孕期及哺乳期经口邻苯二甲酸二(2-乙基己基)酯染毒对大鼠的生殖毒性

目的 观察邻苯二甲酸二(2-乙基己基)酯(DEHP)对大鼠的生殖发育毒性作用.方法 采用围生期毒性试验的研究方法,将清洁级SD大鼠随机分为对照组(玉米油)和4个DEHP染毒组(125、250、500、1 000mg/kg),采用宫内及哺乳期经口灌胃的方式染毒.记录比较孕鼠孕0、20天(GD0、GD20)、仔鼠出生后21天(PND21)母鼠体重及体重增长量,产后第1天(PND1)记录产仔总数及仔鼠平均出生体重;产后第4天(PND4)辨别雌雄仔鼠,分别测量雌雄仔鼠平均肛殖距,于仔鼠断乳(PND21)后,计数着床数,取母鼠各脏器称重并计算脏器系数.结果 母鼠染毒期间,体重及其体重增长量不同程度降低(P＜0.05),各脏器系数均不同程度增大(P＜0.01),各染毒组受孕率差异有统计学意义(χ~2=16.816,P＜0.01);与对照组比较,1 000mg/kg组仔鼠平均活胎数、平均出生体重、子宫着床点数降低(P＜0.05),肛殖距不同程度缩短(P＜0.01).结论 DEHP可降低雌鼠受孕率及母鼠产仔总数,可通过胎盘屏障对仔鼠的生长发育产生毒性作用,导致低出生体重,对仔鼠的生殖发育有毒性作用.

Abstract：

Objective To observe the procreating and developing toxicity effect of phthalate(2-ethylhexyl)ester on rats.Methods The perinatal toxicity test methods was applied,the negative control group(corn oil)and four DEHP exposure groups(125,250,500,1000 mg/kg)were set,the SD pregnant rats were treated with DEHP by gavage.GD0,GD20,PND21 pregnant rats body weight and weight increase were recorded and compared.At PND1,the total number of birth and average birth weight of young rats were recorded;At PND4 male and female rats were distinguished,male and female rats were measured for average anogenital distance.After weaning(PND21),pregnant rats were killed,the numbers of implantation were counted,organs were weighted and organ coefficients were calculated.Results During exposure to different doses of DEHP,pregnant rats body weight and body weight increase reduced in degrees(P＜0.05),the organ coefficients were increased in degrees(P＜0.01),the pregnancy rate of exposure groups showed statistically differences(χ~2=16.816,P＜0.01);Compared with control group,the average number of live births and the average birth weight,the number of uterine implantation of the 1 000 mg/kg group reduced(P＜0.05),anogenital distance reduced in degrees(P＜0.01).Conclusion DEHP can reduce female conception rates and the litter size,may have the toxic effect through the placental barrier on the growth of rats,leading to low birth weight,and have the toxic effect on the reproductive development of rats.     

大鼠孕期及哺乳期邻苯二甲酸二(2-乙基己基)酯暴露致雄性仔鼠脑组织病理学改变

目的观察邻苯二甲酸二(2-乙基已基)酯(DEHP)宫内及哺乳期暴露对子代雄性大鼠脑组织发育的影响。方法采用围生期毒性试验的研究方法,将清洁级SD大鼠随机分为阴性对照组(玉米油)和4个DEHP染毒组(125、250、500、1000mg/kg),采用宫内及哺乳期经口灌胃的方式染毒。记录比较孕鼠孕0、20d(GD0、GD20)、仔鼠出生后21d(PND21)母鼠体重及体重增长量、雄性仔鼠不同发育阶段体重、脑脏器系数;观察雄性仔鼠不同发育阶段脑组织病理学及超微病理学改变。结果母鼠染毒期间,体重及体重增长量不同程度降低(P0.05)。不同发育阶段雄性仔鼠体重显示,0～500mg/kg组随染毒剂量增加而增加,1000mg/kg组体重均明显低于相同发育阶段对照组仔鼠体重,仅PND21仔鼠体重500mg/kg组与对照组比较,差异有统计学意义(P0.05)。PND21雄性仔鼠500mg/kg组脑脏器系数低于对照组,1000mg/kg组高于对照组,差异有统计学意义(P0.05)。各发育阶段海马区锥体细胞和大脑皮质神经元细胞表现为不同程度的核固缩变性,500、1000mg/kg组表现较为严重。电镜结果显示各发育阶段海马区锥体细胞核不同程度固缩、线粒体灶性损伤,粗面内质网不同程度损伤,突触增多。结论 DEHP宫内及孕期暴露可引起雄性仔鼠脑组织病理形态改变,可影响雄性仔鼠脑组织生长。     

邻苯二甲酸二(2-乙基己基)酯、氯氰菊酯单独及联合染毒对青春前期雄性大鼠生殖发育的不良影响

目的探讨邻苯二甲酸二(2-乙基己基)酯(DEHP)和氯氰菊酯(CYP)单独及联合染毒对青春前期雄性大鼠生殖发育的不良影响。方法选择SPF级3周龄雄性SD大鼠24只,随机分为4组,分别为对照组(喂饲玉米油)、DEHP染毒组(500mg/kg)、CYP染毒组(80mg/kg);DEHP、CYP联合染毒组(DEHP 500mg/kg+CYP 80mg/kg),每组6只。采用经口灌胃方式染毒,每天1次,连续染毒30天。于末次染毒24小时后处死动物,测定大鼠体重、睾丸湿重,并计算睾丸系数;测定血清睾酮水平;制备睾丸病理组织切片,光镜观察其组织学改变,电镜观察生殖细胞超微结构;测定睾丸标志酶乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、碱性磷酸酶(ALP)和琥珀酸脱氢酶(SDH)的活性。结果与对照组相比,DEHP、CYP单独及联合染毒组睾丸下降时间和包皮分离时间明显延迟,肛门生殖器间距明显缩短(P<0.05或0.01);DEHP单独染毒组睾丸重量及睾丸系数明显降低,血清睾酮水平显著下降(P<0.05),睾丸匀浆中ALP、ACP和LDH活性明显增高,SDH活性显著下降(P<0.01);DEHP、CYP单独及联合染毒组睾丸病理组织学、生殖细胞超微结构均可见明显异常。结论 DEHP、CYP单独及联合染毒对青春前期雄性大鼠均具有明显的生殖毒性作用,可引起生精细胞、支持细胞和间质细胞的变性、坏死及功能障碍,从而导致雄性生殖系统发育和功能的显著异常。其中,DEHP单独染毒呈现主效应,DEHP、CYP联合染毒对大鼠的生殖毒性未呈现明显交互影响。     

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.     

邻苯二甲酸(2-乙基己基)酯低剂量暴露对雄性小鼠生殖发育的影响

目的观察邻苯二甲酸(2-乙基己基)酯(DEHP)低剂量暴露对雄性小鼠的生殖发育毒性作用。方法将清洁级ICR小鼠随机分为4个DEHP染毒组(1/120LD50,1/60LD50,1/30LD50,1/15LD50,即250、500、1000、2000mg/kg组),阳性对照组(环磷酰胺,40mg/kg)和阴性对照组(玉米油);DEHP染毒组和阴性对照组灌胃染毒30d,阳性对照组灌胃5d,每天1次。采用一般生殖毒性试验和显性致死突变试验的方法,研究DEHP低剂量暴露对雄性小鼠生殖细胞的损伤作用和生育能力的影响。结果一般生殖毒性试验结果显示,低剂量DEHP染毒雄性小鼠睾丸、附睾重量降低(r睾丸=-0.578,P<0.01;r附睾=-0.661,P<0.01),精子总数减少(r=-0.608,P<0.01),精子畸形率增高(r=0.836,P<0.01),精子活动度降低(P<0.05)。显性致死突变试验研究结果显示,250mg/kgDEHP染毒组小鼠受孕率降低,但与阴性对照组比较,差异无统计学意义(P>0.05);DEHP染毒组子代小鼠平均着床数减少(r=-0.892,P<0.01),与阴性对照组比较,差异均具有统计学意义(P<0.01);平均早期死亡胚胎数随染毒剂量增加而增加(r=0.996,P<0.01),250mg/kg染毒组与阴性对照组比较,差异无统计学意义(P>0.05)。结论DEHP低剂量暴露对雄性小鼠具有生殖毒性作用,可降低小鼠受孕率,使子代小鼠平均着床数减少,平均早期死亡胚胎数增加。     

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。     

邻苯二甲酸二丁酯和邻苯二甲酸二(2-乙基己基)酯联合染毒对雄性大鼠生殖毒性的影响

目的探讨邻苯二甲酸二丁酯(di-n-butyl phthalate,DBP)和邻苯二甲酸二(2-乙基己基)酯(di-2-ethylhexyl phthalate,DEHP)联合染毒对雄性大鼠睾丸的脂质过氧化作用以及对生化酶和血清激素水平的影响。方法选择健康成年清洁级雄性SD大鼠32只,按2×2析因设计随机分为4组,分别为阴性对照组(玉米油)、DBP单独染毒组(1/20LD50,1.0g/kg)、DEHP单独染毒组(1/20LD50,1.7g/kg)和DBP+DEHP染毒组(1.0g/kgDBP+1.7g/kgDEHP),每组8只。采用经口灌胃方式进行染毒,染毒剂量为5ml/kg,每天1次,连续染毒8周。测定睾丸组织中超氧化物歧化酶(SOD)、还原性谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、酸性磷酸酶(ACP)、碱性磷酸酶(AKP)、γ-谷氨酰转肽酶(γ-GT)水平,测定血清中雄性激素睾酮(T),黄体生成素(LH)、促卵泡激素(FSH)水平。结果 DBP和DEHP联合染毒对睾丸组织中SOD活力和血清中T水平呈现协同作用,对γ-GT、ACP活力和FSH水平呈现拮抗作用。结论 DBP和DEHP联合染毒对雄性大鼠具有明显的生殖毒性作用,可能是通过破坏氧化-抗氧化系统的平衡和影响睾丸组织中酶的活力以及血清激素水平干扰下丘脑—垂体—睾丸轴的生理平衡,抑制T的分泌,导致雄性生殖功能的降低。     

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     

P,P'-DDE宫内暴露致雄性子代大鼠的生殖毒性

[目的]探讨宫内暴露p,p'-DDE对雄性子代生殖毒性的影响. [方法]母鼠交配成功后,将其随机分为对照(玉米油)组和100 mg/kg p,p'-DDE染毒组,每组8只.染毒组于孕第8～15d采用灌胃方式给予100 mg/kg p,p'-DDE处理,对照组孕鼠给予等容积玉米油.孕鼠自由分娩,观察仔鼠个数和出生性别,测量雄性仔鼠肛殖距及检查乳头存留情况;计算睾丸的脏器系数;利用计算机辅助精子分析系统测定雄性仔鼠的精子质量各相关指标;酶联免疫吸附法测定雄性子代血清睾酮水平. [结果]染毒组仔鼠肛殖距[(0.94±0.12)cm]较对照组仔鼠肛殖距[(1.11±0.13)cm]有所缩短,乳头存留率(34％)较对照组(0％)明显上调,精子数目[(50.00±4.62)×106个/mL],较对照组[(70.63±4.17)×106个/mL]明显降低,精子活力[(62.42±3.32)％],较对照组[(76.75±2.68)％]明显下降,差异均有统计学意义.2组雄性仔鼠雌雄比例、睾丸脏器系数、血清睾酮水平、睾丸重量差异均无统计学意义. [结论]宫内暴露p,p'-DDE可诱导雄性仔鼠出现雌性化特征,精子数目和活力下降,导致雄性子代生殖毒性.     

妊娠期大鼠皮下注射尼古丁对子代发育和行为的影响

[目的]研究妊娠期大鼠皮下注射尼古丁对仔鼠发育和行为的影响。[方法]24只孕期SD大鼠随机分为对照组和1.0、2.0、4.0 mg/kg染毒组,每组6只。受孕第7天起至仔鼠出生前,给予孕鼠皮下注射0、1.0、2.0、4.0 mg/kg尼古丁生理盐水溶液1 m L,1次/d;观察仔鼠出生后生长发育的一般指标(体重、脐带脱落、耳廓展开、萌齿、睁眼)变化,测定早期神经反射、水迷宫及学习记忆能力;观察仔鼠大脑海马区神经元突触超微结构。[结果]与对照组相比,实验组仔鼠体重显著降低(P<0.05或P<0.01);耳廓张开时间,对照组(3.41±0.44)d,4.0 mg/kg组(4.43±0.47)d;萌齿时间,对照组(10.98±1.21)d,4.0 mg/kg组(13.11±1.14)d;开眼时间,对照组(13.56±1.02)d,4.0 mg/kg组(15.89±1.20)d;3项指标两组差异均有统计学意义(P<0.05)。早期神经反射,对照组仔鼠出生后第4天和第7天达标率高于各实验组;水迷宫实验,对照组仔鼠潜伏期(39.66±8.54)s,2.0 mg/kg组(55.96±8.51)s,4.0 mg/kg组(58.99±7.66)s;目标区域停留时间,对照组仔鼠(41.22±6.23)s,1.0 mg/kg组(33.25±6.98)s,2.0 mg/kg组(30.33±8.21)s,4.0 mg/kg组(22.54±8.54)s;穿越平台次数,对照组仔鼠(6.64±0.96)次,2.0 mg/kg组(4.23±1.04)次,4.0 mg/kg组(3.19±1.11)次。超微结构观察显示尼古丁对海马区神经元突触损伤作用与暴露剂量呈正相关。[结论]妊娠中晚期较大剂量尼古丁暴露影响仔鼠的生长发育,但是对仔鼠的早期神经反射及空间学习记忆能力影响相对更明显,这可能是尼古丁主要影响了神经的生长发育。     

孕期三丁基氯化锡染毒对子代雄性大鼠发育及性激素的影响

目的 探讨孕期三丁基氯化锡(TBTC)暴露对子代雄性大鼠发育及性激素的影响.方法 将健康成年SPF级妊娠Wistar大鼠随机分为5.0、2.5、1.0 mg/kg TBTC染毒组和阴性对照组(玉米油),每组4只.从妊娠第12天起,采用经口灌胃方式进行染毒,每天1次,直至妊娠第20天,灌胃剂量为5.0 ml/kg.出生后第70天,每组随机抽取10只雄性仔鼠,称重后断头取血,分离双侧睾丸及附睾组织,称重,计算睾丸和附睾的脏器系数.测定血清中睾酮(T)浓度、黄体生成素(LH)、卵泡刺激素(FSH)水平.结果 各TBTC染毒组孕鼠产仔数及雌雄比例间比较,差异无统计学意义(P＞0.05).与对照组比较,2.5和5.0 mg/kg组雄性仔鼠断乳后体重降低,睾丸的脏器系数升高,差异均有统计学意义(P＜0.01).各TBTC染毒组雄性仔鼠附睾脏器系数间比较,差异无统计学意义(P＞0.05).各TBTC染毒组雄性仔鼠血清中T、LH、FSH浓度间比较,差异均无统计学意义(P＞0.05).结论 在妊娠中后期TBTC染毒对子代雄性大鼠具有内分泌干扰作用,影响其生长发育,但暴露尚未引起雄性仔鼠血清中性激素的变化.

Abstract：

Objective To explore the effects of tributyltin chloride (TBTC) exposure during pregnancy on development and sex hormone level of male offspring Wistar rats. Methods The healthy pregnant Wistar rats were randomly divided into 4 groups, 4 in each group,they were given doses of TBTC (5.0,2.5,1.0 mg/kg) by gavage from days 12-20 of gestation. On postnatal day (PND) 70,10 male offspring rats were randomly selected in each group and sacrificed, the blood samples were collected. The testis and epididymis were weighed for account of organic coefficient. The concentration of testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) in serum was measured. Results There were no significant differences in number and the sex ratio of offspring rats between the control group and the treatments groups (P>0.05). Compared with the control group, an obvious retarded development was observed from PND21-70 and the viscera coefficient of testis were increased significantly in 2.5 or 5.0 mg/(kg·d) group (P<0.01). No significant difference was observed in serum LH,FSH level. Conclusion TBTC exposure during pregnancy can cause retarded development and increase of organic coefficient of testis of male offspring rats.     

Internal exposure of nursery-school children and their parents and teachers to di(2-ethylhexyl)phthalate (DEHP)

Di(2-ethylhexyl)phthalate (DEHP) is the main plasticizer for polyvinyl chloride (PVC) products. It has become widely spread in our environment and among people. DEHP is suspected to be responsible for endocrine-disruptor-like effects in mankind. Children are probably most susceptible to these endocrine effects. In this study we determined the internal exposure of nursery school children (aged 2-6 years) to DEHP and compared it to their parents' and teachers' exposure. The DEHP-metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP) were determined in first morning urine. The sum of the three DEHP metabolites in children's and in adults' urine was 90.0 and 59.1 micrograms/l respectively (median values; p = 0.074). Concentrations of the secondary metabolites 5OH-MEHP (median: 49.6 vs. 32.1 micrograms/l; p = 0.038) and 5oxo-MEHP (median: 33.8 vs. 19.6 micrograms/l; p = 0.015) were significantly higher in children than in adults. MEHP concentrations were low both in adults and children (median: 6.6 micrograms/l vs. 9.0 micrograms/l). Creatinine adjusted values should more accurately reflect the dose taken up with respect to body weight when comparing children with adults. Total creatinine adjusted DEHP metabolites in urine were significantly higher in children than in adults (median values: 98.8 vs. 50.9 micrograms/g creatinine; p < 0.0001). This also applied to the concentrations of both secondary metabolites 5OH-MEHP (55.8 vs. 28.1 micrograms/g creatinine; p < 0.0001) and 5oxo-MEHP (38.3 vs. 17.2 micrograms/g creatinine; p < 0.0001). Creatinine corrected concentrations for the monoester MEHP in children and adults were very similar (8.7 vs. 8.6 micrograms/g creatinine; p = 0.908). Based on the sum of the three determined metabolites we estimated the DEHP dose (in microgram/kg body-weight) taken up by children to be about twice as high as the dose taken up by adults. Routes of the ubiquitous exposure to DEHP remain indistinct. In children's urine the mean relative ratios of MEHP to 5OH-MEHP to 5oxo-MEHP were 1 to 7.1 to 4.9, in adults they were 1 to 3.4 to 2.1. This might indicate an enhanced oxidative metabolism in children. To date no information on the biological activity and toxicity of oxidative metabolites of DEHP is available. Since these are the major metabolites of DEHP toxicological data on these metabolites is urgently needed.     

Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors

Each year thousands of healthy volunteers undergo apheresis procedures to donate blood components and safe lives. However, many disposables used in apheresis contain di(2-ethylhexyl)phthalate (DEHP). This way, donors are exposed to DEHP, which is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. We quantified the DEHP exposure of six plasma donors, six discontinuous-flow platelet donors and six continuous-flow platelet donors by determining three specific metabolites in urine (5OH-MEHP: mono(2-ethyl-5-hydroxyhexyl)phthalate; 5oxo-MEHP: mono(2-ethyl-5-oxo-hexyl)phthalate and MEHP: mono(2-ethylhexyl)phthalate). We found maximum concentrations in urine samples after the discontinuous-flow plateletpheresis procedure with 826 microg/l for 5OH-MEHP, 774 microg/l for 5oxo-MEHP and 266 microg/l for MEHP (mean of the six volunteers). Metabolite excretions were found to be significantly (p<0.0001) higher for both plateletpheresis techniques compared to plasmapheresis and controls. Continuous-flow plateletpheresis led to significantly higher (p<0.0001) excretions than discontinuous-flow plateletpheresis. Mean absolute DEHP exposures were 1.2 mg for discontinuous- and 2.1 mg for continuous-flow plateletpheresis. Exposure for plasmapheresis (0.37 mg) was in the range of the controls (0.41 mg). Mean DEHP doses for both plateletpheresis techniques (18.1 and 32.3 microg/kg/day) were close to or exceeded the reference dose (RfD) of the US EPA and tolerable daily intake (TDI) value of the EU on the day of the apheresis. Therefore, margins of safety might be insufficient to protect especially young men and women in their reproductive age from effects on reproductivity. At present, discontinuous-flow devices should be preferred to avert conceivable health risks from plateletpheresis donors. Strategies to avoid DEHP exposure of donors during apheresis need to be developed.     

甲基汞对亲仔两代大鼠的神经行为毒性效应

目的探讨大鼠妊娠期甲基汞暴露的母体毒性及对仔代的神经行为毒性效应。方法Wistar孕鼠52只于妊娠第6～9天用甲基汞0.00、0.01、0.05、2.00mg/(kg·d)连续灌胃。分别观察母体毒性 ;常规致畸实验 ;记录205只仔鼠早期生理发育和神经行为发育指标 ;10周龄仔鼠32只进行程序控制行为测试 ;分娩后5周母鼠和10周龄仔鼠各24只进行脑组织形态学观察和单胺类神经递质的测定。实验遵循随机、双盲原则。结果未观察到母体毒性和仔代形态畸形 ;3个暴露组胎仔的体重、尾长低于对照组 (P<0.01) ;各暴露组仔鼠体重增长、早期生理及神经行为发育滞后于对照组 (P<0.05) ;程序控制行为学习成绩比对照组降低 (P<0.05) ,有剂量_效应关系 (rs= -0.7273 ,P<0.01) ;各暴露组母鼠和仔鼠脑组织无形态学改变 ,但单胺类神经递质含量均比对照组显著增高 (P<0.05) ,有剂量_效应关系 (rs=0.7124～0.9257 ,P<0.01)。结论本研究剂量的妊娠期甲基汞暴露未观察到对孕鼠的毒性效应 ,但有轻度胚胎毒性 ,影响仔鼠的神经系统发育 ,导致仔鼠学习记忆能力降低 ,亲仔两代大鼠脑组织中单胺类神经递质的含量增高     

丙烯腈对雄性大鼠生殖内分泌系统影响的研究

目的探讨丙烯腈（ＡＮ）对雄性生殖内分泌系统的影响,为保护男工健康提供科学依据。方法应用ＲＩＡ测定大鼠血清和睾丸匀浆中Ｔ、ＬＨ、ＦＳＨ和Ｅ２水平,并对睾丸、附睾做光、电镜组织病理学检查。结果皮下注射染毒ＡＮ３８天各组大鼠各检测指标均未发现有意义的改变;染毒７７天２５ｍｇ·ｋｇ－１组血清中Ｔ下降,ＬＨ升高,睾丸中Ｔ含量下降,ＬＨ、ＦＳＨ、Ｅ２均升高;光、电镜可见间质细胞及生精上皮受到不同程度的损害。结论丙烯腈可对雄性生殖内分泌系统产生损害作用,影响血清及睾丸匀浆中性激素水平,可能危害工人及子代健康,应引起高度重视。     

DEHP对大鼠海马神经元树突和突触形态发育影响

目的 探讨邻苯二甲酸（2-乙基己基）酯[di-2-ethylhexyl）phthalate,DEHP]对大鼠海马神经元树突和突触形态发育的影响。方法 体外培养5 d的新生大鼠海马神经元DEHP暴露5 d后,激光共聚焦显微镜下观察免疫荧光染色后的神经元,分析树突丝、树突棘和突触密度,采用Western blot法检测突触蛋白表达水平。结果 0.10、1、10 μmol/L DEHP显著下调体外培养海马神经元的树突丝、树突棘和突触密度;与对照组比较,1 μmol/L DEHP组海马神经元树突丝、树突棘和突触密度[分别为（6.23±0.19）、（4.91±0.09）、（4.04±0.13）个/20 μm]明显下降（P<0.01）,该作用可被雌激素受体阻断剂ICI182,780部分消除（P<0.01）;1 μmol/L DEHP还可拮抗0.01 μmol/L 17β-E2对树突和突触密度的促进作用（P<0.01）;Western blot分析结果显示,与对照组比较,1 μmol/L DEHP神经细胞突触蛋白synapsin I、PSD-95、N-甲基-D-天冬氨酸（NMDA）受体亚基NR2B、磷酸化胞外调节蛋白激酶（p-ERK）1/2表达[分别为（0.53±0.08）、（0.75±0.03）、（0.66±0.06）、（0.67±0.02）]明显降低（P<0.01）。结论 DEHP可能由雌激素受体介导抑制大鼠海马神经元树突和突触形态发育,其机制可能与突触蛋白和NMDA受体表达水平下降及ERK1/2信号通路抑制有关。