Brominated Diphenyl Ethers Research Articles

The effect of lipopolysaccharide on MMP-2 and MMP-9 in HTR-8/SVneo cells

Brominated diphenyl ether (BDE)-47 is a prevalent flame retardant chemical found in human tissues and is linked to adverse pregnancy outcomes in humans. Because dysregulation of the prostaglandin pathway is implicated in adverse pregnancy outcomes, the present study investigates BDE-47 induction of prostaglandin synthesis in a human extravillous trophoblast cell line, HTR-8/SVneo, examining the hypothesis that BDE-47 increases generation of reactive oxygen species (ROS) to stimulate the prostaglandin response. Treatment with 20 μM BDE-47 significantly increased mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2) at 4, 12 and 24 h, and 24-h treatment significantly increased cyclooxygenase (COX)-2 cellular protein expression and prostaglandin E2 (PGE2) concentration in culture medium. The BDE-47-stimulated PGE2 release was inhibited by the COX inhibitors indomethacin and NS398, implicating COX activity. Exposure to 20 μM BDE-47 significantly increased ROS generation as measured by carboxydichlorofluorescein fluorescence, and this response was blocked by cotreatment with the peroxyl radical scavenger (±)-α-tocopherol. (±)-α-Tocopherol cotreatment suppressed BDE-47-stimulated increases of PGE2 release without significant effects on COX-2 mRNA and protein expression, implicating a role for ROS in post-translational regulation of COX activity. Because prostaglandins regulate trophoblast functions necessary for placentation and pregnancy, further investigation is warranted of BDE-47 impacts on trophoblast responses.

Synthesis and QSPR study on environment-related properties of polychlorinated diphenyl sulfides (PCDPSs)

Twenty-nine congeners of polychlorinated diphenyl sulfide (PCDPS) theoretically possible were synthesized and purified, and their octanol–water partition coefficients (logKow) and high performance liquid chromatography capacity factors (HPLC-logk′) were determined. Then the constitutional and structural descriptors were obtained respectively to establish 2D models and comparative molecular similarity indices analysis (CoMSIA) method was used to establish 3D models. All the models were robust and predictive, indicating that the electrostatic effect may be the primary factor influencing the two properties of PCDPS. The logKow and logk′ values of all PCDPS congeners were predicted based on these models. The establishment of linear equation on logKow between PCDPS and chlorinated or brominated diphenyl ether (PCDE, PBDE) was attempted, and the hydrophobic differences were considered to relate with the size of the molecules.

Focused ultrasound solid–liquid extraction and gas chromatography tandem mass spectrometry determination of brominated flame retardants in indoor dust

This study presents a focused ultrasound solid-liquid extraction (FUSLE) and gas chromatography tandem mass spectrometry method for the determination of brominated diphenyl ethers (BDEs), from mono- to hexa-congeners, in indoor dust. This approach provided a simple, fast, and economical method. After the solvent extraction selection, the FUSLE conditions were studied using a central composite design. Finally, the number of extraction cycles was studied. The selected conditions were 8mL of 3:1 n-hexane-acetone mixture as extraction solvent, at a power of 65% for 20s. The proposed method allowed accurate determination of BDEs, with recovery values around 100% and detection limits between 0.05 and 0.8ngg(-1). It also has advantages over other existing methods in terms of simplicity, analysis time, and solvent consumption. The analysis of several indoor dust samples showed high concentration values of BDEs 47, 99, 100, 153, and 154 in some of the samples, moreover, BDEs 47 and 99 were found in all samples.

Aerosol-Mediated Transport and Deposition of Brominated Diphenyl Ethers to Antarctica

Brominated diphenyl ethers (BDE47, 99, 100, and 209) were measured in air, snow and sea ice throughout western Antarctica between 2001 and 2007. BDEs in Antarctic air were predominantly associated with aerosols and were low compared to those in remote regions of the northern hemisphere, except in Marguerite Bay following the fire at Rothera research station in Sept 2001, indicating that this event was a local source of BDE209 to the Antarctic environment. Aerosol BDE47/100 reflects a mixture of commercial pentaBDE products; however, BDE99/100 is suggestive of photodegradation of BDE99 during long-range atmospheric transport (LRAT) in the austral summer. BDEs in snow were lower than predicted based on snow scavenging of aerosols indicating that atmospheric deposition events may be episodic. BDE47, -99, and -100 significantly declined in Antarctic sea ice between 2001 and 2007; however, BDE209 did not decline in Antarctic sea ice over the same time period. Significant losses of BDE99 and -100 from sea ice were recorded over a 19 day period in spring 2001 demonstrating that seasonal ice processes result in the preferential loss of some BDEs. BDE47/100 and BDE99/100 in sea ice samples reflect commercial pentaBDE products, suggesting that photodegradation of BDE99 is minimal during LRAT in the austral winter.

Comparison of organohalogen compounds in a white-tailed sea eagle egg laid in 1941 with five eggs from 1996 to 2001

Eggs laid by white-tailed sea eagles (Haliaeetus albicilla), one in 1941 and five eggs between 1996 and 2001, all from the same geographical region of the Baltic Sea, were screened for organohalogen substances. The 1941 egg contained hexachlorobenzene (HCB), but did not contain either of the pesticides hexachlorocyclohexane (HCH) or p,p′-DDT, nor any metabolites of the latter. In contrast, the more recent eggs (REs) contained all of these compounds. Of the seven polychlorinated biphenyls (PCBs) analyzed (CB28, −52, −101, −118, −138/−163, −153 and 180), only the more highly chlorinated congeners were detected in the 1941 sample, with CB153 followed by CB180 showing the highest concentrations. All eggs demonstrated the same congener pattern with respect to the more highly chlorinated PCBs, but concentrations were approximately 70–230 times higher in the REs. All of the polychlorinated-p-dioxin and dibenzofuran (PCDD/Fs) congeners analyzed were detected in the eggs, with the dominant congener being 2,3,4,7,8-PeCDF (1250pg/gl.w. in 1941 and 1540pg/gl.w. (GM) for the REs, respectively). None of the other congeners exceeded 400pg/gl.w., and the concentrations of 2,3,7,8-TCDD, 2,3,7,8-TCDF and 1,2,3,7,8-PeCDF were all lower in the REs. None of five congeners of polybrominated diphenyl ethers (PBDEs) found in the REs was detected in the egg from 1941. The three methoxylated brominated diphenyl ethers (MeO-BDEs) analyzed were found at similar levels and with a similar congener pattern in REs as in the egg from 1941.In conclusion, this study has shown the absence of DDE and PBDE and the presence of HCB and PCBs in a white-tailed sea eagle egg laid in 1941, and a strong increase of PCBs, DDE and PBDE in white-tailed sea eagle eggs from the same area in 1996–2001. The MeO-BDEs were found in similar concentrations in the analyzed eggs. The 1941 sample shows substantial concentrations of PCDD/Fs, noteworthy in the same magnitude as in the recent samples, illustrating the historical and recent exposure of these compounds.

Effects of Chronic Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants on the Reproductive and Thyroid System in Adult Male Rats

Brominated flame retardants (BFRs) are incorporated into a wide variety of consumer products, are readily released into home and work environments, and are present in house dust. Studies using animal models have revealed that exposure to polybrominated diphenyl ethers (PBDEs) may impair adult male reproductive function and thyroid hormone physiology. Such studies have generally characterized the outcome of acute or chronic exposure to a single BFR technical mixture or congener but not the impact of environmentally relevant BFR mixtures. We tested whether exposure to the BFRs found in house dust would have an adverse impact on the adult male rat reproductive system and thyroid function. Adult male Sprague Dawley rats were exposed to a complex BFR mixture composed of three commercial brominated diphenyl ethers (52.1% DE-71, 0.4% DE-79, and 44.2% decaBDE-209) and hexabromocyclododecane (3.3%), formulated to mimic the relative congener levels in house dust. BFRs were delivered in the diet at target doses of 0, 0.02, 0.2, 2, or 20 mg/kg/day for 70 days. Compared with controls, males exposed to the highest dose of BFRs displayed a significant increase in the weights of the kidneys and liver, which was accompanied by induction of CYP1A and CYP2B P450 hepatic drug–metabolizing enzymes. BFR exposure did not affect reproductive organ weights, serum testosterone levels, testicular function, or sperm DNA integrity. The highest dose caused thyroid toxicity as indicated by decreased serum thyroxine (T4) and hypertrophy of the thyroid gland epithelium. At lower doses, the thickness of the thyroid gland epithelium was reduced, but no changes in hormone levels (T4 and thyroid-stimulating hormone) were observed. Thus, exposure to BFRs affected liver and thyroid physiology but not male reproductive parameters.

Gastrointestinal absorption, metabolic debromination, and hydroxylation of three commercial polybrominated diphenyl ether mixtures by common carp

The gastrointestinal absorption, metabolic debromination, and hydroxylation of three commercial brominated diphenyl ether (BDE) mixtures were separately studied in juvenile common carp. The absorption rate of penta-BDE was higher than that of octa- and deca-BDE, likely because of the lower molecular volumes of its major congeners. However, no significantly positive relationships were found between the number of bromine atoms and the absorption rate, especially for congeners with a bromine atom number larger than six. The major congeners in fish carcass were, respectively, BDE-47 and BDE-100 in the penta-BDE exposure; BDE-154, -155, -149, and BDE-153 in the octa-BDE exposure; and BDE-154, -155, -149, -188, -179, and BDE-202 in the deca-BDE exposure. Congeners with at least one meta- or para- doubly flanked bromine atom easily undergo metabolic debromination in fish. None of the targeted MeO-polybrominated diphenyl ether (PBDE) congeners were detected in serum samples, implying that the methylation of OH-PBDE is not likely occurring in fish. Eleven OH-PBDEs and several unidentified OH-PBDE congeners were found in penta-BDE-exposed fish. The similar level among three mono-OH-BDE47 congeners suggested that the position of OH in the phenyl ring is not selective. The hydroxylation is not a significant metabolic pathway compared with debromination. No OH-PBDE congeners were found in the serum samples from deca-BDE-exposed fish, which may attributable to the low level of PBDE precursors in fish.

Cyto-genotoxic effects induced by three brominated diphenyl ether congeners on the freshwater mussel Dreissena polymorpha

Polybrominated diphenyl ethers (PBDEs) are a group of highly hydrophobic and persistent chemicals that has been used as flame retardants in several industrial applications. They have been detected in various environmental matrices worldwide and an increasing number of studies have recently been carried out to investigate their potential toxicity on ecosystem communities. Although a variety of biological damage has been documented in vertebrates, the effects on invertebrates are largely unknown. The objective of the present study was to determine the cyto-genotoxic effects induced by single exposure to three concentrations of 2,4,2′,4′-tetra BDE (BDE 47), 2,2′,4,4′,6-penta BDE (BDE-100) and 2,2′,4,4′,5,6′-hexa BDE (BDE-154) on the freshwater mussel Dreissena polymorpha by a multi-biomarker approach. We performed on bivalve hemocytes the Single Cell Gel Electrophoresis (SCGE) assay, the DNA Diffusion assay and the Micronucleus test (MN test) to assess genotoxicity, while the Neutral Red Retention Assay (NRRA) was used to evaluate cytotoxic effects. Results showed that BDE-47 did not produce any genetic damage at the tested concentrations (0.1μg/L, 0.5μg/L and 1μg/L), while BDE-100 and BDE-154 can be considered moderately genotoxic, since both primary and fixed DNA injuries were induced. The NRRA indicated a moderate increase in cellular stress in BDEs-treated bivalves. Thus, our data seems to suggest that investigated BDEs may pose a low risk to freshwater mussels at environmental concentrations.

Concentrations and speciation of polybrominated diphenyl ethers in human amniotic fluid

Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals used as flame retardants in textiles, plastics, and consumer products. Although PBDE accumulation in humans has been noted since the 1970s, few studies have investigated PBDEs within the gestational compartment, and none to date has identified levels in amniotic fluid. The present study reports congener-specific brominated diphenyl ether (BDE) concentrations in second-trimester clinical amniotic fluid samples collected in 2009 from fifteen women in southeast Michigan, USA. Twenty-one BDE congeners were measured by GC/MS/NCI. The average total PBDE concentration was 3795pg/ml amniotic fluid (range: 337–21,842pg/ml). BDE-47 and BDE-99 were identified in all samples. Based on median concentrations, the dominant congeners were BDE-208, 209, 203, 206, 207, and 47 representing 23, 16, 12, 10, 9 and 6%, respectively, of the total detected PBDEs. PBDE concentrations were identified in all amniotic fluid samples from southeast Michigan, supporting a need for further investigations of fetal exposure pathways and potential impacts on perinatal health.

Potential implications of future climate and land‐cover changes for the fate and distribution of persistent organic pollutants in Europe

ABSTRACTAim Climate change is having far‐reaching effects on the global environment. Here, the ALARM (Assessing Large‐scale Risks for Biodiversity with Tested Methods, European Union 6th Framework Programme) climate change scenarios were used to assess changes to the fate of selected persistent organic pollutants (POPs). Scenarios detailing climate and land‐cover changes, such as precipitation, temperature and vegetation cover, were used as input in a European multi‐media chemical fate model to help understand their impact on the environmental fate and behaviour of POPs over the period 1990–2100 in Europe.Location Europe.Methods Chemicals chosen for study included four classical POPs (two polychlorinated biphenyl congeners and two polybrominated diphenyl ether congeners). Using 30‐year time steps, the model was run in steady‐state mode four times for each chemical and each ALARM scenario.Results PCB153 displayed the greatest changes, with a reduction in burden of up to 40% in some Mediterranean compartments (e.g. soil and fresh water) under the worst case climate change scenario. The overall continental persistence of PCB153 was reduced by 1.5 years (12%) due to increased volatilization and degradation in air from a drier and warmer south‐western Europe. This predicted loss resulted in a transfer and redeposition to the cooler and wetter north‐eastern Europe, and increased the burden of PCB153 to Arctic compartments by up to 22%. The remaining chemicals displayed less pronounced changes, particularly under more the sustainable scenarios.Main conclusions Overall, the model simulations suggest that the dominant driver behind differences seen between the present and climate‐changed future scenarios is temperature, resulting in a slight shift in chemical distribution from surface compartments to the air. This subsequently leads to a reduced continental persistence for PCBs and a north‐easterly migration due to prevailing meteorological conditions. As a result of these calculations, it is reasonable to conclude that chemicals with properties similar to PCBs may experience enhanced mobility due to climate change. However, the climate‐induced temperature changes were not large enough to significantly alter the distribution of brominated diphenyl ethers (BDEs), which are less volatile and have greater enthalpies of phase change.

Marine Sponge: A Potential Source for Methoxylated Polybrominated Diphenyl Ethers in the Asia-Pacific Food Web

Marine sponges collected in Palau, Micronesia, were investigated for hydroxylated or methoxylated analogues of brominated diphenyl ethers (BDEs), brominated dibenzo-p-dioxin (BDD), and brominated biphenyls. The neutral fractions of Haliclona sp. and Callyspongia sp. contained 2'-methoxy-2,3',4,5'-tetraBDE, 6-methoxy-2,2',4,4'-tetraBDE, 2',6-dimethoxy-2,3',4,5-tetraBDE 2,2'-dimethoxy-3,3',5,5'-tetrabromobiphenyl, several methoxy-triBDEs, and dimethoxy-penta-/hexaBDEs. The methoxylated BDEs in sponges were strikingly similar to those of local fish living in the western Pacific Ocean. The total concentrations of these compounds (ΣMeO-PBDE) in both sponges were 63.5 μg/g extractable organic matter (EOM) for Haliclona sp. and 36.5 μg/g EOM for Callyspongia sp., which were about 2 orders of magnitude higher than the levels seen in tropical coral reef fish (unicornfish or surgeonfish) (280-290 ng/g lipid) and groupers (550 ng/g lipid) from Okinawan coastal waters. The phenolic fractions of both sponges contained hydroxy-methoxy tetra-/pentaBDEs as well as hydroxy-tetraBDD, in addition to the corresponding phenolic tetraBDE analogues. Although the total concentrations of phenolic products (27-80 μg/g EOM) in both sponges fell within a range comparable to the methoxylated products, ΣOH-PBDE in local fish were trace level (less than 10 ng/g lipid of) or undetectable. This survey indicates that marine sponges are a possible source of the MeO-PBDE analogues that biomagnify via the food chain to the higher trophic organisms in the western Pacific, whereas the distribution of the corresponding hydroxylated analogues is limited.

Levels of Breast Milk PBDEs From Southern Taiwan and Their Potential Impact on Neurodevelopment

In vivo studies have demonstrated that prenatal or neonatal exposure to polybrominated diphenyl ethers (PBDEs) causes developmental neurotoxicity. However, there is a lack of human data. Our hypothesis was that PBDEs would result in lower infant neurodevelopment scores. This is a post hoc analysis of previous studies. Fourteen PBDEs in 70 breast milk were analyzed using a high-resolution gas chromatograph/high-resolution mass spectrometer. Infant neurodevelopment at the age of 8-12 mo was determined using the Bayley Scales of Infants and Toddlers Development, third edition (Bayley-III). The median of Σ14 PBDEs (the sum of 14 PBDE congeners) was 2.92 ng/g lipid. The Σ14 PBDE concentrations were not correlated with Bayley-III scores on cognitive, language, motor, social-emotional, or adaptive behavior scales. A significantly inverse association between brominated diphenyl ether (BDE)-209 and the cognitive scale was found after multivariate stepwise linear regression analyses (B = -0.007, adjusted R = -0.224, p = 0.032). In contrast, the language scale was positively correlated with BDE-196 (B = 0.096, adjusted R = 0.315, p = 0.002). Our results are consistent with most in vivo studies, suggesting that prenatal or postnatal exposure to BDE-209 potentially delays the neurological development.

Brominated diphenyl ether (BDE) levels in liver, adipose, and milk from adult and juvenile rats exposed by gavage to the DE‐71 technical mixture

Brominated diphenyl ethers (BDEs) are used as flame retardants in consumer products. Rodent studies indicate that the liver, thyroid, and nervous system of developing animals are targets of BDEs. To explore the relationship between exposure and health in developing animals, BDE accumulation in adult and juvenile rats was examined in conjunction with changes in liver weight and serum thyroxine (T4). Adult (F0) rats received the commercial BDE mixture DE-71 by gavage at doses of 0.5, 5, and 25 mg kg(-1) body weight (bw)/day for 21 weeks. F0 rats were mated and exposure continued throughout breeding, pregnancy, lactation, and postweaning until the pups (F1 generation) reached postnatal day (PND) 42. Milk was collected from lactating dams. Adipose and liver samples were collected from F0 and F1 males and females for BDE congener analysis. Congener prevalence in rat tissues mimicked congener prevalence in wildlife and humans. Tissue concentrations of all congeners except BDE-153 were lower than would be expected based on dose proportionality, confirming that BDE-153 has a high capacity for bioaccumulation. BDEs were transferred from maternal tissues to milk during lactation. Milk congener profiles differed from maternal tissue profiles indicating that degree of bromination and maternal sequestration influenced BDE transfer to milk. Female F1 rats accumulated more BDEs than F1 males, indicating that female rats were less able to metabolize and/or excrete BDEs. Significant effects on liver weight and serum T4 levels were observed in adults and juveniles in the middle and high dose groups, corresponding to BDE levels in the μg g(-1) range. Although it remains to be determined how human liver and thyroid are affected by exposure to much lower BDE levels, the present study confirmed that gender and reproductive status influence BDE accumulation in tissues and BDE transfer to the neonate via milk.

Circulating Levels of Persistent Organic Pollutants (POPs) and Carotid Atherosclerosis in the Elderly

Background and objective: Increased circulating levels of persistent organic pollutants (POPs) have been associated with myocardial infarction. Because myocardial infarction is an atherosclerotic disease, we investigated, in a cross-sectional study, whether POP levels are related to atherosclerosis.Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1,016 participants 70 years of age), the prevalence of carotid artery plaques was determined by ultrasound. The number of carotid arteries with plaques (0, 1, or 2) was recorded. Also, the intima-media thickness (IMT) and gray scale median of the intima-media complex (IM-GSM) were measured. Twenty-three POPs, comprising 16 polychlorinated biphenyls (PCBs), 5 pesticides, 1 dioxin, and 1 brominated compound (brominated diphenyl ether congener BDE-47), were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry.Results: Seven of the POPs (PCB congeners 153, 156, 157, 170, 180, 206, and 209) were significantly associated with the number of carotid arteries with plaques even after adjusting for multiple risk factors (sex, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, high-density lipoprotein and low-density lipoprotein cholesterol, serum triglycerides, smoking, antihypertensive treatment, and statin use; p = 0.002–0.0001). Highly chlorinated PCBs (congeners 194, 206, and 209) were associated with an echolucent IM-GSM (p < 0.0001 after adjustment), whereas associations between POPs and IMT were modest.Conclusions: Circulating levels of PCBs were associated with atherosclerotic plaques and echogenicity of the intima-media complex independent of cardiovascular risk factors, including lipids. This suggests that POPs may be a risk factor for myocardial infarction, but associations need to be confirmed in prospective studies.

Prenatal Exposure to Polybrominated Diphenyl Ether Flame Retardants and Neonatal Thyroid-Stimulating Hormone Levels in the CHAMACOS Study

Studies published in the last 3 decades have demonstrated global human exposure to polybrominated diphenyl ether (PBDE) flame retardants. A growing body of literature suggests that PBDEs may disrupt thyroid hormone homeostasis. Although thyroid hormones play an essential role in brain development, few studies have investigated relations between prenatal exposure to PBDEs and neonatal thyroid hormone levels, and none have measured thyroid-stimulating hormone (TSH) levels in neonates. The authors measured 10 PBDE congeners in serum collected between October 1999 and October 2000 from 289 pregnant women living in California's Salinas Valley and abstracted TSH levels from their children's medical records. Individual PBDE congeners showed null or weak nonsignificant inverse relations with neonatal TSH. Total serum PBDE was not associated with neonatal TSH (β = 0.00, 95% confidence interval: -0.06, 0.06). Except for brominated diphenyl ether 153, a higher serum PBDE level was related to elevated odds of high TSH (≥80th percentile), but associations were not statistically significant. Associations were not modified by infant sex, age at TSH measurement, maternal serum polychlorinated biphenyl concentration, or mode of delivery. Results were robust to sensitivity analysis. The authors found no conclusive evidence that prenatal exposure to PBDEs at levels similar to those of the general US population is related to neonatal TSH.

Endocrine effects of methoxylated brominated diphenyl ethers in three in vitro models

Methoxylated brominated diphenyl ethers (MeO-BDEs) in aquatic environments have been found to be primarily of natural origin in the marine environment and not from biotransformation of synthetic PBDEs. Two of the eight MeO-PBDEs (2′-MeO-BDE-68 and 6-MeO-BDE-47) that were detected in anchovy from the Yangtze River Delta, were natural products from marine organisms. So 2′-MeO-BDE-68 and 6-MeO-BDE-47 were chosen to study the potential to modulate androgen, estrogen, or thyroid hormone receptor- (AR, ER, ThR) mediated responses by use of reporter gene assays. 2′-MeO-BDE-68 was antiandrogenic at 50μM, estrogenic at 10μM and antiestrogenic at 10 and 50μM (IC50=4.88μM). 2′-MeO-BDE-68 enhanced luciferase expression by 5nM T3 at 50μM. 6-MeO-BDE-47 exhibited potent antiandrogenicity at 1μM and greater (IC50=41.8μM) and possessed estrogenic activity at 10μM and antiestrogenic activity at 10 and 50μM (IC50=6.02μM).

POLYCHLORINATED BIPHENYLS AND ORGANOCHLORINE PESTICIDES PREDICT DEVELOPMENT OF TYPE 2 DIABETES IN THE ELDERLY: THE PROSPECTIVE INVESTIGATION OF THE VASCULATURE IN UPPSALA SENIORS (PIVUS) STUDY

Background and Aims: Persistent Organic Pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, has recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with plasma concentrations of selected POPs among the elderly. Methods:Twenty POPs (including 15 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured in plasma collected at baseline in 725 participants aged 70 years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Results:After adjusting for known risk factors of type 2 diabetes including obesity, odds ratios (ORs) for incident type 2 diabetes (n=36) according to quintiles of a summary measure of plasma concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (95% CI: 1.8-42.7), and 7.5 (1.4-38.8) (Ptrend &lt;0.01). Among 3 OC pesticides, adjusted ORs across concentrations of trans-nonachlor showed P for trend=0.03. Adjusted ORs across quintiles of the sum of 3 OC pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0-11.7) (Ptrend =0.03). Neither BDE47 nor dioxin was significantly associated with incident diabetes. The strength of prediction of incident diabetes was stronger for the sum of PCBs than it was for BMI or waist circumference. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes. Conclusions:This study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population.

Analysis of hydroxylated polybrominated diphenyl ethers in plant samples using ultra performance liquid chromatography-mass spectrometry

A method was developed for the analysis of hydroxylated brominated diphenyl ethers (OH-PBDEs) in plant samples using an ultra performance liquid chromatography-triple quadrupole mass spectrometer (UPLC-ESI-MS/MS) in negative mode. Plant samples were extracted and cleaned up through florisil column, resolved on a 100 mm C18 column with linear gradient elution and detected by mass spectrometry in multiple reaction monitoring (MRM) mode. The method provided good recoveries ranging from 68.2% to 94.6%, relative standard deviation (RSD) in the range of 3.2%–9.1%, and limits of quantification (LOQ) defined as the signal-to-noise ratio of 10 of 0.3–2.1 ng/g. It allowed a fast separation and sensitive quantification of the isomers and homologues of seven OH-PBDE congeners 2′-OH-BDE-3, 3′-OH-BDE-7, 4′-OH-BDE-17, 3′-OH-BDE-28, 3-OH-BDE-47, 5-OH-BDE-47 and 6-OH-BDE-47. The method was successfully applied to identify and quantify the formation of hydroxylated metabolites in alfalfa exposed to BDE-209. Five OH-PBDEs were detected in plant tissues, and more congeners were found in roots than in shoots. To our knowledge, this work represents the first attempt to validate UPLC-MS/MS method to quantify OH-PBDEs in plant samples without derivatization.

Associations of persistent organic pollutants with abdominal obesity in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

ObjectivesIn animal experiments, persistent organic pollutants (POPs) have induced visceral obesity. To address this possibility in humans, we evaluated associations between POPs and abdominal obesity both cross-sectionally and prospectively. MethodsTwenty-one plasma POPs (16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured at baseline in 970 participants aged 70years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), with prospective analyses in 511 participants re-examined after 5years. Abdominal obesity was defined by an increased waist circumference. ResultsIn the cross-sectional analyses, concentrations of the less chlorinated PCBs, OC pesticides such as p,p′-DDE and dioxin had adjusted odds ratios of 2 to 3 for abdominal obesity. Many relations had inverted U-shapes rather than being linear, particularly in women. In contrast, concentrations of highly chlorinated PCBs were strongly inversely associated with abdominal obesity. In a single model including summary measures of the less chlorinated PCBs, highly chlorinated PCBs, and OC pesticides, both the positive associations and inverse associations strengthened. Similar but somewhat weaker associations were seen between POPs and risk of development of abdominal obesity in the prospective analyses. ConclusionUsing both a cross-sectional and a prospective design, low-dose exposure to less chlorinated PCBs, p,p′-DDE, and dioxin, were associated with existence or development of abdominal obesity, while highly chlorinated PCBs had an opposite association in an elderly population, despite the previous observation of higher incident diabetes associated with these same PCBs.

Polychlorinated Biphenyls and Organochlorine Pesticides in Plasma Predict Development of Type 2 Diabetes in the Elderly

OBJECTIVEPersistent organic pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, have recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with selected POPs among the elderly.RESEARCH DESIGN AND METHODSNineteen POPs (14 polychlorinated biphenyl [PCB] congeners, 3 organochlorine pesticides, 1 brominated diphenyl ether, and 1 dioxin) were measured in plasma collected at baseline in 725 participants, aged 70 years, of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).RESULTSAfter adjusting for known type 2 diabetes risk factors, including obesity, odds ratios (ORs) (95% CIs) for type 2 diabetes at age 75 years (n = 36) according to the quintiles of a summary measure of concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (1.8–42.7), and 7.5 (1.4–38.8) (Ptrend <0.01). Among organochlorine pesticides, adjusted ORs across concentrations of trans-nonachlor showed that Ptrend = 0.03. Adjusted ORs (95% CIs) across quintiles of the sum of three organochlorine pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0–11.7) (Ptrend = 0.03). Neither brominated diphenyl ether 47 nor dioxin was significantly associated with incident diabetes. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes.CONCLUSIONSDespite the small number of incident cases, this study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population.