毒理性
识别和使用:环四甲撑四硝胺(HMX)是一种白色结晶固体。HMX的用途与RDX相似,即用作引爆器的基装药,以及作为军事上爆破装药和塑性炸药的成分。人类研究:弹药厂工人的暴露研究表明没有不良影响。然而,一名28岁的男子,无癫痫病史,在手动筛选大量干燥HMX一整天后,晚上出现了癫痫发作,被送往急诊科。动物研究:在大鼠、小鼠和兔中分别单次口服5,447、1,626和50 mg/kg的HMX后,观察到肺部出现“发红”。在大鼠和小鼠单次口服5,447和1,626 mg/kg HMX后,胃肠道中出现了“白色液体”。兔在单次口服100 mg/kg或更高剂量的HMX后出现死亡。在小鼠中,雄性对HMX的致死作用更为敏感。在大鼠中,HMX可能对肾脏产生不利影响。在大鼠和小鼠暴露于1,280和300 mg/kg/天的HMX 14天后,观察到肝细胞增生和细胞质嗜酸性粒细胞增多。在更高剂量8,504 mg/kg/天的HMX下,出现了明显的肝毒性证据,导致雄性大鼠在14天的暴露后出现中央小叶变性。根据大鼠13周饮食研究的结果,估计雄性的NOAEL为50 mg/kg/天,雌性的NOAEL为115 mg/kg/天,以及雄性有毒肝效应的LOAEL为150 mg/kg/天,雌性有毒肾效应的LOAEL为270 mg/kg/天。小鼠14天的研究显示,在100 mg/kg/天时活动性和兴奋性增加。动物研究报道,在急性口服、皮肤和parenteral暴露于HMX后出现了神经学效应。HMX在沙门氏菌中使用Ames试验没有表现出致突变活性。生态毒理学研究:环境研究表明,HMX对鸟类的潜在生殖毒性较低。暴露于受污染地点的爆炸物的新鲜水生无脊椎动物可能在低于25 mg/kg的浓度下通过激素生长增强受到影响,在更高浓度下通过增加死亡率受到影响。通常,在测试的任何藻类、鱼类或无脊椎动物物种中,暴露于32 mg HMX/L没有观察到不良影响。7天大的胖头鱼幼鱼是唯一受到急性影响的生物阶段或物种。尽管RDX和HMX对植物没有不良影响,但这些化合物确实导致了蚯蚓的死亡。爆炸混合物的协同效应被观察到。
IDENTIFICATION AND USE: Cyclotetramethylenetetranitramine (HMX) is a white crystalline solid. HMX has uses similar to RDX, that is, as a base charge for detonators and as an ingredient of bursting-charge and plastic explosives by the military. HUMAN STUDIES: Human exposure of munitions plant workers has indicated no adverse effects. However, a 28-year-old man with no history of epilepsy was admitted to the Emergency Department for seizures that had developed during the night after a full working day when he manually sieved large amounts of dry HMX. ANIMAL STUDIES: Following exposure to a single oral dose of 5,447, 1,626, and 50 mg/kg HMX in rats, mice, and rabbits, respectively, a "reddening" of the lungs was observed. A "white fluid" was noted in the gastrointestinal tract of rats and mice exposed to a single oral dose of 5,447 and 1,626 mg/kg HMX, respectively. Deaths in rabbits were observed following single oral doses of 100 mg/kg or more. In mice, the males appeared to be more sensitive to the lethal effects of HMX. In rats, HMX may adversely affect the kidney. Hepatocyte hyperplasia and cytoplasmic eosinophilia were noted in rats and mice exposed to 1,280 and 300 mg/kg/day HMX, respectively, for 14 days. Clear evidence of hepatotoxicity was observed at a higher dose of 8,504 mg/kg/day HMX, which resulted in centrilobular degeneration in male rats exposed for 14 days. Based on the results of 13 weeks dietary study in rats, a NOAEL of 50 mg/kg/day for males and 115 mg/kg/day for females was estimated, together with a LOAEL of 150 mg/kg/day for toxic liver effects in males and 270 mg/kg/day for toxic renal effects in females. Fourteen day studies in mice showed increased activity and excitability at 100 mg/kg/day. Studies in animals have reported neurological effects following acute oral, dermal, and parenteral exposures to HMX. HMX did not exhibit mutagenic activity in Salmonella typhimurium using the Ames test. ECOTOXICITY STUDIES: Environmental studies suggest that the potential for reproductive toxicity of HMX to birds is low. Freshwater invertebrates exposed to explosives at contaminated sites may be affected at concentrations less than 25 mg/kg through hormetic growth enhancement and at higher concentrations through increased mortality. Generally, no adverse effects of exposure to 32 mg HMX/L were observed among any of the algae, fish, or invertebrate species tested. The 7-day old fry of fathead minnow were the only life stage or species acutely affected. Although RDX and HMX did not have adverse effects on plants, these compounds did cause earthworm mortality. Synergistic effects of explosives mixture were observed.
来源:Hazardous Substances Data Bank (HSDB)