毒理性
对于健康、非职业暴露的人类来说，铜的主要暴露途径是口服。成年人每天的平均铜摄入量介于0.9和2.2毫克之间。在某些情况下，饮用水可能会对每天的总铜摄入量产生重大贡献，特别是在那些腐蚀性水在铜管中停留的家庭中。与口服途径相比，所有其他铜的摄入（吸入和皮肤）都是微不足道的。从灰尘和烟雾中吸入的铜每天增加0.3-2.0微克。使用含铜宫内节育器的女性每天从这一来源接触到的铜只有80微克或更少。铜的体内平衡涉及到元素的二元重要性和毒性。其重要性源于铜特定地结合到大量蛋白质中，用于催化和结构目的。铜在哺乳动物中的摄取、结合到蛋白质中以及输出的细胞途径是由金属本身调节的。铜主要通过胃肠道吸收。饮食中20%到60%的铜被吸收，其余的通过粪便排出。一旦金属通过基底外侧膜，它就会与血清白蛋白结合并运输到肝脏。肝脏是铜体内平衡的关键器官。铜被分配用于通过胆汁排出或结合到细胞内和细胞外蛋白中。主要的排泄途径是通过胆汁。铜运输到外周组织是通过血浆中的血清白蛋白、铜蓝蛋白或低分子量复合物完成的。当铜超出体内平衡控制时，其生物化学毒性源自其对生物大分子（如DNA、膜和蛋白质）的结构和功能的影响，直接或通过氧自由基机制。单次口服铜的毒性在不同物种之间差异很大。主要可溶性盐（硫酸铜(II)、氯化铜(II)）通常比不太可溶的盐（氢氧化铜(II)、氧化铜(II)）更有毒性。死亡前会出现胃出血、心动过速、低血压、溶血性危机、抽搐和麻痹。在大鼠和小鼠中长期暴露没有明显的毒性迹象，除了与摄入剂量相关的生长减少。这些影响包括肝脏发炎和肾小管上皮变性。在大鼠中看到了一些睾丸退化和减少新生儿体重和器官重量。在高剂量水平上看到了胎毒性效应和畸形。口服给药后报告了神经化学变化。有限的免疫毒性研究显示，在饮用水中口服摄入后，小鼠的体液和细胞介导的免疫功能受损。铜是一种必需元素，人类的健康不良影响与缺乏和过量有关。铜缺乏与贫血、中性粒细胞减少和骨骼异常有关，但在人类中临床明显的缺乏相对较少。除了偶尔的急性铜中毒事件外，正常人类群体中几乎没有注意到其他影响。单次暴露后的影响，如自杀或意外口服暴露，据报道包括金属味、上腹痛、头痛、恶心、头晕、呕吐和腹泻、心动过速、呼吸困难和溶血性贫血、血尿、大量胃肠道出血、肝和肾衰竭以及死亡。饮用含有高铜浓度水的一次性和重复摄入也导致了胃肠道的影响，并且据报道，在长期摄入铜后出现了肝衰竭。皮肤暴露没有与系统性毒性相关，但铜可能在敏感个体中诱导过敏反应。在职业环境中吸入高浓度空气中的金属烟雾热已有报道。描述了一些群体，这些群体在铜的体内平衡中出现的紊乱导致对铜缺乏或过量的敏感性高于一般人群。一些疾病有明确的遗传基础。这些包括门克斯病，这是铜缺乏的一种通常致命的表现；威尔逊病（肝豆状核变性），这是一种导致铜逐渐积累的状况；以及遗传性铜蓝蛋白缺乏症，其临床表现为铜过载。印度儿童肝硬化和无缘无故铜中毒是与过铜有关的状况，可能与基于遗传的铜敏感性有关。这些是在早期儿童中致命的状况，其中铜在肝脏中积累。其他可能对铜过量敏感的群体包括血液透析患者和患有慢性肝病的人。铜缺乏风险群体包括婴儿（特别是低出生体重/早产儿、从营养不良中恢复的儿童以及仅以牛奶喂养的婴儿）、患有吸收不良综合症的人（例如，乳糜泻、热带口炎性腹泻、囊性纤维化）以及接受全胃肠外营养的患者。铜缺乏与心血管疾病的发病机制有关。铜的副作用必须与其必要性相平衡。铜是所有生物体必需的元素。至少有12种主要蛋白质需要铜作为其结构的一部分。它对于利用铁形成血红蛋白是必需的，大多数甲壳类动物和软体动物都具有含铜的血蓝蛋白作为其主要携氧血液蛋白。评估铜危险性的一个关键因素是其生物可利用性。铜吸附到颗粒上和有机物的络合作用可以大大限制铜积累的程度。在许多地点，限制生物可利用性的物理化学因素将证明需要更高的铜限制。
For healthy, non-occupationally-exposed humans the major route of exposure to copper is oral. The mean daily dietary intake of copper in adults ranges between 0.9 and 2.2 mg. ... In some cases, drinking water may make a substantial additional contribution to the total daily intake of copper, particularly in households where corrosive waters have stood in copper pipes. ... All other intakes of copper (inhalation and dermal) are insignificant in comparison to the oral route. Inhalation adds 0.3-2.0 ug/day from dusts and smoke. Women using copper IUDs are exposed to only 80ug or less of copper per day from this source. The homeostasis of copper involves the dual essentiality and toxicity of the element. Its essentiality arises from its specific incorporation into a large number of proteins for catalytic and structural purposes. The cellular pathways of uptake, incorporation into protein and export of copper are conserved in mammals and modulated by the metal itself. Copper is mainly absorbed through the gastrointestinal tract. From 20 to 60% of the dietary copper is absorbed, with the rest being excreted through the feces. Once the metal passes through the basolateral membrane it is transported to the liver bound to serum albumin. The liver is the critical organ for copper homeostatis. The copper is partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The primary route of excretion is through the bile. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular weight complexes. ... The biochemical toxicity of copper, when it exceeds homeostatic control, is derived from its effects on the structure and function of biomolecules, such as DNA, membranes and proteins directly or through oxygen-radical mechanisms. The toxicity of a single oral dose of copper varies widely between species. ... The major soluble salts (copper(II) sulfate, copper(II) chloride) are generally more toxic than the less soluble salts (copper(II) hydroxide, copper (II) oxide). Death is preceded by gastric hemorrhage, tachycardia, hypotension, hemolytic crisis, convulsions and paralysis. ... Long-term exposure in rats and mice showed no overt signs of toxicity other than a dose-related reduction in growth after ingestion ... The effects included inflammation of the liver and degeneration of kidney tubule epithelium. ... Some testicular degeneration and reduced neonatal body and organ weights were seen in rats ... and fetotoxic effects and malformations were seen at high dose levels. ... Neurochemical changes have been reported after oral administration ... A limited number of immunotoxicity studies showed humoral and cell-mediated immune function impairment in mice after oral intakes in drinking-water ... Copper is an essential element and adverse health effects /in humans/ are related to deficiency as well as excess. Copper deficiency is associated with anemia, neutropenia and bone abnormalities but clinically evident deficiency is relatively infrequent in humans. .. Except for occasional acute incidents of copper poisoning, few effects are noted in normal /human/ populations. Effects of single exposure following suicidal or accidental oral exposure have been reported as metallic taste, epigastric pain, headache, nausea, dizziness, vomiting and diarrhea, tachycardia, respiratory difficulty, hemolytic anemia, hematuria, massive gastrointestinal bleeding, liver and kidney failure, and death. Gastrointestinal effects have also resulted from single and repeated ingestion of drinking-water containing high copper concentrations, and liver failure has been reported following chronic ingestion of copper. Dermal exposure has not been associated with systemic toxicity but copper may induce allergic responses in sensitive individuals. Metal fume fever from inhalation of high concentrations in the air in occupational settings have been reported ... A number of groups are described where apparent disorders in copper homeostasis result in greater sensitivity to copper deficit or excess than the general population. Some disorders have a well-defined genetic basis. These include Menkes disease, a generally fatal manifestation of copper deficiency; Wilson disease (hepatolenticular degeneration), a condition leading to progressive accumulation of copper; and hereditary aceruloplasminemia, with clinical symptoms of copper overload. Indian childhood cirrhosis and idiopathic copper toxicosis are conditions related to excess copper which may be associated with genetically based copper sensitivity ... These are fatal conditions in early childhood where copper accumulates in the liver. ... Other groups potentially sensitive to copper excess are hemodialysis patients and subjects with chronic liver disease. Groups at risk of copper deficiency include infants (particularly low birth weight/preterm babies, children recovering from malnutrition, and babies fed exclusively with cow's milk), people with maladsorption syndrome (e.g., celiac disease, sprue, cystic fibrosis), and patients on total parenteral nutrition. Copper deficiency has been implicated in the pathogenesis of cardiovascular disease. The adverse effects of copper must be balanced against its essentiality. Copper is an essential element for all biota ... At least 12 major proteins require copper as an integral part of their structure. It is essential for the utilization of iron in the formation of hemoglobin, and most crustaceans and molluscs possess the copper-containing hemocyanin as their main oxygen-carrying blood protein. ... A critical factor in assessing the hazard of copper is its bioavailablity. Adsorption of copper to particles and complexation by organic matter can greatly limit the degree to which copper will be accumulated ... At many sites, physiochemical factors limiting bioavailability will warrant higher copper limits. ...
来源:Hazardous Substances Data Bank (HSDB)
