Tetrabromobisphenol A (TBBPA): A controversial environmental pollutant

Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants and is extensively used in electronic equipment, furniture, plastics, and textiles. It is frequently detected in water, soil, air, and organisms, including humans, and has raised concerns in the scientific community regarding its potential adverse health effects. Human exposure to TBBPA is mainly via diet, respiration, and skin contact. Various in vivo and in vitro studies based on animal and cell models have demonstrated that TBBPA can induce multifaceted effects in cells and animals, and potentially exert hepatic, renal, neural, cardiac, and reproductive toxicities. Nevertheless, other reports have claimed that TBBPA might be a safe chemical. In this review, we re-evaluated most of the published TBBPA toxicological assessments with the goal of reaching a conclusion about its potential toxicity. We concluded that, although low TBBPA exposure levels and rapid metabolism in humans may signify that TBBPA is a safe chemical for the general population, particular attention should be paid to the potential effects of TBBPA on early developmental stages.     

赤子爱胜蚓对不同浓度四溴双酚A代谢的急性与亚急性毒性响应

运用核磁共振一维氢谱研究不同浓度四溴双酚A(TBBPA)急性暴露与亚急性暴露对赤子爱胜蚓(Eisenia fetida)的代谢影响.通过设置不同剂量TBBPA进行急性暴露和亚急性暴露,运用正交偏最小二乘投影分析法(OPLS)比较急性和亚急性暴露下蚯蚓的代谢差异,研究蚯蚓代谢水平与暴露剂量的关系,以找出差异代谢物作为TBBPA毒性效应的代谢标志物.结果表明,急性暴露和亚急性暴露均能很好地区分不同剂量染毒组间的代谢差异,且TBBPA暴露剂量越大,蚯蚓体内代谢与空白组的差异越大.急性暴露和亚急性暴露后,亮氨酸、赖氨酸和甜菜碱等代谢物剂量随TBBPA剂量增加的变化趋势是一致的,亚急性暴露中的变化幅度大于急性暴露.TBBPA暴露剂量为100 mg·kg~(-1)时,赤子爱胜蚓受到毒害作用,体内代谢物变化显著,代谢平衡遭到破坏,差异代谢物对毒性效应的指示作用比较敏感.甜菜碱、亮氨酸和赖氨酸可作为标志性代谢物揭示TBBPA对赤子爱胜蚓在渗透压调节、能量供给以及免疫功能方面的毒性效应,为进一步探索TBBPA毒性机理提供理论基础.     

四溴双酚A在污水脱氮除磷过程中迁移转化试验研究

四溴双酚A(TBBPA)是一种使用广泛的阻燃剂,其扩散到环境介质中,会对生态和人体健康构成威胁,以往研究较少关注TBBPA在脱氮除磷工艺中的迁移转化.采用实验室SBR脱氮除磷反应器,研究了TBBPA在工艺长期运行过程中的去除、在典型周期过程中的变化、在硝化和反硝化过程中的去除.TBBPA在工艺长期运行过程中的去除率为48.4%,其中生物去除率为44.4%,吸附去除率为4.0%.在典型周期中TBBPA浓度受pH影响很大.TBBPA在硝化过程的去除主要是生物作用,而在反硝化过程的去除主要是吸附作用.     

铜绿假单胞菌NY3及其突变株好氧降解四溴双酚A特性研究

为明确铜绿假单胞菌NY3 2个烷羟化酶基因alk B1和alk B2基因在该菌代谢四溴双酚A中的作用,研究了野生NY3菌及其突变菌株(NB1D、NB2D及NB12DD)对四溴双酚A好氧降解特性.研究表明,NY3、NB1D、NB2D及NB12DD菌株均能以四溴双酚A为单一碳源和能源进行生长,并对四溴双酚A进行一定程度上的降解.NY3菌中alk B1基因和alk B2基因的缺失对NY3菌株在四溴双酚A中的生长有抑制作用,而且alk B1基因和alk B2基因在NY3菌降解四溴双酚A中起一定的作用,但不完全,说明NY3菌中还存在其他影响四溴双酚A降解的基因.缺失alk B2基因的突变株NB2D在高浓度的四溴双酚A溶液中降解转化率最少,说明alk B2基因的缺失,对NY3菌降解高浓度四溴双酚A碳源更重要.加入同一易降解共代谢碳源,野生株NY3菌及其各突变株生长特性无明显差异,然而,因共存碳源种类不同,同一菌株细胞生长量、对四溴双酚A降解及其脱溴效率等特性差别明显.加最佳共代谢碳源乳酸钠的体系内,突变株NB2D存在下易积累中间产物3,3',5-三溴双酚A和2-溴-4(异丙基-溴苯)-苯酚等直接脱溴产物,说明alk B1基因可能为NY3菌株代谢四溴双酚A脱溴时的关键基因.     

四溴双酚A厌氧共代谢降解性能研究

基于厌氧共代谢原理构建反应器,分析厌氧共代谢强化四溴双酚A（TBBPA）的转化机理.研究发现,当TBBPA浓度为75μg/L时,TOC和TBBPA去除率都达到最高,分别为88.6%和81.7%;当TBBPA浓度为25μg/L时,生物半衰期最低,为21.97h.根据检测到的中间代谢单环产物3,4-二甲氧基苯甲酸甲酯和TBBPA代谢途径分析可推测TBBPA在厌氧共代谢体系中实现了深度降解,且固氮弧菌属和毛球菌属对TBBPA的厌氧生物降解起到了主要作用.     

四溴双酚A对斑马鱼胚胎体内外发育的毒性效应

四溴双酚A(TetrabromobisphenolA,TBBPA)是广泛使用的溴阻燃剂,在环境中普遍存在.采用斑马鱼胚胎体内外微环境模拟实验,研究了TBBPA对斑马鱼(Danio rerio)胚胎体内外发育的影响.结果发现,斑马鱼胚胎直接暴露在TBBPA溶液中,会造成胚胎心包囊水肿、尾部延伸不全等畸形或使胚胎死亡;当TBBPA浓度高于1.6mg·L-1时,处理斑马鱼胚胎的致死率显著升高,与对照组有极显著差异(p<0.01),且致死效应主要发生在24h内.当TBBPA浓度为6.4mg·L-1时,斑马鱼胚胎在48h内全部死亡.在TBBPA浓度大于0.4mg·L-1的各组中,24h内斑马鱼胚胎在20s内的活动频率明显降低;当胚胎直接接触TBBPA48h,表现出的主要毒性效应为胚胎心包囊水肿,但胚胎的心率没观察到异常变化.当斑马鱼胚胎发育到72h时,TBBPA引起斑马鱼胚胎毒性的主要特征是心包囊水肿和脊柱畸形.另外,TBBPA处理后斑马鱼胚胎的孵化率和生存率均显著降低,这表明斑马鱼胚胎直接暴露在TBBPA污染的环境中,会出现明显的发育障碍,主要表现为心脏功能受损和致死效应,这些毒性特征有显著的剂量-效应关系.当成年亲代斑马鱼暴露在TBBPA溶液(1.5mg·L-1)中3～7d后,子代胚胎的发育表现出明显的毒性效应,其胚胎发育到24h和72h时的致死率均呈现一定的时间-效应关系;72h时的死亡率与对照组有极显著差异,子代胚胎的孵化率降低,但没有统计学差异;但子代胚胎的致畸率却显著升高,并呈现显著差异.研究结果表明,水体中残留的TBBPA对体内外斑马鱼胚胎的发育均有直接影响,对于鱼类的生殖和发育具有潜在的危害.     

环境中四溴双酚A降解技术的进展研究

四溴双酚A(TBBPA)作为一种常见的溴系阻燃剂(BFRs),广泛应用于印刷电路板、绝缘电线以及各种聚碳酸酯塑料中,也是目前全球产量和使用量最大的溴系阻燃剂.由于TBBPA具有持久性,生物累积性和毒性,严重威胁了人类健康和生态系统安全,近年来已经被认定是一种值得探讨与关注的环境内分泌干扰物,TBBPA作为一种新的"POPs问题"成为了目前降解技术研究的热点.通过综合国内外的相关研究,对TBBPA的物理降解、化学降解,生物降解等降解技术进行了综述,并对存在的问题及未来的研究方向进行了讨论与展望.     

Ti/RuO2-IrO2电极电化学方法降解溶液中TBBPA及其降解机理探究

四溴双酚A(TBBPA)是世界上产量和用量最大的溴代阻燃剂之一,在河流、底泥及污水中持久存在,严重威胁环境和人体健康.探讨了阳极为Ti/RuO_2-IrO_2电极的电化学法对溶液中TBBPA的降解效率,并考察了电流密度(5~20 m A·cm~(-2))、初始pH值(3~11)、极板间距(1~3 cm)及电解质浓度(1~40 mmol·L~(-1))对降解速率的影响.研究结果表明,TBBPA的降解遵循一级动力学方程,在溶液初始浓度为5 mg·L~(-1)、电流密度为10 mA·cm~(-2)、电解质浓度为5 mmol·L~(-1)及极板间距为1 cm的条件下,60 min后TBBPA的降解率可达97.2%,且降解速率常数和半衰期分别为0.060 min~(-1)和11.6 min,能量消耗为105.3 k Wh·m~(-3).同时运用HPLC-MS/MS检测出中间产物双酚A(BPA)和2-溴苯酚,并推断其降解途径主要为在羟基自由基(·OH)作用下连续的脱溴过程中,苯环与异丙基之间的C—C键断裂生成BPA和2-溴苯酚.电化学法是一种高效的、有潜力的降解难降解有机污染物的方法,本文将为今后实际废污水中TBBPA的去除提供基础数据和技术参数.     

四溴双酚A降解技术的最新研究进展

作为目前产量和使用量最大的溴系阻燃剂,四溴双酚A(Tetrabromobisphenol A,TBBPA)在其生产、使用及处置等环节会被释放到环境中,由于四溴双酚A具有持久性、累积性和生物毒性等特性而对人类健康和生态环境造成威胁。文章在简单介绍四溴双酚A主要性质和毒性的基础上,结合近几年国内外的研究现状,综述了四溴双酚A在光降解、微生物降解和高级氧化等技术的最新研究进展,并对目前存在的问题及未来的研究方向进行了讨论与展望。     

Re-evaluation of thyroid hormone signaling antagonism of tetrabromobisphenol A for validating the T3-induced Xenopus metamorphosis assay

We developed the T3-induced Xenopus metamorphosis assay, which is supposed to be able to sensitively detect thyroid hormone(TH) signaling disruption of chemicals. The present study aimed to validate the T3-induced Xenopus metamorphosis assay by re-evaluating the TH signaling antagonism of tetrabromobisphenol A(TBBPA), a known TH signaling disruptor. According to the assay we developed, Xenopus tadpoles at stage 52 were exposed to 10–500 nmol/L TBBPA in the presence of 1 nmol/L T3. After 96 hr of exposure, TBBPA in the range of 10–500 nmol/L was found to significantly inhibit T3-induced morphological changes of Xenopus tadpoles in a concentration-dependent manner in term of body weight and four morphological endpoints including head area(HA), mouth width(MW), unilateral brain width/brain length(ULBW/BL), and hind-limb length/snout-vent length(HLL/SVL).The results show that these endpoints we developed are sensitive for characterizing the antagonistic effects of TBBPA on T3-induced metamorphosis. Following a 24-hr exposure,we found that TBBPA antagonized expression of T3-induced TH-response genes in the tail,which is consistent with previous findings in the intestine. We propose that the tail can be used as an alternative tissue to the intestine for examining molecular endpoints for evaluating TH signaling disruption. In conclusion, our results demonstrate that the T3-induced Xenopus metamorphosis assay we developed is an ideal in vivo assay for detecting TH signaling disruption.     

A screening assay for thyroid hormone signaling disruption based on thyroid hormone-response gene expression analysis in the frog Pelophylax nigromaculatus

Amphibian metamorphosis provides a wonderful model to study the thyroid hormone (TH) signaling disrupting activity of environmental chemicals, with Xenopus laevis as the most commonly used species. This study aimed to establish a rapid and sensitive screening assay based on TH-response gene expression analysis using Pelophylax nigromaculatus, a native frog species distributed widely in East Asia, especially in China. To achieve this, five candidate TH-response genes that were sensitive to T3 induction were chosen as molecular markers, and T3 induction was determined as 0.2 nmol/L T3 exposure for 48 hr. The developed assay can detect the agonistic activity of T3 with a lowest observed effective concentration of 0.001 nmol/L and EC50 at around 0.118–1.229 nmol/L, exhibiting comparable or higher sensitivity than previously reported assays. We further validated the efficiency of the developed assay by detecting the TH signaling disrupting activity of tetrabromobisphenol A (TBBPA), a known TH signaling disruptor. In accordance with previous reports, we found a weak TH agonistic activity for TBBPA in the absence of T3, whereas a TH antagonistic activity was found for TBBPA at higher concentrations in the presence of T3, showing that the P. nigromaculatus assay is effective for detecting TH signaling disrupting activity. Importantly, we observed non-monotonic dose-dependent disrupting activity of TBBPA in the presence of T3, which is difficult to detect with in vitro reporter gene assays. Overall, the developed P. nigromaculatus assay can be used to screen TH signaling disrupting activity of environmental chemicals with high sensitivity.     

四溴双酚A和镉复合污染对不同生物体的安全阈值

以赤子爱胜蚓（Eisenia fetida）、斑马鱼（Zebrafish）作为受试生物,进行急性毒性试验,死亡率、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）为效应指标,采用基准剂量（BMD）法推导四溴双酚A （TBBPA）和镉（Cd）单一及联合暴露对不同生物体的安全阈值.结果表明,在本研究的试验剂量范围内,蚯蚓、斑马鱼TBBPA、Cd暴露剂量与死亡率、SOD、CAT活性效应指标存在明显剂量-效应关系.单一暴露下,CAT、SOD活性指标最敏感,蚯蚓和斑马鱼的TBBPA安全阈值分别为0.95,0.44mg/L,Cd安全阈值分别为71.17,0.42mg/L.联合暴露下安全阈值小于单一暴露.蚯蚓、斑马鱼TBBPA安全阈值分别为0.33,0.024mg/L,Cd为6.45,0.176mg/L.     

双酚F和双酚S联合暴露下的斑马鱼富集及神经毒性

为探究双酚F（BPF）和双酚S（BPS）联合暴露下斑马鱼富集及神经毒性,进行为期14d的1,10,100,1000 μg/L BPF和BPS的单一或联合暴露.结果表明,BPF和BPS在斑马鱼组织内的富集水平与暴露浓度和暴露时间呈正相关,BPF富集能力高于BPS,BPF和BPS联合暴露降低了斑马鱼对BPS的富集水平,但对BPF富集水平的影响较小.脑组织中的富集水平低于肠道但远高于肌肉.以脑为目标组织进行了毒性研究,结果表明,BPF诱导的丙二醛（MDA）、8-羟化脱氧鸟苷（8-OHdG）、白细胞介素1β（1L-1β）、肿瘤坏死因子α（TNF-α）等氧化损伤和炎症指标水平高于BPS,且联合暴露存在毒性增强效应.但BPS对皮质醇（COR）、肾上腺素（EPI）和乙酰胆碱酶（AChE）等神经毒性标志物和Syn2a、MBP、Gfap、MAP2、NSE2和S-100B等神经功能有关基因的毒性效应影响高于BPF,联合暴露削减了对AChE、COR和EPI等的影响.     

四溴双酚A的鲫鱼血清蛋白生物标志物研究

以鲫鱼为供试生物,对四溴双酚A(TBBPA)的急性毒性、血清蛋白潜在生物标志物以及相应的毒性靶器官组织病理进行了研究,结果表明TBBPA对鲫鱼96 h的半致死浓度LC50是3.13 mg/L,TBBPA诱导下鲫鱼血清蛋白可区分为11个组分,各组分随时间和浓度的变化规律存在差异。组分11条带清晰,表达量变化幅度最大,在低浓度TBBPA暴露下表达量先降低后升高,第16天达到最高;高浓度时表达量在第2天达到最高。组分11的分子量为24 kDa,可能为鲫鱼斯坦尼小体(CS)中降血钙因子的解聚物。组织病理切片结果显示,鲫鱼肝脏和肾脏均表现出时间-剂量依赖性,且与组分11的诱导差异性表达呈现相应的病理损伤。因此,鲫鱼血清蛋白组分11对TBBPA的诱导具有浓度和时间响应敏感性,且易于识别和鉴定,可作为TBBPA暴露的鲫鱼血清蛋白潜在生物标志物。     

卤系阻燃剂在东江工业水体中的质量浓度及其分配特征

本研究分析了东江工业水体中卤系阻燃剂的浓度,组成分布以及分配特征.结果表明多溴联苯醚(PBDEs)是水体中的主要的卤系阻燃剂,占总卤系阻燃剂的41.0%,其质量浓度范围为1 102.3~3 666.9 pg·L~(-1),其中BDE209是颗粒相的主要成分.四溴双酚A(TBBPA)占总卤系阻燃剂的32.4%,其质量浓度范围为1 120.9~2 856.5 pg·L~(-1),其他卤系阻燃剂如十溴二苯乙烷(DBDPE)、德克隆(DP)和六溴环十二烷(HBCDs)分别占总卤系阻燃剂的16.3%、7.3%和3.0%,其质量浓度范围分别为397.7~1 736.8、235.7~778.1和9.5~266.8 pg·L~(-1).在对水体溶解相和颗粒相分配的研究中发现,PBDEs、DBDPE、DP和HBCDs主要存在于水体颗粒相中,而TBBPA由于其较大的水溶性,主要存在于溶解相中;卤系阻燃剂的lgK_(oc)与lgK_(ow)之间存在显著的相关性,但是lgK_(oc)实测值与其理论预测值有一定差异,这可能是受控于悬浮颗粒(SPM)含量和溶解有机碳(DOC)含量这两个因素,此外,颗粒相和溶解相之间分配是否达到平衡也是影响测量lg Koc值的因素.     

Effects of Cu2+ and humic acids on degradation and fate of TBBPA in pure culture of Pseudomonas sp. strain CDT

Soil contamination with tetrabromobisphenol A(TBBPA) has caused great concerns;however, the presence of heavy metals and soil organic matter on the biodegradation of TBBPA is still unclear. We isolated Pseudomonas sp. strain CDT, a TBBPA-degrading bacterium, from activated sludge and incubated it with ~(14)C-labeled TBBPA for 87 days in the absence and presence of Cu~(2+)and humic acids(HA). TBBPA was degraded to organic-solvent extractable(59.4% ± 2.2%) and non-extractable(25.1% ± 1.3%) metabolites,mineralized to CO_2(4.8% ± 0.8%), and assimilated into cells(10.6% ± 0.9%) at the end of incubation. When Cu~(2+)was present, the transformation of extractable metabolites into non-extractable metabolites and mineralization were inhibited, possibly due to the toxicity of Cu~(2+)to cells. HA significantly inhibited both dissipation and mineralization of TBBPA and altered the fate of TBBPA in the culture by formation of HA-bound residues that amounted to 22.1% ± 3.7% of the transformed TBBPA. The inhibition from HA was attributed to adsorption of TBBPA and formation of bound residues with HA via reaction of reactive metabolites with HA molecules, which decreased bioavailability of TBBPA and metabolites in the culture. When Cu~(2+)and HA were both present, Cu~(2+)significantly promoted the HA inhibition on TBBPA dissipation but not on metabolite degradation. The results provide insights into individual and interactive effects of Cu~(2+)and soil organic matter on the biotransformation of TBBPA and indicate that soil organic matter plays an essential role in determining the fate of organic pollutants in soil and mitigating heavy metal toxicity.     

四溴双酚-A污染对颤蚓的氧化胁迫及毒性

在实验室模拟条件下分别采用动、静态生物慢性实验的方法,研究了不同浓度的四溴双酚-A(Tetrabromobisphenol A, TBBPA)对颤蚓(Monopylephorus limosus)体内抗氧化酶系统及相Ⅱ结合酶系统活性的影响以及颤蚓暴露于单一浓度的TBBPA后,其体内抗氧化酶系统的活性随时间的响应.结果表明,暴露 8d 后,颤蚓体内SOD的活性发生显著变化,变化趋势明显分为升高、降低、再升高3阶段,在0.05ms/L时SOD的活性被最大诱导(p<0.01),达到对照组的7.8倍,各浓度组SOD的活性均显著高于对照组,由对照组的1.5倍到对照组的7.8倍;同时, CAT的活性变化则呈升高、降低、再升高、再降低4阶段,0.5mg/L时其活性达到最大值(p<0.01),除0.005mg/L和0.25mg/L浓度组CAT活性受抑制外,其余浓度组CAT的活性均高于对照组,由对照组的1.1倍到1.9倍,染毒浓度为0.25ms/L时, GST的活性达到最大诱导(p<0.01),其活性先缓慢上升后下降,并且各处理组GST的活性均显著高于对照组(p<0.05).在单一浓度TBBPA污染暴露的10d时间内,颤蚓体内SOD的活性变化趋势形成了一个变形的"M" 形曲线,在第3d时其活性达到最大诱导,而CAT活性的变化则表现为一个不规则的"N"形曲线,在第5d,时其活性达到最大诱导,并且SOD的活性比CAT的活性受时间的影响小,相对来说更稳定.可见, SOD与GST的活性变化似乎更能反映出TBBPA对颤蚓的污染效应及其毒性作用,而SOD的活性变化似乎更为灵敏,但是二者能否作为指示TBBPA污染的生物标志物尚需进一步研究.     

Effects of dissolved organic matter from sewage sludge on sorption of tetrabromobisphenol A by soils

Sorption of tetrabromobisphenol A (TBBPA) by soil influences its fate and transport in the environment. The presence of dissolved organic matter (DOM) may complicate the sorption process in soil. The effects of DOM from sewage sludge on TBBPA sorption by three soils were investigated using batch equilibration experiments in the study. DOM was observed to be sorbed on the soils and the isotherms could be fitted by the Langmuir model. The effects of DOM on TBBPA sorption were dependent on the characteristics ...     

四溴双酚A的辐照降解研究

研究了甲醇-水溶液中四溴双酚A(TBBPA)的电子束辐照降解.通过测定辐照前后TBBPA的浓度变化来研究吸收剂量、初始浓度、pH、自由基清除剂对辐照降解效果的影响.结果表明,TBBPA在甲醇-水溶液的辐照降解是还原性逐步脱溴降解过程,自由电子在降解过程中起主导作用,降解反应遵循一级动力学方程.在辐照剂量为10 kGy时,20 mg.L-1的TBBPA有91.6%发生脱溴降解,当向辐照体系充入氮气并且加入叔丁醇,可将TBBPA的降解效率提高到100%,或者调节辐照体系溶液的pH值至12,TBBPA的降解效率也可以达到100%.辐照降解是处理TBBPA的一种有效手段.     

低浓度TBBPA暴露促进子宫内膜癌细胞侵袭和迁移的毒性效应与机理

为了研究低浓度四溴双酚A(TBBPA)暴露对人子宫内膜癌恶化的影响,本实验采用人子宫内膜癌细胞Ishikawa暴露于不同浓度的TBBPA,探讨其毒性效应及可能存在的分子机理.实验采用MTT法检测Ishikawa细胞的存活率,用倒置显微镜观察TBBPA对Ishikawa细胞形态的影响,用细胞划痕与Transwell实验检测细胞迁移侵袭情况,用实时荧光定量PCR与Western blotting分别检测上皮间充质转化(Epithelial Mesenchymal Transition,EMT)标志物及相关转录因子mRNA与蛋白水平表达量.结果显示,Ishikawa细胞暴露于不同浓度TBBPA(1.00×10-9、1.00×10-8、1.00×10-7mol·L-1)后,细胞存活率明显升高,细胞形态由卵圆形逐渐变为长梭形,细胞侵袭率、细胞划痕愈合率、细胞迁移率与对照组相比显著升高,差异具有统计学意义.在mRNA和蛋白水平上,EMT标志物E-cadherin表达量显著下降,Vimentin和N-cadherin表达量明显上升;EMT上游转录因子Twist和Snail-1的含量也显著增加.结果表明,TBBPA暴露是通过改变细胞内E-cadherin、Vimentin和N-cadherin的含量进而激活Ishikawa细胞上皮间充质转化,导致人子宫内膜癌的恶化;而激活上皮间充质转化的过程可能与TBBPA诱导Twist和Snail-1的表达有关.