REPRODUCTIVE IMMUNOTOXICITY OF PLASTICISER, DEHP IN RODENTS

增塑剂 DEHP 对啮齿动物的生殖免疫毒性

• 批准号: 13672381
• 负责人: UENO Koichi
• 金额: $ 2.18万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672381/
• 关键词: ENVIRONMENTAL HORMONE; di (2-ethylhexyl)phthalate; PLASITICISER; REPRODUCTIVE TOXICITY; IMMUNITY; RODENTS; HUMORAL IMMUNE RESPONSE; DTH REACTION; ラット

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.

在医疗环境中接触邻苯二甲酸二(2-乙基己基)酯(DEHP)特别令人关切，因为接触的量可能很大，而且接触者，如早产儿和其他新生儿或患有危及生命的疾病的成年人，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影响的潜在影响。我们发现DEHP从聚氯乙烯医疗器械管材环境中渗入医用溶液中。在含有吐温80的医用溶液中，DEHP的平均浓度为1.2 mg/L。孕鼠口服DEHP一周后，胎儿及母体血浆、胎盘和羊水中均可检测到DEHP及其代谢物，子代出现免疫学改变。此外，在孕期和哺乳期给药的大鼠和小鼠的乳汁中检测到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对啮齿动物免疫毒性的证据包括雌性F_1大鼠的体液免疫反应显著降低，雌性F_1小鼠的迟发型超敏反应和尘螨抗原诱导的变态反应显著降低。另一方面，DEHP处理的成年F1雄性小鼠睾丸重量明显减轻，细胞免疫反应被激活，表明DEHP具有影响下一代啮齿动物免疫反应的能力，且作用方式存在种属差异和性别差异。

项目成果

日本トキシコロジー学会教育委員会 分担執筆者:上野 光一: "トキシコロジー"朝倉書店. 327 (2002)

日本毒理学会教育委员会合著者：上野浩一：《毒理学》朝仓书店327（2002）。

K.Yamaura, K.Ogawa, T.Yonekawa, T.Nakamura, S.Yano, K.Ueno: "Inhibition of the antibody production by acetaminophen independent of liver injury in mice"Biol. Pharm. Bull.. 25(2). 201-205 (2002)

K.Yamaura、K.Okawa、T.Yonekawa、T.Nakamura、S.Yano、K.Ueno：“对乙酰氨基酚对抗体产生的抑制与小鼠肝损伤无关”Biol。

K. Yamaura, K. Ogawa, T. Yonekawa, T. Nakamura, S. Yano and K. Ueno: "Inhibition of the antibody production by acetaminophen independent of liver injury in mice"Biol. Pharm. Bull.. 25(2). 201-205 (2002)

K. Yamaura、K. Okawa、T. Yonekawa、T. Nakamura、S. Yano 和 K. Ueno：“对乙酰氨基酚对抗体产生的抑制与小鼠肝损伤无关”Biol。

Tomonori Nakamura, Akiko Sakai, Issei Isogami, Kazuhiro Noda, Koichi Ueno, Shingo Yano: "Abatement of Morphine-Induced Slowing in Gastrointestinal Transit by Dai-Kenchu-to, a Traditional Japanise Herbal Medicine"Jpn. J. Pharmacol.,. 88・2. 217-221 (2002)

Tomonori Nakamura、Akiko Sakai、Issei Isogami、Kazuhiro Noda、Koichi Ueno、Shingo Yano：“日本传统草药 Dai-Kenchu-to 减轻吗啡引起的胃肠道传输减慢”Jpn. Pharmacol.，。・2.217-221（2002）

E. Negishi, A. Hirai, N. Yoshizaki, M. Yonezawa, T. Akiba and K. Ueno: "Electronic links between hospitals or clinics and pharmacies : Structure and operation of WAKASHIO pharmacotherapeusis network"YAKUGAKU ZASSHI. 123(3). 191-200 (2003)

E. Negishi、A. Hirai、N. Yoshizaki、M. Yonezawa、T. Akiba 和 K. Ueno：“医院或诊所与药房之间的电子链接：WAKASHIO 药物治疗网络的结构和操作”YAKUGAKU ZASSHI。