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The extent of ongoing exposure to the general public from per- and polyfluoroalkyl substances (PFAS) in drinking water in the United States and worldwide remains uncertain. Here, we analyze publicl...

This commentary presents a scientific basis for managing as one chemical class the thousands of chemicals known as PFAS (per- and polyfluoroalkyl substances). The class includes perfluoroalkyl acids, perfluoroalkylether acids, and their precursors; fluoropolymers and perfluoropolyethers; and other PFAS. The basis for the class approach is presented in relation to their physicochemical, environmental, and toxicological properties. Specifically, the high persistence, accumulation potential, and/or hazards (known and potential) of PFAS studied to date warrant treating all PFAS as a single class. Examples are provided of how some PFAS are being regulated and how some businesses are avoiding all PFAS in their products and purchasing decisions. We conclude with options for how governments and industry can apply the class-based approach, emphasizing the importance of eliminating non-essential uses of PFAS, and further developing safer alternatives and methods to remove existing PFAS from the environment., Environmental Science & Technology Letters, 7 (8), ISSN:2328-8930

Per- and polyfluoroalkyl substances, or PFAS, gained significant public and regulatory attention due to widespread contamination and health harms associated with exposure. Ingestion of PFAS from contaminated food and water results in the accumulation of PFAS in the body and is considered a key route of human exposure. Here we calculate the potential contribution of PFOS from consumption of locally caught freshwater fish to serum levels. We analyzed data for over 500 composite samples of fish fillets collected across the United States from 2013 to 2015 under the U.S. EPA's monitoring programs, the National Rivers and Streams Assessment and the Great Lakes Human Health Fish Fillet Tissue Study. The two datasets indicate that an individual's consumption of freshwater fish is potentially a significant source of exposure to perfluorinated compounds. The median level of total targeted PFAS in fish fillets from rivers and streams across the United States was 9500 ng/kg, with a median level of 11,800 ng/kg in the Great Lakes. PFOS was the largest contributor to total PFAS levels, averaging 74% of the total. The median levels of total detected PFAS in freshwater fish across the United States were 278 times higher than levels in commercially relevant fish tested by the U.S. Food and Drug Administration in 2019-2022. Exposure assessment suggests that a single serving of freshwater fish per year with the median level of PFAS as detected by the U.S. EPA monitoring programs translates into a significant increase of PFOS levels in blood serum. The exposure to chemical pollutants in freshwater fish across the United States is a case of environmental injustice that especially affects communities that depend on fishing for sustenance and for traditional cultural practices. Identifying and reducing sources of PFAS exposure is an urgent public health priority.

BACKGROUND New research has attributed increased significance to the causal link between ultraviolet A (UVA) radiation and immunosuppression and carcinogenesis. In the United States, sunscreens are labeled with only their sun protection factor (SPF) and an imprecise term "broad-spectrum protection." Sunscreen marketing and efficacy evaluations continue to be based primarily on skin redness (sunburn) or erythema. We sought to evaluate the ultraviolet (UV) protection offered by common sunscreen products on the US market using laboratory-measured UV-absorption testing and comparing with computer-modeled protection and the labeled SPF values. This approach enables an investigation of the relationship between the labeled SPF and measured UVA protection, a factor that is ignored in current regulations. METHODS Fifty-one sunscreen products for sale in the United States with SPF values from 15 to 110 and labeled as providing broad-spectrum protection were tested using a commercial laboratory. All products were evaluated using the ISO 24443:2012 method for sunscreen effectiveness. The final absorbance spectra were used for analysis of in vitro UV protection. RESULTS In vitro SPF values from laboratory-measured UV absorption and computer modeling were on average just 59 and 42 percent of the labeled SPF. The majority of products provided significantly lower UVA protection with the average unweighted UVA protection factor just 24 percent of the labeled SPF. CONCLUSION Regulations and marketplace forces promote sunscreens that reduce sunburn instead of products that provide better, more broad-spectrum UV protection. The production and use of products with broad spectrum UV protection should be incentivized, removing the emphasis on sunburn protection and ending testing on people.

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

The health risks of drinking water contaminants and the economic benefits of drinking water standards are typically assessed one chemical at a time, an approach that misses the health impacts of co-occurring contaminants in drinking water. In contrast, a cumulative risk framework has become common in air quality evaluations such as the U.S. Environmental Protection Agency’s National Air Toxics Assessment. We posit that the drinking water field would benefit from making the transition to a unified assessment framework for multiple contaminants that can overcome the long-standing challenge of treating cancer and non-cancer contaminants separately. Here we present a cumulative risk methodology that combines a risk-based cancer metric with a weighted health indicator index for non-cancer contaminants and incorporates disability weights from the Global Burden of Disease study. Our methodology generates a numeric toxicity score reflecting the potential health impacts for the sum of contaminants present in each sample of drinking water. Further research is needed to refine the risk and toxicity parameters for specific contaminants and to address the mode of interaction between co-occurring chemicals. As this cumulative risk model goes through future refinements, we anticipate that it would provide information that can help communities and policy makers evaluate different options for drinking water treatment. Electronic supplementary material The online version of this article (10.1186/s12940-019-0475-5) contains supplementary material, which is available to authorized users.

Drinking water contamination with poly- and perfluoroalkyl substances (PFASs) poses risks to the developmental, immune, metabolic, and endocrine health of consumers. We present a spatial analysis of 2013–2015 national drinking water PFAS concentrations from the U.S. Environmental Protection Agency’s (US EPA) third Unregulated Contaminant Monitoring Rule (UCMR3) program. The number of industrial sites that manufacture or use these compounds, the number of military fire training areas, and the number of wastewater treatment plants are all significant predictors of PFAS detection frequencies and concentrations in public water supplies. Among samples with detectable PFAS levels, each additional military site within a watershed’s eight-digit hydrologic unit is associated with a 20% increase in PFHxS, a 10% increase in both PFHpA and PFOA, and a 35% increase in PFOS. The number of civilian airports with personnel trained in the use of aqueous film-forming foams is significantly associated with the detection of PFASs above the minimal reporting level. We find drinking water supplies for 6 million U.S. residents exceed US EPA’s lifetime health advisory (70 ng/L) for PFOS and PFOA. Lower analytical reporting limits and additional sampling of smaller utilities serving

Per- and polyfluoroalkyl substances (PFASs) are highly persistent synthetic chemicals, some of which have been associated with cancer, developmental toxicity, immunotoxicity, and other health effects. PFASs in grease-resistant food packaging can leach into food and increase dietary exposure. We collected ~400 samples of food contact papers, paperboard containers, and beverage containers from fast food restaurants throughout the United States and measured total fluorine using particle-induced γ-ray emission (PIGE) spectroscopy. PIGE can rapidly and inexpensively measure total fluorine in solid-phase samples. We found that 46% of food contact papers and 20% of paperboard samples contained detectable fluorine (>16 nmol/cm2). Liquid chromatography/high-resolution mass spectrometry analysis of a subset of 20 samples found perfluorocarboxylates, perfluorosulfonates, and other known PFASs and/or unidentified polyfluorinated compounds (based on nontargeted analysis). The total peak area for PFASs was higher in 70% of samples (10 of 14) with a total fluorine level of >200 nmol/cm2 compared to six samples with a total fluorine level of

Summary: The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban. These chemicals may be used in thousands of personal care and consumer products as well as in building materials. Based on extensive peer-reviewed research, this statement concludes that triclosan and triclocarban are environmentally persistent endocrine disruptors that bioaccumulate in and are toxic to aquatic and other organisms. Evidence of other hazards to humans and ecosystems from triclosan and triclocarban is presented along with recommendations intended to prevent future harm from triclosan, triclocarban, and antimicrobial substances with similar properties and effects. Because antimicrobials can have unintended adverse health and environmental impacts, they should only be used when they provide an evidence-based health benefit. Greater transparency is needed in product formulations, and before an antimicrobial is incorporated into a product, the long-term health and ecological impacts should be evaluated. https://doi.org/10.1289/EHP1788

A wide-field localized surface plasmon resonance (LSPR) imaging method using a liquid crystal tunable filter is used to measure the scattering spectra of multiple Ag nanoparticles in parallel. This method provides the ability to characterize moving Ag nanoparticles by measuring the scattering spectra of the particles while simultaneously tracking their motion. Consequently, single-particle diffusion coefficients can be determined. As an example, several single Ag nanoprisms are tracked, the LSPR scattering spectrum of each moving particle is obtained, and the single-particle diffusion coefficient is determined from its trajectory. Coupling diffusion information with spectral information in real time is a significant advance and addresses many scientific problems, both fundamental and biological, such as cell membrane protein diffusion, functional plasmonic distributions, and nanoparticle growth mechanisms.

In molecular transport junctions, current is monitored as a function of the applied voltage for a single molecule assembled between two leads. The transport is modulated by the electronic states of the molecule. For the prototypical delocalized systems, namely, pi-conjugated aromatics, the pi system usually dominates the transport. Herein, we investigate situations where model calculations including only the pi system do not capture all of the subtleties of the transport properties. Including both the sigma and pi contributions to charge transport allows us to demonstrate that while there is generally good agreement, there are discrepancies between the methods. We find that model calculations with only the pi system are insufficient where the transport is dominated by quantum interference and cases where geometric changes modulate the coupling between different regions of the pi system. We examine two specific molecular test cases to model these geometric changes: the angle dependence of coupling in (firstly) a biphenyl and (secondly) a nitro substituent of a cross-conjugated unit.

Molecular electronics is partly driven by the goal of producing active electronic elements that rival the performance of their solid-state counterparts, but on a much smaller size scale. We investigate what constitutes an ideal switch or molecular device, and how it can be designed, by analyzing transmission plots. The interference features in cross-conjugated molecules provide a large dynamic range in electron transmission probability, opening a new area for addressing electronic functionality in molecules. This large dynamic range is accessible through changes in electron density alone, enabling fast and stable switching. Using cross-conjugated molecules, we show how the width, depth, and energetic location of the interference features can be controlled. In an example of a single molecule transistor, we calculate a change in conductance of 8 orders of magnitude with an applied gate voltage. Using multiple interference features, we propose and calculate the current/voltage behavior of a molecular rectifier with a rectification ratio of >150,000. We calculate a purely electronic negative differential resistance behavior, suggesting that the large dynamic range in electron transmission probability caused by quantum interference could be exploited in future electronic devices.

We report on a class of molecules that exhibit nonlinear current/voltage behavior in the low bias tunneling regime. This interesting behavior is attributed to quantum interference. Using site models, we show that interference features, while common, do not necessarily occur at experimentally relevant energies, hindering realization in transport measurements. Calculations made using a nonequilibrium Green’s function code show that quantum interference can be experimentally relevant in cross-conjugated molecules. A detailed bond length analysis of cross-conjugated molecules gives insight into why these molecules have interference at energetically accessible regions. The interference features are shown to be stable to both an electronic dephasing analysis and geometric fluctuations provided by molecular dynamics.

Congenital disorders of glycosylation (CDG) are a group of metabolic disorders with multisystemic involvement characterized by abnormalities in the synthesis of N-linked oligosaccharides. The most common form, CDG-Ia, resulting from mutations in the gene encoding the enzyme phosphomannomutase (PMM2), manifests with severe abnormalities in psychomotor development, dysmorphic features and visceral involvement. While this disorder is panethnic, we present the first cases of CDG-Ia identified in an African American family with two affected sisters. The proband had failure to thrive in infancy, hypotonia, ataxia, cerebellar hypoplasia and developmental delay. On examination, she also exhibited strabismus, inverted nipples and an atypical perineal fat distribution, all features characteristic of CDG-Ia. Direct sequencing demonstrated that the patient had a unique genotype, T237M/c.565-571 delAGAGAT insGTGGATTTCC. The novel deletion-insertion mutation, which was confirmed by subcloning and sequencing of each allele, introduces a stop codon 11 amino acids downstream from the site of the deletion. The presence of this deletion-insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage.

While the inherited deficiency of the enzyme glucocerebrosidase (Gaucher disease) is panethnic in its distribution, there have not been studies of the mutations encountered in specific ethnic groups in the United States, other than those on Ashkenazi Jews. We present the clinical descriptions and genotypes of seven patients of African-American ancestry with type 1 Gaucher disease, and summarize the published literature regarding the genotypes encountered in this population. All seven of the patients had moderate-to-severe manifestations of the disease, and all developed symptoms by adolescence. Genotypic analyses revealed that no two probands shared the same genotype. The common mutations N370S, c.84-85insG, IVS2+1 G-->A, and R463C were not seen. Mutation L444P was present on one allele in each of the patients; but the same mutation was encountered as a single point mutation in three of the patients, and as part of a recombinant allele in four of the patients. Southern blot analyses revealed a glucocerebrosidase fusion allele in one patient, and a duplication resulting from recombination in the region downstream from the glucocerebrosidase gene in three of the patients. Five different point mutations (A90T, R48W, N117D, R170C, and V352L), one deletion mutation (c.222-224 delTAC), and one insertion mutation (c.153-154 insTACAGC) were encountered. Our results demonstrate that there is significant genotypic heterogeneity among African-American patients with type 1 Gaucher disease, and that recombinations in the glucocerebrosidase gene locus are particularly common in this patient group. Published 2001 Wiley-Liss, Inc.

The mechanism for off-resonant electron transport through small organic molecules in metallic junctions is predominantly coherent tunneling. Thus, new device functionalities based on quantum interference could be developed in the field of molecular electronics. We invoke a partitioning technique to give an analytical treatment of quantum interference in a benzene ring. We interpret the antiresonances in the transmission as either multipath zeroes resulting from interfering spatial pathways or resonance zeroes analogous to zeroes induced by sidechains.

We calculate that significant quantum interference effects can be observed in elastic electron transport through acyclic molecules. Interference features are evident in the transmission characteristics calculated for cross-conjugated molecules; significantly, these effects dominate the experimentally observable conduction range. The unusual transport characteristics of these molecules are highlighted through comparison with linearly conjugated and nonconjugated systems. The cross-conjugated molecules presented here show a large dynamic range in conductance. These findings represent a new motif for electron transfer through molecules that exhibit both very high and very low tunneling conductance states accessible at low bias without nuclear motion. In designing single molecule electronic components, a large dynamic range allows a high on/off ratio, a parameter of fundamental importance for switches, transistors, and sensors.

The experimental variation in conductance that can be expected through dynamically evolving Au-molecule-Au junctions is approximated using molecular dynamics to model thermal fluctuations and a nonequilibrium Green's function code (Huckel-IV 2.0) to calculate the charge transport. This generates a statistical set of conductance data that can be used to compare directly with experimental results. Experimental measurements on Au-single molecule junctions show a large variation in conductance values between different identically prepared junctions. Our computational results indicate that the Au-Au and the Au-molecule fluctuations provide extensive geometric freedom and an associated broad distribution in calculated conductance values. Our results show agreement with experimental measurements of the low bias voltage conductance and conductance distribution for both thiol-Au and amine-Au linker structures.

A p-benzenedithiolate (BDT) molecule covalently bonded between two gold electrodes has become one of the model systems utilized for investigating molecular transport junctions. The plethora of papers published on the BDT system has led to varying conclusions with respect to both the mechanism and the magnitude of transport. Conductance variations have been attributed to difficulty in calculating charge transfer to the molecule, inability to locate the Fermi energy accurately, geometric dispersion, and stochastic switching. Here we compare results obtained using two transport codes, TRANSIESTA-C and HUCKEL-IV, to show that upon Au-S bond lengthening, the calculated low bias conductance initially increases by up to a factor of 30. This increase in highest occupied molecular orbital (HOMO) mediated conductance is attributed to charging of the terminal sulfur atom and a corresponding decrease in the energy gap between the Fermi level and the HOMO. Addition of a single Au atom to each terminal of the extended BDT molecule is shown to add four molecular states near the Fermi energy, which may explain the varying results reported in the literature.

Theory and experiment examining electron transfer through molecules bound to electrodes are increasingly focused on quantities that are conceptually far removed from current chemical understanding. This presents challenges both for the design of interesting molecules for these devices and for the interpretation of experimental data by traditional chemical mechanisms. Here, the concept of electronic coupling from theories of intramolecular electron transfer is extended and applied in the scattering theory (Landauer) formalism. This yields a simple sum over independent channels, that is then used to interpret and explain the unusual features of junction transport through cross-conjugated molecules and the differences among benzene rings substituted at the ortho, meta, or para positions.

Molecular dynamics (MD) simulations of 5 ns on protein-DNA complexes of catabolite-activator protein (CAP), lambda-repressor, and their corresponding uncomplexed protein and DNA, are reported. These cases represent two extremes of DNA bending, with CAP DNA bent severely and the lambda-operator nearly straight when complexed with protein. The calculations were performed using the AMBER suite of programs and the parm94 force field, validated for these studies by good agreement with experimental nuclear magnetic resonance data on DNA. An explicit computational model of structural adaptation and computation of the quasiharmonic entropy of association were obtained from the MD. The results indicate that, with respect to canonical B-form DNA, the extreme bending of the DNA in the complex with CAP is approximately 60% protein-induced and 40% intrinsic to the sequence-dependent structure of the free oligomer. The DNA in the complex is an energetically strained form, and the MD results are consistent with a conformational-capture mechanism. The calculated quasiharmonic entropy change accounts for the entropy difference between the two cases. The calculated entropy was decomposed into contributions from protein adaptation, DNA adaptation, and protein-DNA structural correlations. The origin of the entropy difference between CAP and lambda-repressor complexation arises more from the additional protein adaptation in the case of lambda, than to DNA bending and entropy contribution from DNA bending. The entropy arising from protein DNA cross-correlations, a contribution not previously discussed, is surprisingly large.