邻苯二甲酸二(2-乙基己基)酯生物降解研究进展

邻苯二甲酸二 (2 乙基己基 )酯是一种污染严重的有毒难降解有机物 ,自然降解能力很弱 ,降解过程主要为生物降解。运用微生物对其进行生物降解有着十分广阔的前景     

邻苯二甲酸二(2-乙基己基)酯对大鼠不同脏器的损伤

目的 探讨邻苯二甲酸二(2-乙基己基)酯(DEHP)对大鼠各组织器官造成的损伤.方法 选用雄性Wistar大鼠50只.随机分为5组,每组10只,以灌胃方式染毒DEHP,4个染毒组剂量分别为1 500、3 000、4 500、6 000 mg/kg,阴性对照组每天灌胃相同体积的食用油,各组每4d称重1次,28d后称重处死,计算脏器系数,并做病理学检查.结果 4个染毒组随DEHP浓度的升高.其体重均数有依次降低的趋势,各染毒组大鼠体重均数普遍低于溶剂对照组(P<0.05,P<0.01),4 500和6000mg/kg组大鼠染毒24d后,出现了体重停止增长且有体重减轻的现象;大鼠肝脏、肾脏、心脏的脏器系数均高于对照组(P<0.05,P<0.01),而睾丸脏器系数则均低于对照组(P<0.05,P<0.01);同时大鼠肝脏、肾脏、心脏、睾丸在镜下观察均有不程度的损伤.并随着DEHP浓度的逐渐增高,各脏器损伤的程度也随之加重.结论 DEHP对大鼠的脏器可造成一定程度的损伤.并随染毒剂量的增加有加重的趋势.     

邻苯二甲酸二(2-乙基己基)酯对小鼠子宫发育的毒性作用

目的 研究邻苯二甲酸二(2-乙基己基)酯[di- (2-ethylhcxyl)phthalate,DEHP]对未成年小鼠子宫发育的毒性作用.方法 将60只未成年(3周龄)清洁级ICR雌性小鼠随机分为4组,分别为对照(玉米油)组和低、中、高剂量DEHP染毒组(100、400、1600 mg/kg),每组15只.采用灌胃方式进行染毒,每天1次,每周5d,连续6周.测定小鼠子宫内膜及其上皮的厚度.结果 与对照组比较,中、高剂量DEHP染毒组小鼠子宫内膜上皮厚度显著下降,差异均有统计学意义(P＜0.05);而各剂量DEHP染毒小鼠子官内膜厚度无显著改变.且随着DEHP染毒剂量的升高,小鼠子宫内膜上皮的厚度呈下降趋势.结论 在本实验条件下,DEHP染毒未成年雌性小鼠影响了子宫的发育,对子宫发育具有毒性作用.     

邻苯二甲酸二(2-乙基己基)酯毒性作用

邻苯二甲酸二(2 乙基己基)酯(DEHP)作为聚氯乙烯(PVC)等塑料制品的增塑剂,可增加塑料的弹性和韧性,被广泛应用于塑料工业。DEHP在塑料中是以游离的形式存在的,在重量上可达 30%~50%[1],很容易进入环境。作为环境污染物,可以在地表水、地下水、饮用水、空气、土壤及动、植物体内广泛检测到。目前的研究发现其毒性作用主要是作为内分泌干扰物,表现为生殖生长毒性、肝肾毒性及血液和生化方面的改变。随着DEHP产量的逐年增加,其在环境中的浓度也逐渐升高,对人体的毒性作用也越来越受到人们的关注[2]。目前对其健康效应方面的评价尚处…     

邻苯二甲酸二(2-乙基己基)酯及其代谢产物MEHP对体外大鼠卵泡发育的影响

目的利用大鼠腔前卵泡体外培养方法研究邻苯二甲酸二(2-乙基己基)酯(DEHP)及其代谢产物邻苯二甲酸单(2-乙基己基)酯(MEHP)对卵泡体外发育的影响。方法机械性分离大鼠腔前卵泡,单个卵泡在96孔板中连续培养。MEHP设2.5、5、10、20、40和80μg/ml6个浓度,DEHP设33.7、67.5、125、250、500、1000nmol/L6个浓度,同时设二甲基亚砜(DMSO)溶剂对照和阴性对照。每组16～20个卵泡,3次重复。隔天换1/2液,在培养第10天诱导排卵,观察卵泡体外发育情况。结果DEHP对第11天卵泡存活率、有腔形成率、异常卵泡形成率和卵丘-卵母细胞复合体(COCs)排出率无明显的影响,与溶剂对照组差异无显著性(P0.05)。第2天暴露10μg/ml以上剂量的MEHP48h后,第11天卵泡存活率明显下降(54.76%±3.37%),与对照组(91.57%±1.32%)比较差异有显著性(P0.05),剂量与卵泡存活率之间存在一定相关性(R2=0.92);COCs排出(24.99%±3.95%)明显减少,与对照组(52.78%±8.45%)比较差异有显著性(P0.05);异常卵泡出现率(45.24%±3.37%)明显升高,与对照组比较差异有显著性(P0.05);暴露20μg/mlMEHP有腔形成率(46.18%±1.67%)减少,与对照组(85.91%±5.03%)比较差异有显著性(P0.05),且有明显剂量-反应关系。结论MEHP可以抑制体外大鼠腔前卵泡的生长发育。     

邻苯二甲酸(2-乙基己基)酯对雄性小鼠的生殖毒性

为探讨邻苯二甲酸(2-乙基己基)酯[di(2-ethylhexyl)phthalate,DEHP]对小鼠的生殖毒性.将30只成年健康SPF级雄性昆明小鼠随机分成5组,分别为阴性对照(玉米油)组和低(1 250 mg/kg)、中(2 500 mg/kg)、高剂量(5000mg/kg)DEHP染毒组以及阳性对照(环磷酰胺40 mg/kg)组,每组6只.除阳性对照组采用腹腔染毒外,其余各组采用经口灌胃方式进行染毒,染毒容量为0.02 ml/g,每天1次,连续染毒5d.于首次染毒5周后,采用一般生殖毒性实验方法对精子计数和精子存活率、畸形率、活动率进行测定.结果显示,与阴性对照组比较,各剂量DEHP染毒组小鼠精子计数和精子存活率均较低;而中、高剂量DEHP染毒组精子畸形率较高,活动率较低,差异均有统计学意义(P＜0.05).随着DEHP染毒剂量的升高,小鼠精子计数和活动率、精子存活率均呈下降趋势,精子畸形率呈上升趋势.提示DEHP对雄性小鼠具有一定的生殖毒性.     

出生前邻苯二甲酸二(2-乙基己基)酯暴露对子代大鼠血清皮质醇激素水平的影响

目的探讨出生前邻苯二甲酸二(2-乙基己基)酯(DEHP)暴露对大鼠肾上腺功能的潜在干扰作用。方法将32只健康SD孕鼠按体重随机分为溶剂对照组(玉米油)及2、10、50 mg/kg DEHP染毒组,每组8只。自孕14~19 d连续灌胃染毒,每日1次。子代大鼠于出生后第21天断乳,雌雄分笼饲养至70日龄,断头处死,取血及双侧肾上腺,计算肾上腺脏器系数,并采用Luminex液态芯片技术测定血清皮质醇水平。结果成年雌性仔鼠肾上腺脏器系数在各染毒组间有差异,与对照组相比,2 mg/kg染毒组的肾上腺重量及脏器系数较低,差异有统计学意义(P0.05);成年雄性仔鼠肾上腺脏器系数在各染毒组间差异均无统计学意义(P0.05)。与对照组相比,10、50 mg/kg染毒组的成年雌性仔鼠血清皮质醇水平较高,差异有统计学意义(P0.01);而2 mg/kg染毒组与对照组相比无明显差异(P0.05)。与对照组相比,10 mg/kg染毒组的成年雄性仔鼠血清皮质醇水平较高,差异有统计学意义(P0.01);而2、50 mg/kg染毒组与对照组相比无明显差异(P0.05)。结论出生前DEHP暴露可能干扰子代大鼠肾上腺功能。     

出生前邻苯二甲酸二(2-乙基己基)酯暴露对成年后大鼠血清生长激素水平的影响

目的探讨出生前邻苯二甲酸二(2-乙基己基)酯[di(2-ethylhexyl)phthalate,DEHP]暴露对成年后大鼠血清生长激素水平的影响。方法将32只健康成年SPF级妊娠SD大鼠按体重随机分为4组,分别为对照(玉米油)组和2、10、50 mg/kg DEHP染毒组,每组8只。于妊娠第14天(G14)～G19,采用灌胃方式进行染毒,染毒容量为10 ml/kg,每日1次。采用Luminex液态芯片测定血清生长激素(GH)水平,采用荧光定量PCR法检测垂体GHRHR基因的相对表达水平。结果与对照组相比,10、50 mg/kg DEHP染毒组雄性大鼠血清GH的水平降低,而50 mg/kg DEHP染毒组雌性大鼠血清GH的水平升高,差异均有统计学差异(P0.05);随着DEHP染毒剂量的升高,大鼠血清GH的水平均呈先下降后升高的趋势。各剂量DEHP染毒组不同性别大鼠垂体GHRHR基因的表达水平与对照组比较,差异均无统计学意义(P0.05)。结论出生前DEHP暴露可能通过下丘脑-垂体-生长激素轴,主要通过降低雄性子代大鼠血清GH水平和升高雌性子代大鼠血清GH水平影响大鼠的生长发育。     

邻苯二甲酸(2-乙基己基)酯对大鼠血中抗氧化酶的影响

邻苯二甲酸(2-乙基己基)酯[Di-(2-ethylhexyl)phthalate简称DEHP]是一种工业上应用广泛的增塑剂.研究表明:[1]DEHP不仅对人和实验动物产生毒作用,而且还具有致癌性.Garberg[2]报道DEHP可诱发大鼠脂质过氧化作用引起抗氧化酶的改变和过氧化物堆积,这可能是其毒作用和致癌的原因之一,为此我们进行本实验了解DEHP对大鼠血中某些抗氧化酶的影响以进一步探讨其毒性机理.     

邻苯二甲酸二(2-乙基己基)酯对青春前期雄性大鼠的生殖毒性

目的探讨邻苯二甲酸二(2-乙基己)酯(di-2-ethylhexyl phthalate,DEHP)对青春前期雄性大鼠的生殖毒性。方法将32只健康21日龄清洁级雄性SD大鼠按体重随机分为4组,分别为溶剂对照(玉米油)组和250、500、1 000 mg/kg DEHP染毒组,每组8只。采用灌胃方式进行染毒,染毒容量为10 ml/kg,每天1次,连续染毒4周。采用CASA精子分析系统分析精子活力相关指标。结果与对照组比较,1 000 mg/kg DEHP染毒组大鼠的精子密度、精子活动率、活动精子密度、最大侧摆幅度、直线运动的精子密度及A级精子百分率均较低,而D级精子百分率较高;250 mg/kg DEHP染毒组平均直线运动速度、精子运动的向前性均较低;500、1 000 mg/kg DEHP染毒组直线运动的精子个数均较低,差异均有统计学意义(P0.05);而各剂量DEHP染毒组B、C级精子比例和平均曲线运动速度、平均路径速度、平均侧摆幅度、平均鞭打频率、运动的直线性、运动的摆动性、平均移动角度、直线运动精子活率均无明显改变。结论 DEHP对青春前期雄性大鼠精子活力产生明显的毒性作用,从而影响雄性的生殖功能。     

邻苯二甲酸二乙基己基酯对大鼠睾丸细胞DNA损伤和睾丸组织氧化应激影响

目的 探讨邻苯二甲酸二乙基己基酯(DEHP)对大鼠睾丸细胞DNA的损伤和睾丸组织氧化应激的作用.方法 雄性Wistar大鼠25只,随机分为5组,每组5只,通过灌胃的方法摄入DEHP,4个染毒组剂量分别为1 500、3 000、4 500、6000mg·kg-1 ·d-1,1个阴性对照组.用单细胞凝胶电泳技术检测大鼠睾丸细胞DNA的损伤,睾丸组织中活性氧(ROS)、丙二醛(MDA)的水平以及睾丸组织中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)的活力.结果 各染毒组和阴性对照组大鼠睾丸细胞DNA损伤率分别为29.0％、71.0％、89.0％、95.0％和15.0％,各染毒组睾丸细胞DNA损伤程度与对照组比较,差异均有统计学意义(P＜0.05,P＜0.01),且大鼠睾丸细胞DNA损伤率与染毒剂量之间呈剂量-反应关系(r =0.930,P＜0.01);各染毒组大鼠睾丸组织的ROS、MDA的水平均较阴性对照组显著升高(P＜0.05,P＜0.01),而GSH-Px、SOD的活力又较阴性对照组明显下降(P＜0.05,P＜0.01).结论 DEHP可造成大鼠睾丸组织明显的氧化应激并引起睾丸细胞DNA的损伤.     

Effects of di(2-ethylhexyl) phthalate and dibutyl phthalate on the collembolan Folsomia fimetaria

Lethal and sublethal effects of di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) on adult individuals of the collembolan Folsomia fimetaria were investigated in the laboratory by the use of small microcosms. Effects of DEHP and DBP were also tested on newly hatched collembolans in a multidish system. The endpoints were juvenile mortality, growth, and development. When exposed to DEHP, adults and juveniles were unaffected at all test concentrations, that is, up to 5,000 mg/kg. However, DBP caused increased adult mortality at 250 mg/kg and juvenile mortality at 25 mg/kg. For DBP, adult reproduction was a more sensitive endpoint than was survival, with an EC10 and EC50 of 14 and 68 mg/kg, respectively. Juvenile molting frequency seems to be a sensitive parameter, because number of cuticles produced by young springtails was reduced at 1 mg/kg. Toxicity was reduced when soil spiked with DBP was stored at 20 degrees C for a period of up to 28 d before adding the animals. Reduction in toxicity of DBP may be due a combination of degradation, evaporation, and adsorption of DBP to soil material. This was confirmed by chemical analyses, which showed a rapid initial disappearance followed by a much slower disappearance. Our results lead to the overall conclusion that significant adverse effects of phthalates on collembolans are not likely to occur as a result of normal sewage sludge application.     

邻苯二甲酸二(2-乙基)己基酯影响白细胞介素-4蛋白的机制初探

目的 通过研究钙调神经磷酸酶(CaN)在邻苯二甲酸二(2-乙基)己基酯(DEHP)影响白细胞介素(IL)-4蛋白表达中的作用,初步探讨DEHP的免疫毒性机制.方法 以10μg/T佛波酯(PMA)及0.5 mg/L离子霉素(Ion)为激活剂,用10、50 μmol/L DEHP染毒脾淋巴细胞72及96 h,同时用0.5 μmol/L CaN抑制剂FK506进行干预.实验终点检测细胞上清液中乳酸脱氢酶(LDH)漏出、用酶联免疫吸附试验测定细胞上清液中CaN蛋白及IL-4蛋白含量.结果 与PMA+Ion组比较,10、50 μmol/L DEHP均使细胞上清液中LDH漏出明显升高;50 μmol/L DEHP作用细胞72及96 h,使CaN蛋白表达分别增加3.83倍及3.91倍.实验72 h,50 μmol/L DEHP与PMA+Ion组比较明显促进IL-4蛋白表达,且FK506能抑制淋巴细胞分泌IL-4蛋白.结论 CaN在DEHP调控IL-4蛋白表达中具有重要作用.     

Inhibition of alveolar macrophage killing by di(2-ethylhexyl)phthalate

The phthalate ester plasticizer di(2-ethylhexyl) phthalate (DEHP) affected the phagocytosis and killing ofStaphylococcus aureus by rabbit alveolar macrophages. Pre-exposure to DEHP caused a slight increase in phagocytosis and a dose-dependent inhibition of alveolar macrophage killing ofS. aureus, reaching a 14-fold decrease in the killing index at a concentration of 2 mg DEHP per 100 ml of media. The significance of this inhibition is discussed with respect to the role of the plasticizer in lung disease and macrophage research.     

Studies by the National Toxicology Program on di(2-ethylhexyl)phthalate

In a 2-year feed study previously reported by the National Toxicology Program (NTP), the plasticizer di(2-ethylhexyl)phthalate (DEHP) was found to produce increased incidences of hepatocellular neoplasms in both sexes of Fischer 344 (F344) rats and B6C3F1 mice. Further studies by the NTP on this chemical have investigated its genotoxicity, dermal absorption, reproductive and developmental toxicity, and biochemical mechanism of action. DEHP was not mutagenic in Salmonella typhimurium (strains TA98, TA100, TA1535 or TA1537), in L5178Y mouse lymphoma cells, or in Drosophila melanogaster. DEHP did not induce chromosomal aberrations, but did cause a marginal dose-related increase in sister chromatid exchanges in CHO cells. In a dermal absorption study, DEHP was not absorbed well through the skin of F344 rats. In a fertility assessment study, DEHP was shown to be a reproductive toxicant in both male and female CD-1 mice. The teratogenic potential of DEHP was evaluated in F344 rats and CD-1 mice. In the rat study, there were no significant differences in percent fetuses malformed between control and treatment groups, even at dose levels (1.0, 1.5 and 2.0%) which produced significant maternal and fetal toxicity. In the mouse study, the incidence of fetuses with malformations was significantly increased at dose levels which produced maternal and/or fetal toxicity (0.10 and 0.15%), and at a dose level (0.05%) which did not cause maternal or fetal toxicity. The no-observed effect level for developmental toxicity in mice was 0.025% DEHP. Kinetic data on the rates of formation of H2O2 by peroxisomal palmitoyl CoA oxidase, and of degradation of H2O2 by catalase, was used to estimate in vitro steady-state H2O2 concentrations during peroxisomal oxidation of palmitoyl CoA. Increases in steady-state H2O2 in liver homogenates of rats treated with DEHP, di(2-ethylhexyl)adipate, or nafenopin, a hypolipidemic drug, correlated well with the carcinogenic potential of these chemicals determined in previous carcinogenicity studies, and are consistent with but not definitive evidence for the involvement of peroxisome proliferation in the hepatocarcinogenesis of these compounds.     

In vivo studies on the mechanism of di(2-ethylhexyl)phthalate carcinogenesis

In a study sponsored by the National Toxicology Program, di(2-ethylhexyl)phthalate (DEHP) fed in the diet at 1.2% significantly increased the incidence of female rats with hepatocellular carcinomas. Extensive evaluation of DEHP for carcinogenicity has yielded negative results. The present investigations were designed to elucidate the mechanism of DEHP hepatocarcinogenesis under the conditions of the original bioassay. Short-term studies designed to evaluate the promoting capability of DEHP, when administered after initiation, were negative when livers of female Fischer-344 rats were evaluated using multiple histochemical stains to identify foci of cellular alteration. Two different protocols were used to evaluate the initiating potential of DEHP in the liver using histochemically defined foci as the endpoint. In both experiments the results were negative. Chronic exposure to DEHP at 1.2% in the diet for 2 years resulted in elevation of hepatic peroxisomal enzymes while DNA replication, an indication of cell proliferation, was not affected in hepatocytes. The number of foci was not elevated in the DEHP group compared to the controls, even though a low incidence of rats with liver tumors occurred in the treated group. The results of this series, as well as other published results, suggest that DEHP and other peroxisomal proliferating chemicals have unique effects on the development of hepatic neoplasms. The absence of altered foci after chronic administration or in initiation-promotion protocols distinguishes DEHP and perhaps other peroxisomal proliferating chemicals from both classic liver carcinogens and promoters.     

Embryotoxic effects of di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) in mice

Two major compounds of PVC plasticizers, di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP), were mixed with food at levels of 0.05, 0.1, 0.2, 0.4, and 1.0 wt% and given to pregnant mice of ICR-JCL strain throughout gestation. Treatment with 0.2, 0.4, and 1.0% DEHP and 1.0% DBP resulted in decreased maternal weight gain and increased resorption rate. All of the implanted ova died in utero at 0.4 and 1.0% level of DEHP. The malformation rate in term fetuses increased at 0.2% level of DEHP and 1.0% level of DBP, the difference from the control group being at the borderline level of significance. The major malformations observed in the treated groups were neural tube defects (exencephaly and spina bifida), suggesting that the phthalic acid esters could interfere with the closure of neuropores in developing embryos. Treatment with the compounds caused intrauterine growth retardation and delayed ossification with an apparently dose-related response pattern. These results indicate that DEHP and DBP at a high dose level could be embryotoxic and possibly teratogenic mice. The maximum no effect level of the PAEs on mouse fetuses was 70 mg/kg/day, which is far higher than the estimated human current intake from the environment.     

邻苯二甲酸二乙基己基酯对大鼠肝细胞和睾丸细胞DNA单链断裂水平的影响

目的 探讨邻苯二甲酸二乙基已基酯(DEHP)对大鼠肝细胞和睾丸细胞DNA的损伤.方法 选用雄性Wis-ter大鼠25只,随机分为5组,每组5只,通过灌胃的方法摄入DEHP,4个染毒组剂量浓度分别为1 500、3 000、4 500、6 000 mg·kg-1·d-1,1个阴性溶剂对照组,用单细胞凝胶电泳技术(彗星试验)检测大鼠肝细胞和睾丸细胞DNA的损伤.结果 各染毒组和对照组大鼠肝细胞DNA损伤率分别为28.0%、69.0%、86.0%、94.0%和18.0%,各染毒组肝细胞DNA损伤程度与对照组比较差异有显著性(P<0.05,P<0.01),且大鼠肝细胞损伤率与染毒剂量之间呈剂量-反应关系(r=0.942,P<0.01);各染毒组和对照组大鼠睾丸细胞DNA损伤率分别为29.0%、71.0%、89.0%、95.0%和15.0%,各染毒组睾丸细胞DNA损伤程度与对照组比较差异有显著性(P<0.05,P<0.01),且大鼠睾丸细胞损伤率与染毒剂量之间呈剂量-反应关系(r=0.930,P<0.01).结论 DEHP可造成大鼠的肝细胞和睾丸细胞DNA的损伤,并随染毒剂量的增加有加重的趋势.     

Metabolic and peroxisome proliferation studies with di(2-ethylhexyl)phthalate in rats and monkeys

Male Fischer 344 rats and cynomolgus monkeys were treated with various doses of di(2-ethylhexyl)phthalate (DEHP) for at least 21 days. There was metabolic, biochemical, and morphological evidence for peroxisomal proliferation in rats that consumed diets containing 1000 ppm DEHP and above. These diets were estimated to provide average daily doses of about 100 mg/kg of DEHP. In contrast, peroxisomal proliferation was not observed in monkeys that received up to 500 mg/kg/day of DEHP by gavage. The results of this study suggest that rats do not provide a good model for predicting the results of DEHP exposure on peroxisomal proliferation in higher primates.