毒理性
氯化锂是一种白色立方晶体物质。它可溶于水、乙醇、丙酮、吡啶和硝基苯。它用于制造矿泉水;在烟火制造中;焊接铝;在制冷机械中。它被用作干燥剂。人类暴露和毒性:报告了一名男子在服用4剂,每剂2克的氯化锂后急性中毒,导致虚弱、虚脱、眩晕和耳鸣。在摄入非致死剂量的氯化锂并低钠盐饮食后,慢性毒性症状是口渴和多尿。健康成人志愿者(28名男性和25名女性)在温泉水中暴露于氯化锂,每天20分钟,每周五天,连续两周。血清锂水平与对照组的志愿者进行比较,这些志愿者在没有锂的温泉中类似暴露。在任何时间间隔(锂暴露前和每周暴露后一小时内)锂暴露的志愿者与对照组的血清锂水平没有差异。结论是,在使用温泉时,锂不会通过皮肤吸收。将健康成人志愿者的PAH刺激淋巴细胞培养暴露于氯化锂的浓度中。然后在收获前四小时加入三标胸苷。在有氯化锂的培养基中,有丝分裂指数增加。染色体断裂、缺口和卫星关联的发病率增加。在治疗初期,可能会出现急性中毒,但也可能在长期治疗期间的任何时候或急性过量后。毒性症状包括:厌食、口干、恶心、呕吐、腹泻、手颤、肌肉无力、口渴、白细胞增多和注意力及记忆力障碍(尤其是老年人)。这些现象通常出现在治疗初期,通常在治疗继续时消失,除了手颤。在老年人中,可能出现可逆的谵妄状态,表现为混乱、不安和共济失调。出现严重的毒性症状,包括:肌肉颤动、肌肉收缩、反射亢进和肌紧张增高、嗜睡、混乱、有时癫痫样发作、低血压、昏迷、崩溃。无论血浆水平如何,心电图和脑电图都可能发生变化,症状如多尿和多饮,很少出现肾原性尿崩症、腿部溃疡、痤疮和银屑病加重、暂时性高血糖、瘙痒和金属味。在大约5%的病例中,会出现(通常是可逆的)甲状腺功能减退。绝大多数关于患者淋巴细胞、淋巴瘤和骨髓细胞染色体损伤的研究并没有表明锂治疗会增加染色体畸变或姐妹染色单体交换的风险。影响肾小球滤过率的因素对锂的清除有显著影响。因此,慢性肾功能不全的患者特别容易受到锂的暴露。其他可能导致锂中毒的条件包括高龄、不同原因的钠缺乏或使用某些影响肾功能的药物。中等毒性;可能口服致死剂量(人类0.5-5克/千克;对于70千克(150磅)的人,在1盎司和1品脱(或1磅)之间。动物/生态毒性/研究:氯化锂在兔子的皮肤急性毒性测试中被发现具有刺激性。在兔子的Draize测试中,它具有中等刺激性。使用近交系雄性小鼠来确定遗传因素是否在锂毒性中起作用。在皮下注射氯化锂后2小时,小鼠品系之间的血浆、心脏、肝脏、肾脏和大脑中的锂浓度也观察到显著差异,但锂浓度与氯化锂毒性的关系并不明显。结果表明,遗传因素可以影响锂的毒性和药效学。在兔子眼睛机械去除角膜上皮以促进渗透后应用氯化锂溶液,没有明显损伤,但产生了持久的角膜扁平化。在一组52只大鼠和100只对照动物中进行了致畸性研究。动物在饮水中给予氯化锂(LiCl)。在预实验中,这些剂量被认为是刚好亚毒性的。锂暴露的幼崽没有畸形或其他缺陷。这些和未处理的对照之间在大小和重量上也没有差异。如果幼崽在饮水中保持相同的锂浓度,23只幼崽的生长略有降低,但最终发育成与正常大鼠无法区分的成年大鼠。在一项对未成年大鼠的每日皮下注射氯化锂至少15天的研究中,发现了显著的精子生成抑制。在枯草杆菌重组试验中,氯化锂在没有代谢激活的情况下呈阴性。在沙门氏菌Typhimurium TA 98、TA 100、TA 1535和TA 1537株的Ames试验中,氯化锂在有无代谢激活的情况下均呈阴性。氯化锂在浓度下给予小鼠,并提取骨髓。氯化锂诱导了染色体畸变,但没有姐妹染色单体交换。对三种鱼类进行了24小时静态生物测定:Oncorhynchus kisutch、Oncorhynchus tschawytscha和Ptychocheilus orefonensis。在加入测试物质前约2小时,将适应环境的鱼转移到装有4升水(每个容器3条鱼)的容器中。鱼暴露于氯化锂并观察24小时。记录鱼失去平衡或死亡的时间。在6.5-11小时和2.5-6.5小时分别观察到Onc
IDENTIFICATION AND USE: Lithium chloride is a white cubic crystalline material. It is soluble in water, ethanol, acetone, pyridine and nitrobenzene. It is used to manufacture mineral waters; in pyrotechnics; soldering aluminum; in refrigerating machines. It is used as a dessicant. HUMAN EXPOSURE AND TOXICITY: Acute poisoning in man reported after 4 doses of 2 g each of lithium chloride, causing weakness, prostration, vertigo, and tinnitus. Chronic toxicity symptoms following ingestion of nonlethal doses of lithium chloride with low-sodium chloride diets are thirst and polyuria. Human volunteers (28 males, 25 females) were exposed to lithium chloride in spa water at a for 20 minutes/day, five days/week for two consecutive weeks. Serum lithium levels were compared to those of a control group of volunteers similarly exposed in spas without lithium. There were no differences between the serum lithium levels between lithium exposed volunteers and controls at any time interval (before lithium exposure and one hr after each weekly exposure). It is concluded that lithium is not absorbed through the skin during spa use. PAH-stimulated lymphocyte cultures from healthy adult volunteers were exposed to concentrations of lithium chloride. Tritiated thymidine was then added four hrs before harvesting. The mitotic index increased. The incidence of chromosomal breaks, gaps and satellite associations was increased in the presence of lithium chloride in the media. Acute intoxication can occur in the initial phase in a course of therapy, but also at any point of time during long-lasting treatment or after an acute overdose. Signs of toxicity include: anorexia, dry mouth, nausea, vomiting, diarrhea, tremor of the hands, faintness of musculature, thirst, leukocytosis, and concentration and memory disturbances (especially with older people). These phenomena are often seen in the initial phase of a course of treatment and usually disappear when treatment continues, except with the tremor of the hands. In elderly people, reversible delirious conditions can occur with confusion, restlessness, and ataxia.Serious toxic symptoms occur which include: fasciculations, muscle contractions, hyperreflexia and hypertonia, drowsiness, confusion, sometimes epileptiform insults, hypotension, coma, collapse. Independent of the plasma level, changes can occur in the ECG and in the EEC, with symptoms such as polyuria and polydipsia, seldom nephrogenic diabetes insipidus, ulcers of the leg, enhancement of acne and psoriasis, transient hyperglycemia, pruritus, and a metal taste. In about 5% of the cases, a (usually reversible) hypothyroidia develops. The vast majority of the studies on chromosomal damage in leukocytes, lymphocytes and bone marrow cells in patients do not indicate any increased risk by lithium therapy for chromosome aberrations or sister chromatid exchanges. Factors affecting the glomerular filtration rate have a significant influence on the clearance of lithium. Thus, subjects with chronic renal insufficiency are especially vulnerable to lithium exposure. Other conditions predisposing to lithium intoxication include advanced age, sodium depletion of different origin or use of certain drugs affecting the renal function. Moderately toxic; probable oral lethal dose (human 0.5-5 g/kg; between 1 oz and 1 pint (or 1 lb) for 70 kg person (150 lb). ANIMAL/ECOTOXICITY/ STUDIES: Lithium chloride was found to be irritating in the rabbit acute toxicity testing of the skin. It was moderately irritating in the Draize test in rabbit eyes. Inbred strains of male mice were used to determine whether genetic factors play a role in lithium toxicity. Significant differences were also observed between the mouse strains in the concentrations of lithium in plasma, heart, liver, kidney and brain 2 hr after a subcutaneous injection lithium chloride, but the lithium concentrations were not related in an obvious manner to lithium chloride toxicity. The results show that genetic factors can influence the toxicity and pharmacodynamics of lithium. Application of lithium chloride solution to rabbit's eye after mechanical removal of corneal epithelium to facilitate penetration caused no evident injury, but produced long lasting flattening of the cornea. A teratogenicity study was conducted in a group of 52 rats and 100 controls. The animals were administered lithium chloride (LiCl) in a in drinking water. The dose levels were evaluated to be just subtoxic in a for going study. No malformations or other defects in the lithium exposed litters. Neither were there any differences in size and weight among these and untreated controls. If the young were maintained at the same lithium concentration in the drinking water, 23 showed slightly lower growth, but developed finally into adult rats indistinguishable from normal rats. Significant inhibition of spermatogenesis was found in a study in immature rats after daily subcutaneous injections of lithium chloride for at least 15 days. Lithium chloride was negative in the Bacillus subtilis recombination assay without metabolic activation. Lithium chloride tested negative in the Ames test with Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 with or without metabolic activation. Lithium chloride at concentrations was administered to mice and bone marrow was extracted Lithium chloride induced chromosomal aberrations, but not sister chromatid exchanges. A 24 hour static bioassay was conducted in three species of fish: Oncorhynchus kisutch, Oncorhynchus tschawytscha, and Ptychocheilus orefonensis. Acclimatized fish were transferred to vessels in 4 L of water (3 fish per vessel) about 2 hrs prior to addition of test article. The fish were exposed to lithium chloride and observed for 24 hours. The times at which a fish lost its equilibrium or died were noted. Death was seen at 6.5-11 hrs and 2.5-6.5 hrs for Oncorhynchus kisutch and Oncorhynchus tschawytscha, respectively. In two separate tests with Ptychocheilus oregonensis, no signs of toxicity were observed. In a third test death was seen at 2.5-6.5 hrs. The lower limit of these ranges indicate the time that the last observation was made before death. The upper limit indicates the time that death was noted. Loss of equilibrium was not observed. The chronic administration of lithium chloride during the embryogenesis of Bufo arenarum toad has resulted in a teratological development and in some cases an irreversible blockade of morphogenesis. These results vary according to the embryonic stage, the duration of the treatment and the concentration used. The histological analysis of embryos treated non-chronically showed a series of mild-to-severe malformations. According to the results obtained, lithium would alter the gastrulation and organogenesis processes of this species, interfering with the normal succession of developmental stages.
来源:Hazardous Substances Data Bank (HSDB)