Two-generation reproduction studies in rats fed di-isodecyl phthalate
Two-generation reproduction studies in rats fed di-isodecyl phthalate
复制标题
DOI：
10.1016/s0890-6238(01)00109-5
复制
发表时间：
2001-03-01
影响因子：
3.3
通讯作者：
McKee, RH
中科院分区：
文献类型：
--
作者：
Hushka, LJ;Waterman, SJ;McKee, RH
邻苯二甲酸二异癸酯（DIDP）是一种商业增塑剂，在许多动物研究中具有低毒性。采用通常符合现行法规指导原则的两代生殖毒性研究，在Sprague-Dawley大鼠中评估了DIDP饮食给药对生育力和发育参数的影响。膳食水平范围为0.02 - 0.8%（或约15 - 600 mg/kg/天）。在生殖研究中，对生育力无影响，但成年体重沿着降低，肝脏和肾脏重量相应增加，组织病理学变化表明过氧化物酶体增殖。对活产指数没有影响，但在出生后第1至4天观察到后代存活率降低。这种存活率降低在F-2代中更为明显，其中在0.2% DIDP和更高水平下达到统计学显著性。断奶前，后代体重也出现一过性下降，这与后代快速生长和高水平摄食量相对应。发育标志无明显变化。总体而言，这些研究提供了实验定义的无明显不良反应水平（NOAEL），F、后代存活率为0.06%（约50 mg/kg/天），生育力、其他生殖功能指标和发育标志为0.8%（约600 mg/kg/天）。两项研究数据的统计学评价确定108 mg/kg/天（95%下限值为86 mg/kg/天）为F-2后代存活率降低的理论NOAEL。(C)2001 Elsevier Science Inc. All rights reserved.
Di-isodecyl phthalate (DIDP) is a commercial plasticizer with low toxicity in many animal studies. The effects of dietary DIDP administration on fertility and developmental parameters were assessed in Sprague-Dawley rats utilizing two generation reproductive toxicity studies generally consistent with current regulatory guidelines. Dietary levels ranged from 0.02 to 0.8% (or approximately 15 to 600 mg/kg/day). In the reproductive studies, there were no effects on fertility, but there were decreases in adult body weight along with corresponding increases in liver and kidney weights and histopathologic changes indicative of peroxisomal proliferation. There were no effects on live birth index, but reduced offspring survival was observed at postnatal days 1 to 4. This reduced survival was more pronounced in the F-2 generation in which statistical significance was achieved at levels of 0.2% DIDP and greater. There were also transient decreases in offspring body weights prior to weaning, corresponding to rapid offspring growth, and high levels of food consumption. There were no notable alterations in developmental landmarks. Overall, these studies provided experimentally defined No-Observed-Adverse-Effect Levels (NOAELs) of 0.06% (approximately 50 mg/kg/day) for F, offspring survival and 0.8% (approximately 600 mg/kg/day) for fertility, other measures of reproductive function, and developmental landmarks. Statistical evaluation of the data from both studies identified 108 mg/kg/day with a 95% lower bound value of 86 mg/kg/day as a theoretical NOAEL for reduced F-2 offspring survival. (C) 2001 Elsevier Science Inc. All rights reserved.