Environmental pollutant risk factors for worse COVID-19 related clinical outcomes in predominately hispanic and latino populations.

BACKGROUND: Per- and poly-fluorinated compounds (PFAS) and heavy metals constitute two classes of environmental exposures with known immunotoxicant effects. In this pilot study, we aimed to evaluate the impact of exposure to heavy metals and PFAS on COVID-19 severity. We hypothesized that elevated plasma-PFAS concentrations and urinary heavy metal concentrations would be associated with increased odds of ICU admission in COVID-19 hospitalized individuals. METHODS: Using the University of Southern California Clinical Translational Sciences Institute (SC-CTSI) biorepository of hospitalized COVID-19 patients, urinary concentrations of 15 heavy metals and urinary creatinine were measured in n = 101 patients and plasma concentrations of 13 PFAS were measured in n = 126 patients. COVID-19 severity was determined based on whether a patient was admitted to the ICU during hospitalization. Associations of metals and PFAS with ICU admission were assessed using logistic regression models, controlling for age, sex, ethnicity, smoking status, and for metals, urinary dilution. RESULTS: The average age of patients was 55 ± 14.2 years. Among SC-CTSI participants with urinary measurement of heavy metals and blood measures of PFAS, 54.5% (n = 61) and 54.8% (n = 80) were admitted to the ICU, respectively. For heavy metals, we observed higher levels of Cd, Cr, and Cu in ICU patients. The strongest associations were with Cadmium (Cd). After accounting for covariates, each 1 SD increase in Cd resulted in a 2.00 (95% CI: 1.10-3.60; p = 0.03) times higher odds of admission to the ICU. When including only Hispanic or Latino participants, the effect estimates between cadmium and ICU admission remained similar. Results for PFAS were less consistent, with perfluorodecanesulfonic acid (PFDS) exhibiting a positive but non-significant association with ICU admission (Odds ratio, 95% CI: 1.50, 0.97-2.20) and perfluorodecanoic acid (PFDA) exhibiting a negative association with ICU admission (0.53, 0.31-0.88). CONCLUSIONS: This study supports the hypothesis that environmental exposures may impact COVID-19 severity.

Association of Combined Per- and Polyfluoroalkyl Substances and Metals with Chronic Kidney Disease.

Background: Exposure to environmental pollutants such as metals and Per- and Polyfluoroalkyl Substances (PFAS) has become common and increasingly associated with a decrease in the estimated Glomerular Filtration Rate (eGFR), which is a marker often used to measure chronic kidney disease (CKD). However, there are limited studies involving the use of both eGFR and the urine albumin creatinine ratio (uACR), which are more comprehensive markers to determine the presence of CKD and the complexity of pollutant exposures and response interactions, especially for combined metals and PFAS, which has not been comprehensively elucidated. Objective: This study aims to assess the individual and combined effects of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), Cadmium (Cd), Mercury (Hg), and Lead (Pb) exposure on CKD using data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018. Methods: We employed the use of bivariate logistic regression and Bayesian Kernel Machine Regression (BKMR) in our analysis of the data. Results: Logistic regression results revealed a positive association between PFOA and CKD. Our BKMR analysis revealed a non-linear and bi-phasic relationship between the metal exposures and CKD. In our univariate exposure-response function plot, Cd and Hg exhibited a U and N-shaped interaction, which indicated a non-linear and non-additive relationship with both low and high exposures associated with CKD. In addition, the bivariate exposure-response function between two exposures in a mixture revealed that Cd had a U-shaped relationship with CKD at different quantiles of Pb, Hg, PFOA, and PFOS, indicating that both low and high levels of Cd is associated with CKD, implying a non-linear and complex biological interaction. Hg's interaction plot demonstrated a N-shaped association across all quantiles of Cd, with the 75th quantile of Pb and the 50th and 75th quantiles of PFOA and PFOS. Furthermore, the PIP results underscored Cd's consistent association with CKD (PIP = 1.000) followed by Hg's (PIP = 0.9984), then PFOA and PFOS with a closely related PIP of 0.7880 and 0.7604, respectively, and finally Pb (PIP = 0.6940), contributing the least among the five environmental pollutants on CKD, though significant. Conclusions: Our findings revealed that exposure to environmental pollutants, particularly Hg and Cd, are associated with CKD. These findings highlight the need for public health interventions and strategies to mitigate the cumulative effect of PFAS and metal exposure and elucidate the significance of utilizing advanced statistical methods and tools to understand the impact of environmental pollutants on human health. Further research is needed to understand the mechanistic pathways of PFAS and metal-induced kidney injury and CKD, and longitudinal studies are required to ascertain the long-term impact of these environmental exposures.

Paper Spray Mass Spectrometry with On-Paper Electrokinetic Manipulations: Part-Per-Trillion Detection of Per/Polyfluoroalkyl Substances in Water and Opioids in Urine.

We developed a simple, paper-based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter-balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part-per-trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On-paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases.

Physiologically based pharmacokinetic (PBPK) modeling of perfluorohexane sulfonate (PFHxS) in humans.

Per- and polyfluoroalkyl substances (PFAS) are persistent, man-made compounds prevalent in the environment and consistently identified in human biomonitoring samples. In particular, perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) have been identified at U.S. Air Force installations. The study of human toxicokinetics and physiologically based pharmacokinetic (PBPK) modeling of PFHxS has been less robust and has been limited in scope and application as compared to PFOS and PFOA. The primary goal of the current effort was to develop a PBPK model describing PFHxS disposition in humans that can be applied to retrospective, current, and future human health risk assessment of PFHxS. An existing model developed for PFOS and PFOA was modified and key parameter values for exposure and toxicokinetics were calibrated for PFHxS prediction based on human biomonitoring data, particularly general population serum levels from the U.S. Centers for Disease Prevention and Control (CDC) National Health and Nutrition Examination Survey (NHANES). Agreement between the model and the calibration and evaluation data was excellent and recapitulated observed trends across sex, age, and calendar years. Confidence in the model is greatest for application to adults in the 2000-2018 time frame and for shorter-term future projections.

Endocrine Disruptor Potential of Short- and Long-Chain Perfluoroalkyl Substances (PFASs)-A Synthesis of Current Knowledge with Proposal of Molecular Mechanism.

Endocrine disruptors are a group of chemical compounds that, even in low concentrations, cause a hormonal imbalance in the body, contributing to the development of various harmful health disorders. Many industry compounds, due to their important commercial value and numerous applications, are produced on a global scale, while the mechanism of their endocrine action has not been fully understood. In recent years, per- and polyfluoroalkyl substances (PFASs) have gained the interest of major international health organizations, and thus more and more studies have been aimed to explain the toxicity of these compounds. PFASs were firstly synthesized in the 1950s and broadly used in the industry in the production of firefighting agents, cosmetics and herbicides. The numerous industrial applications of PFASs, combined with the exceptionally long half-life of these substances in the human body and extreme environmental persistence, result in a common and chronic exposure of the general population to their action. Available data have suggested that human exposure to PFASs can occur during different stages of development and may cause short- or/and long-term health effects. This paper synthetizes the current literature reports on the presence, bioaccumulation and, particularly, endocrine toxicity of selected long- and short-chain PFASs, with a special emphasis on the mechanisms underlying their endocrine actions.

A Highly Selective Extraction Approach for Per- and Polyfluoroalkyl Substances Based on Protein Affinity.

A selective extraction method with remarkable advantages (i.e., low cost, simplicity, and solvent savings) was developed for the detection of long-chain per- and polyfluoroalkyl substances (PFASs) based on their specific protein affinities. Bovine serum albumin (BSA) was selected to extract PFASs from aqueous samples, which were then desorbed using methanol. Finally, the PFASs were analyzed by high-performance liquid chromatography-tandem mass spectrometry. The optimal extraction conditions were as follows: sample volume, 10 mL; BSA concentration, 2 g/L; equilibration time, 5 min; pH, 3.4; salinity, 6% (w/v) NaCl; and water bath temperature, 80 °C. The protein affinity property was confirmed to be the major extraction mechanism, which significantly increased the selectivity for PFASs. The recoveries of this method for 15 legacy PFASs with CF2 ≥ 6 and three chlorinated polyfluoroether sulfonic acids in tap water, river water, and urine samples with three spiked levels were 73.3-122.3, 83.8-119.4, and 75.0-115.1%, respectively. The method limits of quantification in the three real matrix samples were 4.7-133.3 ng/L. Comparative experiments with conventional solid-phase extraction confirm that the developed approach can be a promising and alternative method for the extraction of PFASs from authentic aqueous samples. Moreover, the proposed method provides a new possibility for screening PFASs exhibiting high bioaccumulation and toxicity.

Legacy and alternative per- and polyfluoroalkyl substances in the U.S. general population: Paired serum-urine data from the 2013-2014 National Health and Nutrition Examination Survey.

Concerns are heightened from detecting environmentally persistent man-made per- and polyfluoroalkyl substances (PFAS) in drinking water systems around the world. Many PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), remain in the human body for years. Since 1999-2000, assessment of exposure to PFOS, PFOA, and other select PFAS in the U.S. general population has relied on measuring PFAS serum concentrations in participants of the National Health and Nutrition Examination Survey (NHANES). Manufacturers have replaced select chemistries ("legacy" PFAS) with PFAS with shorter biological half-lives (e.g., GenX, perfluorobutanoate [PFBA]) which may efficiently eliminate in urine. However, knowledge regarding exposure to these compounds is limited. We analyzed 2682 urine samples for 17 legacy and alternative PFAS in 2013-2014 NHANES participants ≥6 years of age. Concentrations of some of these PFAS, measured previously in paired serum samples from the same NHANES participants, suggested universal exposure to PFOS and PFOA, and infrequent or no exposure to two short-chain PFAS, perfluorobutane sulfonate and perfluoroheptanoate. Yet, in urine, PFAS were seldom detected; the frequency of not having detectable concentrations of any of the 17 PFAS was 67.5%. Only two were detected in >1.5% of the population: PFBA (13.3%) and perfluorohexanoate (PFHxA, 22.6%); the 90th percentile urine concentrations were 0.1 µg/L (PFBA), and 0.3 µg/L (PFHxA). These results suggest that exposures to short-chain PFAS are infrequent or at levels below those that would result in detectable concentrations in urine. As such, these findings do not support biomonitoring of short-chain PFAS or fluorinated alternatives in the general population using urine, and highlight the importance of selecting the adequate biomonitoring matrix.

Per- and polyfluorinated compounds in saleswomen's urine linked to indoor dust in clothing shops.

This study aims to investigate the characteristics of typical per- and polyfluorinated compounds (PFCs) in indoor dust from clothing shops and urine sampled from saleswomen. A total of 58 indoor dust samples and 73 urine samples from saleswomen were collected from clothing shops in Shanghai, China. All samples were analyzed for PFCs using high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-MS/MS). The mean PFC concentrations in indoor dust ranged from 0.42 (PFDA) to 5.04 ng g-1 (PFDoA). PFDoA and PFHxS were the most prominent PFCs, with median concentrations of 2.95 ng g-1 and 1.49 ng g-1, respectively. The median PFC concentrations in urine ranged from 10.15 (PFDS) to 666.1 ng l-1 (PFOA) and PFOA was the most abundant chemical with concentrations ranging from 207 to 907 ng l-1. A significant positive correlation was obtained between long-chain PFCs in dust and in urine (p < 0.01). Daily intake values of PFCs via dust ingestion were also calculated, and even under high-end exposure scenarios, the intake of PFOA (36.5 pg day-1) and PFOS (56.7 pg day-1) were well within the tolerable daily intake values. These results are important to both characterize PFC levels and estimate the saleswomen's exposure to PFCs from indoor dust.

Perfluoroalkyl acids in paired serum, urine, and hair samples: Correlations with demographic factors and dietary habits.

We analyzed paired serum, urine, and hair samples from 94 Korean children and adults to investigate levels of 11 perfluoroalkyl acids (PFAAs). The effects of demographic factors and dietary habits on PFAA exposure were also assessed based on the paired samples. The total PFAA concentrations were 2.4-31 ng/mL in serum, not detected-9.5 ng/mL in urine, and 0.48-15 ng/g in hair. Levels of perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), which have short carbon chains, were 1.5-5 fold higher in urine and hair than in serum. The PFAA concentrations in serum exhibited a decreasing trend with age from young childhood to adolescence, followed by an increasing trend after adolescence. For most PFAA species, concentrations in serum were higher in adult males than in adult females (p < 0.01). No sex difference was evident in the urine and hair samples. In addition, there was no age difference in the urine samples, but in the hair samples, we observed higher concentrations of PFAAs in children than in the other age groups (p < 0.01). The consumption rates of fish and water showed significant correlations with serum (positive correlation) and hair (negative) concentrations, respectively. No relationships between serum and hair/urine levels for most PFAAs were observed, except between serum and hair levels for perfluorooctanoic acid (PFOA).

Per- and polyfluoroalkyl substances and fluorinated alternatives in urine and serum by on-line solid phase extraction-liquid chromatography-tandem mass spectrometry.

Per- and polyfluoroalkyl substances (PFAS), man-made chemicals with variable length carbon chains containing the perfluoroalkyl moiety (CnF2n+1-), are used in many commercial applications. Since 1999-2000, several long-chain PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), have been detected at trace levels in the blood of most participants of the National Health and Nutrition Examination Survey (NHANES)-representative samples of the U.S. general population-while short-chain PFAS have not. Lower detection frequencies and concentration ranges may reflect lower exposure to short-chain PFAS than to PFOS or PFOA or that, in humans, short-chain PFAS efficiently eliminate in urine. We developed on-line solid phase extraction-HPLC-isotope dilution-MS/MS methods for the quantification in 50 µL of urine or serum of 15 C3-C11 PFAS (C3 only in urine), and three fluorinated alternatives used as PFOA or PFOS replacements: GenX (ammonium salt of 2,3,3,3,-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)-propanoate, also known as HFPO-DA), ADONA (ammonium salt of 4,8-dioxa-3H-perfluorononanoate), and 9Cl-PF3ONS (9-chlorohexadecafluoro-3-oxanonane-1-sulfonate), main component of F53-B. Limit of detection for all analytes was 0.1 ng/mL. To validate the method, we analyzed 50 commercial urine/serum paired samples collected in 2016 from U.S. volunteers with no known exposure to the chemicals. In serum, detection frequency and concentration patterns agreed well with those from NHANES. By contrast, except for perfluorobutanoate, we did not detect long-chain or short-chain PFAS in urine. Also, we did not detect fluorinated alternatives in either urine or serum. Together, these results suggest limited exposure to both short-chain PFAS and select fluorinated alternatives in this convenience population.

Using hair, nail and urine samples for human exposure assessment of legacy and emerging per- and polyfluoroalkyl substances.

Non-invasive samples present ethical and practical benefits for investigating human exposure to hazardous contaminants, but analytical challenges and difficulties to interpret the results limit their application in biomonitoring. Here we investigated the potential for using hair, nail and urine samples as a measure of internal exposure to an array of legacy and emerging per- and polyfluoroalkyl substances (PFASs) in two populations with different exposure conditions. Paired urine-serum measurements of PFASs from a group of highly exposed fishery employees displayed strong correlations for PFASs with three to eight perfluorinated carbons (ρ > 0.653; p < 0.01). Consistent statistical correlations and transfer ratios in nails and hair from both populations demonstrated that these non-invasive samples can be used as a measure of internal exposure to perfluorooctane sulfonic acid and C8 chlorinated polyfluoralkyl ether sulfonic acid (C8 Cl-PFESA). Contrastingly, the infrequent detections and/or lack of consistent transfer ratios for perfluorooctanoic acid, perfluorononanoic acid and short-chain PFASs in hair and nail samples indicate passive uptake from the external environment rather than uptake and internal distribution. Collectively, the study supports the use of urine samples as a valid measure of internal exposure for a range of short- and medium-chain PFASs, while the validity of nail and hair samples as a measure of internal exposure may vary for different PFASs and populations. The ubiquitous detection of C8 Cl-PFESA in all sample matrices from both populations indicates widespread exposure to this contaminant of emerging concern in China.

Occurrence of perfluoroalkyl substances in matched human serum, urine, hair and nail.

The purpose of this study was to determine perfluoroalkyl substances (PFASs) in human serum, urine, hair and nail from general populations, and to investigate the possibility for human urine, hair and nail used as the biomonitoring sample for PFASs exposure. We detected the concentrations of PFHxA, PFOA, PFNA, PFDA, PFUnDA, PFDoA, PFHxS and PFOS in 39 matched human serum, urine, hair and nail samples from Shenzhen in China. The detection frequency and the median level of PFOS were all higher than that of the other PFASs in four matrices. The median concentration of PFOS in serum, urine, hair, and nail were 9.24ng/mL, 13.96ng/L, 0.58ng/g and 0.63ng/g, respectively. The results of spearman correlation test indicated that nail was an ideal matrix for biomonitoring PFOS rather than human urine and hair in general populations for the non-invasive sampling.

Gestational exposure to endocrine disrupting chemicals in relation to infant birth weight: a Bayesian analysis of the HOME Study.

BACKGROUND: Pregnant women are exposed to a mixture of endocrine disrupting chemicals (EDCs). Gestational EDC exposures may be associated with changes in fetal growth that elevates the risk for poor health later in life, but few studies have examined the health effects of simultaneous exposure to multiple chemicals. This study aimed to examine the association of gestational exposure to five chemical classes of potential EDCs: phthalates and bisphenol A, perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) with infant birth weight. METHODS: Using data from the Health Outcomes and Measures of Environment (HOME) Study, we examined 272 pregnant women enrolled between 2003-2006. EDC concentrations were quantified in blood and urine samples collected at 16 and 26 weeks gestation. We used Bayesian Hierarchical Linear Models (BHLM) to examine the associations between newborn birth weight and 53 EDCs, 2 organochlorine pesticides (OPPs) and 2 heavy metals. RESULTS: For a 10-fold increase in chemical concentration, the mean differences in birth weights (95% credible intervals (CI)) were 1 g (-20, 23) for phthalates, -11 g (-52, 34) for PFAS, 0.2 g (-9, 10) for PCBs, -4 g (-30, 22) for PBDEs, and 7 g (-25, 40) for OCPs. CONCLUSION: Gestational exposure to phthalates, PFAS, PCBs, PBDEs, OCPs or OPPs had null or small associations with birth weight. Gestational OPP, Pb, and PFAS exposures were most strongly associated with lower birth weight.

Per- and polyfluoroalkyl substances in human serum and urine samples from a residentially exposed community.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are considered chemicals of emerging concern, in part due to their environmental and biological persistence and the potential for widespread human exposure. In 2007, a PFAS manufacturer near Decatur, Alabama notified the United States Environmental Protection Agency (EPA) it had discharged PFAS into a wastewater treatment plant, resulting in environmental contamination and potential exposures to the local community. OBJECTIVES: To characterize PFAS exposure over time, the Agency for Toxic Substances and Disease Registry (ATSDR) collected blood and urine samples from local residents. METHODS: Eight PFAS were measured in serum in 2010 (n=153). Eleven PFAS were measured in serum, and five PFAS were measured in urine (n=45) from some of the same residents in 2016. Serum concentrations were compared to nationally representative data and change in serum concentration over time was evaluated. Biological half-lives were estimated for perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) using a one-compartment pharmacokinetic model. RESULTS: In 2010 and 2016, geometric mean PFOA and PFOS serum concentrations were elevated in participants compared to the general U.S. POPULATION: In 2016, the geometric mean PFHxS serum concentration was elevated compared to the general U.S. POPULATION: Geometric mean serum concentrations of PFOA, PFOS, and perfluorononanoic acid (PFNA) were significantly (p≤0.0001) lower (49%, 53%, and 58%, respectively) in 2016 compared to 2010. Half-lives for PFOA, PFOS, and PFHxS were estimated to be 3.9, 3.3, and 15.5years, respectively. Concentrations of PFOA in serum and urine were highly correlated (r=0.75) in males. CONCLUSIONS: Serum concentrations of some PFAS are decreasing in this residentially exposed community, but remain elevated compared to the U.S. general population.

Toxicological response of Sprague Dawley rats from inhalation exposure to perfluorooctane sulfonyl fluoride (POSF).

Perfluorooctane sulfonyl fluoride (POSF) was a volatile starting material in the production of perfluorooctane sulfonate (PFOS), a stable surfactant that has been extensively studied due to its ubiquitous environmental distribution and slow clearance in humans. Because the inhalation toxicity of POSF on repeated exposure has not been previously reported, the current study evaluated the inhalation toxicity of POSF at 30, 100, and 300ppm (v/v) in rats for up to 13 weeks with a four-week recovery period. The extent of PFOS formation was also measured because POSF hydrolyzed to form PFOS. In addition, detailed urinalysis and examination of the urinary bladder were included to determine if factors associated with the development of bladder cancer were present. Exposure to POSF at 300ppm was associated with reduction in body weight-gain, necrosis of laryngeal cartilage, increased lung and bronchi weight with septal thickening, and changes in alveolar macrophages. The microscopic observations in larynx and lung are consistent with likely hydrolysis of POSF to form hydrogen fluoride (HF). Exposure to POSF at 100 and 300ppm was associated with increased relative liver weight, hepatocellular hypertrophy (except for females exposed to 100ppm POSF), and lowering of serum cholesterol (male only). After 13 weeks of exposure to 30, 100, or 300ppm POSF, serum PFOS concentration approximated 7, 35, or 100µg/mL, respectively. Approximately 0.1% of inhaled POSF was converted to PFOS. No changes indicative of bladder effects were observed in these rats exposed to POSF at any dose.

Occurrence, temporal trends, and half-lives of perfluoroalkyl acids (PFAAs) in occupational workers in China.

Paired serum and urine samples were collected from workers in a fluorochemical plant from 2008 to 2012 (n = 302) to investigate the level, temporal trends, and half-lives of PFAAs in workers of a fluorochemical plant. High levels of perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonate (PFOS) were detected in serum with median concentrations of 764, 427, and 1725 ng mL-1, respectively. The half-lives of PFAAs in workers were estimated by daily clearance rates and annual decline rates of PFAAs in serum by a first-order model. The geometric mean and median value for PFHxS, PFOA, and PFOS were 14.7 and 11.7, 4.1 and 4.0, 32.6 and 21.6 years, respectively, by the daily clearance rates, and they were 3.6, 1.7, and 1.9 years estimated by annual decline rates. The half-lives estimated by the limited clearance route information could be considered as the upper limits for PFAAs, however, the huge difference between two estimated approaches indicated that there were other important elimination pathways of PFAAs other than renal clearance in human. The half-lives estimated by annual decline rates in the present study were the shortest values ever reported, and the intrinsic half-lives might even shorter due to the high levels of ongoing exposure to PFAAs.

Screening of Toxic Chemicals in a Single Drop of Human Whole Blood Using Ordered Mesoporous Carbon as a Mass Spectrometry Probe.

Surface-enhanced laser desorption/ionization (SELDI) is a versatile and high-throughput mass spectrometry (MS) technique that uses a probe for extraction, enrichment, desorption, and ionization of target analytes. Here we report ordered mesoporous carbon as a new SELDI probe for rapid screening and identification of trace amount of toxic chemicals in a single drop of human whole blood without complicated sample preparation procedures. We demonstrate that ordered mesoporous carbon not only can selectively enrich a wide variety of low-mass toxic compounds from whole blood samples but also can be used as an excellent matrix to assist the laser desorption/ionization process of small molecules with low background noise, high repeatability, and good salt tolerance. High sensitivity (detection limits at ppt levels) and good reproducibility for typical toxic compounds were obtained. With CMK-8 as a SELDI probe, we successfully identified and screened six perfluorinated compounds in a single drop of whole blood collected from workers in a perfluorochemical plant. The method was also validated with complex samples such as human urine and environmental water samples. With distinct advantages such as simplicity, rapidness, minimal sample requirement, and high reliability, this method keeps great promise for various aspects of application.

Absorption, distribution, metabolism, excretion, and kinetics of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat, mouse, and cynomolgus monkey.

Ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate has been developed as a processing aid used in the manufacture of fluoropolymers. The absorption, distribution, elimination, and distribution (ADME) and kinetic behavior of this substance has been evaluated in rats, mice, and cynomolgus monkeys by oral and intravenous routes of exposure and studied in both plasma and urine. The test substance is rapidly and completely absorbed in both rats and mice and both in vivo and in vitro experiments indicate that it is not metabolized. The test substance is rapidly eliminated exclusively in the urine in both rats and mice, with rats eliminating it more quickly than mice (approximately 5h elimination half-life in rats, 20 h half-life in mice). Pharmacokinetic analysis in monkeys, rats, and mice indicate rapid, biphasic elimination characterized by a very fast alpha phase and a slower beta phase. The beta phase does not contribute to potential accumulation after multiple dosing in rats or monkeys. Comparative pharmacokinetics in rats, mice, and monkeys indicates that the rat is more similar to the monkey and is therefore a more appropriate rodent model for pharmacokinetics in primates.

Differential accumulation and elimination behavior of perfluoroalkyl Acid isomers in occupational workers in a manufactory in China.

In this study, serum and urine samples were collected from 36 occupational workers in a fluorochemical manufacturing plant in China from 2008 to 2012 to evaluate the body burden and possible elimination of linear and branched perfluoroalkyl acids (PFAAs). Indoor dust, total suspended particles (TSP), diet, and drinking water samples were also collected to trace the occupational exposure pathway to PFAA isomers. The geometric mean concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) isomers in the serum were 1386, 371, and 863 ng mL(-1), respectively. The linear isomer of PFOS, PFOA, and PFHxS was the most predominant PFAA in the serum, with mean proportions of 63.3, 91.1, and 92.7% respectively, which were higher than the proportions in urine. The most important exposure routes to PFAA isomers in the occupational workers were considered to be the intake of indoor dust and TSP. A renal clearance estimation indicated that branched PFAA isomers had a higher renal clearance rate than did the corresponding linear isomers. Molecular docking modeling implied that linear PFOS (n-PFOS) had a stronger interaction with human serum albumin (HSA) than branched isomers did, which could decrease the proportion of n-PFOS in the blood of humans via the transport of HSA.

PFOS and PFOA in paired urine and blood from general adults and pregnant women: assessment of urinary elimination.

Although levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in human blood are well documented, information on elimination of these chemicals is limited. In this study, PFOS and PFOA were analyzed in 81 whole blood-urine paired samples from general adults and pregnant women in Tianjin, China. PFOS and PFOA were detected in 48 and 76% of adult urine (AU) samples, with geometric mean (GM) concentrations of 0.011 and 0.008 ng/mL, respectively; whereas relatively low PFOS and PFOA concentrations were found in maternal urine (MU) samples, with GM concentrations of 0.006 and 0.003 ng/mL, respectively. For PFOA, the coefficients of Pearson's correlation between whole blood concentrations and creatinine-adjusted and creatinine-unadjusted urinary concentrations were 0.348 (p = 0.013) and 0.417 (p = 0.002), respectively. The GM urinary elimination rates of PFOS (PFOSUER) and PFOA (PFOAUER) were 16 and 25%, respectively, for adults. These results indicate that urine is an important pathway of excretion of perfluoroalkyl substances (PFASs). The partitioning ratios of PFAS concentration between urine and whole blood (PFASU/B) in pregnant women (PFOSU/B, 0.0004; PFOAU/B, 0.0011) were significantly lower (p = 0.025 for PFOSU/B, p = 0.017 for PFOAU/B) than the ratios found in non-pregnant women (PFOSU/B, 0.0013; PFOAU/B, 0.0028). Furthermore, our results suggest a clear gender difference in the urinary elimination of PFOA, with male adults (31%) having significantly higher PFOAUER than that of female adults (19%). PFOSUER was significantly inversely correlated with age (r = -0.334, p = 0.015); these findings suggest that urinary elimination of PFOS is faster in young adults than in the elderly.