Suwita E, Abou-Donia M B
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Arch Toxicol. 1990;64(3):237-41. doi: 10.1007/BF02010730.
Hens were given a single oral dose of 50 mg (4.6 microCi)/kg [14C] tri-o-cresyl phosphate (TOCP). Four groups of three hens each were killed after 0.5, 1, 2, and 5 days. The half-life of 14C in plasma was 2 days. TOCP and its metabolites in the plasma, liver, kidneys, and lungs were analyzed by high-performance liquid chromatography and liquid scintillation counting. TOCP reached its highest concentration in plasma between 0.5 and 1 day after administration. Under these experimental conditions, the disappearance of TOCP from the plasma followed monoexponential kinetics with a half-life of 2.2 days. Appreciable concentrations of saligenin cyclic-o-tolyl phosphate, the active neurotoxic metabolite, were detected in the plasma as well as in the liver, kidneys, and lungs at all time points and had half-lives of 2.06, 1.36, 1.11 and 4.44 days, respectively. The presence of this active metabolite of TOCP might contribute to the sensitivity of the hen to TOCP-induced delayed neurotoxicity. Other hydrolytic and oxidative products of TOCP were also identified in tissues.
给母鸡口服单剂量50毫克（4.6微居里）/千克的[14C]磷酸三邻甲苯酯（TOCP）。分别在给药后0.5、1、2和5天处死四组母鸡，每组三只。14C在血浆中的半衰期为2天。采用高效液相色谱法和液体闪烁计数法分析血浆、肝脏、肾脏和肺中的TOCP及其代谢产物。给药后0.5至1天之间，TOCP在血浆中达到最高浓度。在这些实验条件下，TOCP从血浆中的消失遵循单指数动力学，半衰期为2.2天。在所有时间点，血浆以及肝脏、肾脏和肺中均检测到了可观浓度的活性神经毒性代谢产物——邻甲酚磷酸环酯，其半衰期分别为2.06、1.36、1.11和4.44天。TOCP这种活性代谢产物的存在可能导致母鸡对TOCP诱导的迟发性神经毒性敏感。在组织中还鉴定出了TOCP的其他水解和氧化产物。
