Subchronic oral toxicity of Di-n-octyl phthalate and di(2-ethylhexyl) phthalate in the rat
Subchronic oral toxicity of Di-n-octyl phthalate and di(2-ethylhexyl) phthalate in the rat
复制标题
DOI：
10.1016/s0278-6915(96)00064-6
复制
发表时间：
1997-02-01
影响因子：
4.3
通讯作者：
Chu, I
中科院分区：
文献类型：
--
作者：
Poon, R;Lecavalier, P;Chu, I
研究了邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二正辛酯（DNOP）的亚慢性经口毒性。每组10只雄性和10只雌性Sprague-Dawley大鼠在13周内以0、5、50、500或5000 ppm的剂量在饮食中给予DEHP。在一项单独的研究中，10只雄性和10只雌性Sprague-Dawley大鼠在饲料中给予DNOP（5、50、500和5000 ppm），而对照组接受含4%玉米油的基础饲料，阳性对照组喂食含5000 ppm DEHP的饲料。生长速率和摄食量不受任一化合物给药的影响。在给予DEHP的最高剂量组的两种性别动物中观察到肝肿大，但在DNOP处理的动物中未观察到。在最高剂量下，DNOP导致肝脏乙氧基试卤灵-O-脱乙基酶活性增加3倍（雌性）和12倍（雄性），而DEHP则没有。血清生物化学的轻度变化主要局限于DEHP最高剂量组的大鼠，包括两种性别大鼠的血清白蛋白和白蛋白/球蛋白比值升高以及雌性大鼠的胆固醇降低。在暴露于500 ppm DEHP的雄性大鼠中观察到Sertoli细胞轻度空泡化。在5000 ppm DEHP时，雄性大鼠出现轻度至中度生精小管萎缩和支持细胞空泡化，两种性别的大鼠均显示肝过氧化物酶体增殖。5000 ppm的DEHP和DNOP均引起甲状腺轻度组织学变化，包括滤泡大小和胶体密度减小，以及肝脏内皮细胞核突出、核染色过度和异核。在DNOP处理的大鼠中，肝小叶的带状化加重，静脉周围细胞质空泡化增加。在肝脏中检测到痕量（3-5 ppm）DEHP和DNOP，在最高剂量组的脂肪组织中检测到15-31 ppm。DEHP的无毒性作用水平被判定为50 ppm或3.7 mg/kg体重/天，DNOP为500 ppm或36.8 mg/kg体重/天。(C)1997年爱思唯尔科学有限公司
The subchronic oral toxicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP) was studied. Groups of 10 male and 10 female Sprague-Dawley rats were administered DEHP in the diet at 0, 5, 50, 500 or 5000 ppm for 13 wk. In a separate study, groups of 10 male and 10 female Sprague-Dawley rats were given DNOP (5, 50, 500 and 5000 ppm) in the diet while control groups received basal diet containing 4% corn oil and positive control groups were fed a diet containing 5000 ppm DEHP. Growth rate and food consumption were not affected by treatment with either compound. Hepatomegaly was observed in the highest dose groups of both sexes administered DEHP but not in the DNOP-treated animals. At the highest dose, DNOP caused threefold (females) and 12-fold (males) increases in liver ethoxyresorufin-O-deethylase activity while DEHP did not. Mild changes in serum biochemistries were mostly confined to rats in the highest dose group of DEHP, and included increased serum albumin and albumin/globulin ratio in both sexes and decreased cholesterol in female rats. Mild vacuolations in the Sertoli cells were observed in male rats exposed to 500 ppm DEHP. At 5000 ppm DEHP, there was mild to moderate seminiferous tubule atrophy and Sertoli cell vacuolation in males, and rats of both sexes showed hepatic peroxisome proliferation. Both DEHP and DNOP at 5000 ppm caused mild histological changes in the thyroid consisting of reduced follicle size and colloid density, and the liver consisting of endothelial nuclear prominence, nuclear hyperchromicity and anisokaryosis. There was accentuation of zonation of the hepatic lobules and increased perivenous cytoplasmic vacuolation in DNOP-treated rats. Trace quantities (3-5 ppm) of DEHP and DNOP were detected in the liver, and 15-31 ppm were found in adipose tissue of the highest dose groups. The no observed-effect-level was judged to be 50 ppm in the diet or 3.7 mg/kg body weight/day for DEHP, and 500 ppm or 36.8 mg/kg body weight/day for DNOP. (C) 1997 Elsevier Science Ltd.