Systematic evidence mapping of potential correlates of exposure for per- and poly-fluoroalkyl substances (PFAS) based on measured occurrence in biomatrices and surveys of dietary consumption and product use.

Per- and poly-fluoroalkyl substances (PFAS) are widely observed in environmental media and often are found in indoor environments as well as personal-care and consumer products. Humans may be exposed through water, food, indoor dust, air, and the use of PFAS-containing products. Information about relationships between PFAS exposure sources and pathways and the amounts found in human biomatrices can inform source-contribution assessments and provide targets for exposure reduction. This work collected and collated evidence for correlates of PFAS human exposure as measured through sampling of biomatrices and surveys of dietary consumption and use of consumer products and articles. A systematic evidence mapping approach was applied to perform a literature search, conduct title-abstract and full-text screening, and to extract primary data into a comprehensive database for 16 PFAS. Parameters of interest included: sampling dates and locations, cohort descriptors, PFAS measured in a human biomatrix, information about food consumption in 11 categories, use of products/articles in 11 categories, and reported correlation values (and their statistical strength). The literature search and screening process yielded 103 studies with information for correlates of PFAS exposures. Detailed data were extracted and compiled on measures of PFAS correlations between biomatrix concentrations and dietary consumption and other product/article use. A majority of studies (61/103; 59%) were published after 2015 with few (8/103; 8%) prior to 2010. Studies were most abundant for dietary correlates (n = 94) with fewer publications reporting correlate assessments for product use (n = 56), while some examined both. PFOA and PFOS were assessed in almost all studies, followed by PFHxS, PFNA, and PFDA which were included in >50% of the studies. No relevant studies included PFNS or PFPeS. Among the 94 studies of dietary correlates, significant correlations were reported in 83% of the studies for one or more PFAS. The significant dietary correlations most commonly were for seafood, meats/eggs, and cereals/grains/pulses. Among the 56 studies of product/article correlates, significant correlations were reported in 70% of the studies. The significant product/article correlations most commonly were for smoking/tobacco, cosmetics/toiletries, non-stick cookware, and carpet/flooring/furniture and housing. Six of 11 product/article categories included five or fewer studies, including food containers and stain- and water-resistant products. Significant dietary and product/article correlations most commonly were positive. Some studies found a mix of positive and negative correlations depending on the PFAS, specific correlate, and specific response level, particularly for fats/oils, dairy consumption, food containers, and cosmetics/toiletries. Most of the significant findings for cereals/grains/pulses were negative correlations. Substantial evidence was found for correlations between dietary intake and biomatrix levels for several PFAS in multiple food groups. Studies examining product/article use relationships were relatively sparse, except for smoking/tobacco, and would benefit from additional research. The resulting database can inform further assessments of dietary and product use exposure relationships and can inform new research to better understand PFAS source-to-exposure relationships. The search strategy should be extended and implemented to support living evidence review in this rapidly advancing area.

Systematic Evidence Mapping of Potential Exposure Pathways for Per- and Polyfluoroalkyl Substances Based on Measured Occurrence in Multiple Media.

Given that human biomonitoring surveys show per- and polyfluoroalkyl substances (PFAS) to be ubiquitous, humans can be exposed to PFAS through various sources, including drinking water, food, and indoor environmental media. Data on the nature and level of PFAS in residential environments are required to identify important pathways for human exposure. This work investigated important pathways of exposure to PFAS by reviewing, curating, and mapping evidence for the measured occurrence of PFAS in exposure media. Real-world occurrence for 20 PFAS was targeted primarily in media commonly related to human exposure (outdoor and indoor air, indoor dust, drinking water, food, food packaging, articles, and products, and soil). A systematic-mapping process was implemented to conduct title-abstract and full-text screening and to extract PECO-relevant primary data into comprehensive evidence databases. Parameters of interest included the following: sampling dates and locations, numbers of collection sites and participants, detection frequencies, and occurrence statistics. Detailed data were extracted on PFAS occurrence in indoor and environmental media from 229 references and on PFAS occurrence in human matrices where available from those references. Studies of PFAS occurrence became numerous after 2005. Studies were most abundant for PFOA (80% of the references) and PFOS (77%). Many studies analyzed additional PFAS, particularly, PFNA and PFHxS (60% of references each). Food (38%) and drinking water (23%) were the commonly studied media. Most studies found detectable levels of PFAS, and detectable levels were reported in a majority of states in the United States. Half or more of the limited studies for indoor air and products detected PFAS in 50% or more of the collected samples. The resulting databases can inform problem formulation for systematic reviews to address specific PFAS exposure queries and questions, support prioritization of PFAS sampling, and inform PFAS exposure measurement studies. The search strategy should be extended and implemented to support living evidence review in this rapidly advancing area.

Expert assessment of the resilience of drinking water and sanitation systems to climate-related hazards.

We conducted an expert assessment to obtain expert opinions on the relative global resilience of ten drinking water and five sanitation technologies to the following six climate-related hazards: drought, decreased inter-annual precipitation, flood, superstorm flood, wind damage, and saline intrusion. Resilience scores ranged from 1.7 to 9.9 out of a maximum resilience of 10, with high scores corresponding to high resilience. We find that for some climate-related hazards, such as drought, technologies demonstrated a large range in resilience, indicating that the choice of water and sanitation technologies is important for areas prone to drought. On the other hand, the range of resilience scores for superstorm flooding was much smaller, particularly for sanitation technologies, suggesting that the choice of technology is less of a determinant of functionality for superstorm flooding as compared to other climate-related hazards. For drinking water technologies, only treated piped utility-managed systems that use surface water had resilience scores >6.0 for all hazards, while protected dug wells were found to be one of the least resilient technologies, consistently scoring <5.0 for all hazards except wind damage. In general, sanitation technologies were found to have low to medium resilience, suggesting that sanitation systems need to be adapted to ensure functionality during and after climate-related hazards. The results of the study can be used to help communities decide which technologies are best suited for the climate-related challenges they face and help in future adaptation planning.

Water safety plans: bridges and barriers to implementation in North Carolina.

First developed by the World Health Organization, and now used in several countries, water safety plans (WSPs) are a multi-step, preventive process for managing drinking water hazards. While the beneficial impacts of WSPs have been documented in diverse countries, how to successfully implement WSPs in the United States remains a challenge. We examine the willingness and ability of water utility leaders to implement WSPs in the US state of North Carolina. Our findings show that water utilities have more of a reactive than preventive organizational culture, that implementation requires prioritization of time and resources, perceived comparative advantage to other hazard management plans, leadership in implementation, and identification of how WSPs can be embedded in existing work practices. Future research could focus on whether WSP implementation provides benefits such as decreases in operational costs, and improved organization of records and communication.

Relationship between performance deterioration of a polyamide reverse osmosis membrane used in a seawater desalination plant and changes in its physicochemical properties.

While it is known that the performance of reverse osmosis membranes is dependent on their physicochemical properties, the existing literature studying membranes used in treatment facilities generally focuses on foulant layers or performance changes due to fouling, not on the performance and physicochemical changes that occur to the membranes themselves. In this study, the performance and physicochemical properties of a polyamide reverse osmosis membrane used for three years in a seawater desalination plant were compared to those of a corresponding unused membrane. The relationship between performance changes during long-term use and changes in physicochemical properties was evaluated. The results showed that membrane performance deterioration (i.e., reduced water flux, reduced contaminant rejection, and increased fouling propensity) occurred as a result of membrane use in the desalination facility, and that the main physicochemical changes responsible for performance deterioration were reduction in PVA coating coverage and bromine uptake by polyamide. The latter was likely promoted by oxidant residual in the membrane feed water. Our findings indicate that the optimization of membrane materials and processes towards maximizing the stability of the PVA coating and ensuring complete removal of oxidants in feed waters would minimize membrane performance deterioration in water purification facilities.

Drinking water and sanitation: progress in 73 countries in relation to socioeconomic indicators.

OBJECTIVE: To assess progress in the provision of drinking water and sanitation in relation to national socioeconomic indicators. METHODS: We used household survey data for 73 countries - collected between 2000 and 2012 - to calculate linear rates of change in population access to improved drinking water (n = 67) and/or sanitation (n = 61). To enable comparison of progress between countries with different initial levels of access, the calculated rates of change were normalized to fall between -1 and 1. In regression analyses, we investigated associations between the normalized rates of change in population access and national socioeconomic indicators: gross national income per capita, government effectiveness, official development assistance, freshwater resources, education, poverty, Gini coefficient, child mortality and the human development index. FINDINGS: The normalized rates of change indicated that most of the investigated countries were making progress towards achieving universal access to improved drinking water and sanitation. However, only about a third showed a level of progress that was at least half the maximum achievable level. The normalized rates of change did not appear to be correlated with any of the national indicators that we investigated. CONCLUSION: In many countries, the progress being made towards universal access to improved drinking water and sanitation is falling well short of the maximum achievable level. Progress does not appear to be correlated with a country's social and economic characteristics. The between-country variations observed in such progress may be linked to variations in government policies and in the institutional commitment and capacity needed to execute such policies effectively.

Assessing Progress towards Public Health, Human Rights, and International Development Goals Using Frontier Analysis.

Indicators to measure progress towards achieving public health, human rights, and international development targets, such as 100% access to improved drinking water or zero maternal mortality ratio, generally focus on status (i.e., level of attainment or coverage) or trends in status (i.e., rates of change). However, these indicators do not account for different levels of development that countries experience, thus making it difficult to compare progress between countries. We describe a recently developed new use of frontier analysis and apply this method to calculate country performance indices in three areas: maternal mortality ratio, poverty headcount ratio, and primary school completion rate. Frontier analysis is used to identify the maximum achievable rates of change, defined by the historically best-performing countries, as a function of coverage level. Performance indices are calculated by comparing a country's rate of change against the maximum achievable rate at the same coverage level. A country's performance can be positive or negative, corresponding to progression or regression, respectively. The calculated performance indices allow countries to be compared against each other regardless of whether they have only begun to make progress or whether they have almost achieved the target. This paper is the first to use frontier analysis to determine the maximum achievable rates as a function of coverage level and to calculate performance indices for public health, human rights, and international development indicators. The method can be applied to multiple fields and settings, for example health targets such as cessation in smoking or specific vaccine immunizations, and offers both a new approach to analyze existing data and a new data source for consideration when assessing progress achieved.

Amide Link Scission in the Polyamide Active Layers of Thin-Film Composite Membranes upon Exposure to Free Chlorine: Kinetics and Mechanisms.

The volume-averaged amide link scission in the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine was quantified at a variety of free chlorine exposure times, concentrations, and pH and rinsing conditions. The results showed that (i) hydroxyl ions are needed for scission to occur, (ii) hydroxide-induced amide link scission is a strong function of exposure to hypochlorous acid, (iii) the ratio between amide links broken and chlorine atoms taken up increased with the chlorination pH and reached a maximum of ∼25%, (iv) polyamide disintegration occurs when high free chlorine concentrations, alkaline conditions, and high exposure times are combined, (v) amide link scission promotes further chlorine uptake, and (vi) scission at the membrane surface is unrepresentative of volume-averaged scission in the active layer. Our observations are consistent with previously proposed mechanisms describing amide link scission as a result of the hydrolysis of the N-chlorinated amidic N-C bond due to nucleophilic attack by hydroxyl ions. This study increases the understanding of the physicochemical changes that could occur for membranes in treatment plants using chlorine as an upstream disinfectant and the extent and rate at which those changes would occur.

An examination of the potential added value of water safety plans to the United States national drinking water legislation.

National and sub-national governments develop and enforce regulations to ensure the delivery of safe drinking water in the United States (US) and countries worldwide. However, periodic contamination events, waterborne endemic illness and outbreaks of waterborne disease still occur, illustrating that delivery of safe drinking water is not guaranteed. In this study, we examined the potential added value of a preventive risk management approach, specifically, water safety plans (WSPs), in the US in order to improve drinking water quality. We undertook a comparative analysis between US drinking water regulations and WSP steps to analyze the similarities and differences between them, and identify how WSPs might complement drinking water regulations in the US. Findings show that US drinking water regulations and WSP steps were aligned in the areas of describing the water supply system and defining monitoring and controls. However, gaps exist between US drinking water regulations and WSPs in the areas of team procedures and training, internal risk assessment and prioritization, and management procedures and plans. The study contributes to understanding both required and voluntary drinking water management practices in the US and how implementing water safety plans could benefit water systems to improve drinking water quality and human health.

Bulk chlorine uptake by polyamide active layers of thin-film composite membranes upon exposure to free chlorine-kinetics, mechanisms, and modeling.

We studied the volume-averaged chlorine (Cl) uptake into the bulk region of the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine. Volume-averaged measurements were obtained using Rutherford backscattering spectrometry with samples prepared at a range of free chlorine concentrations, exposure times, and mixing, rinsing, and pH conditions. Our volume-averaged measurements complement previous studies that have quantified Cl uptake at the active layer surface (top ≈ 7 nm) and advance the mechanistic understanding of Cl uptake by aromatic polyamide active layers. Our results show that surface Cl uptake is representative of and underestimates volume-averaged Cl uptake under acidic conditions and alkaline conditions, respectively. Our results also support that (i) under acidic conditions, N-chlorination followed by Orton rearrangement is the dominant Cl uptake mechanism with N-chlorination as the rate-limiting step; (ii) under alkaline conditions, N-chlorination and dechlorination of N-chlorinated amide links by hydroxyl ion are the two dominant processes; and (iii) under neutral pH conditions, the rates of N-chlorination and Orton rearrangement are comparable. We propose a kinetic model that satisfactorily describes Cl uptake under acidic and alkaline conditions, with the largest discrepancies between model and experiment occurring under alkaline conditions at relatively high chlorine exposures.

Kinetics of bromochloramine formation and decomposition.

Batch experiments were performed to study the kinetics of bromochloramine formation and decomposition from the reaction of monochloramine and bromide ion. The effects of pH, initial monochloramine and bromide ion concentrations, phosphate buffer concentration, and excess ammonia were evaluated. Results showed that the monochloramine decay rate increased with decreasing pH and increasing bromide ion concentration, and the concentration of bromochloramine increased to a maximum before decreasing gradually. The maximum bromochloramine concentration reached was found to decrease with increasing phosphate and ammonia concentrations. Previous models in the literature were not able to capture the decay of bromochloramine, and therefore we proposed an extended model consisting of reactions for monochloramine autodecomposition, the decay of bromamines in the presence of bromide, bromochloramine formation, and bromochloramine decomposition. Reaction rate constants were obtained through least-squares fitting to 11 data sets representing the effect of pH, bromide, monochloramine, phosphate, and excess ammonia. The reaction rate constants were then used to predict monochloramine and bromochloramine concentration profiles for all experimental conditions tested. In general, the modeled lines were found to provide good agreement with the experimental data under most conditions tested, with deviations occurring at low pH and high bromide concentrations.

Equity in water and sanitation: developing an index to measure progressive realization of the human right.

We developed an index to measure progressive realization for the human right to water and sanitation. While in this study we demonstrate its application to the non-discrimination and equality component for water, the conceptual approach of the index can be used for all the different components of the human right. The index was composed of one structural, one process, and two outcome indicators and is bound between -1 and 1, where negative values indicate regression and positive values indicate progressive realization. For individual structural and process indicators, only discrete values such as -1, -0.5, 0, 0.5, and 1 were allowed. For the outcome indicators, any value between -1 and 1 was possible, and a State's progress was evaluated using rates of change. To create an index that would allow for fair comparisons between States and across time, these rates of change were compared to benchmarked rates, which reflect the maximum rates a State can achieve. Using this approach, we calculated the index score for 56 States in 2010 for which adequate data were available and demonstrated that these index scores were not dependent on factors such as achieved level of coverage or gross national income. The proposed index differs from existing measures of inequality as it measures rate of change and not level of achievement, and thus addresses the principle of progressive realization that is fundamental to human rights.

Sanitation: a global estimate of sewerage connections without treatment and the resulting impact on MDG progress.

Progress toward the sanitation component of Millennium Development Goal (MDG) Target 7c was reassessed to account for the need to protect communities and the wider population from exposure to human excreta. We classified connections to sewerage as "improved sanitation" only if the sewage was treated before discharge to the environment. Sewerage connection data was available for 167 countries in 2010; of these, 77 had published data on sewage treatment prevalence. We developed an empirical model to estimate sewage treatment prevalence for 47 additional countries. We estimate that in 2010, 40% of the global population (2.8 billion people) used improved sanitation, as opposed to the estimate of 62% (4.3 billion people) from the WHO/UNICEF Joint Monitoring Programme (JMP), and that 4.1 billion people lacked access to an improved sanitation facility. Redefining sewerage-without-treatment as "unimproved sanitation" in MDG monitoring would raise the 1990 baseline population using unimproved sanitation from 53% to 64% and the corresponding 2015 target from 27% to 32%. At the current rate of progress, we estimate a shortfall of 28 percentage points (1.9 billion people) in 2010 and a projected 27 percentage point shortfall in 2015.

Bromide ion effect on N-nitrosodimethylamine formation by monochloramine.

N-Nitrosodimethylamine (NDMA) formation experiments conducted in phosphate buffer demonstrated that in waters containing monochloramine, the presence of bromide ion enhanced NDMA formation at the relatively high pH values of 8 and 9 after 24 h of reaction time, which was consistent with literature results. However, at relatively low to neutral pH (6 to 7), the presence of bromide resulted in lower NDMA formation as compared to results obtained in the absence of bromide. The hypothesis that bromamines were the species directly responsible for enhanced NDMA formation at high pH was tested and was shown not to be valid. Additional active bromine species were also tested, including hypobromous acid, hypobromite ion, and tribromide ion, with no species showing an ability to directly enhance NDMA formation. Analysis of the UV spectral data corresponding to the NDMA experiments suggest that the mechanism by which bromide enhances NDMA formation lies in the formation of a haloamine compound, possibly the mixed dihaloamine bromochloramine.

Inactivation of Mycobacterium avium with monochloramine.

Batch experiments were performed to study the inactivation kinetics of Mycobacterium avium in the presence of monochloramine at 5-30 degrees C, pH 6-10, and 0.30-42.3 mg Cl2/ L. For each temperature and pH investigated, limiting high and low inactivation rates were observed for high and low disinfectant concentrations, respectively, within the range investigated. The rate of inactivation transitioned from high to low over a relatively narrow range of intermediate monochloramine concentrations. The observed temperature dependence of inactivation was consistent with an Arrhenius expression with activation energies of 58.0 and 71.7 kJ/mol for the high and low concentration ranges, respectively. The rate of inactivation increased with decreasing pH, consistent with trends reported for the reaction of monochloramine with protein thiols. Experiments performed at pH approximately 3.5 showed that dichloramine was a weaker disinfectant than monochloramine, and that its contribution to the overall inactivation of M. avium with combined chlorine was negligible at pH 6-10. A kinetic model incorporating disinfectant concentration, temperature, and pH effects was used to illustrate that monochloramine efficiency to inactivate M. avium in water could vary broadly from adequate (e.g., 99.9% inactivation efficiency in 32 min at 5 mg Cl2/L, pH 6, 30 degrees C) to impractical (e.g., 99.9% inactivation efficiency in 9 d at 1 mg Cl2/L, pH 9, 5 degrees C).

Inactivation of Mycobacterium avium with chlorine dioxide.

The effects of pH (6-10), temperature (5-30 degrees C), and disinfectant concentration (0.5-5mgClO(2)/L) on the kinetics of Mycobacterium avium inactivation with chlorine dioxide were investigated by performing batch experiments in synthetic 0.01M phosphate and borate buffer solutions. The resulting inactivation curves were generally characterized by a lag phase followed by two subsequent stages, fast and then slow, of pseudo-first-order kinetics consistent with two-population (susceptible and tolerant) kinetics. However, variability that was uncorrelated to experimental conditions was observed; some inactivation curves did not have a lag phase and/or the susceptible population was absent. The inactivation kinetics of the tolerant population was found to be independent of pH and to have temperature dependence according to Arrhenius law with an activation energy of 74.1kJ/mole. Conservative CT requirements for the inactivation of M. avium with chlorine dioxide were estimated using the most pronounced lag phase observed and absence of the susceptible population.

Inactivation of Mycobacterium avium with free chlorine.

The inactivation kinetics of Mycobacterium avium with free chlorine was characterized by two stages: an initial phase at a relatively fast rate followed by a slower second stage of pseudo first-order kinetics. The inactivation rate of each stage was approximately the same for all experiments performed at a certain condition of pH and temperature; however, variability was observed for the disinfectant exposure at which the transition between the two stages occurred. This variability was not a function of the initial disinfectant concentration, the initial bacterial density, or the bacterial stock. However, the transition to the second stage varied more significantly at high temperatures (30 degrees C), while lower variability was observed at lower temperatures (5 and 20 degrees C). Experiments conducted at pH values in the range of 6-9 revealed that the inactivation of M. avium was primarily due to hypochlorous acid, with little contribution from hypochlorite ion within this pH range. The inactivation kinetics was represented with a two-population model. The activation energies for the resulting pseudo first-order rate constants for the populations with fast and slow kinetics were 100.3 and 96.5 kJ/mol, respectively. The magnitude of these values suggested that for waters of relatively high pH and low temperatures, little inactivation of M. avium would be achieved within treatment plants, providing a seeding source for distribution systems.

Single molecule imaging of supported planar lipid bilayer--reconstituted human insulin receptors by in situ scanning probe microscopy.

A 480-kDa disulfide-linked heterodimer single-pass transmembrane protein, the insulin receptor, is autophosphorylated upon insulin binding to its extracellular domain. Remarkably, the structural basis for this activation process remained largely unknown until the recent cryoelectron microscopy studies of the insulin-insulin receptor complex by Luo et al. [Science 285 (1999) 1077]. We report here the results of an in situ study by high-resolution scanning probe microscopy of the full-length insulin receptor reconstituted within supported planar lipid bilayers. Our preliminary studies confirm that (1) the intact receptor can be reconstituted constitutively within a lipid vesicle and (2) fusion of the receptor-containing vesicles to mica resulted in the formation of molecular flat 5.5-nm-thick supported planar bilayers populated by two populations of protrusions, the shape and size of which are consistent with those of the insulin receptor's intra- and extracellular domains as modeled by the cryo-EM data of Ottensmeyer et al. [Biochemistry 39 (2000) 12103]. These results establish a framework for real-time studies of insulin-insulin receptor binding by in situ SPM and single molecule force spectroscopy.