An interlaboratory study of perfluorinated alkyl compound levels in human plasma

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

Perfluorinated compounds in seafood from coastal areas in China

Introduction. Fatty acids (FAs) are essential for fetal growth. Exposure to perfluorinated chemicals (PFCs), which may disrupt FA homeostasis. There is no epidemiological data regarding the effects of PFCs on the levels of FAs. We explored the effects of perfluorooctane sulfonate (PFOS)/ perfluorooctanoate (PFOA) concentrations on the levels of maternal FAs and triglyceride (TG), and the birth size of their offspring. Methods. 306 mother-child pairs were analyzed in this birth cohort between 2002 and 2005 in Japan. The prenatal PFOS and PFOA levels were measured in maternal serum samples by liquid chromatography-tandem mass spectrometry. Maternal blood levels of 9 FAs and TG were measured by gas chromatography–mass spectrometry and TG-IE kits, respectively. Results. The median PFOS and PFOA levels were 5.6 and 1.4 ng/mL, respectively. In the fully adjusted model, including maternal age, parity, annual household income, blood sampling period, alcohol consumption and smoking during pregnancy, PFOS, not PFOA, had a negative association with the levels of palmitic, palmitoleic, oleic, linoleic, α-linolenic, and arachidonic acids (p < 0.001), docosahexaenoic acid (p for trend = 0.03) and TG (p for trend< 0.003). Females born to mothers with prenatal concentrations of PFOS in the fourth quartile compared to first quartile weighed 186.6 g less [95% confidence interval (CI): -363.4 to -9.8]. We observed no association between concentrations of PFOS and birth weight of male infants. Conclusion. Our data suggest an inverse association between low-dose PFOS exposure and the polyunsaturated FA levels in pregnant women. We also found a negative association between PFOS levels and female birth weight.

Information regarding per- and polyfluorinated substances concentrations in biological samples from the Thai population was still lacking. A sensitive bioanalytical method was developed and validated for the quantification of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) levels in human plasma. Simple protein precipitation and LC-MS/MS techniques were used with stable isotope internal standards of 13C8-PFOS and 13C8-PFOA. The validated method followed the ICH bioanalytical validation guideline, and the results showed good accuracy, precision, and reproducibility. The validated analytical method was then applied to determine PFOS and PFOA concentrations in 50 human plasma samples from the National Blood Center, Thai Red Cross Society. The concentrations were found to be in ranges of <0.91-6.27 ng/mL for PFOS and <0.49-2.72 ng/mL for PFOA. PFOS was also measured separately for its isomers, and the geometric means of the linear isomer (L-PFOS) and branched isomer (br-PFOS) in plasma samples were at 1.85 and 0.41 ng/mL, respectively. Both PFOS and PFOA concentrations were lower in comparison to previous reports from other countries. The present study showed the application of our reliable method to determine PFOS and PFOA in biological samples in order to monitor the human exposure of both chemicals in Thailand.

Simultaneous determination of olmesartan and amlodipine in human plasma and urine by ultra performance liquid chromatography tandem mass spectrometry

Per- and polyfluoroalkyl substances (PFAS) in American Red Cross adult blood donors, 2000–2015

A candidate reference measurement procedure (RMP) based on isotope dilution coupled with liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) was developed and validated for the quantification of 17α-hydroxyprogesterone (17-OHP) in human plasma. 17-OHP spiked with a deuterium-labeled internal standard was extracted from plasma by liquid-liquid extraction with 1 mL n-hexane/ethyl acetate (3:2, v/v). Reversed-phase chromatography and positive electrospray ionization were used in the ID-LC-MS/MS. Gradient elution coupled with use of a C18-packed ultrahigh-performance liquid chromatography column allowed complete baseline resolution of 17-OHP from its structural analogue desoxycorticosterone in 6 min. To determine the 17-OHP level in human plasma, a bracketing calibration method was used to give higher accuracy and precision. The limit of detection and the lower limit of the measuring interval for the candidate RMP were 2.1 pg/mL (6.4 pmol/L) and 4.6 pg/mL (13.9 pmol/L), respectively. Extraction recovery was determined to be (96.08 ± 3.03)% (n = 3). Imprecision (intra-assay and interassay) was 4.03% or less at 0.83, 15.19, 64.22, and 313.46 ng/mL (2.51, 45.97, 194.34, and 948.56 nmol/L, respectively). Recoveries ranged from 98.05% to 102.24%. When comparing our RMP results with those obtained with an established RMP via International Federation of Clinical Chemistry and Laboratory Medicine external quality assessment scheme for reference laboratories in laboratory medicine (RELA) samples, we found that the biases ranged from -1.99% to 3.08% against the targets. No interference was observed, and the linear response ranged from 0.47 to 958.63 ng/mL (1.42 to 2900.90 nmol/L). Moreover, the candidate RMP was used to measure the concentration of 17-OHP in human plasma and was compared with an immunoassay using 40 plasma samples. The performance of the method meets the needs of an RMP (total coefficient of variation of 5% or less and bias of 3.08% or less). This method can be used for reference material value assignment of 17-OHP in human plasma matrix. It could also serve as an accurate reference baseline for routine methods to increase the accuracy and precision of certain clinical laboratory measurements. Graphical abstract Selected ion chromatograms obtained by liquid chromatography-tandem mass spectrometry with a C18 column for 17α-hydroxyprogesterone (17-OHP) from a plasma sample.

Quantitative determination of perfluorooctanoic acid in serum and plasma by liquid chromatography tandem mass spectrometry

This report describes the development of a method for the determination and quantification of perfluoroalkyl substances (PFASs) in beer. A total of 93 beer samples were analyzed for the presence of PFASs by means of liquid chromatography tandem mass spectrometry. The results of this study have made it possible to calculate possible PFAS uptake via beer as well as the potential PFAS-related health risk as a result of beer consumption with regard to the tolerable daily intake (TDI) of perfluoro-n-octanoic acid (PFOA) (1,500 ng/kg bodyweight and day) and perfluorooctane sulfonate (PFOS) (150 ng/kg bodyweight and day). PFOS concentrations above the limit of quantification were detected in 50 % of the samples. The highest PFOS concentration detected in any of the beers was 18.4 ng/L, and the highest PFOA concentration was 56.9 ng/L. The calculated maximum uptake of both substances for which a TDI level exists were 2.44 ng/kg bodyweight/day for PFOA and 0.79 ng/kg bodyweight/day for PFOS assuming that an adult consumed his/her total daily liquid uptake exclusively by drinking 3 L of beer, equivalent to the maximum measured concentration (worst-case scenario). In regard to the model calculations made here, the maximum uptake of PFOA and PFOS via consumption of beer can be considered negligible at 0.85 % of the concentration that would be required to reach the TDI for PFOS and 0.16 % for PFOA.

Although perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been identified in milk and dairy products in many regions, knowledge on their occurrence in Xinjiang (China) is rare. This study was conducted to measure the levels of PFOA and PFOS in milk and yogurt from Xinjiang and to investigate the average daily intake (ADI) of these two compounds. PFOA and PFOS levels were analyzed using ultrasonic extraction with methanol and solid-phase extraction followed by liquid chromatography–mass spectrometry. Retail milk and yogurt samples present higher detection rates (39.6% and 48.1%) and mean concentrations (24.5 and 31.8 ng/L) of PFOS than those of PFOA (33.0% and 37.0%; 16.2 and 22.6 ng/L, respectively). For raw milk samples, only PFOS was detected. The differences in the levels of the two compounds between samples from the north and south regions were observed, and northern regions showed higher pollution levels than southern regions. On the basis of the retail milk measurements and consumption data, the ADIs of PFOA and PFOS for Xinjiang adults were calculated to be 0.0211 and 0.0318 ng/kg/day, respectively. Furthermore, the estimated intakes of PFOA and PFOS varied among different groupings (age, area, gender, and race) and increased with increasing age. Relevant hazard ratios were found to be far less than 1.0, and this finding suggested that no imminent health damages were produced by PFOA and PFOS intake via milk and yogurt consumption in the Xinjiang population.

Perfluorooctane sulfonate (PFOS) was measured in 161 samples of liver, kidney, blood, or egg yolk from 21 species of fish-eating water birds collected in the United States including albatrosses from Sand Island, Midway Atoll, in the central North Pacific Ocean. Concentrations of PFOS in the blood plasma of bald eagles collected fromthe midwestern United States ranged from 13 to 2,220 ng/mL (mean: 330 ng/mL), except one sample that did not contain quantifiable concentrations of PFOS. Concentrations of PFOS were greater in blood plasma than in whole blood. Among 82 livers from various species of birds from inland or coastal U.S. locations, Brandt's cormorant from San Diego, CA, contained the greatest concentration of PFOS (1,780 ng/g, wet wt). PFOS was also found in the sera of albatrosses from the central North Pacific Ocean at concentrations ranging from 3 to 34 ng/mL. Occurrence of PFOS in birds from remote marine locations suggests widespread distribution of PFOS and related fluorochemicals in the environment.

Perfluoroalkyl and polyfluoroalkyl substances in entire clutches of Audouin’s gulls from the ebro delta

Exploring the fate, transport and risk of Perfluorooctane Sulfonate (PFOS) in a coastal region of China using a multimedia model

Neuroblastoma is one of the most commonly found solid tumors in children. The monoclonal antibody dinutuximab (DNX) targets the sialic acid-containing glycosphingolipid GD2 expressed on almost all neuroblastoma tumor cells and induces cell lysis. However, the expression of GD2 is not limited to tumor cells only, but is also present on central nerve tissue and peripheral nerve cells explaining dinutuximab toxicity. The most common adverse reactions are pain and discomfort, which may lead to discontinuation of the treatment. Furthermore, there is little to no data available on exposure and effect relationships of dinutuximab. We, therefore, developed an easy method in order to quantify dinutuximab levels in human plasma. Ammonium sulfate (AS) was used to precipitate all immunoglobulins (IgGs) in human plasma. After centrifugation, supernatant containing albumin was decanted and the precipitated IgG fraction was re-dissolved in a buffer containing 0.5% sodium dodecyl sulfate (SDS). Samples were then reduced, alkylated, and digested with trypsin. Finally, a signature peptide in complementarity determining region 1 of DNX heavy chain was quantified on LC-MS/MS using a stable isotopically labeled peptide as internal standard. AS purification efficiently removed 97.5% of the albumin fraction in the supernatant layer. The validation performed on DNX showed that within-run and between-run coefficients of variation (CV) for lower limit of quantification (LLOQ) were 5.5 and 1.4%, respectively. The overall CVs for quality control (QC) low, QC med, and QC high levels were < 5%. Linearity in the range 1–32 mg/L was excellent (r2 > 0.999). Selectivity, stability, and matrix effect were in concordance with EMA guidelines. In conclusion, a method to quantify DNX in human plasma was successfully developed. In addition, the high and robust process efficiency enabled the utilization of a stable isotopically labeled (SIL) peptide instead of SIL DNX, which was commercially unavailable.Graphical abstract

Perfluorooctane sulfonate (PFOS) is a class of specialty chemicals used in a variety of applications, and has been found to be globally distributed in many living organisms including humans. Several analytical methods have been developed for determination of PFOS in environmental samples and biological matrices. However, these methods employ liquid chromatography/tandem mass spectrometry (LC/MS/MS), an instrumentation which has limited accessibility because it is expensive to use and maintain. In the present study we present the development of a robust analytical method using liquid chromatography/mass spectrometry (LC/MS) in combination with solid phase extraction. The high yield and concentration of the present method enabled us to quantify PFOS as low as 0.1 ng/L. This method was applied to the determination of PFOS in 142 surface water samples collected from various geographic locations around Japan. The geometric mean (geometric standard deviation) (ng/L) for river samples (n = 126) was 2.37 (4.13), with a median of 1.68 and a range of 0.3-157 ng/L, and for coastal sea water samples (n = 16) was 1.52 (4.14), with a median of 1.21 and a range of 0.2-25.2 ng/L. However, the concentrations in most of the samples were much lower than the values reported in the US, except for those from the Jinzu (135.0 ng/L) and Tama (157 ng/L) Rivers. Because surface waters in the Ara (13.0-38.5 ng/L), Tama (0.7-157.0 ng/L), and Yodo (0.9-27.3 ng/L) Rivers, sources of drinking water for more than eight million people, were moderately contaminated with PFOS, more work is needed to assess exposure to PFOS.