代谢
放射性标记的给药溶液是通过将(14)C放射性标记的磷酸三(1-氯-2-丙基)与无放射性标记的Fyrol PCF在乙醇、Emulphor和水的载体中混合制备的。给药溶液的制备和分析是为了让大鼠接受大约0.5毫升(2毫升/千克体重),每千克体重含有20或200毫克磷酸三(1-氯-2-丙基)和40微居里的放射性标记磷酸三(1-氯-2-丙基)。进行了两个研究阶段。在恢复阶段,动物接受了剂量,并在8天内11个时间间隔收集尿液、粪便和呼出的空气。每性别至少有5只动物接受了200毫克/千克的口服剂量,而5只雄性各自通过单一口服或静脉给药接受了20毫克/千克。在血浆阶段,动物接受了剂量,并在8天内18个预定时间间隔收集血液样本、尿液和粪便。在这两个阶段中,每性别至少有5只动物接受了200毫克/千克的口服剂量,而5只雄性各自通过单一口服或静脉给药接受了20毫克/千克。收集并分析了尿液、粪便、呼出的空气、组织和系列血液样本的总放射性。磷酸三(1-氯-2-丙基)的代谢物在大鼠的尿液和粪便中被分离、定量和鉴定...可识别的代谢物在两个剂量和两个性别的尿液和粪便中占放射性碳的75-78.5%。0,0-[双(1-氯-2-丙基)]-0-(2-丙酸)磷酸被鉴定为一种主要代谢物,在两个剂量水平下,两个性别的尿液和粪便中占剂量的50%以上。
Radiolabeled dosing solutions were prepared by mixing the (14)C-radiolabeled tris(1-chloro-2-propyl)phosphate with the non-radiolabeled Fyrol PCF in a vehicle of ethanol, Emulphor and water. Dosing solutions were prepared and analyzed so that rats wou1d receive approximately 0.5 mL (2mL/kg body weight) containing either 20 or 200 mg tris(1-chloro-2propyl) phosphate/kg body weight and 40 uCi of radiolabeled tris(1-chloro-2propyl) phosphate. Two study phases were performed. In the recovery phase animals were dosed and urine, feces and expired air were collected at 11 time intervals over 8 days. At least 5 animals per sex received oral doses of 200 mg/kg, while 5 males each received 20 mg/kg by either a single oral or i.v. administration. In the plasma phase animals were dosed and blood samples, urine and feces were collected at 18 predetermined intervals over 8 days. In both phases, at least 5 animals per sex received oral doses of 200 mg/kg, while 5 males each received 20 mg/kg by either a single oral or i.v. administration. Urine, feces, expired air, tissues and serial blood samples were collected and analyzed for total radioactivity. Metabolites of tris (1-chloro-2-propyl)phosphate were isolated, quantitated, and identified in the urine and feces of rats...Identifiable metabolites accounted for 75-78.5% of urinary and fecal radiocarbon at both doses in both sexes 0,0-[bis(l-chloro-2-propyl)]-0-(2-proprionic acid) phosphate was identified as a major metabolite and accounted for over 50% of the dose in the urine and feces of both sexes at both dose levels.
来源:Hazardous Substances Data Bank (HSDB)