代谢
研究了六氯环己烷在大鼠和小鼠体内形成氯酚代谢产物的比较情况。雄性瑞士小鼠和雌性维斯特大鼠被喂食含有每百万份500份六氯环己烷的饮食。两个月后处死动物,使用高效液相色谱法测定肝脏中的氯酚代谢产物。给维斯特大鼠和瑞士小鼠单次腹腔注射200毫克/千克的六氯环己烷后,测定血液中氯酚的循环浓度。24小时后,通过心脏穿刺收集血液,并通过色谱法测定氯酚。还测量了用阿罗科尔1254预处理动物制备的肝微粒体组分中氯酚代谢产物形成的速率差异。确定的氯酚代谢产物包括2,6-二氯酚、2,3,5-三氯酚、2,3,6-三氯酚、2,4,6-三氯酚、2,3,4,5-四氯酚、2,3,5,6-四氯酚和五氯酚。在连续两个月给予六氯环己烷后,从小鼠和大鼠肝脏提取的氯酚色谱图中没有检测到质的种间差异。仅在雄性小鼠肝脏中2,6-二氯酚的含量显著高于大鼠肝脏:小鼠为1292.5纳克/克,大鼠为140.0纳克/克。小鼠和大鼠血液中的氯酚没有观察到质的差异。然而,小鼠血液中2,6-二氯酚的浓度为11.52微克/毫升,而大鼠血液中的浓度为1.65微克/毫升。在体外,大鼠肝微粒体形成的2,4,6-三氯酚为647 pmol/mg/小时,而小鼠肝微粒体形成的为219 pmol/mg/小时。作者认为六氯环己烷可能是一种肿瘤促进剂,其作用是通过促进未知来源的潜在启动细胞的发育。2,6-二氯酚的血浆清除率差异可能解释了其在浓度上的种间差异;然而,它在大鼠肝脏肿瘤诱导中发挥主要作用的可能性不大。
The comparative formation of chlorophenol metabolites of hexachlorocyclohexane was investigated in rats and mice. Male Swiss mice and female Wistar rats were fed a diet containing 500 parts per million hexachlorocyclohexane. Animals were killed after 2 months and hepatic chlorophenol metabolites were determined using hig performance liquid chromatography. Circulating concentrations of chlorophenols were determined in Wistar rats and Swiss mice given a single 200 mg/kg intraperitoneal injection of hexachlorocyclohexane. After 24 hours blood was collected by heart puncture and chlorophenols assayed chromatographically. Species differences in the rate of chlorophenol metabolite formation in vitro were also measured in hepatic microsome fractions prepared from Aroclor 1254 pretreated animals. Chlorophenol metabolites identified were 2,6-dichlorophenol, 2,3,5-trichlorophenol, 2,3,6-trichlorophenol, 2,4,6-trichlorophenol, 2,3,4,5-tetrachlorophenol, 2,3,5,6-tetrachlorophenol, and pentachlorophenol. No qualitative species difference was detected in chromatographic profiles of chlorophenols extracted from mouse and rat liver after continuous 2 month administration of hexachlorocyclohexane. Only 2,6-dichlorophenol was significantly higher in mouse live than that observed in rat liver: 1292.5 ng/g in mouse and 140.0 ng/g in rat. No qualitative difference was observed in the chlorophenols of blood of mice and rats. However, the concentration of 2,6-dichlorophenol was 11.52 ug/ml compared to 1.65 ug/ml in mouse blood. In vitro, 647 pmol/mg/hour 2,4,6-trichlorophenol were formed by rat liver microsomes, compared to 219 pmol/mg/hour by mouse liver microsomes. The authors conclude that hexachlorocyclohexane may be a tumor promoting agent which acts by facilitating the development of latent initiated cells of unknown origin. Differential plasma clearance of 2,6-dichlorophenol may account for species differences in its concentration; however it is unlikely that it plays a major role in the induction of liver tumors in mice.
来源:Hazardous Substances Data Bank (HSDB)