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Objective This study was undertaken to determine the plasma concentration and pharmacokinetic variability of fenfluramine (FFA) and its main active metabolite norfenfluramine (norFFA) in relation to the prevalence of adverse effects in patients with refractory epilepsy treated with FFA. In addition, the interaction with concomitant antiseizure medications including stiripentol (STP) is studied. Methods Patients were recruited at our center from two open-label sources, an investigator-initiated observational study and an international multicenter extension study. Venous blood samples were collected between June 2015 and December 2020. Plasma FFA and norFFA concentrations were determined by liquid chromatography tandem spectrometric analysis. Clinical data were collected retrospectively. Intrapatient coefficient of variation was calculated for all patients with at least three samples. Interpatient variability was calculated based on the concentration to weight-adjusted dose ratio (C/D) of all patients. Results We collected 321 samples from 61 patients (49 with Dravet syndrome, seven with Lennox-Gastaut syndrome, and five with a developmental and epileptic encephalopathy). With a mean daily dose of .33 mg/kg/day (SD = +/-.16), the median FFA plasma concentration was 41.4 mu g/L (range = 5.1-712.5) and median norFFA concentration 28.1 mu g/L (range = 2.6-149.6). The FFA plasma concentration was linearly related to the daily dose (p < .001) and norFFA levels (p < .001). The C/D of FFA increased with age (p < .001). Median FFA C/D was 428% higher (p < .001), norFFA C/D 83% lower (p < .001), and norFFA/FFA 23% lower (p < .001) in patients treated with STP comedication. Higher FFA concentration was associated with fatigue (p = .001) and somnolence (p < .001), but not anorexia (p = .0619) or reduction in seizure frequency (p = .772). Gender and other ASMs were not associated with significant variations in (nor)FFA C/D ratio. Significance Most FFA levels are in the lower range (

IntroductionThe ultrasound-guided interpectoral-pectoserratus plane block is a fascial plane block for superficial surgery of the anterolateral chest wall. This technique involves injecting a relatively large volume of local anesthetics (typically 30 mL of 0.25%–0.50%, ie, 75–150 mg ropivacaine) underneath the major and minor pectoral muscles of the anterior thoracic wall. There is a potential risk of toxic serum concentrations of local anesthetics due to systemic absorption.Methods22 patients scheduled for elective unilateral breast cancer surgery were included in this study. All surgery was performed with general anesthesia and an ultrasound-guided interpectoral-pectoserratus plane block with 2.5 mg/kg ropivacaine. Ten venous blood samples were collected at 0 (two samples) 10, 20, 30, 45, 60, 90 and 120 min and at 4 hours after performing the block. Free and total ropivacaine levels were measured at each time point. Albumin and alpha-1-acid-glycoprotein were measured to monitor shifts between the free and bound fraction of ropivacaine.ResultsSamples of 20 patients were analyzed. The mean dose of ropivacaine was 172.8 (22.5) mg. In 50% of the patients, the potentially toxic threshold of 0.15 µg/mL free ropivacaine concentration was exceeded. Mean peak serum concentration occurred at 20 min postinjection.ConclusionsThis pharmacokinetic study demonstrated that a 2.5 mg/kg ropivacaine interpectoral-pectoserratus plane block may result in exceeding the threshold for local anesthetic systemic toxicity.

ispartof: CLINICAL KIDNEY JOURNAL vol:16 issue:4 pages:760-761 ispartof: location:England status: published

BACKGROUND: As iodine-based contrast can cause deterioration of renal function in patients with impaired kidney function, guidelines advise to measure creatinine and calculate estimated glomerular filtration (eGFR) prior to administration. Point-of-care (POC) devices seem an attractive alternative to central laboratory testing but uncertainty regarding analytical and clinical comparability remains. METHODS: This study compared three POC devices, i-STAT (Abbott), StatSensor (Nova) and epoc (Siemens) with a central laboratory method (enzymatic creatinine, Siemens Vista 1500 platform). 120 patients were included and underwent simultaneous finger prick capillary blood analysis on the StatSensor and heparine whole blood analysis on StatSensor, i-STAT and epoc. RESULTS: All POC devices generated results which showed considerable variability around the creatinine value of the reference standard, with StatSensor having the widest (-1,12-1,11 mg/dL) and epoc the tightest (-0,49-0,49 mg/dL) 95% limits of agreement. I-STAT showed the highest clinical concordance with the reference standard (Kappa: 0,94) and had the smallest average analytical error (6%) for creatinine and eGFR compared to the reference standard, meeting the predefined criteria of 8,87% and 10%, respectively. Epoc only met criteria for eGFR. StatSensor did not meet any of the criteria. CONCLUSIONS: I-STAT and epoc were, analytically and clinically, the most performant POC devices included in this study but showed to be less user-friendly. StatSensor did not meet any of the error criteria, neither for creatinine nor for eGFR measurements, and gave more clinical major classification errors. However, it proved to be more user-friendly compared to the other POC devices. ispartof: CLINICA CHIMICA ACTA vol:497 pages:13-19 ispartof: location:Netherlands status: published

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD. Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library. Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug's dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.

Introduction: Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term treatment. Patient nonadherence is frequent and poses a major problem in maintenance therapy. Aripiprazole once-monthly long-acting injectable (AOM LAI) is a recently US Food and Drug Administration-approved treatment option for maintenance therapy that could be of great value. Areas covered: This paper reviews the pharmacokinetic, efficacy and safety data for AOM LAI in bipolar disorder. Expert opinion: AOM LAI is a safe and efficacious treatment option in the maintenance therapy of bipolar I disorder. However, further research is still needed to determine the position of AOM LAI relative to other available treatment options.

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the microsomal liver function and could be a potential candidate. We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH, and could be used as a supplementary diagnostic tool in clinical practice.

Introduction: A seasonal affective disorder (SAD) is a subtype of unipolar and bipolar major depressive disorders. It is characterized by its annual recurrence of depressive episodes at a particular season, mostly seen in winter and is responsible for 10-20% of the prevalence of major depressive disorders. Some pathophysiological hypotheses, such as the phase delay and the monoamine depletion hypotheses, have been postulated but the exact cause has not been fully unraveled yet. Studies on treatment for SAD in the last decade are lacking. To tackle this chronic disease, attention needs to be drawn to the gaps in this research field. Areas covered: In this systematic review, the authors give a broad overview of the pharmacological therapy available for SAD. Also, nutritional substances fitting well with the postulated hypotheses are reviewed for the treatment and prevention of SAD. There is a specific focus on the quality of the currently performed studies. Expert opinion: Light therapy and fluoxetine are the only proven and effective acute treatment options for SAD, while bupropion is the only registered drug for prevention of SAD. This area of research is in dire need of valid large-scale and sufficiently reproducible randomized control trials.

We assessed the exposure of the Flemish population to brominated flame retardants (BFRs) and perfluorinated compounds (PFCs) by analysis of pooled cord blood, adolescent and adult serum, and human milk. Levels of polybrominated diphenyl ethers (PBDEs) in blood (range 1.66.5 ng/g lipid weight, lw) and milk (range 2.06.4 ng/g lw) agreed with European data. Hexabromocyclododecane ranged between

The analytical characteristics of several new brominated flame retardants (BFRs) were investigated. Spiked dust extracts were used to compare the relative stability and recovery of new BFRs during three clean-up procedures on silica, acidified silica and Florisil. The behaviour of new BFRs in two ionization sources of the mass spectrometer (MS), electron impact (EI) and electron capture negative ionization (ECNI), and on three different capillary columns were studied. It was shown that the simultaneous detection of new BFRs and polybrominated diphenyl ethers (PBDEs) can be achieved using acidified silica as sample clean-up, followed by GC-ECNI/MS analysis on a 15 m × 0.25 mm × 0.10 μm DB-5 column. A very low detection frequency of the investigated new BFRs in selected Belgian indoor dust samples (n = 20) was found, suggesting that these alternate BFRs are only slowly replacing PBDEs in consumer goods.

Human exposure to brominated flame retardants (BFRs) varies widely throughout the world as it depends on country-related usage, production and legislation of these chemicals. US and UK exposure assessments show very diverse levels and patterns which in turn, are likely to differ from those in background exposed countries such as Belgium, where levels tend to be about an order of magnitude lower. The current study assessed human exposure to BFRs through the indoor and outdoor environment (e.g. dust, soil, and air) and food for all age groups in Flanders, Belgium. Most relevant food groups were identified based on a national food consumption survey and food items with Flemish origin were collected. Dust samples were collected using a standardized protocol in 43 homes and 10 offices throughout Flanders. Food, human milk and dust samples were analysed for their polybrominated diphenylethers (PBDE) and hexabromocyclodecane (HBCD) content using GC/MS and LC/MS-MS. An exposure model was developed including all analysed data, complemented with literature data. The model covered human exposure of infants, children and adults through human milk, food, dust/soil ingestion and air inhalation. Total human exposure was compared to the existing toxicological criteria and previous exposure estimates. In general, the exposure levels through human milk are consistent with those of a background exposed European population, whereas dust and food intake are at the low end of what has been reported in previous European intake assessments. Total average intake of ΣHBCD and ΣBDE5 at 50th percentile (P50) levels by newborns equals 3.1 and 12.0 ng/kg body weight (bw) day, respectively. This intake increases to 15.2 and 20.9 ng/kg bw day for ΣHBCD and ΣBDE5, for higher exposed newborns (95th percentile=P95 levels). Due to the limited database on health-based limit values for PBDEs and HBCD, it is difficult to assess the immediate health concern for any of the age groups, although the higher intake of newborns indicates the need for ongoing monitoring. For median exposed individuals, the average ΣHBCD intake peaked at the age 3 to 6 years with an intake of 6.59 ng/kg bw day and declines to ∼1 ng/kg bw day at later age. ΣBDE5 intake exhibited a different profile compared to ΣHBCD with maximal levels for newborns and a decline to ∼0.7 ng/kg bw day at adulthood. Keywords: Flanders, PBDEs, HBCD, Human intake, Food, Dust, Risk assessment

Polychlorinated biphenyl (PCB) and OCP concentrations were determined in the livers of two deep-sea fish species, roughsnout grenadier and hollowsnout grenadier, from the Adriatic Sea. In both species, contaminant concentrations were in the following order: PCBs>DDTs>>HCB. Contaminant load was higher in roughsnout grenadier (PCB: 12,327 ng g −1 ; DDTs: 5357 ng g −1 ; HCB: 13.1 ng g −1 ) than in hollowsnout grenadier (PCB: 1234 ng g −1 ; DDTs: 763 ng g −1 ; HCB 6.3 ng g −1 ). PCB patterns were dominated by higher chlorinated congeners (hexa-CBs: 50.3–52.1%, hepta-CBs: 29.6–35.5%, penta-CBs: 8.0–11.1% and octa-CBs :5.2–5.4%). PCBs 138, 153 180 and 187 were the most abundant. Regarding the DDT pattern, p , p′ -DDE was prevalent in both species (roughsnout grenadier: 99.7%, hollowsnout grenadier: 90%), suggesting no recent DDT input. In both species, the total 2,3,7,8-tetrachlorodibenzo- p -dioxin toxic equivalent (TEQ) concentrations (roughsnout grenadier: mean 43.77 pg/g, hollowsnout grenadier: mean 20.49 pg/g), calculated from non- and mono- ortho PCBs, reached those encountered in marine organisms at higher levels in the trophic chain.

The extent and the sources of contamination with brominated flame retardants (BFRs), such as polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD), in home-produced eggs from free-foraging chicken of Belgian private owners were investigated. Various factors, such as seasonal variability, exposure of chickens through diet (kitchen waste) and soil, and elimination of BFRs through eggs and faeces were assessed. PBDEs were more important than HBCD in terms of concentrations and detection frequency. Concentrations of PBDEs and HBCD in Belgian home-produced eggs were relatively low and comparable with reported levels from other European countries and the US. The concentrations of PBDEs (sum of 13 congeners, including BDE 209) ranged between not detected and 32 ng/g lipid weight (lw), with medians of 3.0 and < 2.0 ng/g lw for the autumn 2006 and spring 2007 campaigns, respectively. When present, BDE 209 was the major PBDE congener (45% of sum PBDEs). When BDE 209 was not detected, the PBDE profile was composed of PentaBDE (BDE 99 and BDE 47), with, in some cases, higher contribution of OctaBDE (BDE 183 and BDE 153). HBCD was also detected (< 0.4 and 2.9 ng/g lw for the autumn 2006 and spring 2007 campaigns, respectively), but at lower detection frequency. The highest HBCD value was 62 ng/g lw. The similarity between profiles and seasonal variations in the concentrations of BFRs in soil and eggs indicate that soil is an important source, but not the sole source, for eggs laid by free-foraging chicken. The contamination of eggs with PBDEs and HBCD appears to be of low concern for public health and the contribution of eggs to the total daily intake of PBDEs appears to be limited (10% for chicken owners and 5% for the average Belgian consumer).

Synthetic musks, such as 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB), musk ketone (MK) and musk xylene (MX), are used as an alternative for natural musk. Due to their widespread use, these synthetic compounds turned up in different environmental compartments, such as wastewater, human and animal tissues. Yet, little is known about their distribution and occurrence in personal care and household products, information needed in order to evaluate the different human exposure routes. This paper gives an overview of the synthetic musk levels in six different product categories: body lotions, perfumes, deodorants, hair care products, shower products and sanitation products. Especially body lotions, perfumes and deodorants contained high levels of synthetic musks. Maximum concentrations of HHCB, AHTN, MX and MK were 22 mg g(-1), 8 mg g(-1), 26 microg g(-1) and 0.5 microg g(-1), respectively. By combining these results with the average usage of consumer products, low-, medium- and high-exposure profiles through dermal application could be estimated. HHCB was the highest contributor to the total amount of synthetic musks in every exposure profile (18-23 700 microg d(-1)). Exposure to MK and MX did not increase substantially (10-20-fold) between low- and high-exposure profiles, indicating that these compounds cover a less broad range. In comparison, exposure to HHCB and AHTN increased up to 10 000 fold between low- and high-exposure.

Although long-range atmospheric transport has been described as the predominant mechanism for exposing polar regions to persistent organic pollutants (POPs), recent studies have suggested that bird activity can also contribute substantially to contaminant levels in some environments. However, because the species so far reported have all been migratory, it has not been demonstrated conclusively whether locally elevated contamination represents transport from lower latitudes by the migrating birds or, alternatively, redistribution and concentration of contaminants that were already present in the high-latitude environments. The present study demonstrates, for the first time, that several POPs are present in elevated concentrations in an environment frequented by a non-migratory species (Adelie penguins) that spends its entire life in the Antarctic. Levels of POPs, such as p,p′-DDE, hexachlorobenzene (HCB), chlordanes (CHLs) and polychlorinated biphenyls (PCBs), were 10 to 100-fold higher in soil samples from penguin colonies than from reference areas. This significant difference is likely related to local penguin activity, such as a higher abundance of guano and the presence of bird carcasses. This hypothesis is also supported by a higher percentage of persistent congeners (PCB 99, 118, 138 and 153) in the soil from the colonies compared to the reference areas. This profile of PCB congeners closely matched profiles seen in penguin eggs or penguin blood.

With the objective to evaluate exposure of the population in Flanders (Belgium) to perfluorinated compounds (PFCs), we measured perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in settled dust in homes and offices, in a selection of food items from local origin, in drinking-water and in human serum. We complemented the data with results from a literature survey. Based on this dataset we calculated intake by children and adults from food, drinking-water, settled dust and soil, and air. Dietary exposure dominated overall intake. For adults, average dietary intake equalled 24.2 (P95 40.9) ng PFOS kg−1 d−1 and 6.1 (P95 9.6) ng PFOA kg−1 d−1, whereas for children the dietary intake was about 3 times higher. Predicted intake is high when compared to assessments in other countries, and to serum levels from Flanders, but comparable to the intakes published by The European Food Safety Authority (EFSA) in 2008. Intake of PFOS and PFOA remained below the Tolerable Daily Intake.

Between 2000 and 2007 pooled muscle tissue samples of the European eel (Anguilla anguilla) from 48 sites in Flanders (Belgium) were analysed for 30 polychlorinated biphenyl (PCB) congeners. There was a large variation between individual sites (range 11–7752 ng/g wet weight (ww) for the sum of the ICES 7 PCBs), eels from the River Meuse basin (mean 1545 ng/g ww) being considerably more polluted than those from the River Scheldt (615) and IJzer (61) basins. Overall, PCB 153, PCB 138 and PCB 180 were the most prominent congeners, however PCB patterns varied between the monitored locations. Analysis of the weight percentage of congeners demonstrates obvious differences in PCB composition between sites, indicating differential sources of pollution. Due to the variation in patterns, atmospheric fallout does not seem to be the main source of the PCB spread, but instead both local and upstream sources linked to industrial activities seem to be the main cause for PCB presence in Flanders.Considering the levels of the Sum 7 PCBs, eels are not compliant with the Belgian legal limits for consumption (75 ng/g ww) in 71% of the sites. Regular consumption of eels from polluted sites leads to a considerable excess of the WHO Acceptable Daily Intake value. Consumption of wild eels should by all means be prevented, as it presents risks for human health, especially for local anglers consuming their catch. Keywords: European eel, PCBs, Bioaccumulation, Human intake, Monitoring network, Flanders

We have reviewed the human exposure to selected emerging organic contaminants, such new brominated flame retardants, organophosphate flame retardants, phthalate substitutes, triclosan, synthetic musks, bisphenol-A, perchlorate, and polycyclic siloxanes. Levels of these emerging contaminants in matrices relevant for human exposure (air, dust, food, water, etc.) and in human matrices (blood, urine, or tissues) have been reviewed, together with some of the relevant health effects reported recently.

Persistent organic pollutants (POPs) are endocrine-disrupting chemicals associated with the development of the metabolic syndrome and type 2 diabetes. In humans, little is known about their role in the potential origin of obesity. This study aims to assess the associations between serum levels of POPs and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross-sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners 153, 138, 180, and 170 and for the organochlorine pesticides, dichloro-diphenyl-dichloroethylene (pp-DDE), and β-hexachlorocyclohexane (βHCH). We established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170, and the sumPCBs. For βHCH, we demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. PCBs 180, 170, and the sum of PCBs correlated significantly negative with homeostasis model assessment for insulin resistance (HOMAIR). βHCH correlated significantly positively with HOMAIR. A strong correlation was established between all POP serum levels and age. We established a positive relationship between high serum levels of βHCH and BMI and HOMAIR, whereas serum PCB levels were inversely correlated with BMI and HOMAIR. Combined, these results suggest that the diabetogenic effect of low-dose exposure to POPs might be more complicated than a simple obesogenic effect.

The increasing time spent indoors combined with the abundant usage of diverse indoor chemicals led to concerns involving the impact of these compounds on human health. The current study focused on two groups of important indoor contaminants i.e. Brominated flame retardants (BFRs) and Perfluorinated compounds (PFCs). Concentrations of both compound classes have been measured in Flemish indoor dust samples from homes and offices. Sigma Polybrominated diphenyl ethers (PBDEs) (BDE 47, 99, 100, 154, 153, 197, 196 and 203) and BDE 209 in homes ranged between 4-1214 ng g(-1) dw (median 35) and

Pooled yellow eel (Anguilla anguilla L.) samples, consisting of 3–10 eels, from 50 locations collected in the period 2000–2006 were used to assess the pollution with PBDEs and HBCDs in Flemish waters (Belgium). Results from this monitoring network are presented and the spatial aspect throughout Flanders is included, linking POP levels to the industrial characteristics of the different sampling locations. The following PBDE congeners were measured using GC/MS: 28, 47, 49, 66, 85, 99, 100, 153, 154, 183 and 209. Concentrations of ∑PBDE ranged between 10 and 5811 ng/g lipid weight (lw) with a median value of 81 ng/g lw. BDE 47 dominated the PBDE profile in the majority of the eel samples, except for six samples, in which BDE 209 was the dominating congener. These latter samples are probably associated with recent exposure to the Deca-BDE mixture. Three HBCD diastereoisomers (α-, β- and γ-HBCD) were measured using LC/MS-MS. ∑HBCDs ranged between 16 and 4397 ng/g lw, with a median value of 73 ng/g lw. α-HBCD was the dominant isomer in all eel samples. Sediment concentrations of PBDEs were available from four locations and were used to compare the PBDE profile with those in eel. An important shift in the profile was observed, especially for BDE 209. While BDE 209 was only found in 12 eel samples, it was the dominant congener in all sediment samples. This could be due to its metabolisation or degradation in biota combined with the poor uptake of BDE 209 from sediments and its very low water solubility. No HBCDs were detected in any of the sediment samples. No significant correlation could be found between concentrations of PBDEs in eel and sediment from the same location. Comparison with previous studies shows that PBDE and HBCD levels in Flemish eels have decreased rapidly between 2000 and 2006 at particular sites, but alarming concentrations can still be found at industrialized hot spots. This finding is reflected in the human exposure to PBDEs and HBCDs through eel consumption. For average consumers (2.9 geel/day), intakes ranged between 3 and 2295 ng/day for ∑PBDEs (with a median value of 16 ng/day) and between 3 and 1110 ng/day for ∑HBCDs (with a median value of 18 ng/day), respectively. Additionally, human intakes were calculated for recreational fishermen, eating up to 12 g or 86 geel/day. Intakes of those risk groups were higher in comparison with average consumers and were above reference doses described in literature which may induce adverse effects. Keywords: Eel, Sediment, PBDEs, HBCDs, Human intake, Monitoring network, Flanders

Bisphenol-A (BPA), Triclosan (TCS) and Tetrabromobisphenol-A (TBBPA) are phenolic organic contaminants used in a variety of household applications. Through manufacture and usage, these contaminants can leach into the environment and can be detected in indoor dust. In this study, we determined the concentrations of BPA, TCS and TBBPA in indoor dust samples from 18 houses and 2 offices in Flanders, Belgium. The analysis was performed using solidliquid extraction, clean-up and measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Median concentrations of the 18 domestic dust samples were 1460, 220 and 10 ng g−1 dust for BPA, TCS and TBBPA, respectively. Concentrations in offices were almost 510 times higher for BPA and TBBPA, while TCS concentrations were comparable at both locations. An assessment of the daily intake of these contaminants through dust was made and the contribution of dust to the total human exposure was calculated. For all three contaminants, dust seems to be a minor contributor (

Background: Hexabromocyclododecane (HBCD) is a high-production-volume chemical used as flame retardant in polystyrene insulation and textiles. Because it is not chemically bound to the polymer, HBCD can migrate into the environment, contaminating indoor dust and foodstuff. Objectives: We examined for the first time the relationship between combined exposure to three HBCD isomers (ÓHBCDs) via ingestion of food (duplicate diets) and indoor dust and HBCD concentrations in serum for 16 Belgian adults (2025 years of age). We also determined the chiral signatures of HBCDs to advance understanding of source-to-human enantioselective degradation and/or metabolism. Methods: Concentrations and chiral signatures of á-, â-, and ã-HBCD in duplicate diets, dust, and serum were measured by liquid chromatography/tandem mass spectrometry. Results: Dietary intakes of ÓHBCDs were 1.220 ng/day (average, 7.2 ng/day), whereas those estimated under average (20 mg dust/day) and high (50 mg dust/day) dust ingestion scenarios were 1.115 ng/day (average intake, 3.2 ng/day) and 2.838 ng/day (average intake, 8.0 ng/day), respectively. Concentrations of ÓHBCDs measured in blood serum were < 0.5 to 11 ng/g lipid weight (lw) (average, 2.9 ng/g lw). ã-HBCD dominated in food, whereas á-HBCD dominated in dust and was the sole isomer in serum. Although exposure via dust ingestion correlated significantly (p < 0.01) with concentrations in serum, no such correlation was evident with dietary exposure (p > 0.1). Although no enantioselective enrichment was detected in either dust or diet, substantial enrichment of ()á-HBCD was observed in serum. Conclusions: Serum concentrations of HBCDs were correlated with the exposure via dust, but not via dietary ingestion. The enrichment of the ()á-HBCD enantiomer in humans appears to be due to in vivo enantioselective metabolism/excretion rather than ingestion of dust or diet.

Polybrominated diphenyl ethers (PBDEs) and naturally-produced organobrominated compounds, such as methoxylated PBDEs (MeO-PBDEs), have been scarcely studied in the Southern Hemisphere. Yet, sources of the latter group of compounds were found in Southern regions, specifically in Australia. The environmental distribution and biomagnification potential of organobrominated compounds were therefore investigated in a representative aquatic food chain (invertebrates and fish) from the Sydney Harbour, Australia. Mean PBDE concentrations ranged from 6.4 ng/g lipid weight (lw) in squid to 115 ng/g lw in flounder. BDE 47 was the dominant congener, followed by BDE 100. Mean levels of MeO-PBDEs (sum of congeners 2’-MeO-BDE 68 and 6-MeO-BDE 47) were as high as 110 ng/g lw in tailor, with a slight dominance of 2’-MeO-BDE 68. Polybrominated hexahydroxanthene derivates (PBHDs), another class of naturally-produced compounds, were found at variable concentrations and ranged from 4.7 ng/g lw in fanbelly and 146 ng/g lw in tailor. The tribrominated PBHD isomer dominated in the samples, except for luderick and squid. The lower levels of PBDEs found in luderick from the harbour compared to those obtained from the upper Parramatta River indicated a terrestrial (anthropogenic) origin of PBDEs, while the higher levels of MeO-PBDEs and PBHDs in the samples from the harbour confirmed the marine (natural) origin of these compounds. The highest trophic magnification factor (TMF) was found for sum PBDEs (3.9), while TMFs for sum MeO-PBDEs and sum PBHDs were 2.9 and 3.4, respectively. This suggests that biomagnification occurs in the studied aquatic food chain for anthropogenic brominated compounds, but also for the naturally-produced organobromines. Keywords: Biomagnification, PBDEs, Brominated natural compounds, MeO-PBDEs, PBHDs, Fish, Invertebrates, Australia, Food chain

Levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured in paired human adipose tissue and liver samples (n = 25) from Belgium. Average concentrations and standard deviation of sum PBDEs (congeners 28, 47, 99, 100, 153, 154 and 183) were 5.3 ± 3.0 (range 1.413.2) and 3.6 ± 2.1 (range 1.010.0) ng g−1 lipid weight (lw) in adipose tissue and liver, respectively. These concentrations were similar to reported PBDE data from Belgium and were at the lower end of the concentration range reported elsewhere in the world. In both tissues under study, BDE 153 and BDE 47 were the most abundant PBDE congeners, contributing approximately 35% and 25% to the total PBDE content. Average concentrations and range of PCBs (sum of 23 congeners) were 490 (range 701130) and 380 (range 901140) ng g−1 lw in adipose tissue and liver, respectively. No correlation between age and concentrations of PBDEs could be found (r = 0.04), while PCB concentrations correlated significantly with age (r = 0.62, p < 0.01, for the sum PCBs; r = 0.64, p < 0.01 for PCB 153 alone). Factors, such as exposure pathways (food, dust and air), rates of bioaccumulation, metabolism and elimination, influence the concentrations of PBDEs differently than those of PCBs in humans.

This study aimed at optimizing and validating a sensitive method for simultaneous determination of bisphenol A (BPA), triclosan (TCS), and tetrabromobisphenol A (TBBPA) in human serum using solid-phase extraction (SPE) and gas chromatography coupled to electron-capture negative-ionization mass spectrometry (GC-ECNI/MS). Sample preparation involved denaturation of serum proteins with formic acid followed by SPE on an Oasis HLB cartridge. Fractionation was performed on Florisil from which the phenolic compounds were eluted with methanol-dichloromethane (DCM) (5:1, v/v). The phenolic fraction was further derivatized with pentafluoropropionic acid anhydride (30 min at 70 degrees C). Further liquid-liquid partitioning using hexane-DCM (4:1, v/v) and K(2)CO(3) 3% aqueous solution was used to eliminate excess reagent and acidic by-products formed during derivatization. The cleaned extract was injected into a GC-ECNI/MS system operated in selected ion monitoring mode. For thorough method validation, each step of the procedure was rigorously optimized. The method limits of quantitation for BPA, TCS, and TBBPA were 0.28 ng mL(-1), 0.09 ng mL(-1) and 0.05 ng mL(-1), respectively. Furthermore, the method was applied to 21 Belgian human serum samples. The median concentrations obtained for BPA (0.71 ng mL(-1)) and TCS (0.52 ng mL(-1)) in Belgian human serum samples were similar to previously reported data for human fluids. Slightly higher levels of TBBPA (0.08 ng mL(-1)) were found in Belgium samples compared to Norwegian serum.

Because of the similarities in European and North American dietary exposure, it has been suggested that the order of magnitude higher body burdens in North Americans may be due to international variations in exposure via ingestion of indoor dust. Furthermore, ingestion of indoor dust has been suggested as a possible source of PBDEs in the blood serum of New Zealanders. Hence, polybrominated diphenyl ethers (PBDEs) were measured in domestic indoor dust from: Amarillo/Austin, Texas, US; Birmingham, UK; Toronto, Canada; and Wellington, New Zealand. Concentrations of BDE 209 in two UK samples were - at 520,000 and 100,000 ng g(-1) - the highest ever recorded in a domestic (or office) indoor dust sample. Median concentrations in ng g(-1) were: in Canada 620 and 560 for Sigma tri-hexa-BDEs and BDE 209 respectively; in New Zealand 96, BDE 209 not determined; in the UK 59 and 2,800; and in the US 1600 and 1300. With respect to BDE 209, concentrations were in the order: UK similar to US>Canada. For Sigma-tri-hexa-BDEs, the order of concentrations was US similar to Canada >> New Zealand similar to UK. Combined with principal component analysis of congener patterns, this suggests that, while North American dusts are contaminated by both Deca- and Penta-BDE commercial formulations, UK dusts are contaminated predominantly by Deca-BDE. The Octa-BDE formulation appears of minimal importance in accordance with available market demand figures. Despite the commercial formulations of PBDEs never having been manufactured in, nor imported into New Zealand, their presence in dusts from that country suggests international trade in PBDE-containing goods is an important pathway effecting their global distribution. (C) 2007 Elsevier Ltd. All rights reserved.

This paper reports the applicability of low-pressure gas chromatography-mass spectrometry operated in electron-capture negative ionization mode (LP-GC-ECNI-MS) for the analysis of decabrominated diphenyl ether (BDE-209). Particular attention was paid to find optimal injector and oven conditions for minimal thermal degradation of BDE-209. The analytical characteristics were compared for LP-GC columns (10 m x 0.53 mm) with different film thicknesses (d(f) 0.15 microm versus 0.25microm) and for a conventional GC column (15 m x 0.25 mm, 0.10 microm d(f)). Short residence times (6.5 and 9.8 min) of BDE-209 were found for the LP-GC systems with 0.15 and 0.25microm d(f), respectively, resulting in a low elution temperature and minimal degradation. Additionally, baseline separation of 22 polybrominated diphenyl ether (PBDE) congeners (major components of PBDE technical mixtures) was possible in less than 12 min using the LP-GC-ECNI-MS system with 0.15microm d(f). The optimized method was applied for the determination of PBDEs in Belgian indoor dust samples. The obtained concentrations of BDE-209 (range 8-292 ng/g dry weight) were in the same range or lower than concentrations in dust from other European countries.

Supplemental Digital Content is available in the text., Objective: Intraplaque neovascularization is an important feature of unstable human atherosclerotic plaques. However, its impact on plaque formation and stability is poorly studied. Because proliferating endothelial cells generate up to 85% of their ATP from glycolysis, we investigated whether pharmacological inhibition of glycolytic flux by the small-molecule 3PO (3-[3-pyridinyl]-1-[4-pyridinyl]-2-propen-1-one) could have beneficial effects on plaque formation and composition. Approach and Results: ApoE−/− (apolipoprotein E deficient) mice treated with 3PO (50 µg/g, ip; 4×/wk, 4 weeks) showed a metabolic switch toward ketone body formation. Treatment of ApoE−/−Fbn1C1039G+/− mice with 3PO (50 µg/g, ip) either after 4 (preventive, twice/wk, 10 weeks) or 16 weeks of Western diet (curative, 4×/wk, 4 weeks) inhibited intraplaque neovascularization by 50% and 38%, respectively. Plaque formation was significantly reduced in all 3PO-treated animals. This effect was independent of intraplaque neovascularization. In vitro experiments showed that 3PO favors an anti-inflammatory M2 macrophage subtype and suppresses an M1 proinflammatory phenotype. Moreover, 3PO induced autophagy, which in turn impaired NF-κB (nuclear factor-kappa B) signaling and inhibited TNF-α (tumor necrosis factor-alpha)–mediated VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) upregulation. Consistently, a preventive 3PO regimen reduced endothelial VCAM-1 expression in vivo. Furthermore, 3PO improved cardiac function in ApoE−/−Fbn1C1039G+/− mice after 10 weeks of treatment. Conclusions: Partial inhibition of glycolysis restrained intraplaque angiogenesis without affecting plaque composition. However, less plaques were formed, which was accompanied by downregulation of endothelial adhesion molecules—an event that depends on autophagy induction. Inhibition of coronary plaque formation by 3PO resulted in an overall improved cardiac function.