the first study to examine gestational PFOA in association with childhood metabolome using untargeted approach. In this study, maternal PFOA concentrations at pregnancy were associated with systemic alterations in metabolic pathways related to energy production, oxidative stress and catabolism in serum collected from 8-year-old children. These results highlight the importance of early life exposure, and suggest that PFOA-related metabolic alterations manifest early in life. Future studies should examine how these PFOA-related alterations contribute to increased risk for childhood adiposity and cardiometabolic risk. KEYWORDS: PFAS, Metabolomics, Children's environmental health

Air Pollution, PFOA, and Preeclampsia in the C8 Studies

Background/Aim: Preeclampsia is a type of pregnancy-induced hypertension that also includes proteinuria. Traffic-related particulate air pollution has been linked to preeclampsia in some previous studies. The C8 Study of perfluorooctanoate (PFOA) and preeclampsia did not consider potential confounding by air pollution. We assessed the association between distance to road (DTR), a marker of traffic related air pollution, and preeclampsia in an area with elevated exposure to PFOA from drinking water contaminated by chemical plant releases.Methods: We calculated distance to nearest major road (class A1, A2, or A3) for 5,960 pregnancies occurring between 1990 and 2006 in twelve Ohio and West Virginia counties that were included in previous publications from the C8 Studies. Generalized additive models (GAM) included smoothing for maternal location at birth to assess spatial patterns of preeclampsia risk. We adjusted for estimated annual serum PFOA exposure, exposure year, maternal age at time of pregnancy, parity, education, and smoking status. We then assessed the contribution of DTR to preeclampsia risk with a spatial GAM and a logistic regression without location.Results: For our adjusted model with PFOA exposure, the odds ratio (OR) for preeclampsia was 1.01 (95% confidence interval (CI): 0.92, 1.12) per interquartile shift in log-transformed DTR in meters. The ORs for preeclampsia analyses with and without adjustment for DTR were both 1.11 (95% CI: 0.99, 1.25) per interquartile shift in log-transformed PFOA. Residual spatial patterns in preeclampsia risk were present after PFOA adjustment and did not change with inclusion of DTR. Conclusion: No associations between DTR and preeclampsia were observed in this large, population-based study with elevated PFOA exposure. We did not find any evidence to suggest DTR confounded the relationship observed with estimated serum PFOA levels. Residual spatial patterns of preeclampsia may be due to other unmeasured confounders or limited adjustment for socioeconomic status.

Perfluorooctanesulfonate and perfluorooctanoate exacerbate airway inflammation in asthmatic mice and in vitro

Emerging evidence suggests associations between Perfluoroalkyl substances (PFASs) exposure and asthma, but the findings are inconsistent. The current study sought to investigate whether perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) could contribute to asthma exacerbation and to clarify the underlying biological mechanisms. The objectives are a) to determine whether PFOS or PFOA could aggravate the mouse asthma and pulmonary inflammation b) to investigate whether PFOS and PFOA regulate the balance of Th1/Th2 through the JAK-STAT signaling pathway and aggravated asthma. Ovalbumin (OVA) induced asthmatic mice were exposed to PFOS or PFOA by gavage. PFOS and PFOA serum level and toxicity in organs were assessed; and the impacts on respiratory symptoms, lung tissue pathology, T helper cell (Th2) response, and STAT6 pathway activity were also evaluated. In vitro Jurkat cells were used to study the mechanisms of PFOS and PFOA mediated Th1 and Th2 responses. Both PFOS and PFOA exacerbated lung tissue inflammation (greater number of eosinophils and mucus hyperproduction), upregulated Th2 cytokine production (IL-4 and IL-13), and promoted Th2 cells and STAT6 activation. Furthermore, PFOS and PFOA enhanced the Th2 response in Jurkat cells via STAT6 activation; and the effect of PFOS exposure on GATA-3, IL-4 and IFN-γ was blocked after the expression of STAT6 was suppressed in Jurkat cells, however, the effects of PFOA exposure were only partially blocked. PFOS and PFOA aggravated inflammation among OVA-induced asthmatic mice, by promoting the Th2 response in lymphocytes and disturbing the balance of Th1/Th2 through the JAK-STAT signaling pathway.

Microbial responses to perfluoroalkyl substances and perfluorooctanesulfonate (PFOS) desulfurization in the Antarctic marine environment

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) acids are ubiquitous in the oceans, including remote regions, and are toxic to fish and mammals. The impact to the lowest trophic levels of the food web, however, remains unknown. We challenged natural bacterial communities inhabiting Antarctic coastal waters (Deception Island) with PFOS and PFOA concentrations ranging from 2 ng/L to 600 ng/L that selected for tolerant taxa. After 48 h, concentrations of PFOS decreased by more than 50% and sulfur metabolism-related transcripts were significantly enriched in the treatments suggesting desulfurization of PFOS. Conversely, no significant differences were found between initial and final PFOA concentrations. Gammaproteobacteria and Roseobacter, two abundant groups of marine bacteria, increased their relative activity after 24 h of incubation, whereas Flavobacteriia became the main contributor in the treatments after 6 days. Community activities (extracellular enzyme activity and absolute number of transcripts) were higher in the treatments than in the controls, while bacterial abundances were lower in the treatments, suggesting a selection of PFOS and PFOA tolerant community in the exposed treatments. Our results show a direct effect of PFOS and PFOA exposure on the composition and functionality of natural Antarctic marine microbial communities. While no evidence of defluorination of PFOS or PFOA was detected, probable desulfurization of PFOS depicts a direct link with the sulfur biogeochemistry of the ocean.

969 Perfluorooctanoate Exposure and Risk of Non-Alcoholic Fatty Liver Disease and Advanced Fibrosis in U.S. Adults: A Population-Based Study

INTRODUCTION: Industrial chemical exposure is an increasingly recognized entity in NAFLD and NASH. Perfluorooctanoate (PFOA) has been widely used in industrial manufacturing, and is linked to cardiovascular, thyroid, oncologic, and liver disease. This study examines its association with NAFLD and Advanced Fibrosis using U.S. nationally representative data. METHODS: A population of 2,833 non-pregnant individuals ages 18-74 were included in this secondary analysis of NHANES 2011-2016. Exclusion criteria: AST/ALT > 500 IU/L, alcohol > 10 drinks/week (females)/ >20 drinks/week (males), transferrin saturation > 50%, positive hepatitis B and C serology. NAFLD was defined by Fatty Liver Index score > 60. Advanced fibrosis was defined by National Fibrosis Score > 0.676. Student’s T-test was used for continuous and Rao-Scott Chi-Square test for categorical variables. Comparison across quartiles were done with simple linear regression for continuous, Rao-Scott Chi-Square test for categorical variables. Demographics and patient confounders were adjusted using multivariate logistic regression (SAS 9.4) for odds of NAFLD/Advanced Fibrosis with respect to PFOA quartile. RESULTS: NAFLD compared to non-NAFLD cohort were significantly more likely to be older, male, less educated, obese, have higher HbA1C, rates of diabetes, hypertension, insulin resistance, more likely Latino, and have higher total cholesterol (see Table 1). For NAFLD, adjusted regression analysis show a positive trend for NAFLD with increased PFOA quartile (Q3, OR 1.16, 95% CI 0.60–2.22), (Q4, OR 1.63, 95% CI 0.88–3.03), and on stratification the association was significant for BMI >30 (Q4 OR 3.25, 95% C.I. 1.33–7.95). Unadjusted regression analysis, participants with increased PFOA exposure were more likely to have Advanced Fibrosis (Q4 OR 1.74, 95% CI 1.03–2.98), and this association was seen particularly in females, smokers, and the obese with advanced fibrosis (Q4 OR 2.99, 95% CI 1.90–4.72), (Q4 OR 2.71, 95% CI 1.30–5.68), (Q4 OR 2.09, 95% CI 1.17–3.72), but was attenuated after adjustment. CONCLUSION: Our findings show a significant association for NAFLD in obese patients with increased PFOA exposure. Both NAFLD and Advanced fibrosis show a positive trend with increased PFOA exposure. This study highlights that PFOA, an established carcinogen and toxic industrial contaminant, may play a role in NAFLD and related comorbidities in the US population. Further studies are needed for confirmation.

Data derived Extrapolation Factors for developmental toxicity: A preliminary research case study with perfluorooctanoate (PFOA)

Guidelines of the United States Environmental Protection Agency (EPA, 1991) and the International Programme on Chemical Safety (IPCS, 2005) suggest two different default positions for dosimetric extrapolation from experimental animals to humans when the dosimetry of the critical effect is not known. The default position of EPA (1991) for developmental toxicity is to use peak concentration (or Cmax) for this dosimetric extrapolation. In contrast, IPCS (2005, page 39) states its default position for dosimetric choice in the absence of data is to use the area under the curve (or AUC). The choice of the appropriate dose metric is important in the development of either a Chemical Specific Adjustment Factor (CSAF) of IPCS (2005) or a Data Derived Extrapolation Factor (DDEF) of EPA (2014). This research shows the derivation of a DDEF for developmental toxicity for perfluorooctanoate (PFOA), a chemical of current interest. Here, identification of the appropriate dosimetric adjustment from a review of developmental effects identified by EPA (2016) is attempted. Although some of these effects appear to be related to Cmax, most appear to be related to the average concentration or its AUC, but only during the critical period of development for a particular effect. A comparison was made of kinetic data from PFOA exposure in mice with newly available and carefully monitored kinetic data in humans after up to 36 weeks of PFOA exposure in a phase 1 clinical trial by Elcombe et al. (2013). Using the average concentration during the various exposure windows of concern, the DDEF for PFOA was determined to be 1.3 or 14. These values are significantly different than comparable extrapolations by several other authorities based on differences in PFOA half-life among species. Although current population exposures to PFOA are generally much lower than both the experimental animal data and the clinical human study, the development of these DDEFs is consistent with current guidelines of both EPA (2014) and IPCS (2005).

Characterization of non-radiolabeled Thyroxine (T4) uptake in cryopreserved rat hepatocyte suspensions: Pharmacokinetic implications for PFOA and PFOS chemical exposure

The alteration of thyroxine (T4) cellular uptake by an environmental chemical can serve as a contributing factor in thyroid hormone (TH) disruption. Herein, we describe a non-radiolabeled (LC-MS/MS) oil-filtration technique designed to characterize the mechanism(s) responsible for T4 cellular uptake in cryopreserved rat hepatocyte suspensions. The environmental chemicals perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) were evaluated for their effect on T4 hepatic uptake. At 37 °C, hepatic assays demonstrated saturable kinetics with increasing T4 concentrations, while a linear uptake rate consistent with passive diffusion was detected at 4 °C. Carrier-mediated (37–4 °C) transport of T4 was the predominant hepatic uptake process versus passive diffusion. Cyclosporin A (CsA) chemically inhibited T4 hepatic uptake, whereas PFOA/PFOS displayed no inhibition of T4 translocation. Increasing PFOA/PFOS concentration levels with the T4 serum carrier-protein transthyretin (TTR) present resulted in a dose-response increase in T4 hepatic uptake rates, correlating with increased T4 free fraction values. Hepatic assays conducted in the presence of PFOA/PFOS and TTR displayed an enhanced first-order T4 hepatic uptake rate consistent with carrier-mediated transport. These in vitro findings characterizing increased T4 hepatic uptake provides mechanistic insight regarding decreased T4 serum levels (hypothyroxinemia) previously observed within in vivo rodent studies following perfluorinated chemical exposure.

Molecular Mechanisms of Perfluorooctanoate-Induced Hepatocyte Apoptosis in Mice Using Proteomic Techniques.

The stability of perfluorooctanoate (PFOA) coupled with its wide use cause serious concerns regarding its potential risk to human health. The molecular mechanisms of PFOA-induced hepatotoxicity relevant to human health was investigated using both in vivo (mouse model) and in vitro (human hepatocyte cells, HL-7702) techniques. Both male and female Balb/c mice were administered PFOA at 0.05, 0.5, or 2.5 mg/kg-d for 28-d, with serum PFOA concentrations after exposure being found at environmentally relevant levels. Liver samples were examined for histology and proteomic change using iTRAQ and Western Blotting, showing dose-dependent hepatocyte apoptosis and peroxisome proliferation. At high doses, genotoxicity resulting from ROS hypergeneration was due to suppression of Complex I subunits in the electron transport chain and activation of PPARα in both genders. However, at 0.05 mg/kg-d, Complex I suppression occurred only in females, making them more sensitive to PFOA-induced apoptosis. In vitro assays using HL-7702 cells confirmed that apoptosis was also induced through a similar mechanism. The dose/gender-dependent toxicity mechanisms help to explain some epidemiological phenomena, i.e., liver cancer is not often associated with PFOA exposure in professional workers. Our results demonstrated that a proteomic approach is a robust tool to explore molecular mechanisms of toxic chemicals at environmentally relevant levels.

Impacts of geocoding uncertainty on reconstructed PFOA exposures and their epidemiological association with preeclampsia

Many epidemiology studies have investigated associations of perfluorooctanoate (PFOA) exposures with a variety of adverse health outcomes for participants in the C8 Health Project. The exposure concentrations (i.e., air and groundwater) used in these studies were determined primarily based on participant’s residential locations. However, for residential addresses that could not be geocoded to the street level, the exposure concentrations were assigned based on population-weighted ZIP code centroid, which may result in exposure mischaracterization. The aim of this current study is to evaluate the potential impact of mischaracterized exposure concentrations due to geocoding uncertainty on the predicted serum PFOA concentrations and the epidemiological association between PFOA exposure and preeclampsia. For both workplace addresses and incompletely geocoded residential addresses, we used Monte Carlo (MC) simulation to assign alternate geographic locations within the reported ZIP code (instead of population-weighted ZIP code centroids) and the corresponding exposure concentrations. We found that mischaracterization of residential exposure due to population-weighted ZIP code centroid assignment had no significant impact on the serum PFOA concentration predictions and the epidemiological association of PFOA exposure with preeclampsia. In contrast, the uncertainty in workplace exposure moderately impacted the rank exposure among the participants. We observed a 41% increase in the average adjusted odds ratio of preeclampsia occurrence that may be due to differing proportions of cases (64.3%) and controls (54.5%) with workplace address geocodes during pregnancy. This finding suggests that differential exposure mischaracterization can be reduced by obtaining accurate exposure information such as street addresses and tap water consumption, for both workplaces and residences. The analysis we present is one approach for estimating the potential impacts of positional errors in a geocoding-based exposure assessment on exposure estimates and epidemiological study results.

Low dose perfluorooctanoate exposure promotes cell proliferation in a human non-tumor liver cell line

Perfluorooctanoate (PFOA) is a well-known persistent organic pollutant widely found in the environment, wildlife and humans. Medical surveillance and experimental studies have investigated the potential effects of PFOA on human livers, but the hepatotoxicity of PFOA on humans and its underlying mechanism remain to be clarified. We exposed a human liver cell line (HL-7702) to 50μM PFOA for 48h and 96h, and identified 111 significantly differentially expressed proteins by iTRAQ analysis. A total of 46 proteins were related to cell proliferation and apoptosis. Through further analysis of the cell cycle, apoptosis and their related proteins, we found that low doses of PFOA (50–100μM) promoted cell proliferation and numbers by promoting cells from the G1 to S phases, whereas high doses of PFOA (200–400μM) led to reduced HL-7702 cell numbers compared with that of the control mainly due to cell cycle arrest in the G0/G1 phase. To our knowledge, this is the first report on the promotion of cell cycle progression in human cells following PFOA exposure.

Variability and epistemic uncertainty in water ingestion rates and pharmacokinetic parameters, and impact on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population

We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion, our study shows that the change of the rank exposure among the study participants due to variability and epistemic uncertainty in the independent exposure parameters was large enough to cause a 25% bias towards the null. This suggests that the true AOR of the association between PFOA and preeclampsia in this population might be higher than the originally reported AOR and has more uncertainty than indicated by the originally reported confidence interval.

Prenatal exposure to perfluorinated chemicals and neurodevelopment in early infancy: The Hokkaido Study

Perfluorinated chemicals (PFCs) are ubiquitous and persistent pollutants widely detected in blood samples of animals and humans across the globe. Although animal studies have shown the potential neurotoxicity of PFCs, there are few epidemiological studies regarding neurological effects of PFCs in humans, and those studies have had inconclusive results. In this study, we conducted a hospital-based prospective birth cohort study between 2002 and 2005 (n=514) to examine the associations between prenatal perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) exposures and the neurodevelopment of infants at 6 (n=173) and 18 (n=133) months of age. Using the second edition of the Bayley Scales of Infant Development (BSID II), the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) were assessed. PFOS and PFOA were measured in maternal serum samples by liquid chromatography–tandem mass spectrometry. After controlling for confounders, prenatal PFOA concentrations were associated with the MDI of female (but not male) infants at 6months of age (β=−0.296; 95% confidence interval (CI): −11.96, −0.682). Furthermore, females born to mothers with prenatal concentrations of PFOA in the fourth quartile had MDI scores −5.05 (95% CI: −10.66 to 0.55) lower than females born to mothers with concentrations of PFOA in the first quartile (p for trend=0.045). However, PFOA concentrations were not significantly associated with neurodevelopmental indices at 18months of age. In addition, we did not observe any significant association between PFOS concentrations and neurodevelopmental outcomes in early infancy. In conclusion, our results suggest that prenatal PFOA exposure may affect female mental scales of neurodevelopment at 6months of age. Further studies with larger sample sizes and longer observation periods are required to clarify sex difference of the neurodevelopmental effects.

Neutral polyfluorinated compounds in indoor air in Germany – The LUPE 4 study

Perfluoroalkyl- and polyfluoroalkyl-substances (PFAS) have been detected in many types of environmental media and biota including humans. We determined volatile PFAS, including fluorotelomer alcohols (FTOHs), fluorotelomer acrylates (FTACs), perfluorooctane sulfonamides (FOSAs), and perfluorooctane sulfonamidoethanols (FOSEs), in indoor air of residences and schools in Germany.FTOHs, FTACs, FOSEs, and FOSAs were quantified with median levels in schools (in residences) of 11,783pg/m3 (13,198pg/m3), 737pg/m3 (450pg/m3), 130pg/m3 (278pg/m3), and 243pg/m3 (110pg/m3), respectively.Using our data and previously published results in a simplified model based on the medians and 95th percentiles, the “typical” and “high” daily non-dietary exposures were calculated to be 4.2ng/kg body weight (9.9ng/kgb.w.) for Σ-FTOHs and 0.1ng/kgb.w. (0.8ng/kgb.w.) for Σ-FOSEs/FOSAs in children. Inhalation was the dominant intake pathway for FTOHs; however, dust ingestion contributed significantly to the total intake of FOSEs/FOSAs.In organisms, 8:2 FTOH is degraded to perfluorooctanoate (PFOA). Assuming that 1% of 8:2 FTOH is converted to PFOA, 8:2 FTOH exposure in Germany has a negligible contribution to the total daily PFOA exposure, which is mainly driven by dietary intake.

Perfluorooctanoate Exposure And Pregnancy Outcomes In The C8 Health Project: Do Modeled Exposures Pose A High Risk Of Bias?

Introduction: Residential histories and a suite of environmental models and integrated exposure and pharmacokinetic model were previously used to estimate individual perfluoroocatanoate (PFOA) seru...

Anthropometry in 5- to 9-Year-Old Greenlandic and Ukrainian Children in Relation to Prenatal Exposure to Perfluorinated Alkyl Substances.

BackgroundIn some animal studies, perfluorinated alkyl substances are suggested to induce weight gain. Human epidemiological studies investigating these associations are sparse.ObjectiveWe examined pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and the prevalence of offspring overweight (> 1 SD) and waist-to-height ratio (WHtR) > 0.5 at 5–9 years of age.MethodsSera from 1,022 pregnant women enrolled in the INUENDO cohort (2002–2004) from Greenland and Kharkiv (Ukraine) were analyzed for PFOA and PFOS using liquid chromatography–tandem mass spectrometry. Relative risks (RR) of being overweight and having WHtR > 0.5 in relation to continuous and categorized (tertiles) PFOA and PFOS were calculated at follow-up (2010–2012) using generalized linear models.ResultsPooled PFOA median (range) was 1.3 (0.2–5.1) and PFOS median (range) was 10.8 (0.8–73.0) ng/mL. For each natural logarithm-unit (ln-unit) increase of pregnancy PFOA, the adjusted RR of offspring overweight was 1.11 [95% confidence interval (CI): 0.82, 1.53] in Greenlandic children. In Ukrainian children, the adjusted RR of offspring overweight was 1.02 (95% CI: 0.72, 1.44) for each ln-unit increase of pregnancy PFOA. Prenatal exposure to PFOS was not associated with overweight in country-specific or pooled analysis. The adjusted RR of having WHtR > 0.5 for each ln-unit increase of prenatal exposure to PFOA was 1.30 (95% CI: 0.97, 1.74) in the pooled analysis. For 1–ln-unit increase of prenatal exposure to PFOS, the adjusted RR of having a WHtR > 0.5 was 1.38 (95% CI: 1.05, 1.82) in the pooled analysis.ConclusionsThe results indicate that prenatal PFOA and PFOS exposures may be associated with child waist-to-height ratio > 0.5. Prenatal PFOA and PFOS exposures were not associated with overweight.CitationHøyer BB, Ramlau-Hansen CH, Vrijheid M, Valvi D, Pedersen HS, Zviezdai V, Jönsson BA, Lindh CH, Bonde JP, Toft G. 2015. Anthropometry in 5- to 9-year-old Greenlandic and Ukrainian children in relation to prenatal exposure to perfluorinated alkyl substances. Environ Health Perspect 123:841–846; http://dx.doi.org/10.1289/ehp.1408881

Pregnancy serum concentrations of perfluorinated alkyl substances and offspring behaviour and motor development at age 5-9 years--a prospective study.

BackgroundIn animal studies, perfluorinated alkyl substances affect growth and neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was to investigate the association between pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring behaviour and motor development at 5–9 years of age.MethodsMaternal sera from the INUENDO cohort (2002–2004) comprising 1,106 mother-child pairs from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA, using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into country specific as well as pooled tertiles as well as being used as continuous variables for statistical analyses. Child motor development and behaviour at follow-up (2010–2012) were measured by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ), respectively. Exposure-outcome associations were analysed by multiple logistic and linear regression analyses.ResultsIn the pooled analysis, odds ratio (OR) (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing children prenatally exposed to the highest PFOA tertile with those exposed to the lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in the lowest PFOS tertile showed elevated but statistically non-significant OR of hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was associated with higher SDQ-total scores indicating more behavioural problems (β (95% CI) =1.0 (0.1, 2.0)) and elevated PFOA was associated with higher hyperactivity sub-scale scores indicating more hyperactive behaviour (β (95% CI) = 0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with motor difficulties.ConclusionsPrenatal exposure to PFOS and PFOA may have a small to moderate effect on children’s neuro-behavioural development, specifically in terms of hyperactive behaviour. The associations were strongest in Greenland where exposure contrast is largest.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-069X-14-2) contains supplementary material, which is available to authorized users.