REPRODUCTIVE IMMUNOTOXICITY OF PLASTICISER, DEHP IN RODENTS

在医疗环境中接触邻苯二甲酸二（2-乙基己基）酯（DEHP）尤其令人关注，因为接触量可能很大，而且接触者，如早产儿和其他新生儿或患有危及生命疾病的成年人，可能特别容易受到有毒化学品的影响。目的是确定DEHP对生殖免疫毒性的影响，并评估免疫抑制和生殖效应的潜在影响。我们发现DEHP从PVC医疗器械管材中浸出到医疗溶液中。在含有Tween 80的医疗溶液中以平均浓度1.2mg/L测量了DEHP。妊娠大鼠口服DEHP 1周后，胎儿及母体血浆、胎盘、羊水中均检测到DEHP及其代谢物，子代出现免疫改变。此外，在母鼠和小鼠妊娠至哺乳期对DEHP进行处理时，测定母鼠乳汁和幼鼠的DEHP和MEHP。DEHP能够穿过胎盘屏障，影响发育中的胎儿和新生儿的免疫系统。DEHP暴露鼠的免疫毒性表现为雌性F_1大鼠体液免疫应答显著降低，DTH应答和螨抗原诱导的过敏反应显著降低。另一方面，DEHP预处理母鼠的成年F_1雄性小鼠睾丸重量明显减少，细胞介导的免疫应答被激活。这些结果表明，DEHP具有影响啮齿动物下一代免疫反应的能力，其作用方式存在物种差异和性别差异。

di-(2-ethylhexyl) phthalate (DEHP) exposure occurring in the medical setting are of particular concern because the amount of exposure can be substantial and because those exposed, such as premature infants and other neonates or adults with life-threatening illnesses, may be particularly vulnerable to the effect of toxic chemicals. The objectives are to determine the impact of DEHP on reproductive immunotoxicity and evaluate potential impacts of immunosuppression and reproductive effects.We found that DEHP leached from PVC medical device tubing settings into medical solutions. DEHP has been measured in medical solutions at a mean concentration of 1.2mg/L in solutions containing Tween 80. When DEHP was administered orally for a week of gestation in pregnant rats, DEHP and its metabolite were detected in fetuses as well as in maternal plasma, placenta and amniotic fluid, and the offspring showed the immunological alterations. In addition, when DEHP was treated from gestation to lactating period in maternal rats and mice, DEHP and MEHP were measured in maternal milk and the infants.DEHP was able to cross the placental barrier and influenced the immune system of developing fetuses and neonates. Evidence of immunotoxicity in the DEHP exposed dams in rodents included a significant decrease in humoral immune responses of the female F_1 rat, and in DTH responses and mite antigens induced allergic reactions of female F_1 mice. On the other hands, a significant decrease of testis weights and the activation of cell-mediated immune responses were observed in adult F_1 male mice from the DEHP pretreated maternal mice.These results indicate that DEHP possesses the abilities to influence the immune response of the next generation in rodents, and there are species differences and sex differences in the mode of action.