The derivation of a Reference Dose (RfD) for perfluorooctane sulfonate (PFOS) based on immune suppression.

Exposure to perfluorooctane sulfonate (PFOS) is ubiquitous in populations and environments worldwide. Its long half-life in humans, indefinite persistence in the environment, and awareness of its widespread presence in drinking water make the human health assessment of PFOS a priority. While developmental, endocrine, and hepatic effects, and increased serum cholesterol are among the outcomes resulting from PFOS exposure, immunosuppression has also consistently emerged as an adverse effect. An in-depth review of the relevant scientific literature on the toxicology of PFOS has identified immunosuppression as a sensitive endpoint for PFOS toxicity. Here, we focus specifically on that endpoint and provide a detailed derivation of a Reference Dose (RfD) of 1.8 × 10-6 mg/kg/day for chronic human exposure to PFOS. This RfD is based on decreased plaque-forming cell (PFC) response in mice, an endpoint that reflects suppression of the immune response to a foreign antigen. We additionally identify two endpoints in the epidemiology literature, decreased vaccine response and increased incidence of childhood infections, that are associated with PFOS exposure and that are consistent with and support the decreased PFC response endpoint from animal studies. We provide a weight of evidence analysis integrating the evidence from animal and epidemiology endpoints. Finally, we compare this RfD to the PFOS RfD derived by the United States Environmental Protection Agency (USEPA) Office of Water based on a developmental endpoint. Based on this comparison, and given our assessment, the USEPA RfD does not provide sufficient protection against the adverse health effects of PFOS. The RfD derived herein is intended to be public health protective and appropriately minimizes PFOS exposure based on available evidence.

Guideline levels for PFOA and PFOS in drinking water: the role of scientific uncertainty, risk assessment decisions, and social factors.

Communities across the U.S. are discovering drinking water contaminated by perfluoroalkyl and polyfluoroalkyl substances (PFAS) and determining appropriate actions. There are currently no federal PFAS drinking water standards despite widespread drinking water contamination, ubiquitous population-level exposure, and toxicological and epidemiological evidence of adverse health effects. Absent federal PFAS standards, multiple U.S. states have developed their own health-based water guideline levels to guide decisions about contaminated site cleanup and drinking water surveillance and treatment. We examined perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) water guideline levels developed by the U.S. Environmental Protection Agency (EPA) and state agencies to protect people drinking the water, and summarized how and why these levels differ. We referenced documents and tables released in June 2018 by the Interstate Technology and Regulatory Council (ITRC) to identify states that have drinking water and groundwater guideline levels for PFOA and/or PFOS that differ from EPA's health advisories (HAs). We also gathered assessment documents from state websites and contacted state environmental and health agencies to identify and confirm current guidelines. Seven states have developed their own water guideline levels for PFOA and/or PFOS ranging from 13 to 1000 ng/L, compared to EPA's HA of 70 ng/L for both compounds individually or combined. We find that the development of PFAS guideline levels via exposure and hazard assessment decisions is influenced by multiple scientific, technical, and social factors, including managing scientific uncertainty, technical decisions and capacity, and social, political, and economic influences from involved stakeholders. Assessments by multiple states and academic scientists suggest that EPA's HA is not sufficiently protective. The ability of states to develop their own guideline levels and standards provides diverse risk assessment approaches as models for other state and federal regulators, while a sufficiently protective, scientifically sound, and enforceable federal standard would provide more consistent protection.

Substitution of PFAS chemistry in outdoor apparel and the impact on repellency performance.

Intensifying legislation and increased research on the toxicological and persistent nature of per- and polyfluoroalkyl substances (PFASs) have recently influenced the direction of liquid repellent chemistry use; environmental, social, and sustainability responsibilities are at the crux. Without PFAS chemistry, it is challenging to meet current textile industry liquid repellency requirements, which is a highly desirable property, particularly in outdoor apparel where the technology helps to provide the wearer with essential protection from adverse environmental conditions. Herein, complexities between required functionality, legislation and sustainability within outdoor apparel are discussed, and fundamental technical performance of commercially available long-chain (C8) PFASs, shorter-chain (C6) PFASs, and non-fluorinated repellent chemistries finishes are evaluated comparatively. Non-fluorinated finishes provided no oil repellency, and were clearly inferior in this property to PFAS-finished fabrics that demonstrated good oil-resistance. However, water repellency ratings were similar across the range of all finished fabrics tested, all demonstrating a high level of resistance to wetting, and several non-fluorinated repellent fabrics provide similar water repellency to long-chain (C8) PFAS or shorter-chain (C6) PFAS finished fabrics. The primary repellency function required in outdoor apparel is water repellency, and we would propose that the use of PFAS chemistry for such garments is over-engineering, providing oil repellency that is in excess of user requirements. Accordingly, significant environmental and toxicological benefits could be achieved by switching outdoor apparel to non-fluorinated finishes without a significant reduction in garment water-repellency performance. These conclusions are being supported by further research into the effect of laundering, abrasion and ageing of these fabrics.

Atmospheric chlorinated polyfluorinated ether sulfonate and ionic perfluoroalkyl acids in 2006 to 2014 in Dalian, China.

Chlorinated polyfluorinated ether sulfonate (Cl-PFESA; trade name F-53B) is an alternative product for perfluorooctane sulfonate (PFOS) used in metal plating; little is known about its levels in the environment and its risks. To our knowledge, the present study constitutes the first report of Cl-PFESA in the atmosphere. In 2006 to 2014, C8 Cl-PFESA, along with ionic perfluoroalkyl acids (PFAAs), was detected in atmospheric particulate matter in Dalian, China. Concentrations of C8 Cl-PFESA increased from 140 pg/m3 in 2007 to 722 pg/m3 in 2014. Levels of 11 (total) ionic PFAAs increased in 2006 to 2008 and decreased afterward, with a range of 35.7 to 860 pg/m3 . The PFAAs in the particulate matter were dominated by perfluorocarboxylates, with perfluorooctanoate detected at the highest concentration at a mean level of 71.7 pg/m3 , followed by perfluoroheptanoate and perfluorohexanoate. Perfluorosulfonates were detected at lower levels, with mean concentrations of PFOS, perfluorobutanesulfonate, and perfluorohexane sulfonate of 5.73, 1.64, and 1.24 pg/m3 , respectively. Back-trajectory analysis suggested that the air mass approaching Dalian during the sampling originated from the northwest, where fluorochemical industry parks and metal plating industries are densely located. No significant correlation was observed between Cl-PFESA and the ionic PFAAs. The relatively high Cl-PFESA concentrations suggested that it possibly contributed largely to the previously reported exposure to undefined organic fluorine compounds, for which further research on emission and environmental risks is needed. Environ Toxicol Chem 2017;36:2581-2586. © 2017 SETAC.

Recent experimental results of effects of perfluoroalkyl substances in laboratory animals - Relation to current regulations and guidance values.

The detection of perfluoroalkyl substances (PFAS) in surface and drinking water from various countries raised the attention to the presence of these chemicals in environmental probes and led to several regulatory actions to limit exposure in human beings. There was particular concern about perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), due to their former wide-spread use. Recently, several institutions published revisions of former regulatory or recommended maximum concentrations in drinking water and food, which are markedly lower than the former values. The present short overview describes the current regulations for PFAS and compares them with the outcome of several experimental studies in laboratory animals at low-level exposure to PFOA and PFOS. In addition, regulations for short-chain PFAS are presented which, due to lack of toxicological information, are evaluated according to the concepts of Threshold of Toxicological Concern (TTC) or the Health-related Indication Values (HRIV).

Polar stir bars for isolation and preconcentration of perfluoroalkyl substances from human milk samples prior to UHPLC-MS/MS analysis.

BACKGROUND: A new method for the determination of four perfluoroalkyl carboxylic acids (from C5 to C8) and perfluorooctane sulfonate in human milk samples using stir-bar sorptive extraction-ultra-HPLC-MS/MS has been accurately optimized and validated. METHODOLOGY: Polydimethylsiloxane and polyethyleneglycol modified silicone materials were evaluated. DISCUSSION: Overall, polyethyleneglycol led to a better sensitivity. After optimizing experimental variables, the method was validated reaching detection limits in the range of 0.05-0.20 ng ml(-1); recovery rates from 81 to 105% and relative standard deviations fewer than 13% in all cases. The method was applied to milk samples from five randomly selected women. All samples were positive for at least one of the target compounds with concentrations ranging between 0.8 and 6.6 ng ml(-1), being the most abundant perfluorooctane sulfonate.

Polyfluorinated substances in abiotic standard reference materials.

The National Institute of Standards and Technology (NIST) has a wide range of Standard Reference Materials (SRMs) which have values assigned for legacy organic pollutants and toxic elements. Existing SRMs serve as homogenous materials that can be used for method development, method validation, and measurement for contaminants that are now of concern. NIST and multiple groups have been measuring the mass fraction of a group of emerging contaminants, polyfluorinated substances (PFASs), in a variety of SRMs. Here we report levels determined in an interlaboratory comparison of up to 23 PFASs determined in five SRMs: sediment (SRMs 1941b and 1944), house dust (SRM 2585), soil (SRM 2586), and sludge (SRM 2781). Measurements presented show an array of PFASs, with perfluorooctane sulfonate being the most frequently detected. SRMs 1941b, 1944, and 2586 had relatively low concentrations of most PFASs measured while 23 PFASs were at detectable levels in SRM 2585 and most of the PFASs measured were at detectable levels in SRM 2781. The measurements made in this study were used to add values to the Certificates of Analysis for SRMs 2585 and 2781.

Characterization of a reverse-phase perfluorocarbon emulsion for the pulmonary delivery of tobramycin.

BACKGROUND: Aerosolized delivery of antibiotics is hindered by poor penetration within distal and plugged airways. Antibacterial perfluorocarbon ventilation (APV) is a proposed solution in which the lungs are partially or totally filled with perfluorocarbon (PFC) containing emulsified antibiotics. The purpose of this study was to evaluate emulsion stability and rheological, antibacterial, and pharmacokinetic characteristics. METHODS: This study examined emulsion aqueous droplet diameter and number density over 24 hr and emulsion and neat PFC viscosity and surface tension. Additionally, Pseudomonas aeruginosa biofilm growth was measured after 2-hr exposure to emulsion with variable aqueous volume percentages (0.25, 1, and 2.5%) and aqueous tobramycin concentrations (Ca=0.4, 4, and 40 mg/mL). Lastly, the time course of serum and pulmonary tobramycin concentrations was evaluated following APV and conventional aerosolized delivery of tobramycin in rats. RESULTS: The initial aqueous droplet diameter averaged 1.9±0.2 µm with little change over time. Initial aqueous droplet number density averaged 3.5±1.7×10(9) droplets/mL with a significant (p<0.01) decrease over time. Emulsion and PFC viscosity were not significantly different, averaging 1.22±0.03×10(-3) Pa·sec. The surface tensions of PFC and emulsion were 15.0±0.1×10(-3) and 14.6±0.6×10(-3) N/m, respectively, and the aqueous interfacial tensions were 46.7±0.3×10(-3) and 26.9±11.0×10(-3) N/m (p<0.01), respectively. Biofilm growth decreased markedly with increasing Ca and, to a lesser extent, aqueous volume percentage. Tobramycin delivered via APV yielded 2.5 and 10 times larger pulmonary concentrations at 1 and 4 hr post delivery, respectively, and significantly (p<0.05) lower serum concentrations compared with aerosolized delivery. CONCLUSIONS: The emulsion is bactericidal, retains the rheology necessary for pulmonary delivery, is sufficiently stable for this application, and results in increased pulmonary retention of the antibiotic.

Development of PFOS and PFOA criteria for the protection of freshwater aquatic life in China.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two widely used perfluorinated compounds. They have been detected in various environmental media and have harmed aquatic life and systems. The toxic effects of PFOS and PFOA on freshwater organisms were explored with the goal of protecting aquatic ecosystems in this study. Data from acute toxicity tests using nine aquatic species and chronic toxicity tests using three species were analyzed, along with PFOS and PFOA toxicity data for representative Chinese aquatic biota that have been published in the Chinese and international literature. Using the method recommended by the United States Environmental Protection Agency (US EPA), the criterion maximum concentration (CMC) for PFOS was calculated to be 3.78 mg/L, and the criterion continuous concentration (CCC) was calculated to be 0.25mg/L. For PFOA, the CMC was calculated to be 45.54 mg/L, and the CCC was calculated to be 3.52 mg/L. The criteria derived in this study provide the scientific basis for development of water quality standards and aquatic ecosystem risk evaluation.

Determination of perfluorinated compounds in fish fillet homogenates: method validation and application to fillet homogenates from the Mississippi River.

We report herein a simple protein precipitation extraction-liquid chromatography tandem mass spectrometry (LC/MS/MS) method, validation, and application for the analysis of perfluorinated carboxylic acids (C7-C12), perfluorinated sulfonic acids (C4, C6, and C8), and perfluorooctane sulfonamide (FOSA) in fish fillet tissue. The method combines a rapid homogenization and protein precipitation tissue extraction procedure using stable-isotope internal standard (IS) calibration. Method validation in bluegill (Lepomis macrochirus) fillet tissue evaluated the following: (1) method accuracy and precision in both extracted matrix-matched calibration and solvent (unextracted) calibration, (2) quantitation of mixed branched and linear isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) with linear isomer calibration, (3) quantitation of low level (ppb) perfluorinated compounds (PFCs) in the presence of high level (ppm) PFOS, and (4) specificity from matrix interferences. Both calibration techniques produced method accuracy of at least 100±13% with a precision (%RSD) ≤18% for all target analytes. Method accuracy and precision results for fillet samples from nine different fish species taken from the Mississippi River in 2008 and 2009 are also presented.

Determination of perfluorinated alkyl acid concentrations in human serum and milk standard reference materials.

Standard Reference Materials (SRMs) are certified reference materials produced by the National Institute of Standards and Technology that are homogeneous materials well characterized with values for specified properties, such as environmental contaminant concentrations. They can be used to validate measurement methods and are critical in improving data quality. Disagreements in perfluorinated alkyl acid (PFAA) concentrations measured in environmental matrices during past interlaboratory comparisons emphasized the need for SRMs with values assigned for PFAAs. We performed a new interlaboratory comparison among six laboratories and provided, for the first time, value assignment of PFAAs in SRMs. Concentrations for perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and other PFAAs in two human serum and two human milk SRMs are reported. PFAA concentration measurements agreed for serum SRM 1957 using different analytical methods in six laboratories and for milk SRM 1954 in three laboratories. The interlaboratory relative standard deviation for PFOS in SRM 1957 was 7%, which is an improvement over past interlaboratory studies. Matrix interferences are discussed, as well as temporal trends and the percentage of branched vs. linear isomers. The concentrations in these SRMs are similar to the present-day average concentrations measured in human serum and milk, resulting in representative and useful control materials for PFAA human monitoring studies.

Some issues relating to the use of perfluorooctanesulfonate (PFOS) samples as reference standards.

Samples of potassium perfluorooctanesulfonate (PFOSK) from three suppliers were analyzed by LC-ESI-MS/MS for purity and by LC-ESI-MS for the percentage of linear isomer present. Our data indicated that the purity ranged from 80% to 98% and the percentages of linear isomer from 67% to 79%. The proportion of branched isomers present in the samples was also estimated using (19)F NMR. These results agreed quite closely with those found by LC-ESI-MS indicating that there is essentially no difference in overall SIM response factor for the branched isomers vs. that of the linear isomer. Several further observations relevant to the use of standards when analyzing for PFOS were encountered during this study. It appears unlikely that matrix effects attributable to the cation (sodium or potassium) present in PFOSNa or PFOSK internal standards is an issue. In seeking potential matrix effects, it was found that the chromatography was improved substantially when the standard was injected as a solution in 80:20 methanol/water rather than 100% methanol. Notably, in concert with the improvement in chromatography, an increase of about 10% in response was observed. In some closely related studies, when (18)O(2) mass-labeled perfluorohexanesulfonate was used as an internal standard, the actual and theoretical concentration ratios matched closely those for related native sulfonates as long as they did not co-elute. However, when they did co-elute, the peak intensities of the native species were enhanced by about 5%, while those of the labeled compound were suppressed by a similar amount. If this effect were not taken into account, the concentration of the native would be inflated by 10%.

Perfluorinated compounds in coastal waters of Hong Kong, South China, and Korea.

Perfluorinated compounds (PFCs), such as perfluorooctanesulfonate (PFOS) and related compounds, have recently been identified in the environment. PFOS, the terminal degradation product of many of the PFCs, has been found globally in many wildlife species, as well as open ocean waters, even in remote regions far from sources. In this study, a solid-phase extraction procedure coupled with high-performance liquid chromatography interfaced to high-resolution mass spectrometry was used to isolate, identify, and quantify small concentrations of PFCs in seawater. These techniques were applied to investigate the local sources of PFCs in several industrialized areas of Asia and provide information on how the PFCs are circulated by coastal currents. Ranges of concentrations of PFOS in coastal seawaters of Hong Kong, the Pearl River Delta, including the South China Sea, and Korea were 0.09-3.1, 0.02-12, and 0.04-730 pg/mL, respectively, while those of perfluorooctanoic acid (PFOA) were 0.73-5.5, 0.24-16, and 0.24-320 pg/mL, respectively. Potential sources of PFCs include major industrialized areas along the Pearl River Delta of southern China and major cities of Korea, which are several of the fastest growing industrial and economic regions in the world. Detectable concentrations of PFOS and PFOA in waters of southern China were similar to those in the coastal marine environment of Japan and certain regions in Korea. Concentrations of PFCs in several locations in Korean waters were 10-100-fold greater than those in the other locations on which we report here. The spatial and seasonal variations in PFC concentrations in surface seawaters in the Pearl River Delta and South China Sea indicate the strong influence of the Pearl River discharge on the magnitude and extent of PFC contamination in southern China. All of the concentrations of PFOS were less than those that would be expected to cause adverse effects to aquatic organisms or their predators except for one location in Korea adjacent to an industrialized area. Hazard quotients were from <0.001 to 0.002 for aquatic animals and ranged from <0.001 to 17 for predatory birds.

Solute-solvent interactions in micellar electrokinetic chromatography. 6. Optimization of the selectivity of lithium dodecyl sulfate-lithium perfluorooctanesulfonate mixed micellar buffers.

The optimization of the composition of mixed surfactants used as micellar electrokinetic chromatography (MEKC) pseudostationary phases is proposed as an effective method for the separation of complex mixtures of analytes. The solvation parameter model is used to select two surfactants (lithium dodecyl sulfate, LDS, and lithium perfluorooctanesulfonate, LPFOS) with contrasting solvation properties. Combination of these two surfactants allows variations of the solvation properties of MEKC pseudostationary phase along a wide range. Thus, the convenient variation of the proportion of both surfactants allows an effective control of the selectivity in such systems. An algorithm that predicts the overall resolution of a given mixture of compounds is described and applied to optimize the composition of the mixed surfactant for the separation of the mixture. The algorithm is based on the calculation of peak purities on simulated chromatograms as a function of the composition of the mixed LDS/LPFOS micellar buffer from data at several micellar buffer compositions. Successful separations were achieved for mixtures containing up to 20 compounds, in less than 12 min.

Contrast agent stability: a continuous B-mode imaging approach.

The stability of contrast agents in suspensions with various dissolved gas levels has not been reported in the literature. An in vitro investigation has been carried out that studied the combined effect of varying the acoustic pressure along with degassing the suspension environment. In this study, the contrast agents were introduced into suspensions with different oxygen concentration levels, and their relative performance was assessed in terms of decay rate of their backscatter echoes. The partial pressures of oxygen in those solutions ranged between 1.5 and 26 kPa. Two IV and one arterial contrast agents were used: Definity, Quantison, and Myomap. It was found that Quantison and Myomap released free bubbles at high acoustic pressure that also dissolved faster in degassed suspensions. The backscatter decay for Definity did not depend on the air content of the suspensions. The destruction of bubbles was dependent on acoustic pressure. Different backscatter performance was observed by different populations of bubbles of the last two agents. The physical quantity of "overall backscatter" (OB) was defined as the integral of the decay rate over time of the backscatter of the contrast suspensions, and improved significantly the understanding of the behaviour of the agents. A quantitative analysis of the backscatter properties of contrast agents using a continuous imaging approach was difficult to achieve. This is due to the fact that the backscatter in the field of view is representative of a bubble population affected by the ultrasound (US) field, but this bubble population is not representative of the contrast suspension in the whole tank. Single frame insonation is suggested to avoid the effects of decay due to the ultrasonic field, and to measure a tank-representative backscatter. The definition of OB was useful, however, in understanding the behaviour of the agents.