Klein D, Kessler W, Semder B, Pütz C, Lichtmannegger J, Otter R, Filser J G
Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany; Institute for Toxicology and Environmental Hygiene, Technical University of Munich, Biedersteiner Str. 29, 80802 Munich, Germany.
Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
Toxicol Lett. 2016 Sep 30;259:80-86. doi: 10.1016/j.toxlet.2016.07.025. Epub 2016 Jul 22.
Di-(2-propylheptyl) phthalate (DPHP) does not act as a reproductive toxicant or endocrine disruptor in contrast to other phthalates. Considering adverse effects of phthalates to be linked to their metabolism, it was the aim of the present study to investigate in the rat the blood burden of DPHP and its metabolites as a basis for understanding the toxicological behavior of DPHP. Rats were administered single oral doses of DPHP of 0.7 and 100mg/kg body weight. Concentration-time courses of DPHP and metabolites were monitored in blood. The areas under the concentration-time curves in blood (AUCs), normalized for the dose of DPHP, showed the following order: DPHP<mono-(2-propyl-6-oxoheptyl) phthalate<mono-(2-propyl-6-hydroxyheptyl) phthalate=mono-(2-propylheptyl) phthalate<mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). Glucuronidation of the monoesters accounted for less than 5% of total compounds. The elimination half-lives of the compounds ranged from 2.3h (DPHP) to 8.2h (cx-MPHP). The normalized AUCs of the metabolites were lower at the high dose of DPHP than at the low one indicating saturation kinetics of intestinal DPHP hydrolysis. The absence of toxicity to reproduction of DPHP may be related to the comparatively low bioavailability of the parent compound and its metabolites.
与其他邻苯二甲酸酯不同，邻苯二甲酸二（2-丙基庚基）酯（DPHP）并非生殖毒物或内分泌干扰物。鉴于邻苯二甲酸酯的不良反应与其代谢相关，本研究旨在探究大鼠体内DPHP及其代谢产物的血药浓度，以此作为理解DPHP毒理行为的基础。给大鼠单次口服0.7和100mg/kg体重的DPHP。监测血液中DPHP及其代谢产物的浓度-时间过程。经DPHP剂量标准化后的血药浓度-时间曲线下面积（AUCs）呈现以下顺序：DPHP＜邻苯二甲酸单（2-丙基-6-氧代庚基）酯＜邻苯二甲酸单（2-丙基-6-羟基庚基）酯 = 邻苯二甲酸单（2-丙基庚基）酯＜邻苯二甲酸单（2-丙基-6-羧基己基）酯（cx-MPHP）。单酯的葡萄糖醛酸化占总化合物的比例不到5%。这些化合物的消除半衰期从2.3小时（DPHP）到8.2小时（cx-MPHP）不等。高剂量DPHP时代谢产物的标准化AUCs低于低剂量时，表明肠道DPHP水解存在饱和动力学。DPHP对生殖无毒性可能与其母体化合物及其代谢产物相对较低的生物利用度有关。
