National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, Seoul 122-704.
Toxicol Res. 2010 Mar;26(1):75-82. doi: 10.5487/TR.2010.26.1.075.
This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2 (ethylhexyl) phthalate (DEHP) , di (n-butyl) phthalate (DBP) , di-n-octyl phthalate (DnOP) , diethyl phthalate (DEP) , butylbenzyl phthalate (BBP) , dimethyl phthalate (DMP) , di-isodecyl phthalate (DIDP) , diundecyl phthalate (DUP) , and di-isononyl phthalate (DINP) and five phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP) , monobutyl phthalate (MBuP) , monobenzyl phthalate (MBeP) , monoethyl phthalate (MEP) , monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP,DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 mg/kg/day) -treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.
本研究旨在研究包括邻苯二甲酸二(2-乙基己基)酯(DEHP)、邻苯二甲酸二丁酯(DBP)、邻苯二甲酸二正辛酯(DnOP)、邻苯二甲酸二乙酯(DEP)、邻苯二甲酸丁基苄基酯(BBP)、邻苯二甲酸二甲酯(DMP)、邻苯二甲酸二异癸酯(DIDP)、邻苯二甲酸二正十一酯(DUP)和邻苯二甲酸二异壬酯(DINP)在内的 9 种邻苯二甲酸酯二酯和包括邻苯二甲酸单(2-乙基己基)酯(MEHP)、邻苯二甲酸单丁酯(MBuP)、邻苯二甲酸单苄基酯(MBeP)、邻苯二甲酸单乙酯(MEP)、邻苯二甲酸单甲酯(MMP)和邻苯二甲酸在内的 5 种邻苯二甲酸单酯在 Sprague-Dawley 雄性大鼠体内的短期毒性。动物经口给予 250mg/kg/天(单酯和 PA)或 500mg/kg/天(二酯)的邻苯二甲酸 2 周。所有动物均进行体重和器官重量、血液血液学、血清生化和尿液分析检查。与对照组相比,BBP、DBP、DINP、MEHP、MBuP 和 PA 处理组的体重增加明显较低。与对照组相比,DEHP、DBP、DnOP、DIDP 和 MEHP 组的肝脏重量显著增加。与对照组相比,仅 DEHP-、DnOP-和 DIDP-处理组的睾丸重量显著降低。在任何处理组中均未观察到血液学变化的显著差异。DEHP、MEHP 和 MBeP 组的血糖水平显著升高。DBP、MBuP 和 MBeP 组的天门冬氨酸氨基转移酶(AST)水平显著升高,而仅 DEHP 和 MEHP 组的丙氨酸氨基转移酶(ALT)水平显著升高。与对照组相比,邻苯二甲酸二酯(500mg/kg/天)处理组的血清碱性磷酸酶(ALP)水平显著升高。然而,DEHP 和 DIDP 处理组的总胆固醇水平显著降低,而 DINP、MEHP 和 MBuP 处理组的血清甘油三酯(TG)水平升高。这些结果表明,邻苯二甲酸单酯的短期毒性产生的不良反应与 Sprague-Dawley 大鼠中的邻苯二甲酸二酯相似。