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。     

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。     

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(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(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。     

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。     

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.     

Effects of in utero and lactational exposure to di(2-ethylhexyl)phthalate on somatic and physical development in rat offspring

Di(2-ethylhexyl)phthalate (DEHP) has been reported to act as an antiandrogen and to affect the reproductive organs and accessory genital glands. Thus, to assess the reproductive toxicity of DEHP it is important to examine both its adverse effects on the development of offspring following maternal exposure and its effects on sexual function and fertility. In the present study, we examined whether in utero and lactational exposure to DEHP affects postnatal somatic growth of offspring in the rat. Pregnant females were orally administered various doses of DEHP (0, 25, 100 or 400 mg/kg body weight/day) from gestational day (GD) 6 through postnatal day (PND) 20. There were no significant changes in body weight, body length, tail length, or the weight of individual organs between the control and DEHP-treated groups. Somatic hormonal parameters were the same for all DEHP doses. These findings suggest that in utero and lactational exposure to various concentrations of DEHP has very little effect on postnatal development or endocrine and physical status of male and female rat offspring under the experimental conditions of the present study.     

青春期前邻苯二甲酸二(2-乙基)己酯暴露对雌性大鼠生殖发育及过氧化物酶体增殖剂激活受体的影响

目的探讨邻苯二甲酸二(2-乙基)己酯(DEHP)暴露对青春期前雌性大鼠性发育及生殖内分泌功能的影响及其可能机制。方法将40只健康3周龄雌性SD大鼠,随机分成对照组(玉米油)和3个实验组,每组10只。实验组按50、150、500mg/kg DEHP经口灌胃,连续染毒28天。观察阴道开口、乳房发育、第一次发情周期的日龄及体重,于末次染毒24小时后进行阴道涂片,确定动情间期,处死动物。Real-time PCR测定卵巢组织相关基因表达水平;ELISA法检测血清中卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、孕酮(P4)及睾酮(T)水平;通过病理学观察卵巢组织的变化;免疫组织化学法测定卵巢组织中PPARγ的表达。结果 500mg/kg组阴道开口日龄提前,150、500mg/kg组阴道开口时体重增加(P<0.05);150、500mg/kg组芳香化酶(P450Arom)mRNA表达与对照组比较,显著下降;各剂量组与对照组相比,T水平明显下降,150、500mg/kg组FSH、E2水平明显减少,而LH水平明显升高(P<0.05);150、500mg/kg组闭锁卵泡明显增多、黄体数目明显减少;150、500mg/kg组卵泡颗粒细胞和黄体颗粒细胞中PPARγ阳性光密度相对量明显高于对照组及50mg/kg组(P<0.05)。结论青春期前DEHP暴露对雌性大鼠性发育及生殖内分泌功能产生影响,其作用机制可能与激活PPARs有关。     

Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate

Several members of the phthalate ester family have antiandrogenic properties, yet little is known about how exposure to these ubiquitous environmental contaminants early in development may affect sexual development. We conducted experiments to determine effects of in utero and lactational exposure to the most prevalent phthalate ester, di(2-ethylhexyl) phthalate (DEHP), on male reproductive system development and sexual behavior. Sprague-Dawley rats were dosed with corn oil or DEHP (0, 375, 750, or 1,500 mg/kg/day, per os) from gestation day 3 through postnatal day (PND) 21. Dose-related effects on male offspring included reduced anogenital distance, areola and nipple retention, undescended testes, and permanently incomplete preputial separation. Testis, epididymis, glans penis, ventral prostate, dorsolateral prostate, anterior prostate, and seminal vesicle weights were reduced at PND 21, 63, and/or 105-112. Additional dose-related effects included a high incidence of anterior prostate agenesis, a lower incidence of partial or complete ventral prostate agenesis, occasional dorsolateral prostate and seminal vesicle agenesis, reduced sperm counts, and testicular, epididymal, and penile malformations. Many DEHP-exposed males were sexually inactive in the presence of receptive control females, but sexual inactivity did not correlate with abnormal male reproductive organs. These results suggest that in utero and lactational DEHP exposure also inhibited sexually dimorphic central nervous system development. No major abnormalities were found in any of eight control litters, but DEHP caused severe male reproductive system toxicity in five of eight litters at 375 mg/kg/day, seven of eight litters at 750 mg/kg/day, and five of five litters at 1,500 mg/kg/day. These results demonstrate that the male reproductive system is far more sensitive to DEHP early in development than when animals are exposed as juveniles or adults. The effects of DEHP on male reproductive organs and sexual behaviors and the lack of significant effects on time to vaginal opening and first estrus in their littermates demonstrate that DEHP (and/or its metabolites) affects development of the male reproductive system primarily by acting as an antiandrogen. The pattern of effects of in utero and lactational DEHP exposure differed from patterns caused by other phthalate esters, and the preponderance of anterior prostate agenesis appears to be unique among all chemicals. These results suggest that DEHP acts partly by mechanisms distinct from those of other antiandrogens.     

In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy

Di-(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer in flexible polyvinylchloride formulations, is a ubiquitous environmental contaminant. To date, no information exists on the potential health hazards from exposure to DEHP and/or its main metabolite, mono-(2-ethylhexyl)phthalate (MEHP), in high-risk conditions, such as pregnancy and during the neonatal period. The aim of this study was to evaluate prenatal exposure to DEHP and/or MEHP and its possible biologic effects. We measured serum DEHP and MEHP concentrations in the cord blood of 84 consecutive newborns by high-performance liquid chromatography. Relationships between DEHP/MEHP and infant characteristics were tested using Fisher's exact test, unpaired t-tests, and univariate linear regression analyses, and significant differences on univariate analysis were evaluated using multiple logistic regression analysis. We found detectable cord blood DEHP and/or MEHP concentrations in 88.1% of the samples. Either DEHP or MEHP was present in 65 of 84 (77.4%) of the examined samples. Mean concentrations of DEHP and MEHP were 1.19 +/- 1.15 microg/mL [95% confidence interval (CI), 0.93-1.44, range = 0-4.71] and 0.52 +/- 0.61 microg/mL (95% CI, 0.39-0.66, range = 0-2.94), respectively. MEHP-positive newborns showed a significantly lower gestational age compared with MEHP-negative infants (p = 0.033). Logistic regression analysis results indicated a positive correlation between absence of MEHP in cord blood and gestational age at delivery (odds ratio = 1.50, 95% CI, 1.013-2.21; p = 0.043). These findings confirm that human exposure to DEHP can begin in utero and suggest that phthalate exposure is significantly associated with a shorter pregnancy duration.     

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.     

Urine phthalate determinations as an index of occupational exposure to phthalic anhydride and di(2-ethylhexyl)phthalate

Although it has been estimated that over 600 000 workers in the United States are exposed to di(2-ethylhexyl)phthalate (DEHP), an animal carcinogen, and that over 100 000 are exposed to phthalic anhydride (PA), few data are available on levels of phthalates in biological fluids of these workers. For a determination of occupational exposure to PA and DEHP at a plant manufacturing DEHP from PA and 2-ethylhexanol, air samples were taken for PA and DEHP, and pre- and postshift urine samples were collected for the determination of total phthalates. Urine samples were obtained from 48 workers in jobs with high exposure to phthalates and from 47 workers in jobs with low exposure. The airborne concentrations of DEHP ranged from 20 to 4 110 micrograms/m3, and the concentrations of PA ranged from 4 to 203 micrograms/m3. The most heavily exposed workers had the highest mean postshift urine phthalate concentration (geometric mean 7.6 nmol/ml) (p = 0.015), and also the greatest mean increase (4.4 nmol/ml) in preshift to postshift urine phthalate levels. Twofold increases over the shift in urine phthalate concentration and postshift phthalate levels of greater than 10 nmol/ml were observed in 8 (25%) of 32 chemical operators, but in none of 52 other workers. These data suggest that measurement of urine phthalate levels may have utility for monitoring the exposure of workers manufacturing or using PA.     

Concentration of di(2-ethylhexyl) phthalate (DEHP) in foods and its dietary exposure in China

Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in food contact materials that has been reported as an endocrine disruptor. In the present study, DEHP concentrations were analyzed in foods in order to determine dietary exposure among the Chinese population, including the general population (aged 2–100) and four age group, that is children aged 2–6, adolescent aged 7–12, young people aged 13–17 and adults aged 18 years old and above. 1704 food samples were collected during 2011–2012 and categorized into 12 food groups which covered major foods in China. Food consumption data were taken from China National Nutrient and Health Survey which was performed in 2002 and includes data from 68,959 subjects. Mean concentrations of DEHP were combined with individual food consumption data to estimate dietary exposure. It was found that DEHP levels in foods ranged from not detected to 3.41 mg/kg, with highest mean values in meat (0.23 mg/kg) and vegetable oils (0.21 mg/kg). Mean dietary intakes of DEHP in the general population, children, and adults were 2.34, 4.51, 2.03 μg/kg bw per day, respectively. The 97.5% intakes in these populations were 5.22, 8.43, 3.64 μg/kg bw per day, respectively. The main food sources of DEHP dietary intake were cereals (39.44%), drinking water (16.94%) and meat (15.81%) in children, and cereals (44.57%), meat (15.70%) and drinking water (12.28%) for adults. These findings suggested that dietary exposure to DEHP among Chinese population was lower than tolerable daily intake of DEHP and there are no health concerns based on generally accepted exposure limits.     

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.