Abstract  Female rats were given aqueous solutions of n-butanol containing 0.24, 0.8 and 4% n-butanol (0.3; 1.0 and 5.0 g/kg/day) for 8 weeks before and during gestation. The control animals received tap water. The experiment was performed in two stages. The first comprised of the assessment of the oestrous cycle before exposure and then during 4-5 and 7-8 weeks of exposure, and the second stage of the fertility of female rats and their foetal development. The duration of the cycle and its individual stages in the control and the exposed females were similar. It was found that n-butanol alcohol is a foetotoxic agent and produces developmental anomalies in a foetus's skeleton and central nervous system.

Abstract  Epidemiological studies and case reports show that even a relatively minor degree of maternal hypothyroxinemia during the first half of gestation is potentially dangerous for optimal fetal neurodevelopment. Our experimental approach was designed to result in a mild and transient period of maternal hypothyroxinemia at the beginning of corticogenesis. Normal rat dams received the goitrogen 2-mercapto-1-methyl-imidazole for only 3 d, from embryonic d 12 (E12) to E15. Maternal thyroid hormones decreased transiently to 70% of normal serum values, without clinical signs of hypothyroidism. Dams were injected daily with 5-bromo-2'-deoxyuridine (BrdU) during 3 d, from E14-E16 or E17-E19. Their pups were tested for audiogenic seizure susceptibility 39 d after birth (P39) and killed at P40. Cells that had incorporated BrdU were identified by immunocytochemistry, and quantified: numerous heterotopic cells were found, whether labeled at E14-E16 or E17-E19, that were identified as neurons. The cytoarchitecture and the radial distribution of BrdU-labeled neurons was significantly affected in the somatosensory cortex and hippocampus of 83% of the pups. The radial distribution of gamma-aminobutyric acidergic neurons was, however, normal. The infusion of dams with T4 between E13 and E15 avoided these alterations, which were not prevented when the T4 infusion was delayed to E15-E18. In total, 52% of the pups born to the goitrogen-treated dams responded to an acoustic stimulus with wild runs, followed in some by seizures. When extrapolated to man, these results stress the need for prevention of hypothyroxinemia before midpregnancy, however moderate, and whichever the underlying cause.

Abstract  This study investigated in vitro endocrine disrupting effects of three mixtures of POPs: 'Marine mix' extracted from Atlantic cod liver, and two mixtures extracted from burbot liver, 'Mjosa mix' and 'Losna mix'. The POP mixtures were chemically characterized. Co-culture of theca and granulosa cells, were exposed for 48h with different doses of 'Marine mix', 'Mjosa mix' or 'Losna mix'. As an end point cell viability was determinated by LDH test, steroid analysis by EIA and caspase-3 by colorimetric substrate. Chemical characterization of the mixtures demonstrated that the 'Marine mix' contained high levels of DDTs and PCBs. In the 'Mjosa mix', the dominant pollutants were BDEs and HBCD. The concentrations of POPs measured in the 'Losna mix' were considerably lower. All mixtures used in the present study had a stimulatory effect on testosterone and estradiol secretion with 'Marine mix'>'Mjosa mix'>'Losna mix'. These results show that even a mixture containing background concentrations of POPs significantly affected steroid secretion. A higher steroidogenic response in low dose ranges, compared with high dose ranges indicated xenobiotic-conditioning hormesis. This could complicate predictions of effects in risk assessments.

Abstract  OBJECTIVES: The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. METHODS: In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. RESULTS: Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p´­dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. CONCLUSION: Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.

Abstract  alpha-, beta-, and gamma-hexabromocyclododecane diastereomers (HBCDs) were measured in house dust from Birmingham, U.K. (n=31, median concentration=730 ng sigmaHBCDs g(-1)); Amarillo/Austin, TX (n=13, 390 ng g(-1)); and Toronto, Canada (n=8, 640 ng g(-1)). Concentrations in dust (n=6, 650 ng g(-1)) from U.K. offices were within the range for UK homes. Concentrations from each country were statistically indistinguishable. In one UK house dust sample, 110,000 ng g(-1) was recorded-the highest recorded in indoor dust to date. While upper bound average U.K. dietary exposures for adults and toddlers, respectively, are 413 and 240 ng sigmaHBCDs day(-1), U.K. adults and toddlers daily ingesting, respectively, 50 and 200 mg of dust contaminated at the 95th percentile concentration are exposed, respectively, to 1100 and 4400 ng sigmaHBCDs day(-1). Normalized to body weight, this high-end exposure scenario estimate for toddlers is within the range reported elsewhere for occupationally exposed adults. While in commercial formulations gamma-HBCD predominates (>80%), alpha-HBCD in dust constitutes 14-67% of sigmaHBCDs (average 32%). Hence the predominance of the alpha-diastereomer in humans may arise partly from dust ingestion, and not solely to in vivo metabolism (when alpha-HBCD is formed from bioisomerization of other diastereomers), or dietary exposure (where alpha-HBCD predominates in most foodstuffs).

Abstract  Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tris(1-chloropropyl) phosphate (TCPP) belong to a group of chemicals collectively known as triester organophosphate flame retardants (OPFRs). OPFRs are used in a wide range of consumer products and have been detected in biota, including free-living avian species; however, data on toxicological and molecular effects of exposure are limited. An in vitro screening approach was used to compare concentration-dependent effects of TDCPP and TCPP on cytotoxicity and messenger RNA (mRNA) expression in cultured hepatocytes and neuronal cells derived from embryonic chickens. TDCPP was toxic to hepatocytes (LC₅₀ = 60.3 ± 45.8μM) and neuronal cells (LC₅₀ = 28.7 ± 19.1μM), whereas TCPP did not affect viability in either cell type up to the highest concentration administered, 300μM. Real-time reverse transcription-PCR revealed alterations in mRNA abundance of genes associated with phase I and II metabolism, the thyroid hormone (TH) pathway, lipid regulation, and growth in hepatocytes. None of the transcripts measured in neuronal cells (D2, D3, RC3, and Oct-1) varied in response to TDCPP or TCPP exposure. Exposure to ≥ 10μM TDCPP and TCPP resulted in significant upregulation of CYP2H1 (4- to 8-fold), CYP3A37 (13- to 127-fold), and UGT1A9 (3.5- to 7-fold) mRNA levels. Transthyretin was significantly downregulated more than twofold by TCPP at 100μM; however, TDCPP did not alter its expression. Liver fatty acid-binding protein, TH-responsive spot 14-α, and insulin-like growth factor-1 were all downregulated (up to 10-fold) in hepatocytes exposed to ≥ 0.01μM TDCPP and TCPP. Taken together, our results indicate that genes associated with xenobiotic metabolism, the TH pathway, lipid regulation, and growth are vulnerable to TDCPP and TCPP administration in cultured avian hepatocytes. The mRNA expression data were similar to those from a previous study with hexabromocyclododecane.

Abstract  The management of electronic wastes (e-wastes) has become a global issue as it may release large quantities of hazardous materials such as heavy metals and brominated flame retardants (BFRs) to the environment. Solvent-based recycling is a newly developed, efficient and environmentally beneficial technology for the removal or recovery of BFRs from e-wastes. However, little is known about the behavior of BFRs in the solvents and to what extent they may be affected by co-existing heavy metals. This study quantified the rates of transformation of hexabromocyclododecane (HBCD), a widely used BFR, in the presence of different solvents (i.e. acetone, methanol or toluene) and metals (i.e. Ni, Cu, Zn, Fe or Al). Our experimental results showed that less than 20% of HBCD was transformed in all pure solvent systems within 24h at 50 degrees C. The presence of Ni greatly increased the transformation of HBCD (45-99%) in these solvent systems, whereas other metals had little or no effect on extraction process. The kinetics study showed that transformation of HBCD in Ni-containing systems followed pseudo-first-order kinetics and that the highest transformation rate constant (1.2+/-0.1h(-1)) of HBCD was recorded in the Ni+acetone system. The formation of HBr and pentabromocyclododecene in the acetone+Ni system suggested that transformation of HBCD proceeded via dehydrobromination. Collectively, these results indicated that acetone should not be applied in the recycling or extraction of HBCD from Ni-rich e-wastes, as debromination of HBCD may occur during these processes, even at mild extraction temperatures.

Abstract  The first screening of polybrominated diphenyl ethers (PBDEs) in sediments and blue mussels (Mytilus edulis) collected in the Danish marine and freshwater environment is presented in this work. 10 marine and 6 freshwater sediments, together with blue mussels from 15 locations were analysed for PBDEs. The sum of 5 PBDE congeners (BDE47, BDE99, BDE100, BDE153, and BDE209) is in the range of 0.06-24.7 and 0.07-10.6 ng g-1 dry weight in marine and freshwater sediments, respectively. In blue mussels the sum of the 4 lower brominated congeners (BDE47, BDE99, BDE100, and BDE153) is in the range of 0.08-0.81 ng g-1 wet weight. The highest contamination with PBDEs are found in sediment and blue mussels close to populated areas. Generally, freshwater sediments contained higher levels of PBDEs compared to marine sediments, except for the high levels found in Copenhagen harbour. Ranking of the concentration of PBDEs in sediment from Denmark gives the following order: BDE209 > BDE99 > BDE47 > BDE100 > BDE153. The congener pattern in the industrial product Bromkal 70-5DE is compared with the pattern found in sediment, blue mussels and fish from the Danish environment. The comparisons show that BDE47 is both bioconcentrated and biomagnified to a higher degree than any of the other congeners, whereas the amount of BDE99 decreases at higher trophic levels.

Abstract  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 6.4ng/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 146ng/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.

Abstract  In a previous study the biodegradation of hexabromocyclododecane (HBCD) was reported to occur under realistic environmental concentrations in soils and freshwater aquatic sediments with biotransformation half-lives ranging from approximately 2 days to 2 months. In this study we extend our knowledge as to the environmental behavior of HBCD with respect to the fate of the three major diastereomers of HBCD (alpha, beta, and gamma) as well as to the identification of major intermediate metabolites formed during degradation. Substantial biological transformation of the alpha-, beta-, and gamma-[14C]HBCD diastereomers was observed in wastewater (i.e., digester) sludge and in freshwater aquatic sediment microcosms prepared under aerobic and anaerobic conditions. Concomitant with the loss of [14C]HBCD in these matrixes there was a concurrent production of three [14C]products. Using a combination of high performance liquid chromatography atmospheric pressure photoionization mass spectrometry and gas chromatography electron impact ionization mass spectrometry these metabolites were identified as tetrabromocyclododecene, dibromocyclododecadiene, and cyclododecatriene. We propose that HBCD is sequentially debrominated via dihaloelimination where at each step there is the loss of two bromines from vicinal carbons with the subsequent formation of a double bond between the adjacent carbon atoms. These results demonstrate that microorganisms naturally occurring in aquatic sediments and anaerobic digester sludge mediate complete debromination of HBCD.

Abstract  The biological transformation of hexabromocyclododecane (HBCD), a brominated fire retardant commonly used in a variety of consumer goods, was investigated in aerobic and anaerobic soils and freshwater sediments. Soil, river water, and aquatic sediments were collected from several locations in the United States and transformation of HBCD was evaluated in the correspondingly composed microcosms based on the Organisation for Economic Co-Operation and Development (OECD) Test Guidelines 307 (Aerobic and Anaerobic Transformation in Soil) or 308 (Aerobic and Anaerobic Transformation in Aquatic Sediment Systems). Soil and sediment reaction mixtures, prepared under either aerobic or anoxic conditions, were dosed with HBCD at a concentration ranging from approximately 10 to 80 ng/g dry weight. The soils and sediments were then placed at 20 degrees C for approximately 4 months and the concentration of HBCD in the microcosms was determined at selected time intervals utilizing high-performance liquid chromatography-mass spectrometry (LC-MS). HBCD loss was observed in both the aerobic and anaerobic soils and sediments although the rates were appreciable faster under anoxic conditions. Biologically mediated transformation processes (i.e., biotransformation) accelerated the rate of loss of HBCD when compared to the biologically inhibited (i.e., autoclaved) soils and sediments. Biotransformation half-lives for HBCD were determined to be 63 and 6.9 days in the aerobic and anaerobic soils, respectively, while biotransformation half-lives for HBCD in the two river systems ranged from 11 to 32 days and 1.1 to 1.5 days under aerobic and anaerobic conditions, respectively. Brominated degradation products were not detected in any of the soils or sediments during the course of the study.

Abstract  Polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDs), tetrabromobisphenol-A (TBBP-A), and polychlorinated biphenyls (PCBs) were measured in floor dust from U.K. child daycare center and primary school classrooms (n = 43, 36 for PCBs). Concentrations of HBCDs exceeded significantly (p < 0.05) those reported previously for U.K. houses and offices, while those of TBBP-A exceeded significantly those in U.K. cars and offices. PCB concentrations were statistically indistinguishable from those in U.K. house dust but lower than in U.S. classroom dust, while BDEs 47, 99, 100, 153, 196, 197, 203, and 209 in classrooms were significantly below concentrations in U.K. cars. Exposure of young U.K. children via classroom dust exceeds that of U.K. adults via office dust for all contaminants monitored. Overall dust exposure of young U.K. children was estimated including car, classroom, and house dust. Exposure to TBBP-A was well below a U.K. health-based limit value (HBLV). Though no HBLVs exist for non-dioxin-like PCBs and HBCDs; dust exposure to PCBs fell well below U.K. dietary and inhalation exposure. Contrastingly, a high-end estimate of HBCD dust exposure exceeded U.K. dietary exposure substantially. Moreover, high-end estimates of dust exposure to BDE-99 and BDE-209 (4.3 and 13000 ng/kg bw/day, respectively) exceeded HBLVs of 0.23-0.30 and 7000 ng/kg bw/day respectively.

Abstract  Biomonitoring survey conducted with glaucous gulls from Svalbard have demonstrated that this top-predator-scavenger species accumulates a wide array of chemicals of environmental concern, including organohalogens, trace elements, organometals, and several non-halogenated and non-metallic-compounds. Among these contaminants are those subjected to global bans or restrictions in North America and Europe (e.g., legacy OC's, penta-, and octa-PBDE technical mixtures and mercury). In addition, some currently produced chemicals were found in gulls that lack and global use regulation (e.g., deca-PBDE , HBCD, and other non-PBDE BFR additives, siloxanes, and selected PFASs). Svalbard glaucous gulls are also exposed to contaminant metabolites that, at time, are more bioactive than their precursors (e.g., oxychlordane, p,p'-DDE, OH- and MeSo2-PCBs, and OH-PBDEs) Concentrations of legacy OCs (PCBs, DDTs, CHLs, CBzs, dieldrin, PCDD/Fs, and mirec) in tissues, blood, and eggs of Svalbard glaucous gulls have displayed the highest contamination levels among glaucous gull populations that inhabit Greenland (Cleemann et al. 2000) Jan Mayen (Gabrielsen et al. 1997), Alaska (Vander Pol et al. 2009), and the Canadian Arctic (Braune et a. 2005). To date, measurements obtaines on more novel organohalogens (e.g., OH- and MeSo2-containing metabolites, BFRs and PFASs) in Svalbard glaucous gull samples generally confirm that the spatial and trophodynamic trends of the legacy OC concentrations, whereas no clear trend emerges from surveys of trace elements and organometals. Using the glaucous gull as biosentinel species provides clear evidence that Svalbard and the European Arctic environment is exposed to a complex mixture of legacy and more recently introduced PBT-like substances.

Abstract  A method for the determination of tetrabromobisphenol A (TBBPA) in human serum utilizing solid-phase extractions (SPEs) and liquid chromatography (LC) with electrospray ionization tandem MS (MS/MS) has been developed. After purification and concentration of TBBPA using consecutive SPEs on reversed-phase and normal-phase cartridges, the serum sample was subjected to LC. TBBPA was separated on a C18 reversed-phase column by gradient elution with a mixture of water, methanol, and acetonitrile as the mobile phase, and then detected with electrospray ionization MS/MS in negative ion mode. 13C12-TBBPA was suitable as an internal standard for the reproducible determination of TBBPA in human serum samples (5 g). The method has been validated in TBBPA concentration range of 5-100 pg per g serum, and the recoveries in the concentration range were higher than 83.3%. The repeatabilities of the proposed method of non-spiked control serum (6.3 pg per g serum) and spiked serum (added 5-100 pg per g serum) were within 10.0% as relative standard deviations. The limit of quantification (LOQ) for TBBPA was 4.1 pg per g serum, which was corresponded to 0.63 fmol on column.

Abstract  Reactions of hexabromocyclododecane (HBCD), a widely used brominated flame retardant, with reduced sulfur species (e.g., polysulfide and bisulfide) were investigated in well-defined solutions under anoxic conditions. It is likely that reactions of HBCD with reduced sulfur species such as polysulfides and bisulfide present in anoxic subregions of coastal water bodies and sediments could have a significant impact on the fate of HBCD. The second-order reaction rate constant of HBCD with polysulfides in 80% methanol/20% water at 40°C is 2.2 (±0.3)×10(-2) M(-1) s(-1). The second-order reaction rate constant of HBCD with bisulfide is 8.9 (±2.8)×10(-4) M(-1) s(-1) under the same conditions. The formation of two products was observed with either of the two reduced sulfur species. The experiments also indicate that the γ-isomer of HBCD is reacting significantly faster with reduced sulfur species than the α-isomer.

Abstract  A new 16-day echinoid early life stage (ELS) bioassay was developed to allow for prolonged observation of possible adverse effects during embryogenesis and larval development of the sea urchin Psammechinus miliaris. Subsequently, the newly developed bioassay was applied to study the effects of key marine persistent organic pollutants (POPs). Mortality, morphological abnormalities and larval development stages were quantified at specific time points during the 16-day experimental period. In contrast to amphibians and fish, P. miliaris early life development was not sensitive to dioxin-like toxicity in the prolonged early life stage test. Triclosan (TCS) levels higher than 500 nM were acutely toxic during embryo development. Morphological abnormalities were induced at concentrations higher than 50 nM hexabromocyclododecane (HBCD) and 1000 nM tetrabromobisphenol A (TBBPA). Larval development was delayed above 25 nM HBCD and 500 nM TBBPA. Heptadecafluorooctane sulfonic acid (PFOS) exposure slightly accelerated larval development at 9 days post-fertilization (dpf). However, the accelerated development was no longer observed at the end of the test period (16 dpf). The newly developed 16-day echinoid ELS bioassay proved to be sensitive to toxic effects of POPs that can be monitored for individual echinoid larvae. The most sensitive and dose related endpoint was the number of developmental penalty points. By manipulation of the housing conditions, the reproductive season could be extended from 3 to 9 months per year and the ELS experiments could be performed in artificial sea water as well.

Abstract  An efficient microwave-assisted extraction (MAE) procedure coupled with high performance liquid chromatography-electrospray-ion-trap mass spectrometry (HPLC-ESI-ITMS) has been evaluated to determine hexabromocyclododecane diastereoisomers (alpha-, beta- and gamma-HBCD) in marine sediments. The composition of the LC mobile phase (consisting of water, methanol and acetonitrile) and the parameters of electrospray ionization (ESI) were evaluated to obtain chromatographic baseline separation and high sensitivity for the detection of these diastereoisomers. The effects of various operating parameters on the quantitative extraction of the HBCDs through MAE were systematically investigated. The three diastereoisomers were then quantitated by HPLC-ITMS employing ESI operated in the negative ionization mode. The HBCDs were extracted from the sediments through MAE using 40mL of acetone/n-hexane (1/3, v/v) at 90 degrees C for 12min. The limits of quantitation (LOQ) ranged from 25 to 40pg/g (dry weight) in 5g of the sediment samples. The recoveries of the HBCDs in spiked sediment samples ranged from 68 to 91% (relative standard derivation: 2-11%). The extraction efficiency of the MAE technique was also compared with Soxhlet extraction and pressurized liquid extraction.

Abstract  BFR burdens in abiotic media have been less studied than in biota, despite their essential value as an aide to identifying sources, temporal and geographic trends and exposure routes. Many polymer products consist of several percent by weight of BFRs. Global trade in these can result in rapid and wholesale BFR movement. Loss from in-use products of nonreactive BFRs may be important, particularly in respect to indoor exposure. In the case of BDE-209, discharges from publicly owned treatment works may be substantial. BFR burdens in air, water and sewage sludge respond rapidly to changes in environmental BFR inputs. PBDEs have been the most widely studied. In many locales PBDE burdens in these media now surpass those of PCBs. Air and water near sources and urban areas are typically enriched relative to rural locales. The more volatile PBDEs dominate in the vapor phase, while BDE-209 typically predominates on particulates. Evidence exists for long-range transport of the more volatile PBDEs. A greater diversity of BFRs (mostly PBDEs, HBCD and TBBP-A) has been detected in sewage sludges. Land application of these sludges on agricultural fields is one conduit for soil contamination. In general, environmental concentrations of BDE-209 appear to be increasing, while penta-BDE burdens in Europe may have peaked. Sediments function as longer-term integrators of environmental burdens. Concentrations of common BFRs therein may be substantial near point sources. Evidence for debromination in the environment has been limited to date. However, some laboratory and field observations suggest it is possible to a limited extent.

Abstract  In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure-activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecularproperties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200-320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure-activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.

Abstract  An input-output balance study was performed for polybrominated diphenyl ethers, polychlorinated biphenyls and some organochlorine pesticides on three captive, juvenile grey seals (Halichoerus grypus). The animals were fed a diet of herring for six months, during the last three months of which this study was performed. A supplement of decabromodiphenyl ether was included in the diet during the second month of the study. Consistently high absorption (>89%) was observed for all of the chemicals studied, whereas work on other animals has generally shown high (>80%) net absorption at log K(OW) < approximately 6, dropping towards higher log K(OW), and very low absorption of decabromodiphenyl ether. The half-life of decabromodiphenyl ether in blood was estimated to be between 8.5 and 13 days. Measurable concentrations of decabromodiphenyl ether were detected in seal blubber at the end of the study, indicating that this chemical can be stored in adipose and may bioaccumulate. Current understanding of the mechanism of absorption of organohalogen chemicals and the potential for accumulation of decabromodiphenyl ether will need reassessing in the light of these results.

Abstract  Since 2000, a surprisingly high number of macroscopical gonad alterations has been reported in whitefish (Coregonus spp.) from Lake Thun, Switzerland. This unique phenomenon is still unexplained and has received much public attention. As one possible trigger for these effects, the presence of persistent, bioaccumulative and toxic compounds acting as endocrine disruptors in the lake has been discussed. In this study, concentrations of selected persistent organic pollutants were examined in two morphs of whitefish from Lake Thun and their link to the observed abnormalities was investigated. Analyzed compound classes included polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated naphthalenes, polybrominated diphenyl ethers and hexabromocyclododecanes. The target substances were identified in all samples and concentrations of the analyzed compounds were highly correlated among each other. These correlations show that the analyzed substances have the same distribution pattern throughout the lake and that uptake, accumulation and elimination processes are similar. Significant differences in contaminant levels within the samples existed between the two analyzed morphs of whitefish, most likely due to different age, food patterns and growth rate. No difference in contaminant levels was observed between fish with abnormal gonads and fish with normal gonads, suggesting no causal link between the investigated lipophilic organohalogen compounds present in fish and the observed gonad abnormalities in whitefish from Lake Thun. A comparison to existing data shows that concentrations in Lake Thun whitefish are at the lower bound of contaminant levels in whitefish from Swiss lakes or from European waters.

Abstract  This paper critically examines indoor exposure to semivolatile organic compounds (SVOCs) via dermal pathways. First, it demonstrates that--in central tendency--an SVOC's abundance on indoor surfaces and in handwipes can be predicted reasonably well from gas-phase concentrations, assuming that thermodynamic equilibrium prevails. Then, equations are developed, based upon idealized mass-transport considerations, to estimate transdermal penetration of an SVOC either from its concentration in skin-surface lipids or its concentration in air. Kinetic constraints limit air-to-skin transport in the case of SVOCs that strongly sorb to skin-surface lipids. Air-to-skin transdermal uptake is estimated to be comparable to or larger than inhalation intake for many SVOCs of current or potential interest indoors, including butylated hydroxytoluene, chlordane, chlorpyrifos, diethyl phthalate, Galaxolide, geranyl acetone, nicotine (in free-base form), PCB28, PCB52, Phantolide, Texanol and Tonalide. Although air-to-skin transdermal uptake is anticipated to be slow for bisphenol A, we find that transdermal permeation may nevertheless be substantial following its transfer to skin via contact with contaminated surfaces. The paper concludes with explorations of the influence of particles and dust on dermal exposure, the role of clothing and bedding as transport vectors, and the potential significance of hair follicles as transport shunts through the epidermis. PRACTICAL IMPLICATIONS: Human exposure to indoor pollutants can occur through dietary and nondietary ingestion, inhalation, and dermal absorption. Many factors influence the relative importance of these pathways, including physical and chemical properties of the pollutants. This paper argues that exposure to indoor semivolatile organic compounds (SVOCs) through the dermal pathway has often been underestimated. Transdermal permeation of SVOCs can be substantially greater than is commonly assumed. Transport of SVOCs from the air to and through the skin is typically not taken into account in exposure assessments. Yet, for certain SVOCs, intake through skin is estimated to be substantially larger than intake through inhalation. Exposure scientists, risk assessors, and public health officials should be mindful of the dermal pathway when estimating exposures to indoor SVOCs. Also, they should recognize that health consequences vary with exposure pathway. For example, an SVOC that enters the blood through the skin does not encounter the same detoxifying enzymes that an ingested SVOC would experience in the stomach, intestines, and liver before it enters the blood.

Abstract  The critical role of thyroid hormone (TH) in brain development is well-established. Evidence shows that severe deficiencies lead to significant neurological dysfunction. Much less information is available on more modest perturbations of TH on brain function. The present study induced varying degrees of developmental hypothyroidism by administration of low doses of the TH synthesis inhibitor, propylthiouracil (PTU 0, 1, 2, and 3 ppm) to the drinking water of pregnant rats. This regimen produced dose-dependent reductions in circulating levels of T4 in dams and offspring on postnatal days (PN) 15 and 22, with return to control levels in adulthood upon termination of treatment at weaning. Modest reductions in T3 were observed in the high-dose group on PN15. Synaptic function in the dentate gyrus was examined in adult euthyroid offspring using in vivo field potentials. Excitatory synaptic transmission (excitatory postsynaptic potential [EPSP] slope amplitude) was significantly reduced at 2 and 3 ppm PTU, with no statistically reliable effect detected in the population spike. Paired-pulse functions estimating the integrity of inhibitory synaptic processing were modestly reduced by 3 ppm PTU. Long-term potentiation (LTP) of the EPSP slope was impaired at all dose levels. Trace fear conditioning to context and to cue was impaired at the highest dose level when a distractor stimulus was present, whereas conditioning in a standard trace fear paradigm paradoxically revealed "enhanced" performance at the intermediate dose and a return to control values in the high-dose group. Biphasic dose-response profiles were evident in some measures (trace fear conditioning and LTP) but not others and serve to exemplify the complexity of the role of TH in brain development and its consequences for brain function.