Comprehensive target analysis and TOP assay of per- and polyfluoroalkyl substances (PFAS) in wild boar livers indicate contamination hot-spots in the environment.

The suitability of wild boar liver as a bioindicator of per- and polyfluoroalkyl substances (PFAS) in the terrestrial environment was investigated. Samples from 50 animals in three different areas associated with (1) contaminated paper sludges distributed on arable land (PS), (2) industrial emissions of PFAS (IE) and (3) background contamination (BC) were analyzed for 66 PFAS, including legacy PFAS, novel substitutes and precursors of perfluoroalkyl acids (PFAAs). Additionally, the Total Oxidizable Precursor (TOP) assay was performed to determine the formation potential of PFAAs from precursors. In total, 31 PFAS were detected with site-specific contamination profiles. PFAS concentrations in livers from area PS and IE (567 and 944 µg kg-1 wet weight, respectively) were multiple times higher than from area BC (120 µg kg-1). The dominating PFAS were the legacy compounds perfluorooctane sulfonic acid (PFOS) in areas PS and BC (426 and 82 µg kg-1, respectively) and perfluorooctanoic acid (PFOA) in area IE (650 µg kg-1). In area IE, the compounds 4,8-dioxa-3H-perfluorononanoic acid (DONA) and hexafluoropropylene oxide dimer acid (HFPO-DA) - which are used as substitutes for PFOA - were determined at 15 and 0.29 µg kg-1, respectively. The formation potential of PFAAs was highest in area PS, but generally lower than the contamination with PFAAs. The pattern of perfluoroalkyl carboxylic acids (PFCAs) in wild boar liver reflects the contamination of the local soil at the two hot-spot areas IE and PS. This first comparison of PFAS contamination between wild boars and soil suggests that wild boar livers are suitable bioindicators for PFAS contamination in the terrestrial environment. Moreover, in terrestrial samples from area IE, legacy PFAS were found to be retained for a longer period as compared to riverine samples (suspended particulate matter and chub filet).

Differences in the internal PFAS patterns of herbivores, omnivores and carnivores - lessons learned from target screening and the total oxidizable precursor assay.

Per- and polyfluorinated alkyl substances (PFAS) are a group of anthropogenic chemicals, which are not (fully) biodegradable and accumulate in different environmental compartments worldwide. A comprehensive, quantitative analysis - consisting of target analysis (66 different analytes, including e. g. ultrashort-chain perfluorinated carboxylic acids (PFCAs), precursor compounds and novel substitutes) and the Total Oxidisable Precursor (TOP) assay (including trifluoroacetic acid (TFA)) - were conducted to analyse the PFAS concentrations and patterns in 12 mammalian and two bird species from different areas of Germany and Denmark. The PFAS contamination was investigated in dependance of the trophic class (herbivores, omnivores, carnivores), ecological habitat (terrestrial, (semi-) aquatic) and body tissue (liver, musculature). PFAS concentrations were highest in carnivores, followed by omnivores and herbivores, with ∑PFAS concentration ranging from 1274 µg/kg (Eurasian otter liver) to 22 µg/kg (roe deer liver). TFA dominated in the herbivorous species, whereas perfluorooctanesulfonic acid (PFOS) and the long-chain PFCAs covered the majority of the PFAS contamination in carnivorous species. Besides trophic class, ecological habitat also affected the PFAS levels in the different species, with terrestrial herbivores and omnivores showing higher PFAS concentration than their aquatic counterparts, whereas for carnivores this relationship was reversed. The TOP assay analysis indicated similar trends, with the PFCA formation pattern differing significantly between the trophic classes. TFA was formed predominantly in herbivorous and omnivorous species, whereas in carnivorous species a broad spectrum of PFCAs (chain-length C2-C14) was formed. Musculature tissue of six species exhibited significantly lower PFAS concentrations than the respective liver tissue, but with similar PFAS patterns. The comprehensive approach applied in the present study showed, that primarily the trophic class is decisive for the PFAS concentration, as herbivores, omnivores and carnivores clearly differed in their PFAS concentrations and patterns. Additionally, the TOP assay gave novel insights in the PFCA formation potential in biota samples.

Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention.

S-adenosylmethionine (SAM) is essential for methyl transfer reactions. All SAM is produced de novo via the methionine cycle. The demethylation of SAM produces S-adenosylhomocysteine (SAH), an inhibitor of methyltransferases and the precursor of homocysteine (Hcy). The measurement of SAM and SAH in plasma has value in the diagnosis of inborn errors of metabolism (IEM) and in research to assess methyl group homeostasis. The determination of SAM and SAH is complicated by the instability of SAM under neutral and alkaline conditions and the naturally low concentration of both SAM and SAH in plasma (nM range). Herein, we describe an optimised LC-MS/MS method for the determination of SAM and SAH in plasma, urine, and cells. The method is based on isotopic dilution and employs 20 µL of plasma or urine, or 500,000 cells, and has an instrumental running time of 5 min. The reference ranges for plasma SAM and SAH in a cohort of 33 healthy individuals (age: 19-60 years old; mean ± 2 SD) were 120 ± 36 nM and 21.5 ± 6.5 nM, respectively, in accordance with independent studies and diagnostic determinations. The method detected abnormal concentrations of SAM and SAH in patients with inborn errors of methyl group metabolism. Plasma and urinary SAM and SAH concentrations were determined for the first time in a randomised controlled trial of 53 healthy adult omnivores (age: 18-60 years old), before and after a 4 week intervention with a vegan or meat-rich diet, and revealed preserved variations of both metabolites and the SAM/SAH index.

Filling the knowledge gap: A suspect screening study for 1310 potentially persistent and mobile chemicals with SFC- and HILIC-HRMS in two German river systems.

Persistent and mobile chemicals (PM chemicals) were searched for in surface waters by hydrophilic interaction liquid chromatography (HILIC) and supercritical fluid chromatography (SFC), both coupled to high resolution mass spectrometry (HRMS). A suspect screening was performed using a newly compiled list of 1310 potential PM chemicals to the data of 11 surface water samples from two river systems. In total, 64 compounds were identified by this approach. The overlap between HILIC- and SFC-HRMS was limited (31 compounds), confirming the complementarity of the two methods used. The identified PM candidates are characterized by a high polarity (median logD -0.4 at pH 7.5), a low molecular weight (median 187 g/mol), are mostly ionic (54 compounds) and contain a large number of heteroatoms (one per four carbons on average). Among the most frequently detected novel or yet scarcely investigated water contaminants were cyanoguanidine (11/11 samples), adamantan-1-amine (10/11), trifluoromethanesulfonate (9/11), 2-acrylamido-2-methylpropanesulfonate (10/11), and the inorganic anions hexafluorophosphate (11/11) and tetrafluoroborate (10/11). 31% of the identified suspects are mainly used in ionic liquids, a chemically diverse group of industrial chemicals with numerous applications that is so far rarely studied for their occurrence in the environment. Prioritization of the findings of PM candidates is hampered by the apparent lack of toxicity data. Hence, precautionary principles and minimization approaches should be applied for the risk assessment and risk management of these substances. The large share of novel water contaminants among these findings of the suspect screening indicates that the universe of PM chemicals present in the environment has so far only scarcely been explored. Dedicated analytical methods and screening lists appear essential to close the analytical gap for PM compounds.

A Homozygous Deletion of Exon 5 of KYNU Resulting from a Maternal Chromosome 2 Isodisomy (UPD2) Causes Catel-Manzke-Syndrome/VCRL Syndrome.

Vertebral, Cardiac, Renal and Limb Defect Syndrome (VCRL), is a very rare congenital malformation syndrome. Pathogenic variants in HAAO (3-Hydroxyanthranilate 3,4-dioxygenase), NADSYN1 (NAD+ Synthetase-1) and KYNU (Kynureninase) have been identified in a handful of affected individuals. All three genes encode for enzymes essential for the NAD+ de novo synthesis pathway. Using Trio-Exome analysis and CGH array analysis in combination with long range PCR, we have identified a novel homozygous copy number variant (CNV) encompassing exon 5 of KYNU in an individual presenting with overlapping features of VCRL and Catel-Manzke Syndrome. Interestingly, only the mother, not the father carried the small deletion in a heterozygous state. High-resolution SNP array analysis subsequently delineated a maternal isodisomy of chromosome 2 (UPD2). Increased xanthurenic acid excretion in the urine confirmed the genetic diagnosis. Our findings confirm the clinical, genetic and metabolic phenotype of VCRL1, adding a novel functionally tested disease allele. We also describe the first patient with NAD+ deficiency disorder resulting from a UPD. Furthermore, we provide a comprehensive review of the current literature covering the genetic basis and pathomechanisms for VCRL and Catel-Manzke Syndrome, including possible phenotype/genotype correlations as well as genetic causes of hypoplastic left heart syndrome.

Perfluoroalkyl substances (PFASs) in the Ugandan waters of Lake Victoria: Spatial distribution, catchment release and public exposure risk via municipal water consumption.

Perfluoroalkyl substances (PFASs) have scarcely been studied in the Lake Victoria Basin and Africa in general. We investigated spatial profiles of PFASs in the Ugandan part of Lake Victoria, their influxes and human exposure via drinking water. We analyzed open lake water, riverine water (Rivers Kagera and Sio), urban drainage water (Nakivubo Channel), over-lake bulk atmospheric deposition and municipal tap water (Kampala, Jinja and Entebbe). The average concentrations (ng/L) for individual target PFASs were in the ranges of 0.08-23.8 (Nakivubo Channel), 0.01-10.8 (Murchison Bay), R. Kagera, >R. Sio > Nakivubo Channel. Perfluorohexanoic acid (PFHxA) and perfluorooctane sulfonic acid (PFOS) had the highest influx and retention estimates, respectively. Perfluoroalkane sulfonates (PFSAs) were mostly associated with urban drainage samples. PFASs were likely recycled from the Nakivubo Channel, through the Murchison Bay, into municipal drinking water. The estimated human exposure to ∑11PFASs via drinking water indicated low risk of adverse health effects.

Spatial profiles of perfluoroalkyl substances and mercury in fish from northern Lake Victoria, East Africa.

There is an acute deficit of data on per- and polyfluoroalkyl substances (PFASs) and mercury (Hg) in the open waters of Lake Victoria, East Africa, relative to nearshore areas. We analyzed stable isotopes (δ15N and δ13C), PFASs and Hg in Nile Perch and Nile Tilapia muscle and liver samples from nearshore and open lake locations from the Ugandan part of the lake. The δ15N values of Nile Perch muscle indicated a higher trophic level for samples from the open lake than from nearshore locations. Averages of ∑PFAS concentrations in Nile Perch muscle and liver (0.44 and 1.75 ng/g ww, respectively) were significantly higher than in Nile Tilapia (0.24 and 0.50 ng/g ww, respectively). ∑PFAS concentrations in muscle of open lake Nile Perch were significantly higher than for nearshore samples. A similar observation was made for total mercury concentrations in muscle (THg_Muscle) of Nile Perch. THg was dominated by methyl mercury (MeHg+, 22-124 ng/g ww) and mercuric mercury (Hg2+,

Determination of transformation products of per- and polyfluoroalkyl substances at trace levels in agricultural plants.

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in the environment. However, only a limited number of predominantly persistent perfluoroalkyl acids (PFAAs) have been analyzed in edible plants so far. We present a generic trace analytical method that allows for quantification of 16 intermediate fluorotelomer alcohol (FTOH)- or perfluoroalkane sulfonamidoethanol (FASE)-based transformation products as well as 18 PFAAs in plants. Additionally, 36 suspected intermediate PFAS transformation products were qualitatively analyzed. The ultrasound-assisted solid-liquid extraction of wheat and maize grain, maize leaves, Jerusalem artichoke and ryegrass (1-5 g plant sample intake) was followed by a clean-up with dispersive solid-phase extraction using graphitized carbon adsorbent (5-10 mg per sample) and chemical analysis by reversed phase liquid chromatography-tandem mass spectrometry. The method was based on matrix matched and extracted calibration and displayed good precision with relative standard deviations in triplicate analyses typically below 15% for all quantified analytes and matrices. An average deviation of 12% between quantified concentrations obtained by matrix matched and extracted calibration and a method based on isotopically labelled internal standards underlines the good trueness of the method. The method quantification limits for the majority of analytes in all plant samples were in the low ng/kg concentration range on a dry weight basis. Plant matrices were analyzed from crops grown on agricultural fields that have been contaminated with PFASs. FTOH- and/or FASE-based intermediate transformation products were detected in all samples with N-ethyl perfluorooctane sulfonamidoacetic acid (EtFOSAA) and perfluorooctane sulfonamide (FOSA) as the prevailing compounds in concentrations up to several hundred ng/kg in maize leaves. The 9:3 Acid (a transformation product of 10:2 FTOH) was tentatively identified. In accordance with these findings, the final degradation products perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDA) were frequently detected. For perfluoroalkyl carboxylic acids (PFCAs), according to earlier findings, short chain homologues generally displayed the highest levels (up to 98 µg/kg for perfluorobutanoic acid (PFBA) in maize leaves). However, maize grain was an exception showing the highest concentrations for long chain PFCAs, whereas PFBA was not detected. The uptake of high levels of PFASs into plants is of concern since these may be used as animal feed or represent a direct exposure medium for humans.

A rapid method for quantification of persistent and mobile organic substances in water using supercritical fluid chromatography coupled to high-resolution mass spectrometry.

Persistent and mobile organic substances (PM substances) are a threat to the quality of our water resources. While screening studies revealed widespread occurrence of many PM substances, rapid trace analytical methods for their quantification in large sample sets are missing. We developed a quick and generic analytical method for highly mobile analytes in surface water, groundwater, and drinking water samples based on enrichment through azeotrope evaporation (4 mL water and 21 mL acetonitrile), supercritical fluid chromatography (SFC) coupled to high-resolution mass spectrometry (HRMS), and quantification using a compound-specific correction factor for apparent recovery. The method was validated using 17 PM substances. Sample preparation recoveries were between 60 and 110% for the vast majority of PM substances. Strong matrix effects (most commonly suppressive) were observed, necessitating a correction for apparent recoveries in quantification. Apparent recoveries were neither concentration dependent nor dependent on the water matrix (surface or drinking water). Method detection and quantification limits were in the single- to double-digit ng L-1 ranges, precision expressed as relative standard deviation of quadruplicate quantifications was on average < 10%, and trueness experiments showed quantitative results within ± 30% of the theoretical value in 77% of quantifications. Application of the method to surface water, groundwater, raw water, and finished drinking water revealed the presence of acesulfame and trifluoromethanesulfonic acid up to 70 and 19 µg L-1, respectively. Melamine, diphenylguanidine, p-dimethylbenzenesulfonic acid, and 4-hydroxy-1-(2-hydroxyethyl)-2,2,6,6-tetramethylpiperidine were found in high ng L-1 concentrations. Graphical abstract.

Membrane/Water Partitioning and Permeabilities of Perfluoroalkyl Acids and Four of their Alternatives and the Effects on Toxicokinetic Behavior.

The search for alternatives to bioaccumulative perfluoroalkyl acids (PFAAs) is ongoing. New, still highly fluorinated alternatives are produced in hopes of reducing bioaccumulation. To better estimate this bioaccumulative behavior, we performed dialysis experiments and determined membrane/water partition coefficients, Kmem/w, of six perfluoroalkyl carboxylic acids (PFCAs), three perfluoroalkanesulfonic acids, and four alternatives. We also investigated how passive permeation might influence the uptake kinetics into cells, measuring the passive anionic membrane permeability Pion through planar lipid bilayers for six PFAAs and three alternatives. Experimental Kmem/w and Pion were both predicted well by the COSMO-RS theory (log RMSE 0.61 and 0.46, respectively). Kmem/w values were consistent with the literature data, and alternatives showed similar sorption behavior as PFAAs. Experimental Pion values were high enough to explain observed cellular uptake by passive diffusion with no need to postulate the existence of active uptake processes. However, predicted pKa and neutral permeabilities suggest that also the permeation of the neutral species should be significant in case of PFCAs. This can have direct consequences on the steady-state distribution of PFAAs across cell membranes and thus toxicity. Consequently, we propose a model to predict pH-dependent baseline toxicity based on Kmem/w, which considers the permeation of both neutral and anionic species.

Mucosal-associated invariant T-Cell (MAIT) activation is altered by chlorpyrifos- and glyphosate-treated commensal gut bacteria.

Mucosal-associated invariant T-cells (MAIT) can react to metabolites of the vitamins riboflavin and folate which are produced by the human gut microbiota. Since several studies showed that the pesticide chlorpyrifos (CPF) and glyphosate (GLP) can impair the gut microbiota, the present study was undertaken to investigate the impact of CPF and GLP treatment on the metabolism of gut microbiota and the resulting bacteria-mediated modulation of MAIT cell activity. Here, Bifidobacterium adolescentis (B. adolescentis), Lactobacillus reuteri (L. reuteri), and Escherichia coli (E. coli) were treated with CPF (50-200 µM) or GLP (75-300 mg/L) and then used in MAIT cell stimulation assays as well as in vitamin and proteome analyses. All three bacteria were nonpathogenic and chosen as representatives of a healthy human gut microflora. The results showed that E. coli activated MAIT cells whereas B. adolescentis and L. reuteri inhibited MAIT cell activation. CPF treatment significantly increased E. coli-mediated MAIT cell activation. Treatment of B. adolescentis and L. reuteri with CPF and GLP weakened the inhibition of MAIT cell activation. Riboflavin and folate production by the test bacteria was influenced by CPF treatment, whereas GLP had only minor effects. Proteomic analysis of CPF-treated E. coli revealed changes in the riboflavin and folate biosynthesis pathways. The findings here suggest that the metabolism of the analyzed bacteria could be altered by exposure to CPF and GLP, leading to an increased pro-inflammatory immune response.

Partition coefficients of four perfluoroalkyl acid alternatives between bovine serum albumin (BSA) and water in comparison to ten classical perfluoroalkyl acids.

Perfluoroalkyl acids (PFAAs) are persistent, ubiquitous environmental contaminants and their long-chain representatives are bioaccumulative. The phase-out of these compounds (e.g. PFOA and PFOS) shifted the production to alternatives. However, little is known about the bioaccumulative behaviour of the alternatives, which are still highly fluorinated. PFAAs are predominantly detected in blood, where they bind to the transport protein serum albumin. This sorption can be described by the albumin/water partition coefficient. It is unclear whether the partition coefficients of the alternatives are lower than or in the same range as those of classical PFAAs. We determined albumin/water partition coefficients for seven perfluoroalkyl carboxylates, three perfluoroalkane sulfonates and four alternatives by dialysis experiments in a physiologically representative system. Quantification was done by LC-MS/MS and a mass balance approach. Logarithmic albumin/water partition coefficients for PFAAs range from 2.8 to 4.8 [Lwater kgalbumin-1] and increase with increasing chain length. Perfluorinated sulfonates sorb more strongly than their carboxylate counterparts. The albumin/water partition coefficients for the alternatives (HFPO-DA, DONA, 9Cl-PF3ONS and PFECHS) are in the same range as for classical PFAAs. Structural modifications such as the introduction of ether groups into the chain do not reduce sorption to albumin, whereas the chlorine atom in 9Cl-PF3ONS seems to even increase the sorption to albumin. We further investigated whether the sorption strength could be affected in the presence of medium- or long-chain fatty acids. Binding competition between medium-chain fatty acids and PFAAs appeared to be possible. However, the presence of physiologically more relevant long-chain fatty acids should not alter the albumin/water partition coefficients of PFAAs.

Perfluoroalkyl Acids (PFAAs) in Children's Serum and Contribution from PFAA-Contaminated Drinking Water.

We investigated associations between serum perfluoroalkyl acid (PFAA) concentrations in children aged 4, 8, and 12 years (sampled in 2008-2015; n = 57, 55, and 119, respectively) and exposure via placental transfer, breastfeeding, and ingestion of PFAA-contaminated drinking water. Sampling took place in Uppsala County, Sweden, where the drinking water has been historically contaminated with perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS), perfluorooctanesulfonate (PFOS), perfluoroheptanoate (PFHpA), and perfluorooctanoate (PFOA). PFOS showed the highest median concentrations in serum (3.8-5.3 ng g-1 serum), followed by PFHxS (1.6-5.0 ng g-1 serum), PFOA (2.0-2.5 ng g-1 serum), and perfluorononanoate (PFNA) (0.59-0.69 ng g-1 serum) in children. Including all children, serum PFOA, PFHxS, and PFOS concentrations in children increased 10, 10, and 1.3% (adjusted mean), respectively, per unit (ng g-1 serum) of increase in the maternal serum level (at delivery), the associations being strongest for 4 year-old children. PFHxS and PFOS significantly increased 3.9 and 3.8%, respectively, per month of nursing, with the highest increase for 4 year-olds. PFOA, PFBS, PFHxS, and PFOS increased 1.2, 207, 7.4, and 0.93%, respectively, per month of cumulative drinking water exposure. Early life exposure to PFOA, PFHxS, and PFOS is an important determinant of serum concentrations in children, with the strongest influence on younger ages. Drinking water with low to moderate PFBS, PFHxS, PFOS, and PFOA contamination is an important source of exposure for children with background exposure from other sources.

Occurrence of emerging persistent and mobile organic contaminants in European water samples.

The release of persistent and mobile organic chemicals (PMOCs) into the aquatic environment puts the quality of water resources at risk. PMOCs are challenging to analyze in water samples, due to their high polarity. The aim of this study was to develop novel analytical methods for PMOCs and to investigate their occurrence in surface and groundwater samples. The target compounds were culled from a prioritized list of industrial chemicals that were modeled to be persistent, mobile, and emitted into the environment. Analytical screening methods based on mixed-mode liquid chromatography (LC), hydrophilic interaction LC, reversed phase LC, or supercritical fluid chromatography in combination with mass spectrometric detection were successfully developed for 57 target PMOCs and applied to 14 water samples from three European countries. A total of 43 PMOCs were detected in at least one sample, among them 23 PMOCs that have not been reported before to occur in environmental waters. The most prevalent of these novel PMOCs were methyl sulfate, 2-acrylamino-2-methylpropane sulfonate, benzyltrimethylammonium, benzyldimethylamine, trifluoromethanesulfonic acid, 6-methyl-1,3,5-triazine-diamine, and 1,3-di-o-tolylguanidine occurring in ≥50% of the samples at estimated concentrations in the low ng L-1 up to µg L-1 range. The approach of focused prioritization combined with sensitive target chemical analysis proved to be highly efficient in revealing a large suite of novel as well as scarcely investigated PMOCs in surface and groundwater.

Longitudinal trends of per- and polyfluoroalkyl substances in children's serum.

Studies suggest negative health impacts from early life exposure to per- and polyfluoroalkyl substances (PFASs). However, information on longitudinal exposure to PFASs during childhood is scarce for background-exposed individuals. This study sought to fill this gap by investigating children's longitudinal exposure trends through measurement of PFAS serum concentrations and calculation of body burdens (µg, total in body). Blood of 54 Finnish children was sampled 2005-2015 and analyzed for 20 PFASs at 1, 6 and 10.5 years of age. The body burden was calculated by multiplying the serum concentration by the volume of distribution and the bodyweight for each individual. Associations between serum concentrations or body burdens and parameters, such as sex, breastfeeding duration, body mass index as well as indoor dust and air PFAS concentrations, were evaluated. Serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) decreased significantly (p < 0.001) with age. In contrast to serum concentrations, body burdens stayed unchanged or even increased significantly (p < 0.05), except for PFOA in female children. Breastfeeding duration was positively correlated (p < 0.001) with serum concentrations of PFHxS, PFOS, PFOA and PFNA at 1 year of age. Some associations were found at 10.5 years with sex and indoor PFAS concentrations. Observations of longitudinal decreasing trends of serum concentrations can be misleading for understanding exposure levels from external media during childhood, as the serum concentration is influenced by parallel temporal changes and growth dilution. Body burdens account for growth dilution and thus better reflect differences in early-life to adolescence exposure than serum concentrations.

Zürich Statement on Future Actions on Per- and Polyfluoroalkyl Substances (PFASs).

Per- and polyfluoroalkyl substances (PFASs) are man-made chemicals that contain at least one perfluoroalkyl moiety, [Formula: see text]. To date, over 4,000 unique PFASs have been used in technical applications and consumer products, and some of them have been detected globally in human and wildlife biomonitoring studies. Because of their extraordinary persistence, human and environmental exposure to PFASs will be a long-term source of concern. Some PFASs such as perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) have been investigated extensively and thus regulated, but for many other PFASs, knowledge about their current uses and hazards is still very limited or missing entirely. To address this problem and prepare an action plan for the assessment and management of PFASs in the coming years, a group of more than 50 international scientists and regulators held a two-day workshop in November, 2017. The group identified both the respective needs of and common goals shared by the scientific and the policy communities, made recommendations for cooperative actions, and outlined how the science-policy interface regarding PFASs can be strengthened using new approaches for assessing and managing highly persistent chemicals such as PFASs. https://doi.org/10.1289/EHP4158.

Perfluoroalkyl acids and their precursors in floor dust of children's bedrooms - Implications for indoor exposure.

We analysed floor dust samples from 65 children's bedrooms in Finland collected in 2014/2015 for 62 different per- and polyfluoroalkyl substances (PFASs) with a simple and highly efficient method. Validation results from the analysis of standard reference material (SRM) 2585 were in good agreement with literature data, while 24 PFASs were quantified for the first time. In the dust samples from children's bedrooms, five perfluoroalkyl carboxylic acids (PFCAs) and perfluorooctane sulfonic acid (PFOS) were detected in more than half of the samples with the highest median concentration of 5.26 ng/g for perfluorooctanoic acid (PFOA). However, the dust samples were dominated by polyfluoroalkyl phosphoric acid esters (PAPs) and fluorotelomer alcohols (FTOHs) (highest medians: 53.9 ng/g for 6:2 diPAP and 45.7 ng/g for 8:2 FTOH). Several significant and strong correlations (up to ρ = 0.95) were found among different PFASs in dust as well as between PFASs in dust and air samples (previously published) from the same rooms. The logarithm of dust to air concentrations (log Kdust/air) plotted against the logarithm of the octanol-air partition coefficient (log Koa) resulted in a significant linear regression line with R2 > 0.88. Higher dust levels of PFOS were detected in rooms with plastic flooring material in comparison to wood (p < 0.05). Total estimated daily intakes via dust (EDIdust) and air (EDIair) of perfluoroalkyl acids (PFAA), including biotransformation of precursors to PFAAs, were calculated for 10.5-year-old children. The total EDIdust for PFOA and PFOS were estimated to be 0.007 ng/kg bw/day and 0.006 ng/kg bw/day, respectively, in an intermediate exposure scenario. The sum of the total EDIs for all PFAAs was slightly higher for dust than air (0.027 and 0.019 ng/kg bw/day). Precursor biotransformation was generally important for total PFOS intake, while for the PFCAs, FTOH biotransformation was estimated to be important for air, but not for dust exposure.

Using REACH registration data to rank the environmental emission potential of persistent and mobile organic chemicals.

Organic chemicals that are persistent and mobile in the aquatic environment exhibit a hazard to contaminate drinking water resources. In this study an emission score model was developed to rank the potential of substances registered under the REACH legislation to be emitted into the environment. It was applied to a list of 2167 REACH registered substances that were previously identified to be persistent and mobile organic chemicals (PMOCs) in groundwater or to be hydrolyzed to form transformation products fulfilling the PMOC criteria. The emission score model is based on the tonnage placed on the European market and on seven emission-related use characteristics (high release to environment, wide dispersive use, intermediate use, closed system use, professional use, consumer use, and substance in article), reported in the companies' registrations under REACH. Applying the model resulted in a list of 1110 substances (936 PMOCs and 174 precursors to PMOCs) that were estimated to be released into the environment, while 1054 substances had indicators of negligible environmental emissions and 3 substances could not be evaluated due to severe data gaps. The 936 PMOCs and the 174 precursors were ranked in two lists with regard to their emission potential. The model was shown to be fit for purpose in terms of suggesting and prioritizing substances for scientific investigations with a focus on environmental water quality. Though targeted for PMOCs, the presented scoring system is illustrative of how REACH registration data can be used to assess the emission potential of various substances.

Perfluoroalkyl Acids (PFAAs) in Serum from 2-4-Month-Old Infants: Influence of Maternal Serum Concentration, Gestational Age, Breast-Feeding, and Contaminated Drinking Water.

Little is known about factors influencing infant perfluorinated alkyl acid (PFAA) concentrations. Associations between serum PFAA concentrations in 2-4-month-old infants ( n = 101) and determinants were investigated by multiple linear regression and general linear model analysis. In exclusively breast-fed infants, maternal serum PFAA concentrations 3 weeks after delivery explained 13% (perfluoroundecanoic acid, PFUnDA) to 73% (perfluorohexanesulfonate, PFHxS) of infant PFAA concentration variation. Median infant/maternal ratios decreased with increasing PFAA carbon chain length from 2.8 for perfluoroheptanoic acid and perfluorooctanoic acid (PFOA) to 0.53 for PFUnDA and from 1.2 to 0.69 for PFHxS and perfluorooctanesulfonate (PFOS). Infant PFOA, perfluorononanoic acid (PFNA), and PFOS levels increased 0.7-1.2% per day of gestational age. Bottle-fed infants had mean concentrations of PFAAs 2 times lower than and a mean percentage of branched (%br) PFOS isomers 1.3 times higher than those of exclusively breast-fed infants. PFOA, PFNA, and PFHxS levels increased 8-11% per week of exclusive breast-feeding. Infants living in an area receiving PFAA-contaminated drinking water had 3-fold higher mean perfluorobutanesulfonate (PFBS) and PFHxS concentrations and higher mean %br PFHxS. Prenatal PFAA exposure and postnatal PFAA exposure significantly contribute to infant PFAA serum concentrations, depending on PFAA carbon chain length. Moderately PFBS- and PFHxS-contaminated drinking water is an important indirect exposure source.

Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight gain and growth.

We investigated if maternal body burdens of perfluoroalkyl acids (PFAAs) at the time of delivery are associated with birth outcome and if early life exposure (in utero/nursing) is associated with early childhood growth and weight gain. Maternal PFAA body burdens were estimated by analysis of serum samples from mothers living in Uppsala County, Sweden (POPUP), sampled three weeks after delivery between 1996 and 2011. Data on child length and weight were collected from medical records and converted into standard deviation scores (SDS). Multiple linear regression models with appropriate covariates were used to analyze associations between maternal PFAA levels and birth outcomes (n=381). After birth Generalized Least Squares models were used to analyze associations between maternal PFAA and child growth (n=200). Inverse associations were found between maternal levels of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and birth weight SDS with a change of -0.10 to -0.18 weight SDS for an inter-quartile range (IQR) increase in ng/g PFAA. After birth, weight and length SDS were not significantly associated with maternal PFAA. However, BMI SDS was significantly associated with PFOA, PFNA, and PFHxS at 3 and 4years of age, and with PFOS at 4 and 5years of age. If causal, these associations suggest that PFAA affects fetal and childhood body development in different directions.