权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Reproductive toxicity of endocrine-disrupting chemicals and the mechanism via peroxisome proliferators-activated receptor in relation to the risk assessment

内分泌干扰物的生殖毒性及过氧化物酶体增殖物激活受体的机制与风险评估的关系

基本信息

批准号：
11470095
负责人：
NASU Tamie
金额：
$ 8.19万
依托单位：
Nagoya University (2001)Shinshu University (1999-2000)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Phthalic acid esters are typical plasticizer, which is recently noted as an endocrine-disrupting chemical. These chemicals are known as a ligand to peroxisome proliferators-activated receptor a (PPARα). Reproductive toxicity of di(2-ethylhexyl) phthalate (DEHP) and the mechanism were investigated using wild-type Sv/129 mice and PPARα-null mice on the same genetic background. A 0.05% DEHP diet was prepared with commercial rodent chow. DEHP treatment increased the resolution of fetus and mortality of new born pups per pair in wild-type mice, but not in the PPARα-null mice. Although PPARα was related to testosterone level in serum of male mice, DEHP also decreased the level in wild-type mice, not in the PPARα-null mice. These results suggest that the reproductive effect of DEHP and effect on testosterone level in serum are closely related to the expression of PPARα. Phthalic acid esters other than DEHP induced PPARα dependently on the lipid solubility. 2,4-Dichlorophenoxyacetic acid, one of herbicides, induced PPARα and decreased testosterone level in male mice, which is due, in part, to downregulate cholesterol-synthetic enzymes.We also measured DEHP concentration in meals including coffee or tea of 16 persons, and then calculated the total intake per day. DEHP was found in all samples, and the concentration levels were 30〜370ug/kg, and the average was 124ug/kg, which was estimated at 70〜1200ug/day (average 320ug/day).

邻苯二甲酸酯类是典型的增塑剂，近年来被认为是一种内分泌干扰物。这些化学物质被认为是过氧化物酶体增殖物激活受体α（PPARα）的配体。采用野生型Sv/129小鼠和相同遗传背景的过氧化物酶体增殖物激活受体（PPARα）基因敲除小鼠，研究了邻苯二甲酸二（2-乙基己基）酯（DEHP）的生殖毒性及其机制。用市售啮齿动物饲料制备0.05% DEHP饲料。DEHP处理增加了野生型小鼠中每对新生幼仔的胎儿分辨率和死亡率，但在PPARα缺失小鼠中没有。虽然PPARα与雄性小鼠血清中的睾酮水平相关，但DEHP也降低了野生型小鼠的水平，而不是在PPARα缺失小鼠中。结果提示，DEHP的生殖效应和对血清睾酮水平的影响与PPARα的表达密切相关。邻苯二甲酸酯（DEHP除外）诱导的PPARα依赖于脂溶性。除草剂2，4-二氯苯氧乙酸（2，4-Dichlorophenoxyacetic acid，2所有样本中均发现DEHP，浓度水平为30 ~ 370 ug/kg，平均值为124 ug/kg，估计为70 ~ 1200 ug/天（平均值为320 ug/天）。