Bioaccumulation of lead (Pb) and its effects on human: A review
铅 (Pb) 的生物累积及其对人体的影响：综述

3.1. Effect of lead on the nervous system
3.1.铅对神经系统的影响

Lead toxicity affects the nervous system drastically when compared to the other organ systems in the human body. Symptoms worsen and give rise to paralysis, coma, or even death (Gilani et al., 2015). Lead is considered to be a neurotoxin. The half-life of Pb in the brain is 2 to 3 years whereas in the blood it is 30 days. Encephalopathy is a condition where there is a progressive deterioration in the parts of the human brain, major manifestations of encephalopathy including headache, dullness, poor attention span, memory loss, and hallucinations within a few weeks of exposure (Karri et al., 2008; Arora et al., 2015).
与人体其他器官系统相比，铅毒性对神经系统的影响极大。症状恶化并导致瘫痪、昏迷甚至死亡（ Gilani et al., 2015 ）。铅被认为是一种神经毒素。铅在大脑中的半衰期为 2 至 3 年，而在血液中的半衰期为 30 天。脑病是人类大脑部分进行性恶化的病症，脑病的主要表现包括头痛、迟钝、注意力不集中、记忆力减退以及在接触病毒后几周内出现幻觉（ Karri et al., 2008 ；阿罗拉等人，2015 ）。

Children are more likely to get affected by Pb toxicity in their developing stages than adults (Needleman, 2004). Pb toxicity in children is mostly asymptomatic, while children below 5years show some symptoms like lethargy, abdominal cramps, vomiting, irritability, and loss of appetite. Epidemiological studies reveal that children with Blood Lead Level BPb (BPb -‘Biomarker’ is a term used to measure the interactions between the biological system and an external environmental agent) less than 10 µg/dL are affected severely (Garza et al., 2006 ; Sander et al., 2009). Astrocytes, a type of glial cells in the brain, along with neurons and the extracellular matrix contain the physical Blood-Brain Barrier (BBB). As Pb²⁺ions easily substitute Ca²⁺ions, it crosses the BBB swiftly and accumulates in the brain cells (Florea et al., 2013). Joint F. A. O et al. performed experiments on the children's IQ. As Pb²⁺ions easily substitute Ca²⁺ions, it crosses the Blood-Brain-Barrier (BBB) swiftly and accumulates in the brain cells. Pb²⁺replaces Ca²⁺ in Protein Kinase C(PKC) Enzyme assay, a calcium-dependent process, changes the behavior of endothelial brain cells and disrupts the functions of BBB (Joint F. A. O., & WHO Expert Committee on Food Additives, F.A.O. 2002). On testing the intelligence, it was found that IQ dropped by 3 points when BPb level increased from 10 µg/dL to 20 µg/dL and WHO concluded that for every 10 µg/dL increase in BPb levels, IQ decreases by 1–5 points (Bellinger et al.,  2005, Reuben et al., 2017). Lanphear et al. examined 4853 children of NHANES(III) (National Health and Nutrition Examination Survey – it is a program that is designed to assess the health and nutrition of adults and children in the US) and conducted psychometric tests for them (Lanphear et al., 2000). He disclosed that the mean BPb level was 1.8–1.9 µg/dL and also found that children had neural development, linguistic and processing problems, decrement in the memory power, and difficulty in comprehension of visuospatial skills (Rogan et al., 2001). Stokes et al. in their research studies stated that occupational exposure is a major source of Pb accumulation in adults and affects the PNS.
儿童在发育阶段比成人更容易受到铅中毒的影响（ Needleman，2004 ）。儿童铅中毒大多无症状，而5岁以下儿童则表现出嗜睡、腹部绞痛、呕吐、烦躁、食欲不振等症状。流行病学研究表明，血铅水平BPb（BPb -“生物标志物”是一个用于测量生物系统与外部环境因素之间相互作用的术语）低于 10 µg/dL 的儿童会受到严重影响（ Garza 等人，2006 年）桑德等人，2009 ）。星形胶质细胞是大脑中的一种神经胶质细胞，与神经元和细胞外基质一起构成了物理血脑屏障 (BBB)。由于Pb ²⁺离子很容易取代Ca ²⁺离子，因此它能迅速穿过血脑屏障并在脑细胞中积聚( Florea et al., 2013 )。联合 FA O 等人。对孩子们的智商进行了实验。由于Pb ²⁺离子很容易取代Ca ²⁺离子，因此它能迅速穿过血脑屏障(BBB)并在脑细胞中积聚。 Pb ²⁺在蛋白激酶 C (PKC) 酶测定中取代 Ca ²⁺ ，这是一种钙依赖性过程，会改变内皮脑细胞的行为并破坏 BBB 的功能（FAO 和 WHO食品添加剂联合专家委员会， FAO）2002）。在智力测试中，发现当 BPb 水平从 10 µg/dL 增加到 20 µg/dL 时，智商下降 3 分，世界卫生组织得出结论，BPb 水平每增加 10 µg/dL，智商下降 1-5 分（ Bellinger 等人，2005 年； Reuben 等人，2017 年）。兰菲尔等人。对 NHANES(III)（国家健康和营养检查调查 - 这是一项旨在评估美国成人和儿童的健康和营养的计划）的 4853 名儿童进行了检查，并对他们进行了心理测试（ Lanphear 等人，2000 年） ）。他透露，平均 BPb 水平为 1.8–1.9 µg/dL，并发现儿童存在神经发育、语言和处理问题、记忆力下降以及视觉空间技能理解困难（ Rogan 等，2001 ）。斯托克斯等人。在他们的研究中指出，职业暴露是成人铅积累的主要来源，并影响三七总皂甙。

Silbergeld et al. proposed that there can be two types of neurotoxicity:
西尔伯格德等人。提出可能有两种类型的神经毒性：

• (1)

  Neurodevelopmental Pb that disturbs the functions of CNS.
  神经发育铅会干扰中枢神经系统的功能。

• (2)

  Neuropharmacological Pb intrudes and alters the ionic mechanisms of the neurotransmitters.
  神经药理学 铅侵入并改变神经递质的离子机制。

Observations state that high BPb concentrations >4 µM result in acute Encephalopathy, Apoptosis, dysfunction of the Blood-Brain Barrier (BBB), and severe conditions leading to hemorrhage and schizophrenia (Ishaq et al., 2021). Tetraethyl lead (TEL) is a powerful neurotoxin and an additive in motor fuel and 25 workers died in 1925 due to longtime exposure to Pb. Pb²⁺also can replace Ca²⁺ ions, thus increasing the Pb²⁺ concentration in the cells. Even nanomolar concentrations of Pb²⁺ disturb the mitochondrial functions and kill brain cells via apoptosis (Yang et al., 2014). This state is initiated when the mitochondria dysfunctions. Mitochondrial dysfunction is caused by the increase in intercellular Ca²⁺ ions or by the accumulation of Pb²⁺ions. Pb²⁺ ions disrupt Ca²⁺ homeostasis leading to higher Ca²⁺ ions in cells.
观察表明，高 BPb 浓度 >4 µM 会导致急性脑病、细胞凋亡、血脑屏障 (BBB) 功能障碍，以及导致出血和精神分裂症的严重病症（ Ishaq 等人，2021 ）。四乙基铅(TEL) 是一种强效神经毒素，也是汽车燃料的添加剂，1925 年有 25 名工人因长期接触铅而死亡。 Pb ²⁺还可以取代Ca ²⁺离子，从而增加细胞内Pb ^{2+ 的}浓度。即使是纳摩尔浓度的 Pb ²⁺也会扰乱线粒体功能并通过细胞凋亡杀死脑细胞（ Yang et al., 2014 ）。当线粒体功能障碍时，就会启动这种状态。线粒体功能障碍是由细胞间Ca ²⁺离子增加或Pb ²⁺离子积累引起的。 Pb ²⁺离子破坏Ca ²⁺稳态，导致细胞内Ca ²⁺离子增多。

3.2. Effect of lead on the skeletal system-Bone
3.2.铅对骨骼系统——骨的影响

Lead exposure from both occupational and environmental sources causes an increase in levels of lead in the bone matrix throughout childhood and most of adulthood. The major Pb2+ concentration is detected in the bone tissues of human beings which can be seen in Fig. 4. In a case study, it has been reported that a woman with acute lead toxicity was diagnosed with abdominal and knee pain, neurological symptoms, hypertension, chronic kidney disease, and anemia with basophilic stippling. It was observed that, compared to her previous pregnancy, lead levels in her body tripled in her subsequent one. This increase in blood lead concentration was likely due to the skeletal mobilization without any new lead exposure. This acute lead toxicity traced is due to mobilization and redistribution of lead from the bone by pathophysiological and physiological conditions. The subject had a serious failure in her neurologic, renal, orthopedic, hematologic, and gastrointestinal systems and her reproductive system (Riess & Halm,Matthias 2007). It was reported that occupational exposure to lead decreased the calcitriol formation resulting in lowered absorption of phosphorous and calcium at the renal and intestinal tracts. It was observed that the total serum calcium levels and serum ionized calcium levels decreased by 14–21% in all the study groups and similarly the serum phosphorous levels were also decreased by 14–19%. It was also reported that this increased lead exposure showed a slight elevation in systolic (7–13%) and diastolic (5–17%) pressure (Dongre et al.,NN 2013; Rodríguez & Mandalunis,J. 2018). It is reported that lead affects osteoblasts, osteoclasts, and chondrocytes, and increases the risk of osteoporosis. Women undergoing menopause are at a higher risk of experiencing osteoporosis. Moreover, Pb exposed individuals suffer a serious fracture and recover at a very slow rate in comparison with non-exposed individuals (Carmouche et al.,  2005).
职业和环境来源的铅暴露会导致整个儿童期和成年期大部分时间骨基质中的铅含量增加。主要的Pb2+浓度是在人类的骨组织中检测到的，如图4所示。在一项案例研究中，据报道，一名患有急性铅中毒的女性被诊断出患有腹部和膝盖疼痛、神经系统症状、高血压、慢性肾病和嗜碱性点画贫血。据观察，与前一次怀孕相比，她体内的铅含量在接下来的怀孕中增加了两倍。血铅浓度的增加可能是由于骨骼动员而没有任何新的铅暴露所致。所追踪的这种急性铅毒性是由于病理生理和生理条件下铅从骨中的动员和重新分布造成的。该受试者的神经、肾脏、骨科、血液、胃肠系统以及生殖系统出现严重衰竭（Riess & Halm, Matthias 2007 ）。据报道，职业接触铅会减少骨化三醇的形成，导致肾脏和肠道对磷和钙的吸收减少。据观察，所有研究组的血清总钙水平和血清离子钙水平下降了 14-21%，同样，血清磷水平也下降了 14-19%。另据报道，铅暴露的增加表明收缩压（7-13%）和舒张压（5-17%）略有升高（Dongre 等，2017）。， NN 2013 ；罗德里格斯和曼达鲁尼斯， J. 2018 ）。据报道，铅会影响成骨细胞、破骨细胞和软骨细胞，并增加骨质疏松症的风险。经历更年期的女性患骨质疏松症的风险较高。此外，与未接触铅的个体相比，接触铅的个体会遭受严重骨折，并且恢复速度非常慢（ Carmouche等，2005 ）。

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Fig. 4. The half-life of lead in bones.
图4 .铅在骨骼中的半衰期。

3.3. Effect of lead on the reproductive system
3.3.铅对生殖系统的影响

The reproductive system of both males and females are affected by increased BPb levels. Studies reveal that pregnant women tend to have greater complications due lead accumulations (Vigeh et al.,M. 2010). Men with BPb levels greater than 25 µg/dL experience reduced sperm mobility, fertility, sperm count, and abnormal sperm morphology. On the other hand, women with 10 µg/dL BPb level face complications like preterm birth, low birth weight, infertility, miscarriage, neural defects in early childhood, and maternal hypertension (van Straaten, 2000). BPb level in the range 10–15 µg/dL in women of childbearing age directly affects the developing fetus. Generally, women who give birth after 30–35 years are more vulnerable to having Pb in their breast milk (Bellinger, D.C. 2005; Shannon,M. 2003). Assent et al. studied the sperm count of lead workers. His-studies reported Teratospermia (genetic damage to sperm), Hypospermia (low sperm count), and chromosomal aberrations (Telišman et al., 2007). Protamine (HP2) is a Zn protein that protects the sperm DNA. Pb tends to replace this Zn and causes sperm DNA damage (Quintanilla-Vega et al.,  2000). It has also been observed that the fetus has 19% more BPb level than the mother at the time of birth (Cleveland et al., 2008). At 12 weeks of the gestation period, the lead easily crosses the placenta (Hatzidaki et al., 2005). A fetus accumulates about 30 g of calcium into the fetal skeleton during the gestation period. During the bone resorption, a bone lead that has been accumulated for years is transferred to the fetal circulations through the placenta. (Téllez-Rojo, M.M. 2004)
男性和女性的生殖系统都会受到 BPb 水平升高的影响。研究表明，孕妇往往会因铅积累而出现更大的并发症（Vigeh 等人， M. 2010 ）。 BPb 水平高于 25 µg/dL 的男性精子活动能力、生育能力、精子数量和精子形态异常都会降低。另一方面，BPb水平为10 µg/dL的女性面临早产、低出生体重、不孕、流产、幼儿期神经缺陷和产妇高血压等并发症（ van Straaten，2000 ）。育龄妇女的 BPb 水平在 10–15 µg/dL 范围内会直接影响发育中的胎儿。一般来说，30-35 岁后分娩的女性更容易受到母乳中铅的影响（Bellinger, DC 2005 ；Shannon, M. 2003 ）。同意等人。研究了领头工人的精子数量。他的研究报告了畸形精子症（精子的遗传损伤）、精子减少症（精子数量低）和染色体畸变（ Telišman 等，2007 ）。鱼精蛋白(HP2) 是一种保护精子 DNA 的锌蛋白。 Pb 往往会取代 Zn 并导致精子 DNA 损伤（ Quintanilla-Vega 等，2000 ）。 据观察，胎儿出生时的 BPb 水平比母亲高 19%（ Cleveland 等，2008 ）。在妊娠期 12 周时，导线很容易穿过胎盘（Hatzidaki 等，2005）。胎儿在​​妊娠期间会在胎儿骨骼中积累约30克钙。在骨吸收过程中，多年积累的骨铅通过胎盘转移到胎儿循环中。 （特莱斯-罗霍， MM2004年）

3.4. Effect of lead on the hematopoietic system
3.4.铅对造血系统的影响

Lead directly affects the hematological system at very low BPb levels-10 µg/dL. It restrains the synthesis of hemoglobin by the inhibition of important enzymes involved in heme synthesis and reduces the life span of erythrocytes by the destabilization and increasing fragility of its cell membrane. This directly results in anemia and high blood Pb levels lead to Frank's anemia (iron deficiency anemia) (Ameen et al.,2009). Acute lead exposure leads to hemolytic anemia, where the red blood cells are destroyed as fast as they are made (Guidotti et al.,2008). A key enzyme for the synthesis of heme is δ-aminolevulinic acid dehydratase (ALAD). δ-ALAD, a cytoplasmic enzyme rich in SH groups, is the enzyme that catalyzes the formation of porphobilinogen from δ-aminolevulinic acid (ALA). Nikkanen et al. in their studies demonstrated that δ-ALAD is inhibited when the BPb levels are as low as 5 µg/dL and leads to behavioral changes and childhood lead encephalopathy. The inhibition of δ-ALAD results in the accumulation of δ-ALA in the plasma and excess of δ-ALA leads to severe neurological effects (Dehari-Zeka et al., 2020). δ- ALA in urine is also used as an indicator for lead exposure among industrial workers. Ferrochelatase is another mitochondrial enzyme that catalyzes the incorporation of iron (Fe2+) into the porphyrin ring. Lead toxicity inhibits this enzyme and in case of low availability Fe2+, Zn2+ is substituted and also interferes with the trans-mitochondrial transport of iron (Jangid et al.,  2012). More than 90% of Pb in the blood is bound to the RBC keeping plasma lead concentrations constant at 2–3 µg/dL even when BPb concentration is 10–150 µg/dL (Mrugesh et al., 2011; Patrick, 2006). These lead to decrease in hemoglobin in human beings, followed by anemia, weight loss, complications during pregnancy, kidney malfunctioning, and cancer in severe cases are some direct effects.
铅在 BPb 水平极低（10 µg/dL）时直接影响血液系统。它通过抑制参与血红素合成的重要酶来抑制血红蛋白的合成，并通过破坏细胞膜的稳定性和增加其脆性来缩短红细胞的寿命。这直接导致贫血，而高血铅水平导致弗兰克氏贫血（缺铁性贫血）（Ameen et al.,2009）。急性铅暴露会导致溶血性贫血，红细胞在产生的同时就被破坏（Guidotti 等， 2008 ）。合成血红素的关键酶是δ-氨基乙酰丙酸脱水酶（ALAD）。 δ-ALAD 是一种富含 SH 基团的细胞质酶，是催化 δ-氨基乙酰丙酸 (ALA) 形成胆色素原的酶。尼卡宁等人。他们的研究表明，当 BPb 水平低至 5 µg/dL 时，δ-ALAD 会受到抑制，并导致行为改变和儿童铅脑病。抑制 δ-ALAD 会导致血浆中 δ-ALA 的积累，过量的 δ-ALA 会导致严重的神经系统影响 ( Dehari-Zeka et al., 2020 )。尿液中的δ-ALA也被用作产业工人铅暴露的指标。铁螯合酶是另一种线粒体酶，可催化铁 (Fe2+) 掺入卟啉环。铅毒性会抑制这种酶，在 Fe2+ 可用性较低的情况下，Zn2+ 会被取代，并且还会干扰铁的跨线粒体转运（ Jangid 等，2012 ）。 血液中超过 90% 的铅与红细胞结合，即使 BPb 浓度为 10–150 µg/dL，血浆铅浓度也能恒定在 2–3 µg/dL（ Mrugesh 等，2011 ； Patrick，2006 ）。这些会导致人类血红蛋白减少，随之而来的是贫血、体重减轻、怀孕期间的并发症、肾功能障碍，严重时甚至会引发癌症。

3.5. Effect of lead on the renal system
3.5.铅对肾脏系统的影响

The mechanism of lead nephrotoxicity, renal cancer-role of the lead binding protein, adverse effect of low level environmental and chronic lead exposure in neurotoxicity, renal toxicity, renal cancer, renal dysfunction, and other complications were reported (Assi et al., 2016). Jia, et al. reported the mechanism of lead nephrotoxicity and formation of inclusion bodies such as lead-protein complex due to accumulation of lead in proximal renal tubular lining cells with cause proximal tubular dysfunction (Jia et al.,Q. 2012). The effect of lead in nephrotoxicity was reported to be occurring in three stages, primarily reversible or acute nephropathy, next stage is chronic nephropathy and the final stage is the renal tubular cell neoplasia or adenocarcinoma (Flora et al., 2012). Clinical manifestation includes a decrease in energy-dependent transport functions, including glycosuria, aminoaciduria, and changes in specific ion transport (Niemann and Serkova, 2007). Reduced glomerular filtration rate, decreased inulin clearance, and decreased maximal reabsorption of glucose are also observed in chronic nephropathy (Wang et al., 2002). Lead can bind with proteins and creates the risk of renal cancer. Kidney-specific proteins act as receptors and facilitate interactions with DNA in renal proximal tubular cells, the altered gene results in cancer (Silbergeld et al., 2000). Lead exposure also influenced renal plasma excretion and plasma renin activity. Lead poisoning in mitochondria creates deficiency of ATP, this reduces the reabsorption of sodium, an important process of kidney and increased renal excretion of sodium is observed (Marsden,P.A. 2003). Patients with acute and chronic renal injury were observed with excretion of more than 600 μg of lead over 72 h after an EDTA-mobilization test (Fontanellas et al.,A 2002). Almost 99% of blood lead bounded to zinc-dependent delta-aminolaevulinic acid dehydratase (ALAD) are stored in erythrocytes, since ALAD is inhibited this reflects in suppression of the heme synthesis (Siddarth et al.,M 2018).
铅肾毒性的机制、肾癌-铅结合蛋白的作用、低水平环境和慢性铅暴露对神经毒性、肾毒性、肾癌、肾功能障碍和其他并发症的不利影响（ Assi等，2016） ）。贾，等。报道了铅肾毒性的机制以及由于铅在近端肾小管衬里细胞中积累导致近端肾小管功能障碍而形成包涵体（例如铅-蛋白复合物）（Jia等人， Q.2012 ）。据报道，铅的肾毒性作用分三个阶段发生，首先是可逆性或急性肾病，下一阶段是慢性肾病，最后阶段是肾小管细胞瘤或腺癌（ Flora等，2012 ）。临床表现包括能量依赖性转运功能下降，包括糖尿、氨基酸尿和特定离子转运的变化（ Niemann 和 Serkova，2007 ）。在慢性肾病中还观察到肾小球滤过率降低、菊粉清除率降低和葡萄糖最大重吸收降低（ Wang et al., 2002 ）。铅可以与蛋白质结合并产生患肾癌的风险。 肾脏特异性蛋白质充当受体并促进与肾近端肾小管细胞中的 DNA 相互作用，改变的基因会导致癌症（ Silbergeld 等，2000 ）。铅暴露还影响肾血浆排泄和血浆肾素活性。线粒体中的铅中毒导致 ATP 缺乏，这减少了钠的重吸收，这是肾脏的一个重要过程，并且观察到钠的肾脏排泄增加（Marsden， PA 2003 ）。观察到患有急性和慢性肾损伤的患者在 EDTA 动员试验后 72 小时内排泄了超过 600 μg 的铅（Fontanellas 等人， A 2002 ）。几乎 99% 与锌依赖性 δ-氨基乙酰丙酸脱水酶 (ALAD) 结合的血铅储存在红细胞中，因为 ALAD 受到抑制，这反映了血红素合成的抑制 (Siddarth et al., M 2018 )。

A study collected workers' renal biopsies and analyzed for various parameters like inclusion bodies glomeruli filtrate rate, the plasma concentration of urinary excretion of ALA, renal excretion of lead, and lead-induced nephropathy. The samples with acute exposure showed the presence of nuclear inclusion bodies in the proximal tubular lining and greater urinary excretion of lead and the biopsy samples with chronic exposure showed peritubular fibrosis (Karimooy et al.,H.N. 2010).
一项研究收集了工人的肾活检并分析了各种参数，如包涵体肾小球滤过率、尿排泄 ALA 的血浆浓度、肾排泄铅和铅诱发的肾病。急性暴露的样本显示近端肾小管内壁存在核包涵体，并且尿中铅排泄较多，而慢性暴露的活检样本显示肾小管周围纤维化（Karimooy 等人， HN 2010 ）。

3.6. Effect of lead on the cardiovascular system
3.6.铅对心血管系统的影响

Lead also affects the cardiovascular system and has a significant impact on the human heart. Besides inducing increased blood pressure and hypertension, it has been observed that exposure to high levels of lead is also associated with increased risks of stroke, peripheral arterial disease, coronary heart disease, and cardiovascular functional abnormalities such as left ventricular hypertrophy and alterations in the cardiac rhythm (Lustberg & Silbergeld,M. 2002; Menke et al.,2006; Navas-Acien et al.,A. 2004; Schober et al.,2006).Another study demonstrated the positive association between blood lead levels and total peripheral resistance, reduced cardiac output, and reduced stroke volume in response to acute stress in children (9 to 11 years) when the blood lead level was below 10 µg/dL (Gump et al., 2011). At the blood lead level >5 µg/dL, the percentage of adults above the threshold of systolic blood pressure elevates as the age group increases. A report on steel factory workers in Poland revealed a significantly higher left ventricle mass and lower ejection fraction when the results were compared to the administrative workers of the same factory (Kasperczyk et al., 2005). The workers who were in contact with higher concentrations of lead had developed weakened diastolic functions when compared with the workers who were not exposed to lead (Beck & Steinmetz, B. 2005). Lead can also escalate the release of pro-inflammatory cytokines by stimulating the endothelial and peripheral mononuclear cells in humans (Nawrot et al., 2002). Inflammatory cytokines cause an increase in endothelial inflammation along with cardiovascular damage (Cao et al., 2015). Lead has the potential to play a role in arterial stiffness and the mechanism of involvement of metals in cardiovascular pathology has been studied. Pre-school children who are exposed to e-waste show a positive response to future cardiovascular diseases, as the elevated blood lead level is associated with the heightened vascular endothelial inflammation (Zheng et al.,  2019). Thus the effect of lead on the cardiovascular systems is first noticed when there is an increase in blood pressure. However, this becomes apparent when the blood lead level crosses the threshold level of 5 µg/dL (Navas-Acien et al., 2007).
铅还会影响心血管系统，对人的心脏有重大影响。除了引起血压升高和高血压外，据观察，接触高浓度的铅还会增加中风、外周动脉疾病、冠心病和心血管功能异常（如左心室肥大和心脏功能改变）的风险。 (Lustberg & Silbergeld, M. 2002 ; Menke et al.,2006 ; Navas-Acien et al., A. 2004 ; Schober et al., 2006 )。另一项研究表明血铅水平与总外周阻力之间呈正相关当血铅水平低于 10 µg/dL 时，儿童（9 至 11 岁）因急性应激而导致心输出量减少和每搏输出量减少（ Gump 等人，2011 年）。当血铅水平 >5 µg/dL 时，超过收缩压阈值的成年人比例随着年龄组的增加而升高。一份关于波兰钢铁厂工人的报告显示，与同一工厂的管理人员相比，其左心室质量明显较高，射血分数较低（ Kasperczyk 等，2005 ）。 与未接触铅的工人相比，接触较高浓度铅的工人的舒张功能较弱（Beck & Steinmetz, B. 2005 ）。铅还可以通过刺激人类的内皮细胞和外周单核细胞来增加促炎细胞因子的释放（ Nawrot 等，2002 ）。炎症细胞因子导致内皮炎症增加以及心血管损伤（ Cao et al., 2015 ）。铅有可能在动脉硬化中发挥作用，并且金属参与心血管病理学的机制已被研究。接触电子垃圾的学龄前儿童对未来的心血管疾病表现出积极的反应，因为血铅水平升高与血管内皮炎症加剧有关（ Zheng et al., 2019 ）。因此，当血压升高时，首先会注意到铅对心血管系统的影响。然而，当血铅水平超过 5 µg/dL 的阈值水平时，这一点就会变得明显（ Navas-Acien 等人，2007 年）。

3.7. Effect of lead on the saliva, hair, nail, and tooth
3.7.铅对唾液、头发、指甲和牙齿的影响