2002 Fiscal Year Final Research Report Summary
REPRODUCTIVE IMMUNOTOXICITY OF PLASTICISER, DEHP IN RODENTS
| Project/Area Number |
13672381
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
UENO Koichi CHIBA UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・薬学研究院, 教授 (60125903)
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| Project Period (FY) |
2001 – 2002
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| Keywords | ENVIRONMENTAL HORMONE / di (2-ethylhexyl)phthalate / PLASITICISER / REPRODUCTIVE TOXICITY / IMMUNITY / RODENTS / HUMORAL IMMUNE RESPONSE / DTH REACTION |
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| Research Abstract |
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.
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