|Year : 2019 | Volume
| Issue : 2 | Page : 66-71
Sources and toxicological effects of lead on human health
Bikash Debnath, Waikhom Somraj Singh, Kuntal Manna
Department of Pharmacy, Tripura University (A Central University), Agartala, Tripura, India
|Date of Submission||13-Nov-2018|
|Date of Decision||19-Feb-2019|
|Date of Acceptance||01-Apr-2019|
|Date of Web Publication||24-May-2019|
Dr. Kuntal Manna
Department of Pharmacy, Tripura University (A Central University), Suryamaninagar, Agartala - 799 022, Tripura
Source of Support: None, Conflict of Interest: None
Lead toxicity is one of the most hazardous metal toxicities. It can enter the body through lead-based paint, dust, water, soil, tableware, and folk medicines. Children are especially prone to develop lead toxicity. Lead acts by inducing oxidative stress due to inefficient replenishment of glutathione. Lead can also cause hemolytic anemia due to disruption of the cellular membrane by lipid peroxidation. Lead toxicity also affects neurotransmitter levels and causes severe health issues related to organ damage, some even leading to death. The main aim of this review article is to summarize lead toxicity detection, its sources, and its mechanism including various toxicological effects on human health. It also focuses on the prevention and treatment of lead toxicity.
Keywords: Lead toxicity, prevention of toxicity, toxicological effects
|How to cite this article:|
Debnath B, Singh WS, Manna K. Sources and toxicological effects of lead on human health. Indian J Med Spec 2019;10:66-71
|How to cite this URL:|
Debnath B, Singh WS, Manna K. Sources and toxicological effects of lead on human health. Indian J Med Spec [serial online] 2019 [cited 2019 Jun 26];10:66-71. Available from: http://www.ijms.in/text.asp?2019/10/2/66/258987
| Introduction|| |
The environment (waters, soils, and dust) contains different types of heavy metals, and these cannot be degraded. Different types of anthropic activities such as mining, smelting, and different kinds of industrial wastes are the main sources of heavy metals. Lead is a bluish-grey-colored heavy metal with low melting point. It can be molded easily into any shape and forms alloys with other metals. Lead toxicity is of prime concern in childhood because of environmental source in developing countries. Such poisoning occurs from different kinds of human-related activities such as painting of home, smoking-related activities, leaded petrol, contaminated food, and drinking water; smelting; and especially from the industries, which have been carrying out manufacturing processes. It is also found in human milk. Excessive exposure of the human body to lead results in disturbance of body function, which can be neurological, cardiovascular, hematologic, and reproductive. Blood containing high level of lead causes inadequate functioning of the central nervous system (CNS) and consequently leads to encephalopathy and edema that mainly affects the cerebellum., In pregnant women, high amount of lead in the body can cause miscarriage. Prolonged lead exposure was found to decrease potency of males.,
Five micrograms per deciliter is endorsed as a reference to identify blood lead levels (BLLs) in children by the Centers for Disease Control and Prevention (CDC) in the United States. An effort has been made to decrease the amount of lead in the occupational environment for the reduction of lead poisoning. Particularly in children, even a small concentration of lead has been reported to induce dyscognitive behavior. The CDC recommends testing for the presence of lead in the blood in all children at the age of 12 months and if possible, once more at the age of 24 months. Novel chelating agent is used for treatment if the BLL is 45 μg/dL or more.
| Detection Of Lead Poisoning|| |
Lead poisoning is screened by determining the level of lead in fingerprick blood sample. Changes in the bones of the children can be detected using X-ray. There are techniques that have been used for the detection of lead poisoning in blood cells (10 μg/dL for adults and 5 μg/dL for children of the whole blood). Since children are in the stage of development, they are more susceptible toward lead poisoning. Wherever contamination is feasible, regular checkup and lead levels of blood have to be set.
| Burden Of Diseases From Lead Exposure|| |
In 2016, the Institute for Health Metrics and Evaluation (IHME) estimated that worldwide 540,000 deaths and loss of 13.9 million healthy life, disability-adjusted life years (DALYs), due to lead poisoning were recorded. IHME also predicted that in 63.8% of cases of lead exposure, there was a liability to develop intellectual disability. Low- and middle-income countries were most commonly affected. It poses a continuous and serious impact on public health. This also adds to burden of these countries, which are already affected with other extensively familiar public health challenges. For a generalization of sustenance and capital rising, high number of DALYs associated with the exposure of lead may be used for the remediation of toxic waste.,,,
| Possible Sources of Lead Exposure|| |
Lead in paint
Until 1978, in every house, lead was used as common paint; later on, Consumer Product Safety Commission restricted lead in household paint. Before 1978, several buildings that were constructed had been painted with lead-based paints, and approximately, 74% of lead remains. Houses, which were built before 1950, pose a high chance of lead poisoning due to the use of lead-based paint. Exposure of children to lead paints through direct and indirect ways is common because of deferred maintenance and living in old house. Ingestible lead dust may be hazardous. Old toys, furniture, and playground that are equipped with the lead-based paint have high lead content.
Lead in dust
Among children, common exposure source is the lead paint dust. Lead as dust is better and easily absorbed. Interior of the house can be contaminated with lead or lead dust due to damage to painted walls, and airborne exposure can occur due to fall out of lead. When painted surfaces such as windows or doors rub against each other, fine lead dust is formed, thereby contaminating the air. It can accumulate together on the surface of carpets, toys, and other objects, especially on the floors, which later affects the children since they have a high chance of putting their contaminated hands into mouth. A study in young children shows that amount of lead in house paint has a greater association with the BLLs than the quantity of lead dust in the house., Statistical analysis of 12 new studies has shown connection between lead in the dust to BLLs among children (age group: 6–36 months) and also a linear involvement between lead dust stacking and threat of possessing an elevated BLL.
Lead in water
Some old well pumps may have the possibility of being contaminated by lead. During the last two decades, measures have been taken to reduce the lead exposure through the use of tap water as per the safe drinking water act and a consequent Environmental Protection Agency Regulation (The Lead and Copper Rule) under the requirements of the 1986 and 1996 amendments. The formulation prepared for the consumption of infants with lead-contaminated water has a higher risk due to over intake of water as compared to their body size. If lead is suspected in plumbing, hot water taps should not be used and cold water taps should be flushed every morning for several minutes before use.
Lead in tableware
Lead may be present in pewter, brass, old, handmade, imported or poorly glazed ceramic dishes, and pottery. An acidic substance present in these pieces could act together with the glaze and increase the release of lead. Thus, the storage of acidic food such as tomato sauce, wine, orange, tomato and other fruit juices, and vinegar in glazed containers is more hazardous.
Lead in soil
The lead dust from the exterior of a house, which is painted with lead-based paint, can also combine with soil. It may cause problems to the workers during remodeling of the old house. The mixture of lead-contaminated soil can be stirred up by wind and may blow inside the house and surroundings. Metal smelting and battery manufacturing are other important sources of soil contamination by lead. This easily flows into the environment and thus easily mixes up with soil from the nearby homes. For children, lead-contaminated soil has high risk of elevated BLL (EBLL); however, the lead content of interior dust is of less importance. Children have a high BLL from exposure to play area soil and then from other locations.
Lead in folk medicines and cosmetics
Some folk medicines (greta, azarcon, and pay-loo-ah) may contain lead. These are frequently brought from Southeast Asia, India, Middle East, the Dominican Republic, or Mexico. These folk medications may contain high amount (approximately 90%) of lead. Various cosmetic products such as surma, kohl (alkohl), kajal, tiro, and tozali also contain a high amount of lead. Application of Kohl's results in successive ingestion of particles through hand-to-eye-to-mouth. Lead content of folk medicines and cosmetics is a vital predictor of the adult and children's risk for EBLL.,
Lead in occupational sources
Occupational exposure is an important source of lead poisoning in adults. In the United States, >3 million employees are potentially exposed to lead in the factory due to working equipment (radiation protector, some surgical equipment, developing dental X-ray films processing to digital X-rays, and electronic fetal monitors) that involves lead-containing products. Workers who frequently come in contact with these kinds of equipment have higher chances of toxicity. People, who work in the lead-based zone, unintentionally expose their family to lead poisoning by carrying lead dust into their car, their clothes, and bodies. Increasing amounts of lead in occupational sources have a strong correlation with the BLLs of adult.
Lead in metal costume jewelry
Lead poisoning in children has been most serious for the last decade. Children are encountered by lead toxicity from the metal costume jewelry containing lead. Charms are being manufactured without testing for lead. A high amount of lead (99.1%) is contained in charm and is considered dangerous as it raises BLLs up to three times the BLL seen in children.
Lead in toys
Toys and other useful goods for children are found with a high range of lead and pose lead poisoning threats. Maximum parents would not ever believe that their child's sports accessory set could have a high amount of lead. The Center for Environmental Health (CEH) discovered those lead toxic toys over the past few decades. CEH (since 2007) has carried out trial on thousands of toys for lead and has exposed abundant hazardous products. All sources of lead exposure are summarized in [Table 1].
| Mechanism of Lead Poisoning|| |
In the human body, lead toxicity occurs when the cell experiences oxidative stress [Figure 1]. Increased production of free radicals and overwhelming of antioxidant mechanism result in oxidative stress and consequential destruction. Antioxidant mostly protects the body and invalidates the generated reactive oxygen species (ROS). A tripeptide sulfhydryl group's glutathione (GSH) is the most important antioxidant-producing cell. In mammalian tissues, it is present in lesser quantity. It is a chief antioxidant for free-radical scavenging. ROS are stabilized by GSH which in turn converts to glutathione disulfide (GSSG) and with the help of enzyme glutathione-disulfide reductase, GSSG is reduced back to GSH. Lead binds to GSH's sulfhydryl group, inactivates GSH, and increases oxidative stress. Lead blocks the enzymes (δ-aminolevulinic acid dehydratase [ALAD], glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) activity and further reduces GSH levels. Inducing lead in a human body at high level causes destabilization of cellular membrane through lipid peroxidation, which can cause hemolytic anemia. Neurological toxicity of lead is due to an ionic mechanism that permits calcium ions to pass through the blood–brain barrier (BBB). Sodium ion concentration is also affected by lead toxicity; therefore, hampering cell-to-cell communication and uptake of neurotransmitters. Even in a very small amount, it can affect protein kinase C which is responsible for prolonged neural excitation and memory storage.
| Sign and Symptoms|| |
At first, lead poisoning can be difficult or hard to detect because even people with high amounts of lead in their blood might seem to be fully healthy. Usually, signs and symptoms are not noticeable until unsafe concentration has accumulated in the body. According to the age of the patient, symptoms may vary [Table 2].
| Toxicological Effect of Lead|| |
Neurotoxicity means exposure of the entire body to lead toxic agents and the imbalance in the neurophysiological function. There are two main symptoms caused by such exposures; they are psychiatric disturbances and neurocognitive symptoms. It predominantly influences the CNS, generally the developing brain, and affects almost every organ system. Therefore, children suffer more from neurotoxic effects than adults and are at a greater risk [Table 3] of lead toxicity. An effective receptor N-methyl-D-aspartate is involved in the maturation of brain plasticity that occurs in brain organization; lead blocks this receptor and results in the interruption of long-term potentiating and storage of newly learned knowledge. Lead easily crosses the endothelial cells at the BBB, which plays a significant role in brain fitness and is regularly compromised in disease. Blood lead concentration of children >10 μg/dL represents a higher risk for toxicity.
Lead can cause hypertension and affect blood vessels. Lead-blocked blood vessels can lead to immediate heart attack and death. Increasing BLLs significantly correlate with an increase in cardiovascular morbidity and mortality. Chronic and acute both types of lead poisoning can cause cardiac dysfunction and vascular damage. Recently, researchers have found an intriguing correlation between low blood leads concentration and cardiovascular toxicity, and recently, some studies suggest that low levels of lead may be associated with high blood pressure.
Due to lead toxicity, anemia is the classic clinical manifestation in erythrocytes. Young and iron-deficient children have more likelihood of developing lead-induced clinical anemia. A high amount of lead exposure in the human body causes hemolytic anemia. More than 99% of lead is distributed in red blood cells rather than plasma. Lead causes anemia by blocking the activity of ferrochelatase, aminolevulinic acid synthetase, and ALAD. Lead also inhibits enzymes related to heme synthesis. Heme is an oxygen-carrying moiety in hemoglobin, which consists of a porphyrin ring that holds iron ion in the center.,
When lead affects the kidneys, medical experts call it “lead-related nephrotoxicity.” Due to lead exposure, nephrotoxicity occurs because lead is eliminated through the kidney. In the renal tubules, lead is absorbed by proximal tubular cells, and it binds to specific lead-binding proteins. These lead-binding proteins produce intercellular inclusions of proximal tubular cells.
Lead toxicity affects both the male and female reproductive systems. During the pregnancy, it crosses the placenta resulting in prematurity, intrauterine deaths, and low birth weight. Differentin vivo study proves that constant exposure to lead may cause inhibition of menstruation, ovulation and follicular growth, delayed vaginal opening, and a decrease in frequency of implanted ova. Usually, BLLs of >40 μg/dl are more damaging to the human reproductive organs, sometimes, even at levels of <10 μg/dl lead can be dangerous.
A significant reduction in the bone calcium content upon lead intoxication has been observed. This decrease in calcium content may be because of the increased bone resorption. Lead is one of the risk factors for the development of osteoporosis by altering bone mineral metabolism. Osteopenia, osteoporosis, and osteomalacia with increased bone fragility in humans and experimental animals were observed because of lead exposure. Long-term exposure to lead damages different body tissues.
Toxicity in human cells
Overexposure of lead in the human body influences the activation of mitogen by raising the secretion of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α and chemokines IL-8. Major cellular functions such as expression of cellular metabolic enzymes, metallothionein expression, and protein kinase activity were affected by lead toxicity.
| Prevention and Treatment|| |
In the United States, childhood lead toxicity prevention has taken a major concern in the public health for the reduction of blood lead concentrations in children. An excellent approach to lessen the lead toxicity is to suggest people, mostly uneducated people about CDC guidelines and by creating awareness about lead poisoning. Every parent should frequently wash their children's hands and prevent children from placing their hands in mouth habitually. It is suggested that every family should use cold water because hot water contains high amounts of lead. Vitamin C has antioxidant properties, which is capable of removing free radicals and alleviating oxidative stress. Therefore, the physician should suggest that taking Vitamin C containing food in the diet regularly because they minimize lead toxicity easily. A chelation therapy is a novel therapeutic technique for removing lead from the body. If BLLs are 45 μg/dL or greater chelation therapy can be recommended. Lead chelating agent has much more attraction toward lead than calcium and is excreted in urine.
| Conclusion|| |
Since the 18th century humankind has known and experienced lead poisoning, lifestyle, socioecology, and age are mainly associated with higher concentrations of lead. The main complication of lead toxicity is impairment of the nervous system and blood disorders that may lead to encephalopathy and edema in the cerebellum. The brain and kidney are the main parts affected by lead toxicity in both adults and children. Even at low concentration, it can induce cognitive behavioral disturbances. Lead toxicity increases oxidative stress, neurological abnormalities, affects the sodium ion concentration, other severe health complications, and even death. Children are more prone to lead toxicity due to certain habits such as putting hands that might be contaminated in their mouth. Antioxidants, especially vitamin C, are used for the treatment and improvement of oxidative stress-induced toxicity of lead until now. Chelation treatment is employed for blood lead toxicity if the level is 45 μg/dL or greater. Lead toxicity and associated morbidity and mortality can be reduced by regulating ongoing medical diagnosis, creating health awareness, and timely medical treatment.
The authors are grateful for the E-resources provided by Tripura University (A Central University), Suryamaninagar, Tripura, India-799022. We are also grateful to the University Grant Commission, Government of India, for providing Startup Grant (F. 20-2 /2012 [SR]) for newly recruited faculty and as financial support. We are also acknowledging the Department of Science and Technology (DST), Government of India, for awarding DST Fast Track Scheme (NO.SB/FT/CS-150/2012). The authors are also indebted to Ms. Mayanglangbam Sana, research scholar, Department of English, Tripura University (A Central University), Suryamaninagar, Tripura, India-799022, and Dr. Rashmi Rajput, Senior Resident, Department of Medicine, Lady Hardinge Medical College, New Delhi, India-110001 for English editing of the manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wu Q, Leung JY, Geng X, Chen S, Huang X, Li H, et al.
Heavy metal contamination of soil and water in the vicinity of an abandoned e-waste recycling site: Implications for dissemination of heavy metals. Sci Total Environ 2015;506-507:217-25.
Pal M, Sachdeva M, Gupta N, Mishra P, Yadav M, Tiwari A. Lead exposure in different organs of mammals and prevention by curcumin-nanocurcumin: A review. Biol Trace Elem Res 2015;168:380-91.
Rao JV, Vengamma B, Naveen T, Naveen V. Lead encephalopathy in adults. J Neurosci Rural Pract 2014;5:161-3.
] [Full text]
Amadi CN, Igweze ZN, Orisakwe OE. Heavy metals in miscarriages and stillbirths in developing nations. Middle East Fertil Soc J 2017;22:91-100.
Vigeh M, Smith DR, Hsu PC. How does lead induce male infertility? Iran J Reprod Med 2011;9:1-8.
Burns MS, Gerstenberger SL. Implications of the new centers for disease control and prevention blood lead reference value. Am J Public Health 2014;104:e27-33.
Lowry JA. Oral chelation therapy for patients with lead poisoning. Am Acad Pediatr 2010;116:1036-46.
Wani AL, Ara A, Usmani JA. Lead toxicity: A review. Interdiscip Toxicol 2015;8:55-64.
Cao J, Li M, Wang Y, Yu G, Yan C. Environmental lead exposure among preschool children in Shanghai, China: Blood lead levels and risk factors. PLoS One 2014;9:e113297.
Seedat YK, Rayner BL; Southern African Hypertension Society. South African hypertension guideline 2011. S Afr Med J 2011;102:57-83.
Caravanos J, Carrelli J, Dowling R, Pavilonis B, Ericson B, Fuller R. Burden of disease resulting from lead exposure at toxic waste sites in Argentina, Mexico and Uruguay. Environ Health 2016;15:72.
Ferguson KT, Cassells RC, MacAllister JW, Evans GW. The physical environment and child development: An international review. Int J Psychol 2013;48:437-68.
Gould E. Childhood lead poisoning: Conservative estimates of the social and economic benefits of lead hazard control. Environ Health Perspect 2009;117:1162-7.
Dhimal M, Karki KB, Aryal KK, Dhimal B, Joshi HD, Puri S, et al.
Correction: High blood levels of lead in children aged 6-36 months in Kathmandu Valley, Nepal: A cross-sectional study of associated factors. PLoS One 2017;12:e0185773.
Ji JS, Schwartz J, Sparrow D, Hu H, Weisskopf MG. Occupational determinants of cumulative lead exposure: Analysis of bone lead among men in the VA normative aging study. J Occup Environ Med 2014;56:435-40.
Flora G, Gupta D, Tiwari A. Toxicity of lead: A review with recent updates. Interdiscip Toxicol 2012;5:47-58.
Nemsadze K, Sanikidze T, Ratiani L, Gabunia L, Sharashenidze T. Mechanisms of lead-induced poisoning. Georgian Med News 2009;172-173:92-6.
Kim HC, Jang TW, Chae HJ, Choi WJ, Ha MN, Ye BJ, et al.
Evaluation and management of lead exposure. Ann Occup Environ Med 2015;27:30.
Tobwala S, Wang HJ, Carey JW, Banks WA, Ercal N. Effects of lead and cadmium on brain endothelial cell survival, monolayer permeability, and crucial oxidative stress markers in anin vitro
model of the blood-brain barrier. Toxics 2014;2:258-75.
Neal AP, Guilarte TR. Mechanisms of heavy metal neurotoxicity: Lead and manganese. J Drug Metab Toxicol 2012;S5:1-13. [Doi: 10.4172/2157-7609.S5-002].
Rehman K, Fatima F, Waheed I, Akash MS. Prevalence of exposure of heavy metals and their impact on health consequences. J Cell Biochem 2018;119:157-84.
Mason LH, Harp JP, Han DY. Pb neurotoxicity: neuropsychological effects of lead toxicity. Biomed Res Int 2014;2014:840547. [Doi: 10.1155/2014/840547].
Jakubowski M. Low-level environmental lead exposure and intellectual impairment in children – The current concepts of risk assessment. Int J Occup Med Environ Health 2011;24:1-7.
Klingberg T. Training and plasticity of working memory. Trends Cogn Sci 2010;14:317-24.
Blair C, Ursache A. A bidirectional model of executive functions and self-regulation. Handbook of Self-Regulation: Research, Theory, and Applications. Vol. 2. Guilford Press; 2011. p. 300-20.
Richards JC, Rodgers TS. Approaches and Methods in Language Teaching. Cambridge, UK: Cambridge University Press; 2014.
Robinson LE. Effect of a mastery climate motor program on object control skills and perceived physical competence in preschoolers. Res Q Exerc Sport 2011;82:355-9.
Sanders T, Liu Y, Buchner V, Tchounwou PB. Neurotoxic effects and biomarkers of lead exposure: A review. Rev Environ Health 2009;24:15-45.
Brunton LL. Goodman and Gilman's Manual of Pharmacology and Therapeutics. New York: McGraw-Hill; 2014.
Akil L, Ahmad HA. Relationships between obesity and cardiovascular diseases in four Southern states and Colorado. J Health Care Poor Underserved 2011;22:61-72.
Baker RD, Greer FR; Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics 2010;126:1040-50.
Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, et al.
Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: Possible role in lead-induced nephrotoxicity. Environ Health Perspect 2015;123:120-7.
Nakade UP, Garg SK, Sharma A, Choudhury S, Yadav RS, Gupta K, et al.
Lead-induced adverse effects on the reproductive system of rats with particular reference to histopathological changes in uterus. Indian J Pharmacol 2015;47:22-6.
] [Full text]
Bhardwaj P, Rai DV. Effect of lead toxicity on bone calcium content and morphometric parameters. Int J Res Med Sci 2016;4:177-80.
Gillis BS, Arbieva Z, Gavin IM. Analysis of lead toxicity in human cells. BMC Genomics 2012;13:344.
Gupta S, Ghulmiyyah J, Sharma R, Halabi J, Agarwal A. Power of proteomics in linking oxidative stress and female infertility. Biomed Res Int 2014;2014:916212.
Ferreirós-Martínez R, Esteban-Gómez D, Tóth É, de Blas A, Platas-Iglesias C, Rodríguez-Blas T, et al.
Macrocyclic receptor showing extremely high Sr(II)/Ca(II) and Pb(II)/Ca(II) selectivities with potential application in chelation treatment of metal intoxication. Inorg Chem 2011;50:3772-84.
[Table 1], [Table 2], [Table 3]