Herr D W, Sanders J M, Matthews H B
Experimental Toxicology Branch, National Institute of Environmental Health Sciences Research Triangle Park, NC 27709.
Drug Metab Dispos. 1991 Mar-Apr;19(2):436-42.
Tris(2-chloroethyl) phosphate (TRCP) is a flame retardant that has a wide variety of industrial applications. In subchronic studies, oral administration of TRCP to rats and mice has been reported to produce dose-, sex-, and species-dependent lesions in the hippocampal brain region. The present investigation has examined the metabolism, elimination, and regional brain distribution of [14C]TRCP in male and female rats. [14C]TRCP was administered by gavage (0, 175, 350, or 700 mg/kg) and urine, feces, exhaled volatiles, CO2, and selected tissues were collected. Regional brain distribution of 14C was determined 2 hr following single doses of TRCP to male and female rats, and 24 hr after a single dose and the last of 14 daily doses of TRCP to female rats. Results of these studies indicate that TRCP is readily absorbed from the gastrointestinal tract, distributed to all brain regions, and that metabolism and excretion are nearly complete in 72 hr. Most of the TRCP-derived radioactivity was excreted in urine (up to 85%), with feces, volatiles, and CO2 combined accounting for less than 10% of the dose. Predominant signs of toxicity associated with TRCP administration (350 and 700 mg/kg) were seizures within 2 hr of treatment, when most of the TRCP-derived radioactivity present in brain tissue was in the form of the parent compound. Traces of inextractable 14C were detected at later times, but this material was not concentrated in brain relative to other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
磷酸三（2-氯乙基）酯（TRCP）是一种具有广泛工业应用的阻燃剂。在亚慢性研究中，据报道给大鼠和小鼠口服TRCP会在海马脑区产生剂量、性别和物种依赖性损伤。本研究检测了[14C]TRCP在雄性和雌性大鼠体内的代谢、消除及脑区分布情况。通过灌胃给予[14C]TRCP（0、175、350或700毫克/千克），并收集尿液、粪便、呼出的挥发物、二氧化碳及选定组织。在给雄性和雌性大鼠单次给予TRCP后2小时，以及给雌性大鼠单次给予和连续14天每日给予TRCP最后一剂后24小时，测定14C的脑区分布。这些研究结果表明，TRCP易于从胃肠道吸收，分布至所有脑区，且在72小时内代谢和排泄几乎完成。大部分源自TRCP的放射性物质经尿液排出（高达85%），粪便、挥发物和二氧化碳排出量合计占剂量不到10%。与给予TRCP（350和700毫克/千克）相关的主要毒性迹象是在治疗后2小时内出现癫痫发作，此时脑组织中大部分源自TRCP的放射性物质为母体化合物形式。在之后的时间检测到微量不可萃取的14C，但相对于其他组织，该物质在脑中未富集。（摘要截短至250字）
