Do polybrominated diphenyl ethers (PBDE) increase the risk of thyroid cancer?

An increased incidence of thyroid cancer has been reported in many parts of the world including the United States during the past several decades. Recently emerging evidence has demonstrated that polyhalogenated aromatic hydrocarbons (PHAH), particularly polybrominated diphenyl ethers (PBDE), alter thyroid hormone homeostasis and cause thyroid dysfunction. However, few studies have been conducted to test whether exposure to PBDE and other PHAH increases the risk of thyroid cancer. Here, we hypothesize that elevated exposure to PHAH, particularly PBDE, increases the risk of thyroid cancer and may explain part of the increase in incidence of thyroid cancer during the past several decades. In addition, genetic and epigenetic variations in metabolic pathway genes may alter the expression and function of metabolic enzymes which are involved in the metabolism of endogenous thyroid hormones and the detoxification of PBDE and other PHAH. Such variation may result in different individual susceptibilities to PBDE and other PHAH and the subsequent development of thyroid cancer. The investigation of this hypothesis will lead to an improved understanding of the role of PBDE and other PHAH in thyroid tumorigenesis and may provide a real means to prevent this deadly disease.     

多溴二苯醚(PBDEs)对环境的污染及其生态化学行为

作为一种良好的防火溴代阻燃剂(brominnted flamt retardants, BFRS),多溴二苯醚(polybrominated diphenyl ethers, PBDEs)主要应用于各种家用和工业产品中,包括各种电子产品和家庭装饰产品.近年来,环境中PBDEs的浓度在不断上升.PBDEs具有很高的亲脂性和持久性,使得其在环境中易于富集和生物放大;同时,PBDEs又具有一定的挥发性,能够长途迁移至偏远地区;PBDEs具有一定的生物致毒作用和内分泌干扰作用.本文从生态化学行为和生态毒性两个方面综合论述了PBDEs在环境中的分布及存在水平、一般毒性效应和内分泌干扰行为,分析了当前研究中存在的问题,展望了PBDEs污染的研究方向.     

Development of enzyme-linked immunosorbent assay for determination of polybrominated diphenyl ether BDE-121

Our interests are in the development of immunoassay-based fast scanning methods for persistent organic pollutants. To develop the immunoassay method of polybrominated diphenyl ether (PBDE), a model compound of PBDE, 2,3′,4,5′,6-pentabromodiphenylether (BDE-121), has been chosen to develop its antibody and the competitive indirect enzyme-linked immunosorbent assay (ELISA) is developed. The hapten of BDE-121 containing reactive carboxylic acid was synthesized and conjugated to carrier proteins (bovine serum albumin [BSA] and ovalbumin [OVA]). Anti-BDE-121 polyclonal antibody was then developed in rabbits as a result of immunization with the BDE-121–BSA conjugate. The optimal amount of coating antigen BDE-121–OVA conjugate and the dilution of antiserum needed in the ELISA were determined with the checkerboard method, and the effects of the properties of PBST (phosphate-buffered saline and Tween 20) buffer (pH and salt concentration) and chemical solvent (types and concentrations) on the ELISA were investigated to achieve a rapid robust assay with high sensitivity. Under the optimized conditions, the developed indirect ELISA shows a linear detection range from 1.74 to 84.1 ng/ml, with an IC₅₀ value of 8.07 ng/ml and a detection limit of 0.644 ng/ml. In total, 11 kinds of compounds were tested for calculating the cross-reactivity, which was less than 8% for nearly all of them. Real samples were analyzed by the proposed immunoassay and gas chromatography/mass spectrometry (GC/MS).     

多溴联苯醚的微生物降解机制研究进展

多溴联苯醚(PBDEs)是世界范围内广泛使用的一类溴代阻燃剂,在环境中被频繁检出。因其具有生物积累性、生物毒性和持久性等特点,如今PBDEs已成为全球分布的有机化学毒素。探究PBDEs的降解极为重要,文中从PBDEs微生物降解的角度出发,分别阐释了好氧条件和厌氧条件下细菌降解PBDEs的代谢途径研究进展,并结合原位降解研究推断古菌的降解潜能,比较分析了多种降解途径的特性和综合因素,同时对PBDEs降解微生物未来的研究趋势和PBDEs降解体系设计应用进行了展望。     

A novel chlorinated diphenyl ether from Byrsonima microphylla (Malpighiaceae)

The isolation is described of an unusual chlorinated diphenyl ether named methyl 3,5-dichloro-6-(6-hydroxy-4-methoxy-3-methoxycarbonyl-2-methylphenoxy)-2-hydroxy-4-methylbenzoate that was obtained from the trunk of Byrsonima microphylla (Malpighiaceae). The structure was elucidated by a spectroscopic data analysis, and the presence of this compound in heartwood was confirmed by HPLC and HPTLC analyses.     

Biomonitoring of mercury pollution: A case study from the Dniester River

Biomonitoring of mercury pollution of Dubasari reservoir of the Dniester River has been carried out using macrophytes, epiphytosuspensions and lichens. Macrophytes uptake mercury from water column and bottom sediments in the succession Potamogeton pectinatus L. > Myriophyllum verticillatum L. > Potamogeton perfoliatus L. > Butomus umbellatus L. These species possess the properties of bio-indicators. The mercury content in their biomass is in good positive correlation (r = 0.908–0.990) with the mercury content both in water and bottom sediments. It has been shown that the maximum mercury content in these bio-indicators is found in the area of the Rezina–Rybnitsa industrial complex that consists of two cement plants and a metallurgical one. The use of lichens as bio-indicators for the ecological state of the air in the vicinity of the investigated aquatic ecosystem and of the epiphytosuspensions precipitated on submerged macrophytes, denote the active state of the source for mercury pollution of the Dubasari reservoir.     

Effects of electron donors on anaerobic microbial debromination of polybrominated diphenyl ethers (PBDEs)

Polybrominated diphenyl ethers (PBDEs) are a class of widely used flame retardants that have been highly accumulated in sediments. It is reported that microorganisms play an important role in the reductive debromination of PBDEs in anaerobic sediments. However, little is known about the effects of electron donors on the microbial community structure and their debromination capacity in PBDE transformation. In this study, alternate carbon substrates were used as electron donors to enrich the PBDE-debrominating microbial consortia to evaluate the effects of electron donors on PBDE microbial debromination. Decabromodiphenyl ether (BDE-209) was found to be the dominant (more than 50%) PBDEs congener in all consortia, and the percentage of BDE-209 was deceased by 12% (methanol), 11% (ethanol), 8% (acetate), 9% (lactate), 5% (pyruvate), and 11% (no electron donors), while the relative abundances of most lesser-brominated PBDEs increased after 90-day incubation compared to the initial profile of PBDEs. Substantial shifts in the microbial community structure among different amendments were observed based on denaturing gradient gel electrophoresis results. Pseudomonas spp. were identified to be the predominant organisms and the abundances of Band R, which was associated with Pseudomonas sp. SCSWA09, was well correlated with the biodegradation rate of BDE-209. Finally, the microbial community structure was highly correlated with the concentration of deca-BDE, octa-BDE and total nitrogen. These results provide insights into in situ bioremediation of environments contaminated by PBDEs and our understanding of microbial ecology associated with PBDE-debromination.     

多溴二苯醚的环境暴露与生态毒理研究进展

多溴二苯醚(PBDEs)是一类具有生态风险的新型环境有机污染物.作为阻燃剂,PBDEs已经被愈来愈广泛地添加到工业产品中,并因此对大气、水体、沉积物和土壤等环境介质及相关生态系统产生日益广泛的污染.鉴于这一环境新问题的产生,本文基于有限的资料,初步探讨了PBDEs的人为来源和环境暴露途径,大致给出了PBDEs在不同生物和人体不同组织器官中可能的存在及含量水平;在扼要介绍其基本性质的基础上,从甲状腺、神经系统和生殖发育毒性等三个方面分析了PBDEs对动物和人体可能产生的毒性效应与生态影响,以及PBDEs在生态系统中可能具有的生物积累和生物放大风险;并对今后研究PBDEs的环境暴露与生态效应以及人体健康影响等方面的工作重点进行了展望.     

Pleurozium schreberi as an ecological indicator of polybrominated diphenyl ethers (PBDEs) in a heavily industrialized urban area

Polybrominated diphenyl ethers (PBDEs) are toxic contaminants with a persistent character and adverse effects on humans and wildlife. Therefore, the deposition of these chemicals in vegetation must be carefully controlled. Our objective was to determine PBDE concentrations (BDEs 28, 47, 66, 85, 99, 100, 153, 154, 183 and 209) in Pleurozium schreberi collected in a heavily industrialized urban agglomeration. High PBDE concentrations in the moss confirm the presence of active sources of atmospheric pollution in an area tested. The distribution of these xenobiotics was related to the vegetation cover being lower in sites surrounded by forests which indicates that PBDEs may have a tendency to be trapped from the air by tree leaves and needles. Congener profiles in P. schreberi were dominated by BDE 209 which was for 79% (in case of the coke smelter) to 95% (in case of the chemical plant) part of the total PBDE burden in this moss. The principal component and classification analysis classifying the concentration of PBDEs in P. schreberi allowed us to distinguish the pattern of these compounds characteristic for the origin of pollution. P. schreberi may be used as a bioindicator for PBDEs in areas contaminated with these chemicals.     

Antifouling activity of sponge-derived polybrominated diphenyl ethers and synthetic analogues

The antifouling (AF) activity of 2-hydroxy-4-(3-hydroxy-5-methylphenoxy)- 6-methylbenozoic acid methyl ester (1), 3,5-dibromo-2-(2′,4′-dibromophenoxy)phenol (2); 3,4,5-tribromo-2-(2′,4′-dibromophenoxy)phenol (3), 3,4,5-tribromo-2-(2′-bromophenoxy)phenol (4), 3,5-dibromo-2(2′,4′-dibromophenoxy)phenol (5), 3,4,5,6-tetrabromo-2-(2′-bromophenoxy)phenol (6); 4-phenoxyphenol (7), 4-phenoxyaniline (9), 1-chloro-4-phenoxybenzene (10); 1-bromo-4-phenoxybenzene (13) was investigated against marine bacteria, a diatom, barnacle larvae and mussel juveniles. The naturally occurring compound 2 showed the strongest AF activity in all bioassays but lacked toxicity. It inhibited the growth of all tested bacterial strains (MIC = 0.02 – 1.52 μM) and its 50% effective concentrations (EC₅₀) were 0.24 μM (diatom test), 0.66 μM (mussel test) and 1.26 μM (barnacle test). Among the commercially available derivates, compound 7 was the most active in bacterial and diatom bioassays but its activity was lower than that of compound 2. Overall, the naturally occurring compounds showed stronger activity than the commercially available analogues and could be possible future non-toxic AF candidates.     

Antifouling activity of sponge-derived polybrominated diphenyl ethers and synthetic analogues

The antifouling (AF) activity of 2-hydroxy-4-(3-hydroxy-5-methylphenoxy)- 6-methylbenozoic acid methyl ester (1), 3,5-dibromo-2-(2',4'-dibromophenoxy)phenol (2); 3,4,5-tribromo-2-(2',4'-dibromophenoxy)phenol (3), 3,4,5-tribromo-2-(2'-bromophenoxy)phenol (4), 3,5-dibromo-2(2',4'-dibromophenoxy)phenol (5), 3,4,5,6-tetrabromo-2-(2'-bromophenoxy)phenol (6); 4-phenoxyphenol (7), 4-phenoxyaniline (9), 1-chloro-4-phenoxybenzene (10); 1-bromo-4-phenoxybenzene (13) was investigated against marine bacteria, a diatom, barnacle larvae and mussel juveniles. The naturally occurring compound 2 showed the strongest AF activity in all bioassays but lacked toxicity. It inhibited the growth of all tested bacterial strains (MIC = 0.02 - 1.52 microM) and its 50% effective concentrations (EC(50)) were 0.24 microM (diatom test), 0.66 microM (mussel test) and 1.26 microM (barnacle test). Among the commercially available derivates, compound 7 was the most active in bacterial and diatom bioassays but its activity was lower than that of compound 2. Overall, the naturally occurring compounds showed stronger activity than the commercially available analogues and could be possible future non-toxic AF candidates.     

Biomonitoring of environmental pollution hazards from a nickel smelter waste dump

Longterm field exposure study was carried out on 10 rabbits placed for 6 months in a bioindication station located about 3 km downwind of a disposal site of nickel smelter waste dump. As revealed by the method of atomic absorption spectrophotometry, all of these animals showed elevated nickel and chromium levels in their body organs and hair. These findings were paralleled by histologic abnormalities in the lungs and liver tissues. Average dustfall values at the site of exposure did not exceed 5.5 g X m-2 X 30 d-1 during the period of observation. Dustfall deposits in this location contained nickel and chromium in amounts that were higher than in control locality. Analogous experiments on Wistar rats were carried out in a laboratory exposure chamber (exposure 4 h/day, 5 days/week, for a period of 6 months). After exposures to 50 mg X m-3 of metallic dust, lung parenchyma of rats was characterized by the presence of dust particles in various phases of phagocytosis as well as the presence of badly damaged or disintegrated alveolar macrophage cells, which pointed to metallic aerosol toxicity for biomembranes. The technique of air pollution biomonitoring on animals, correlated with the data on ambient air concentrations of the suspended particulate matter and its content of trace metals, appears to be a well suitable tool in establishing the potential air pollution hazards to the exposed populations living in the area of concern.     

A pathogenic fungi diphenyl ether phytotoxin targets plant enoyl (acyl carrier protein) reductase

Cyperin is a natural diphenyl ether phytotoxin produced by several fungal plant pathogens. At high concentrations, this metabolite inhibits protoporphyrinogen oxidase, a key enzyme in porphyrin synthesis. However, unlike its herbicide structural analogs, the mode of action of cyperin is not light dependent, causing loss of membrane integrity in the dark. We report that this natural diphenyl ether inhibits Arabidopsis (Arabidopsis thaliana) enoyl (acyl carrier protein) reductase (ENR). This enzyme is also sensitive to triclosan, a synthetic antimicrobial diphenyl ether. Whereas cyperin was much less potent than triclosan on this target site, their ability to cause light-independent disruption of membrane integrity and inhibition of ENR is similar at their respective phytotoxic concentrations. The sequence of ENR is highly conserved within higher plants and a homology model of Arabidopsis ENR was derived from the crystal structure of the protein from Brassica napus. Cyperin mimicked the binding of triclosan in the binding pocket of ENR. Both molecules were stabilized by the pi-pi stacking interaction between one of their phenyl rings and the nicotinamide ring of the NAD(+). Furthermore, the side chain of tyrosine is involved in hydrogen bonding with a phenolic hydroxy group of cyperin. Therefore, cyperin may contribute to the virulence of the pathogens by inhibiting ENR and destabilizing the membrane integrity of the cells surrounding the point of infection.     

A spectrophotometric assay of trout (Salvelinus fontinalis) liver diphenyl ether hydroxylase activity

Subcellular fractions of trout (Salvelinus fontinalis) liver homogenate metabolized diphenyl ether mainly to the 4-hydroxy derivative, but with traces of other compounds, including the 3-hydroxy derivative and possibly the 4,4-dihydroxy derivative. An ultraviolet spectrophotometric method for the determination of 4-hydroxydiphenyl ether is described.     

Structure-based design of caspase-1 inhibitor containing a diphenyl ether sulfonamide

A series of compounds was designed and prepared as inhibitors of interleukin-1beta converting enzyme (ICE), also known as caspase-1. These inhibitors, which employ a diphenyl ether sulfonamide, were designed to improve potency by forming favorable interactions between the diphenyl ether rings and the prime side hydrophobic region. An X-ray crystal structure of a representative member of the diphenyl ether sulfonamide series bound to the active site of caspase-1 was obtained.     

Protoporphyrinogen oxidase as a molecular target for diphenyl ether herbicides.

Diphenyl ether herbicides induce an accumulation of protoporphyrin IX in plant tissues. By analogy to human porphyria, the accumulation could be attributed to decreased (Mg or Fe)-chelatase or protoporphyrinogen oxidase activities. Possible effects of acifluorfen-methyl on these enzymes were investigated in isolated corn (maize, Zea mays) etioplasts, potato (Solanum tuberosum) and mouse mitochondria, and yeast mitochondrial membranes. Acifluorfen-methyl was strongly inhibitory to protoporphyrinogen oxidase activities whatever their origins [concn. causing 50% inhibition (IC50) = 4 nM for the corn etioplast enzyme]. By contrast, it was roughly 100,000 times less active on (Mg or Fe)-chelatase activities (IC50 = 80-100 microM). Our results lead us to propose protoporphyrinogen oxidase as a cellular target for diphenyl ether herbicides.     

Development of a noncompetitive phage anti-immunocomplex assay for brominated diphenyl ether 47

We present a new application of the noncompetitive phage anti-immunocomplex assay (PHAIA) by converting an existing competitive assay to a versatile noncompetitive sandwich-type format using immunocomplex binding phage-borne peptides to detect the brominated flame retardant, brominated diphenyl ether 47 (BDE 47). Three phage-displayed 9-mer disulfide-constrained peptides that recognize the BDE 47-polyclonal antibody immunocomplex were isolated. The resulting PHAIAs showed variable sensitivities, and the most sensitive peptide had a dose-response curve with an SC₅₀ (concentration of analyte producing 50% saturation of the signal) of 0.7 ng/ml BDE 47 and a linear range of 0.3-2 ng/ml, which was nearly identical to the best heterologous competitive format (IC₅₀ of 1.8 ng/ml, linear range of 0.4-8.5/ml). However, the PHAIA was 1400-fold better than homologous competitive assay. The validation of the PHAIA with extracts of house furniture foam as well as human and calf sera spiked with BDE 47 showed overall recovery of 80-113%. The PHAIA was adapted to a dipstick format (limit of detection of 3.0 ng/ml), and a blind test with six random extracts of local house furniture foams showed that the results of the PHAIA and dipstick assay were consistent, giving the same positive and negative detection.     

Semi-synthesis and bio-evaluation of polybrominated diphenyl ethers from the sponge Dysidea herbacea

The sponge Dysidea herbacea was collected from the Mandapam Coast, Tamilnadu, India. Isolated gram quantities of hydroxylated polybrominated diphenyl ether (HO-PBDE) and semi-synthesized a series of new PBDEs derivatives and tested them for antibacterial and cytotoxic activities.