Lington A W, Bird M G, Plutnick R T, Stubblefield W A, Scala R A
Exxon Biomedical Sciences, Inc., East Millstone, New Jersey, 08875-2350, USA.
Fundam Appl Toxicol. 1997 Mar;36(1):79-89. doi: 10.1006/faat.1997.2286.
Groups of 110 Fischer 344 rats/sex were fed diisononyl phthalate (DINP) at dietary levels of 0, 0.03, 0.3, and 0.6 wt% for periods up to 2 years. Interim sacrifices of 10 predesignated rats/sex/dose were at 6, 12, and 18 months with surviving animals sacrificed at 24 months. At study termination, survival was in excess of 60% for every group. At the mid or high dose, the following biological effects were noted: slight decreases in food consumption and body weight; slight increase in mortality; a dose-related increase in relative organ weights of liver and kidney; and some slight effects on urinalysis, hematologic, and clinical chemistry parameters. No peroxisome induction was observed in livers of treated rats compared with controls. No clear treatment-related nonneoplastic or neoplastic lesions were found. However, mononuclear cell leukemia (MNCL) and changes known to be associated with an increased incidence of MNCL were seen in the mid-dose and high-dose groups. A literature review suggests that MNCL is a common finding in aging F344 rats and that this increased incidence in rats treated with DINP is not relevant to man. A clear no-observed-effect level was demonstrated for all biological end points at a dietary level of 0. 03 wt% or approximately 17 mg/kg/day of DINP.
将110只雄性和110只雌性Fischer 344大鼠分为几组，分别喂食邻苯二甲酸二异壬酯（DINP），其在饮食中的含量水平为0、0.03、0.3和0.6 wt%，持续时间长达2年。在6个月、12个月和18个月时，对预先指定的每组10只雄性和10只雌性大鼠进行中期处死，其余存活动物在24个月时处死。在研究结束时，每组的存活率均超过60%。在中剂量或高剂量组中，观察到以下生物学效应：食物消耗量和体重略有下降；死亡率略有上升；肝脏和肾脏的相对器官重量呈剂量相关增加；对尿液分析、血液学和临床化学参数有一些轻微影响。与对照组相比，在处理过的大鼠肝脏中未观察到过氧化物酶体诱导现象。未发现明确的与处理相关的非肿瘤性或肿瘤性病变。然而，在中剂量组和高剂量组中发现了单核细胞白血病（MNCL）以及已知与MNCL发病率增加相关的变化。文献综述表明，MNCL在衰老的F344大鼠中很常见，并且用DINP处理的大鼠中这种发病率的增加与人类无关。在饮食中DINP含量水平为0.03 wt%或约17 mg/kg/天时，所有生物学终点均显示出明确的未观察到效应水平。
