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Feline hyperthyroidism is a rather new disease, first reported from the North American east coast in 1979. The prevalence is increasing, especially in older cats, and hyperthyroidism is now reported worldwide as the most common feline endocrinopathy. Several studies have been performed trying to identify important etiological factors such as exposure to persistent organic pollutants, and especially brominated flame retardants, have been suggested to be of importance for the development of the disease. Recent studies have shown higher concentrations of these contaminants in serum of hyperthyroid cats in comparison to cats with normal thyroid status. However, other still unknown factors are most probably of importance for the development of this disease.

We investigated the serum concentrations of two brominated flame retardants (BFRs) - polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) -in 59 women aged between 23 and 42 from the United Kingdom. We also collected demographic data, including age, bodyweight and height in order to test for associations with BFR levels. Temporal and global differences were also assessed using previously published data. HBCDD was detected in 68% of samples with a mean concentration of 2.2 ng/g lipid (range = <0.3-13 ng/g lipid). The dominant stereoisomer was α-HBCDD with an average contribution of 82% (0-100%) towards ΣHBCDD, was followed by γ-HBCDD (average contribution = 17%). PBDEs were detected in 95% of samples with a mean ∑PBDE (sum of BDEs -28, -47, -99, -100, -153, -154 and -183) concentration of 2.4 ng/g lipid (range = <0.4-15 ng/g lipid). BDEs -153 and -47 were the dominant congeners, contributing an average of 40% and 37% respectively, to the average ΣPBDE congener profile. Data from this study suggests that HBCDD levels decrease with age, it also suggests a positive association between bodyweight and HBCDD levels, which likewise requires a large-scale study to confirm this. The data also show that 10 years after their European ban, PBDE body burden has begun to decrease in the UK. Whilst it is too early to draw any firm conclusions for HBCDDs, they appear to be following a similar pattern to PBDEs, with levels decreasing by a factor of >2.5 since 2010. Whilst the human body burden appear to be decreasing, both PBDEs and HBCDD are still consistently detected in human serum, despite legislative action limiting their production and use. This highlights the need to continuously assess human exposure and the effectiveness of policy aimed at reducing exposure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Previous studies have linked prenatal polybrominated diphenyl ether (PBDE) exposure to adverse birth outcomes. Reductions in placental size might mediate those adverse effects. We examined whether umbilical cord blood PBDEs concentrations were associated with placental size at birth. A total of 121 mother-newborn pairs residing in Wenzhou were enrolled in this study. Concentrations of 19 PBDEs in umbilical cord blood were determined by gas chromatography tandem mass spectrometry (GC-MS). Placental length, breadth and surface area was measured by medical professionals after delivery. BDE-206, 207, 208, 209 and the total of 19 PBDE congeners concentrations were negatively associated with placental length, breadth and surface area. Our results suggest that prenatal PBDEs exposure may suppress placental growth, resulting in reduced placental size., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Brominated flame retardants (BFRs) and Dechlorane Plus (DP) were measured in both human hair and paired serum samples from a cohort of university students in South China. Segmental analysis was conducted to explore gender difference and the relationships between the hair and serum. The concentrations of total PBDEs in the hair and serum samples were in a range of 0.28-34.1ng/g dry weight (dw) and 0.16-156ng/g lipid weight (lw), respectively. Concentrations of ∑DPs (sum of the syn-DP and anti-DP isomers) in all hair samples ranged from nd-5.45ng/g dry weight. Concentrations of most PBDEs and decabromodiphenylethane (DBDPE) in distal segments (5-10cm from the scalp) were higher than those in the proximal segments (0-5cm from the scalp) (t-test, p < 0.05), which could be due to the longer exposure time of distal segments. The proximal segments exhibited a unique congener profile, more close to that in the serum rather than the distal segments of hair. An obvious gender difference was found in the levels of ∑PBDEs using integrated hair samples, while the difference disappeared when considering alone the proximal segments of hair (0-5cm from scalp) for both genders. This paper provides supplement to the current knowledge on sources of BFRs and DPs in hair and declares the importance of segmental analysis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to determine the effects of persistent organic pollutants (POPs) and biometric variables on circulating levels of steroid hormones (androgens, estrogens and progestagens) in male polar bears (Ursus maritimus) from Svalbard, Norway (n = 23). Levels of pregnenolone (PRE), progesterone (PRO), androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2) and 17β-estradiol (βE2) were quantified in polar bear serum by gas chromatography tandem mass spectrometry (GC-MS/MS), while POPs were measured in plasma. Subsequently, associations between hormone concentrations (9 steroids), POPs (21 polychlorinated biphenyls (PCBs), 8 OH-PCBs, 8 organochlorine pesticides (OCPs) and OCP metabolites, and 2 polybrominated diphenyl ethers (PBDEs)) and biological variables (age, head length, body mass, girth, body condition index), capture date, location (latitude and longitude), lipid content and cholesterol levels were examined using principal component analysis (PCA) and orthogonal projections to latent structures (OPLS) modelling. Average concentrations of androgens, estrogens and progestagens were in the range of 0.57-83.7 (0.57-12.4 for subadults, 1.02-83.7 for adults), 0.09-2.69 and 0.57-2.44 nmol/L, respectively. The steroid profiles suggest that sex steroids were mainly synthesized through the Δ-4 pathway in male polar bears. The ratio between androgens and estrogens significantly depended on sexual maturity with androgen/estrogen ratios being approximately 60 times higher in adult males than in subadult males. PCA plots and OPLS models indicated that TS was positively related to biometrics, such as body condition index in male polar bears. A negative relationship was also observed between POPs and DHT. Consequently, POPs and body condition may potentially affect the endocrinological function of steroids, including development of reproductive tissues and sex organs and the general condition of male polar bears., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The residents of Shandong Province, China, are exposed to high concentrations of halogenated flame retardants because large amounts of halogenated flame retardants are produced in the province. We determined the concentrations of eight polybrominated diphenyl ether congeners (PBDEs), seven novel brominated flame retardants (NBFRs), and the two dechlorane plus isomers (DPs) in serum from residents of Shandong Province. The aim was to identify temporal trends in the concentrations of these pollutants. The mean total concentrations of PBDEs, NBFRs and DPs were 41, 2.2 and 2.1ng/g lipid in pooled serum samples collected in 2014, and were 32, 3.5 and 3.1ng/g lipid in pooled serum samples collected in 2015, respectively. Decabromodiphenyl ether was the dominant PBDE congener in all of the samples. The novel brominated flame retardant and dechlorane plus concentrations were between one and two orders of magnitude lower than the PBDE concentrations. The PBDE concentrations in serum decreased significantly between 2007 and 2015, but the pentabromobenzene, pentabromotoluene, and dechlorane plus concentrations were relatively stable., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate associations between serum concentrations of brominated flame retardants and personal characteristics, including diet, in adults participating in a population-based study in Sweden 2010-11. Moreover, observed concentrations were used in a health risk assessment, using published health-based reference values. Serum samples of 170 adult individuals of both sexes were analyzed for 10 PBDE congeners and HBCD by GC-MS. When including concentrations between LOD and LOQ, highest median serum concentration was observed for BDE-153 (1.2 ng/g serum lipid), followed by BDE-209 (0.95 ng/g lipid), BDE-47 (0.49 ng/g lipid) and BDE-100 (0.21 ng/g lipid). Median concentration of HBCD was 0.10 ng/g lipid. A few markedly elevated concentrations of BDE-209, HBCD (77-78 ng/g lipid) and BDE-47 (44 ng/g lipid) were observed. The only statistical significant findings were higher BDE-153 concentrations in men than in women, and positive associations between serum BDE-153 concentrations and consumption of fish (total), beef, mutton and poultry. PBDE concentrations were in accordance with concentrations reported in other European countries but generally lower than those found in North America. Median PBDE serum concentrations observed in adults from Sweden suggest sufficient health protection, when compared with published health-based reference values, although some outliers with high serum concentrations had lower safety margins., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hexabromocyclododecanes (HBCDD) were measured in 67 pooled serum samples collected between 2002 and 2015 in South East Queensland, Australia. These data are the first report of HBCDD in Australian human serum. Temporal and demographic (age and gender) trends were investigated. HBCDD were detected in measurable concentrations in 69% of samples. The average ∑HBCDD concentration was 3.1ng/g lipid, whilst the range was <0.5 to 36ng/g lipid. α-HBCDD was the dominant stereoisomer making up an average of 60% of ∑HBCDD. The remainder was made up by γ-HBCDD. In contrast to another group of brominated flame retardants (BFRs, (polybrominated diphenyl ethers (PBDEs)), HBCDD were found in the lowest concentrations in pools from children aged 0-4 years. This could be attributed to differences in exposure, usage, and/ or the much lower half-life of HBCDD in the human body compared to PBDEs. HBCDD concentrations appear to be significantly higher in females than in males, however the reasons for this are unclear., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Exposure to persistent organic pollutants (POPs) during prenatal and postnatal life has been extensively studied in relation to adverse health effects in children., Objectives: The aim was to identify determinants of the concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (polybrominated diphenyl ethers, PBDEs; polybrominated biphenyl, PBB), and organochlorine pesticides (OCPs) in blood samples from pregnant women and children in The Norwegian Mother and Child Cohort Study (MoBa)., Methods: Blood samples were collected from two independent subsamples within MoBa; a group of women (n=96) enrolled in mid-pregnancy during the years 2002-2008 and a group of 3 year old children (n=99) participating during 2010-2011. PCB congeners (74, 99, 138, 153, 180, 170, 194, 209, 105, 114, 118, 156, 157, 167, and 189), brominated flame retardants (PBDE-28, 47, 99, 100, 153, 154, and PBB-153), as well as the OCPs hexachlorobenzene (HCB), oxychlordane, 4,4'dichlorodiphenyltrichloroethane (DDT), and 4,4'dichlorodiphenyldichloroethylene (DDE) were measured in both pregnant women and children., Results: Age, low parity, and low pre-pregnant BMI were the most important determinants of increased plasma concentrations of POPs in pregnant women. In 3 year old children, prolonged breastfeeding duration was a major determinant of increased POP concentrations. Estimated dietary exposure to PCBs during pregnancy was positively associated with plasma concentrations in 3 year old children, but not in pregnant women. Plasma concentrations were approximately 40% higher in children compared to pregnant women., Conclusions: Several factors associated with exposure and toxicokinetics, i.e. accumulation, excretion and transfer via breastmilk of POPs were the main predictors of POP levels in pregnant women and children. Diet, which is the main exposure source for these compounds in the general population, was found to predict PCB levels only among children. For the PBDEs, for which non-dietary sources are more important, toxicokinetic factors appeared to have less predictive impact., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Many species are adapted for fasting during parts of their life cycle. For species undergoing extreme fasts, lipid stores are mobilized and accumulated contaminants can be released to exert toxicological effects. However, it is unknown if short-term fasting events may have a similar effect. The objective of this study was to determine if short successive fasts are related to contaminant levels in liver and plasma of birds. In ring-billed gulls (Larus delawarensis), both members of the pair alternate between incubating the nest for several hours (during which they fast) and foraging, making them a useful model for examining this question. Birds were equipped with miniature data loggers recording time and GPS position for two days to determine the proportion and duration of time birds spent in these two activities. Liver and plasma samples were collected, and halogenated flame retardants (HFRs) (PBDEs and dechlorane plus) and organochlorines (OCs) (PCBs, DDTs, and chlordane-related compounds) were determined. Most birds (79%) exhibited plasma lipid content below 1%, indicating a likely fasted state, and plasma lipid percent declined with the number of hours spent at the nest site. The more time birds spent at their nest site, the higher were their plasma and liver concentrations of HFRs. However, body condition indices were unrelated to either the amount of time birds fasted at the nest site or contaminant levels, suggesting that lipid mobilization might not have been severe enough to affect overall body condition of birds and to explain the relationship between fasting and HFR concentrations. A similar relationship between fasting and OC levels was not observed, suggesting that different factors are affecting short-term temporal variations in concentrations of these two classes of contaminants. This study demonstrates that short fasts can be related to increased internal contaminant exposure in birds and that this may be a confounding factor in research and monitoring involving tissue concentrations of HFRs in wild birds., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The metabolites of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as well as other halogenated phenolic contaminants (HPCs) have been shown to have endocrine-disrupting properties, and have been reported with increasing frequency in the blood of wildlife, and mainly in mammals and birds. However, little is known about the persistence, accumulation and distribution of these contaminants in long-lived freshwater reptiles. In the present study, in addition to a large suite of chlorinated and brominated contaminants, metabolites and HPCs, we assessed and compared hydroxylated (OH) PCBs and OH-PBDEs relative to PCBs and PBDEs, respectively, in the plasma of adult male common snapping turtles (Chelydra serpentina). Blood samples were collected from 62 snapping turtles (2001-2004) at 12 wetland sites between the Detroit River and the St. Lawrence River on the Canadian side of the Laurentian Great Lakes of North America. Turtles were sampled from sites designated as Areas of Concern (AOCs) and from a relatively clean reference site in southern Georgian Bay (Tiny Marsh), Lake Huron. Plasma concentrations of Σ46PCB (10-340 ng/g wet weight (ww)) and Σ28OH-PCB (3-83 ng/g ww) were significantly greater (p<0.05) in turtles from the Turkey Creek and Muddy Creek-Wheatley Harbour sites in Lake Erie compared with the reference site turtles. The HPC, pentachlorophenol (PCP), had a mean concentration of 9.6±1.1 ng/g ww. Of the 28 OH-CB congeners screened for, 4-OH-CB187 (42±7 ng/g ww) was the most concentrated of all HPCs measured. Of the 14 OH-BDE congeners examined, four (4'-OH-BDE17, 3-OH-BDE47, 5-OH-BDE47 and 4'-OH-BDE49) were consistently found in all plasma samples. p,p'-DDE was the most concentrated of the 18 organochlorine pesticides (OCPs) examined. The mean concentrations of circulating total thyroxine (TT4), dehydroretinol and retinol in the plasma of the male snapping turtles regardless of sampling site were 5.4±0.3, 81±4.7 and 291±13 ng/mL, respectively. Significant (p<0.05) negative (e.g. cis-chlordane) or positive (e.g. BDE-99) correlations between some of the target contaminants and TT4, dehydroretinol or retinol were observed. To our knowledge, we report for the first time on HPC (e.g. OH-PCBs) and methylsulfonyl- (MeSO2-) PCB metabolite contaminants in the plasma of any freshwater turtle or freshwater reptilian species. Our findings also show that the accumulation of OH-PCBs, MeSO2-PCBs, OH-PBDEs and some OCPs in the snapping turtles from Lake Erie and Lake Ontario (in 2001-2004) had the potential for eliciting endocrine disruption. Exposure to these contaminants and associated adverse effects on the endocrine system in freshwater reptiles and the related mechanisms require further investigation., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Pooling of surplus serum from individual samples, collected between 2007 and 2009 during Cycle 1 of the Canadian Health Measures Survey (CHMS), was performed to develop a national baseline estimate of brominated flame retardants in Canadians. Serum samples were categorized by sex and distributed by five age groups ranging from 6 to 79years. Nearly 5000 (4583) serum samples were used to form 59 composite pools. Serum pools were created to ensure a high detection frequency of these analytes in serum because low volume samples had previously resulted in non-detectable concentrations. The analytes of interest in these serum pools included 23 polybrominated diphenyl ethers (PBDEs) and three hexabromocyclododecane (HBCD) isomers (α-, β- and γ-HBCD). PBDEs were observed in all samples tested and total PBDE concentrations ranged from 27ngg(-1) lipid to 130ngg(-1) lipid (geometric mean [GM] 46ngg(-1) lipid). ∑PBDE concentrations were significantly elevated in samples representing the 6-11year old age group (GM 65ngg(-1) lipid) relative to ages above 40years, although no difference in concentration was observed between the sexes. PBDE concentrations in Canadian sera from the general population were higher than reported in Europe and Asia, but a little lower than observed in the US. PBDE 47 was the greatest contributor to ∑PBDE concentrations and the GM concentration for this congener was 22ngg(-1) lipid. The other dominant contributors to ∑PBDE concentrations were in descending order: 153 [GM 9.4ngg(-1) lipid]>99 [GM 4.6ngg(-1) lipid]≅100 [GM 4.1ngg(-1) lipid]>209 [GM 1.1ngg(-1) lipid] and 183 [GM 0.42ngg(-1) lipid]. ∑HBCD was detected in all samples analysed, although most samples were observed at concentrations <1ngg(-1) lipid, similar to global concentrations. α-HBCD was the dominant contributor to ∑HBCD concentrations in Canadians although β- and γ-HBCD were detected in 23% and 35% of the samples, respectively. No differences in ∑HBCD concentration were associated with age or sex. This dataset represents the first national data describing HBCD isomers and some PBDEs (e.g., 183, 209) in Canadians., (Crown Copyright © 2013. All rights reserved.)

The concentrations of tetrabromobisphenol A (TBBPA) and hexabromocyclododecanes (HBCDs), and their correlations with thyroid hormones, were investigated in sera from 26 infants with congenital hypothyroidism, 12 healthy infants, and their mothers. The analyte concentrations were not significantly different in the two infant groups. Polybrominated diphenyl ethers (measured in a previous study) were the dominant brominated flame retardants, contributing 42-87% of the total, and HBCDs contributed 5-18%. TBBPA concentrations were 2-5 times higher in the infants than in the mothers. The TBBPA concentrations decreased dramatically with age for 2-3 months after birth, which might be caused by its relatively high maternal transfer rate, short half-life, and fast excretion. Significant correlations were found between mothers and infants in the TBBPA and HBCD concentrations, implying that maternal transfer was important. TBBPA correlated weakly with thyroid hormones, showing a positive relationship with FT4 but a negative relationship with T3., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Polychlorinated and polybrominated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs and PBDD/Fs) were measured in serum of twelve firefighters sampled after a fire event in San Francisco, California, along with polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), p,p'-DDE, hexachlorobenzene (HCB), perfluorinated chemicals (PFCs), bisphenol-A (BPA) and tetrabromobisphenol-A (TBBPA). TEQPCDD/F concentrations were relatively low (mean 5pgg(-1) (lipid weight), lw, range 1-11pgg(-1)lw), but concentrations of 1,2,3,4,6,7,8-HpCDD, a congener indicative of exposure during firefighting, were elevated. Tentative WHO2005-TEQs calculated for PBDD/Fs in our samples (mean 104pgg(-1)lw, range 0.2-734pgg(-1)lw) suggested that PBDD/Fs may contribute substantially to dioxin-like toxicity in individual firefighters. PBDE concentrations were elevated in firefighter serum (mean 135ngg(-1)lw, range 48-442ngg(-1)lw). PBDE-209, PBDE-47 and PBDE-153 were prevalent congeners; PBDE-209 contributed >50% of the total PBDE concentration in four individuals, implying continuous occupational exposure to deca-BDE. Perfluorooctanesulfonate (PFOS) was the dominant PFC in serum (mean 12ngml(-1) (wet weight), ww, range 3ngml(-1)ww to 59ngml(-1)ww), followed by perfluorooctanoic acid (PFOA) (mean 7ngml(-1)ww, range 2ngml(-1)ww to 12ngml(-1)ww). Concentrations of perfluorononanoic acid (PFNA) (mean 2ngml(-1)ww, range 1-4ngml(-1)ww) were higher than those reported in the high-smoke exposure group of World Trade Center fire responders, suggesting that the California firefighters were exposed to PFNA in smoke during firefighting. Given their elevated rates of cancers, these results illustrate the importance of monitoring halogenated contaminants including PBDD/Fs in firefighters., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse., Methods: As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH., Results: A two-fold increase of the sum of serum PBDE's was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE's on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests., Conclusions: This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.

Brominated flame retardants, including hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs) are used to reduce the flammability of a multitude of electrical and electronic products, textiles and foams. The use of selected PBDEs has ceased, however, use of decaBDE and HBCD continues. While elevated concentrations of PBDEs in humans have been observed in Australia, no data is available on other BFRs such as HBCD. This study aimed to provide background HBCD concentrations from a representative sample of the Australian population and to assess temporal trends of HBCD and compare with PBDE concentrations over a 16 year period. Samples of human milk collected in Australia from 1993 to 2009, primarily from primiparae mothers were combined into 12 pools from 1993 (2 pools); 2001; 2002/2003 (4 pools); 2003/2004; 2006; 2007/2008 (2 pools); and 2009. Concentrations of ∑HBCD ranged from not quantified (nq) to 19 ng g(-1)lipid while α-HBCD and γ-HBCD ranged from nq to 10 ng g(-1)lipid and nq to 9.2 ng g(-1)lipid. β-HBCD was detected in only one sample at 3.6 ng g(-1)lipid while ∑(4)PBDE ranged from 2.5 to 15.8 ng g(-1)lipid. No temporal trend was apparent in HBCD concentrations in human milk collected in Australia from 1993 to 2009. In comparison, PBDE concentrations in human milk show a peak around 2002/03 (mean ∑(4)PBDEs=9.6 ng g(-1)lipid) and 2003/04 (12.4 ng g(-1)lipid) followed by a decrease in 2007/08 (2.7 ng g(-1)lipid) and 2009 (2.6 ng g(-1)lipid). In human blood serum samples collected from the Australian population, PBDE concentrations did not vary greatly (p=0.441) from 2002/03 to 2008/09. Continued monitoring including both human milk and serum for HBCD and PBDEs is required to observe trends in human body burden of HBCD and PBDEs body burden following changes to usage., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A solid-phase extraction (SPE) method for the simultaneous extraction of hexabromocyclododecanes (HBCDs)/tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ethers (PBDEs) in human serum was developed. The extracts of HBCDs/TBBPA and PBDEs were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS), respectively. The samples with the spiked internal standards, 13C(12)-HBCD, 13C(12)-TBBPA, 3, 3', 4, 4'-tetrabromodiphenyl ether (BDE-77) and 13C(12)-decabromodiphenyl ether (BDE-209), were extracted using the mixture of methyl tert-butyl ether (MTBE) and hexane (1:1, v/v). Then the co-extracted lipid was removed by sulfuric acid treatment. The newly obtained extract was purified using SPE with an LC-Si column and two fractions of HBCDs/TBBPA and PBDEs were finally got. The determination of HBCDs/TBBPA was performed on a 50 mm BEH C18 column in the multi-reaction monitoring (MRM) mode and the determination of PBDEs was on a 15 m capillary column in the selected ion-monitoring (SIM) mode. The limits of detection (LODs, S/N = 3) ranged from 1.81 to 42.16 pg/g. The average recoveries were from 80.3% to 108.8% at two spiked levels of 0.5 and 5 ng/g for HBCDs, 0.05 and 0.5 ng/g for TBBPA and BDE-209 with the relative standard deviations between 1.02% and 11.42% (n = 5). The developed method has been successfully applied to the determination of the 12 analytes in 42 pooled human serum samples. The levels of TBBPA in the samples ranged from < LOD to 6.58 ng/g, that of alpha-HBCD diastereoisomer ranged from < LOD to 7.22 ng/g, which was the most abundant isomer comparing with beta- and gamma-HBCD. The total PBDEs found ranged from 2.90 to 89.69 ng/g. This method was validated to be accurate and sensitive for the analysis of HBCDs, TBBPA and PBDEs in serum samples.

Methyl bromide (MeBr) is a toxic gas used to fumigate agricultural fields and some produce. The U.S. Department of Agriculture (USDA) requires MeBr fumigation of grapes imported from Chile to prevent invasion by the Chilean false red mite, Brevipalpus chilensis. In 2010, two workers were exposed intermittently to MeBr over several months as part of their job inspecting produce at a cold-storage facility in Carson, California. Both workers had disabling neurologic symptoms (e.g., ataxia, memory difficulties, and dizziness) and elevated serum bromide concentrations. An environmental investigation revealed the potential for MeBr to accumulate in enclosed areas during the transportation and storage of fumigated grapes. Some MeBr air concentrations measured at a single point in time exceeded current 8-hour exposure limits, suggesting that exposure in confined areas could result in poisoning. Possible measures for facilities managers to consider to reduce postfumigation MeBr exposures include 1) increased aeration time, 2) reduction of packaging that might absorb MeBr or limit aeration, and 3) changes in the stacking of pallets to improve air flow. Facilities should monitor air MeBr levels if they store MeBr-fumigated commodities in enclosed spaces entered by workers. Clinicians should consider occupational and environmental exposures in their differential diagnosis, and workers who might become exposed to fumigants should be informed of the health hazards related to these pesticides.

Human serum samples (n=61) were collected in Attika, Greece between June and October 2007 and analyzed for polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). Thirty samples were collected from computer clerks of a large computer company in Athens working full-time with computers, and thirty-one from a control population in the Attika region with no computer use. Σ(5)PBDE concentrations (sum of tri- to hexa-BDEs) in all samples (n=61) ranged from 0.68 to 13.3 ng g(-1) lipid, with a median of 1.07 ng g(-1) lipid. These concentrations are on the lower end of those reported from other countries, probably reflecting lower usage of PBDE-containing products or lower exposures to these chemicals. Individual and Σ(5)PBDE concentrations did not statistically differ between the two groups of computer clerks and non-computer users (p>0.05), with the exception of BDE 153 (p=0.033). The predominant congener was BDE 153, followed by BDEs 47, 100, 99, 183, 154 and 28. HBCD was also detected in 70% of the samples. BDE 209 was detected in 8 out 61 samples (13%), with concentrations ranging from 1.18 to 19.1 ng g(-1) lipid, and a median of 2.94 ng g(-1) lipid. No age dependency was found for PBDEs. Σ(11)PCB (sum of PCBs 74, 99, 118, 138, 146, 153, 156, 170, 180, 183 and 187,) in all samples (n=61) ranged from 36 to 402 ng g(-1) lipid, with a median of 110 ng g(-1) lipid. pp'-DDE concentrations ranged from 53.8 to 1649 ng g(-1) lipid, with a median of 268 ng g(-1) lipid. This is the first study to report levels of PBDEs in a possibly occupationally exposed subset of the Greek population., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

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 1.6-6.5 ng/g lipid weight, lw) and milk (range 2.0-6.4 ng/g lw) agreed with European data. Hexabromocyclododecane ranged between <2.1-5.7 ng/g lw in milk. Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) dominated in blood and ranged between 1 and 171 ng/mL and <0.9-9.5 ng/mL, respectively. Total PFC levels in milk ranged between <0.5-29 ng/mL. A significant increase in PBDE concentrations was detected from newborns (median 2.1) to the adolescents and adults (medians 3.8 and 4.6 ng/g lw, respectively). An identical trend was observed for PFOS, but not for PFOA. We estimated that newborn exposure to BFRs and PFCs occurs predominantly post-natally, whereas placental transfer has a minor impact on the body burden., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The influence of the implicit solvent model on transition state structures of two S N2 reactions of biochemical importance is presented. In the considered methyl transfer reaction, we show experimentally that the rate constant in blood serum is about 60% slower than in the aqueous solution and that the implicit solvent model with slightly modified parameters for water captures correctly the energetics of this reaction. With the example of the reaction between 4-methyl-1,2,4-triazol-3-thione and ethyl bromoacetate, we show that relative stabilities of the conformationally different transition states depend upon the solvent inclusion strategy.

Background: Brominated flame retardants, especially polybrominated diphenyl ethers (PBDEs), have been widely used in North America, but little is known about the level of exposure of human populations to these compounds., Objectives: We set out to assess the internal exposure of postmenopausal Canadian women to selected organobromine compounds and to investigate factors associated with this exposure., Methods: We measured concentrations of four PBDEs, one polybrominated biphenyl, and for comparative purposes, 41 polychlorinated biphenyl (PCB) congeners in plasma samples from 110 healthy postmenopausal women who were recruited at a mammography clinic in 2003-2004., Results: PBDE-47 was the major PBDE congener, with a mean (geometric) concentration of 8.1 ng/g lipids and extreme values reaching 1,780 ng/g. By comparison, the mean concentration of the major PCB congener (PCB-153) was 41.7 ng/g and the highest value was 177 ng/g. PBDEs 47, 99, and 100 were strongly intercorrelated, but weaker correlations were noted with PBDE-153. As the sum of PBDEs (summation operatorPBDEs) increased, the relative contribution of PBDE-47 to the summation operatorPBDEs increased, whereas that of PBDE-153 decreased. PBDE-153 was the only brominated compound correlated to PCB-153. PBDE levels were not linked to any sociodemographic, anthropometric, reproductive, or lifestyle variables documented in the present study. Age and body mass index gain since the age of 18 years were significant predictors of PCB-153 plasma levels., Conclusion: Our results suggest that exposure to PBDE-47 likely occurs through direct contact with the penta-PBDE formulation, whereas exposure to PBDE-153 may originate in part from the food chain.

In experimental models, polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants, have caused effects in a number of biological end-points, including neurobehavioural effects, disturbances in thyroid and steroid hormone homeostasis, and other steroid-related effects. Almost exclusively, only external dose metrics (dose per body weight basis) have been studied in connection to the observed effects. In this study we report on new analyses of plasma PBDE levels in surplus samples from earlier studies on thyroid hormones (TH) in exposed rodents. Female, 7-week old Sprague-Dawley rats were given either Bromkal 70-5 DE (Study I; 18 or 36 mg/kg bw/day) or BDE-47 (Study II; 1, 6 or 18 mg/kg bw/day) daily by gavage for two weeks. At an external dose of 18 mg/kg bw/day significant TH effects (decreased plasma free thyroxin levels) were observed in both studies, corresponding to an internal (plasma) dose of 463 microg sumPBDE/g lipid (Study I) or 421 microg BDE-47/g lipid (Study II). If we compare the contribution of different BDE congeners to the total BDE level in rat plasma after Bromkal exposure (Study II), and in the Bromkal mixture itself, the most important congener in the Bromkal mixture were also found in plasma. However, the relative concentration of BDE-99 was lower, and that of BDE-153 was higher, than that of the mixture, indicating selectivity in uptake, metabolism and/or excretion of the individual BDE congeners. Explicitly, the possible in vivo conversion of BDE-99 to BDE-47, and of BDE-154 to BDE-153 could not be excluded. The internal dose in the present rat study could be compared to reported human serum doses of PBDE. Human serum/blood levels have a wide range, from 3 to 6 ng sumPBDE/g lipid in background samples from Europe, about 10 times higher in US sample, and up to 100 times higher (300-600 ng/g lipid) in upper-end levels in collected samples from USA. As a consequence, the margin between effects levels in the rat and exposure levels in man varies widely, with a quotient roughly from 1000 to 100,000. Generally, it could be expected that this margin is lower than if external dose metrics would be used. An even lower margin could be expected as recent studies have shown effects in offspring at lower doses than those giving effects in our studies. Lastly, it should be noted that humans are already exposed to a mixture of chemicals in daily life, a fact that complicates this kind of comparison.

Levels of tri- to decabrominated diphenyl ethers (BDEs), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and 1,2-bis(pentabromophenyl)ethane (DeBDethane) were determined in air, sedimentary dust and human plasma from five households in Sweden. The levels of the individual BDEs in the plasma samples were in the same order of magnitude as in other studies of the general population in Scandinavia, and varied between non-detectable (<0.41 ng g(-1) l.w.) to 17 ng g(-1) (l.w.). BDE#28 and #47 were present in all air samples, with mean values of 0.015 and 0.12 ng m(-3), respectively, except for one sample where the BDE#47 concentration was below the limit of detection (<0.17 ng m(-3)). BDE#209 was found in one of the five air samples at a concentration of 0.26 ng m(-3). DeBDethane was also detected in one sample, in which the BDE#209 level was below LOD (<0.021 ng m(-3)), at a level of 0.023 ng m(-3). All the target compounds were found in the sedimentary dust samples at levels from 0.51 to 1600 ng g(-1), the highest concentration representing BDE#209. The most abundant components in plasma, air and dust were BDE#47, #99 and #209. In the plasma samples BDE#207 and #206 were also present at similar concentrations as BDE#47. In the sedimentary dust samples, DeBDethane was also among the most abundant BFRs. A positive relationship was found for the sumBDE concentrations in dust and plasma, although the relationship was strongly dependent on one of the five observations. BFR levels in dust and air were not dependent on the house characteristics such as living area, floor material or number of electronic devices.

The isotope dilution technique was applied for the analysis of new polybrominated diphenylethers (PBDEs) calibration standard (both labeled and non-labeled) using high-resolution gas chromatography-high-resolution mass spectrometry (HRGC-HRMS). The relative response factor (RRF) and relative standard deviation (RSD) for new calibration standard in Finnigan Thermo Electron (MAT-95XL) and Micromass (Autospec Ultima) were more or less identical with mean RRF (0.9882), RSD (0.0865) and CV% of (8.75). The results also revealed for DeBDE-209 quantification; labeled DeBDE-209 is essential. Furthermore, we recommend on column injection technique with a thin film instead of splitless injection in order to reduce the thermal degradation of DeBDE-209 and formation of octabromodibenzofurans (OBDF). Besides, analysis of human blood (n = 156) of FEBRA-intake and non-FEBRA-intake individuals elucidated frequent detection of eighteen PBDE congeners. The average PBDE concentrations in non-FEBRA intake and FEBRA-intake humans were 6000-11,000 (mean: 8400) and 5400-15,000 (mean: 9900) respectively on pg/g fat basis. Although FEBRA-intake individuals showed slightly greater PBDEs, computer-normalized concentrations of TeBDE-47 corroborate FEBRA-intake individual from four family showed reduced concentrations. The contamination profiles of PBDEs varied in between family, gender as well as geography. International comparison with predominant PBDE congener (TeBDE-47) prevailed lower levels in Japan when compared to Korea, Germany and USA nevertheless, congener specific profiles were different which is in accordance with different technical PBDE usage in between countries.

Polybrominated diphenyl ethers (PBDEs) are used as additives in polymers and textiles to prohibit the development of fires. Because of the production and use of PBDEs, their lipophilic characteristics, and persistence, these compounds have become ubiquitous environmental contaminants. The aim of the present study was to determine potential exposures of PBDEs to clerks working full-time at computer screens and personnel at an electronics-dismantling plant, with hospital cleaners as a control group. Five PBDE congeners--2,2',4,4'-tetraBDE; 2,2',4,4',5,5'-hexaBDE; 2,2',4,4',5, 6'-hexaBDE; 2,2',3,4,4',5',6-heptaBDE; and decaBDE--were quantified in blood serum from all three categories of workers. Subjects working at the dismantling plant showed significantly higher levels of all PBDE congeners in their serum as compared to the control group. Decabromodiphenyl ether is present in concentrations of 5 pmol/g lipid weight (lw) in the personnel dismantling electronics; these concentrations are comparable to the concentrations of 2,2',4, 4'-tetraBDE. The latter compound was the dominating PBDE congener in the clerks and cleaners. The major compound in personnel at the dismantling plant was 2,2',3,4,4',5',6-heptaBDE. Concentrations of this PBDE congener are almost twice as high as for 2,2',4, 4'-tetraBDE in these workers and seventy times the level of this heptaBDE in cleaners. The total median PBDE concentrations in the serum from workers at the electronics-dismantling plant, clerks, and cleaners were 37, 7.3, and 5.4 pmol/g lw, respectively. The results show that decabromodiphenyl ether is bioavailable and that occupational exposure to PBDEs occurs at the electronics-dismantling plant.

Objectives: To determine the activity of glutathione transferase and to measure the S-methylcysteine adducts in blood proteins, after acute inhalation exposure to methyl bromide. To examine the influence of the polymorphism of glutathione-S-transferase theta (GSTT1) on the neurotoxicity of methyl bromide., Methods: Two workers acutely exposed to methyl bromide with inadequate respiratory protective devices were poisoned. Seven weeks after the accident, blood samples were drawn from both patients, for measurement of glutathione transferase activity in erythrocytes (conjugator status--that is, GSTT1 phenotype) and measurement of binding products of methyl bromide with blood proteins. Conjugator status was determined by a standard procedure. The binding product of methyl bromide, S-methylcysteine, was measured in globin and albumin., Results: Duration and intensity of exposure were identical for both patients as they worked together with the same protective devices and with similar physical effort. However, one patient had very severe poisoning, whereas the other only developed mild neurotoxic symptoms. The first patient was a "conjugator" with normal glutathone transferase activity, whereas this activity was undetectable in the erythrocytes of the second patient, who consequently had higher concentrations of S-methylcysteine adduct in albumin (149 v 91 nmol/g protein) and in globin (77 v 30 nmol/g protein)., Conclusions: Methyl bromide is genotoxic and neurotoxic. Its genotoxicity seems to be the consequence of the alkylating activity of the parent compound, and conjugation to glutathione has a protective effect. The data presented here suggest a different mechanism for methyl bromide neurotoxicity which could be related to the transformation of methylglutathione into toxic metabolites such as methanethiol and formaldehyde. If such metabolites are the ultimate toxic species, N-acetylcysteine treatment could have a toxifying rather than a detoxifying effect.