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1、interdisciplinaryLead toxicity:a reviewAb Latif WANI 1,Anjum ARA 1,Jawed Ahmad USMANI 21 Section of Genetics,Department of Zoology,Faculty of Life Science,Aligarh Muslim University,Aligarh,Utter Pradesh,India2 Department of Forensic Medicine,Faculty of Medicine,Jawaharlal Nehru Medical College and H
2、ospital,Aligarh Muslim University,Aligarh,Utter Pradesh,IndiaITX080215R01 Received:23 January 2015 Revised:14 April 2015 Accepted:17 April 2015ABSTRACTLead toxicity is an important environmental disease and its effects on the human body are devastating.There is almost no function in the human body w
3、hich is not affected by lead toxicity.Though in countries like US and Canada the use of lead has been controlled up to a certain extent,it is still used vehemently in the developing countries.This is primarily because lead bears unique physical and chemical properties that make it suitable for a lar
4、ge number of applications for which humans have exploited its benefits from historical times and thus it has become a common environmental pollutant.Lead is highly persistent in the environment and because of its continuous use its levels rise in almost every country,posing serious threats.This arti
5、cle reviews the works listed in the literature with recent updates regarding the toxicity of lead.Focus is also on toxic effects of lead on the renal,reproductive and nervous system.Finally the techniques available for treating lead toxicity are presented with some recent updates.KEY WORDS:lead toxi
6、city;lead poisoning;heavy metals;environmental health Correspondence address:Ab Latif Wani Section of Genetics,Department of ZoologyFaculty of Life Science,Aligarh Muslim UniversityAligarh,Utter Pradesh,202002 IndiaE-MAIL:in lead toxicity,both in children and adults.The toxicity in children is howev
7、er of a greater impact than in adults.This is because their tissues,internal as well as external,are softer than in adults.Long-term exposure of adults can result in decreased performance in some tests of cognitive performance that measure functions of the nervous system.Infants and young children a
8、re especially sensitive to even low levels of lead,which may contribute to behavioural problems,learning deficits and lowered IQ(Rubin&Strayer,2008).Long-time exposure to lead has been reported to cause anaemia,along with an increase in blood pressure,and that mainly in old and middle aged people.Se
9、vere damage to the brain and kidneys,both in adults and children,were found to be linked to exposure to heavy lead levels resulting in death.In pregnant women,high exposure to lead may cause miscarriage.Chronic lead exposure was found to reduce fertility in males(Sokol&Berman,1991).Blood disorders a
10、nd damage to the nervous system have a high occurrence in lead toxicity.Detection of lead poisoningSeveral methods are used to detect elevated blood lead levels.The presence of changes in blood cells visible under the microscope or deletion of dense lines in the bones of children seen on X-ray are s
11、igns used for detecting lead poisoning.However the main tool to detect elevated levels of body lead is to measure the level of lead in blood samples.This test gives however only an account of lead present in IntroductionLead is the most important toxic heavy element in the environment.Due to its imp
12、ortant physico-chemical properties,its use can be retraced to historical times.Globally it is an abundantly distributed,important yet dangerous environmental chemical(Mahaffay,1990a).Its important properties like softness,malleability,ductility,poor conductibility and resistance to corrosion seem to
13、 make difficult to give up its use.Due to its non-biode-gradable nature and continuous use,its concentration accumulates in the environment with increasing hazards.Human exposure to lead and its compounds occurs mostly in lead related occupations with various sources like leaded gasoline,industrial
14、processes such as smelting of lead and its combustion,pottery,boat building,lead based painting,lead containing pipes,battery recycling,grids,arm industry,pigments,printing of books,etc.Though its widespread use has discontinued in many countries of the world,it is still used in many industries like
15、 car repair,battery manufacturing and recycling,refining,smelting,etc.Lead is a highly poisonous metal affecting almost every organ in the body.Of all the organs,the nervous system is the mostly affected target Interdiscip Toxicol.2015;Vol.8(2):5564.doi:10.1515/intox-2015-0009Copyright 2015 SETOX&IE
16、PT,SASc.This is an Open Access article distributed under the terms of the Creative Commons Attribu-tion License(http:/creativecommons.org/licenses/by/2.0),which permits unrestricted use,distribution,and reproduction in any medium,provided the original work is properly cited.REVIEW ARTICLE56Ab Latif
17、Wani,Anjum Ara,Jawed Ahmad UsmaniLead toxicityISSN:1337-6853(print version)|1337-9569(electronic version)circulating blood but cannot show how much lead is stored in the body.As of 2012,the Centers for Disease Control and Prevention(USA)have set the standard elevated blood lead level for adults to b
18、e 10 g/dL and for children 5 g/dL of the whole blood(CDC,2012).Previously,the standard lead level for children was 10 g/dL.The appear-ance of clinical manifestations varies from individual to individual depending on other environmental factors.In some there is a clear appearance of clinical features
19、 even at lower levels,while some are asymptomatic even at higher levels of lead present in their body fluids.Children are more prone to the effects of lead because usually their organs are in a developing stage.Thus blood lead levels have to be set lower and must be frequently checked,particularly w
20、here contamination is expected.Eff ects of lead poisoningAll along human history,lead poisoning has been reported to have severe effects.Occasional lead poison-ing was found to be caused by lead salts used in pottery glazes leached by acidic fruit juices.Beethovens death has been treated in various
21、reports.Many of them have concluded that he died because of the toxic doses of lead-based treatment administered by his doctor.Analysis of his hair was found to contain elevated levels of lead(Mai,2006).It is also assumed that in the eighteenth and early nineteenth century lead was illegally added t
22、o wine both as a sweetener and to make it appear fresh(Mai,2006).Lead poisoning is believed to be primarily responsible for the collapse of the Roman Empire,in which lead acetate was used as a sweetener of wine.Its prolonged use was considered to have caused dementia to many Roman emperors.Lead pois
23、oning has also been found to be the cause of anaemia in a number of cases as lead inhibits porphobilinogen synthase and ferrochelatase,preventing both porphobilinogen formation and the incorporation of iron into protoporphyrin IX,which prevents heme synthesis(Cohen et al.,1981)or causes ineffective
24、heme synthesis and subsequently microcytic anaemia.One of the mechanisms by which lead interferes with cognition is that it acts as calcium analogue which interferes with ion channels.It has been observed that Pb2+is a potent Figure 1.Illustration how people are exposed to chemicals in the environme
25、nt and the eff ect of such chemicals on human health.57Full-text also available online on PubMed CentralInterdisciplinary Toxicology.2015;Vol.8(2):5564Copyright 2015 SETOX&Institute of Experimental Pharmacology and Toxicology,SASc.reversible and selective blocker of voltage-dependent calcium channel
26、s at low concentrations(Busselberg et al.,1993).In a recent study,the authors showed that the toxic effects on blood cells of rats caused by lead nitrate was alleviated by sodium selenite.They also showed that effects of lead nitrate were more harmful in diabetic than in non-diabetic rats(Bas et al.
27、,2015).Oxidative stress was studied by low level lead exposure in first grade Uruguayan children,suggesting its potentially adverse effects on oxidative stress(Roy et al.,2015).Impaired respiratory function was observed in workers exposed to lead with elevated blood lead concentration and zinc proto
28、porphyrin concentration(Jurdziak et al.,2015).In a recent study lead and cadmium contents were investigated in counterfeit cigarettes seized in the United States by various law enforcement agencies.Both lead and cadmium levels were found to be markedly higher than in their genuine equivalents.The re
29、sults suggest the pos-sibility of a higher risk of serious consequences to public health caused by counterfeit cigarettes(He et al.,2015).Possible pathway of lead poisoningPoisoning due to lead occurs mainly by ingestion of food or water contaminated with lead.However accidental ingestion of contami
30、nated soil,dust or lead based paint may also result in poisoning.Lead is thought to be quickly absorbed in the blood stream and is believed to have adverse effects on certain organ systems like the central nervous system,the cardiovascular system,kidneys,and the immune system(Bergeson,2008).Most pha
31、rma-ceutical companies have set a limit for maximum daily intake of lead as 1.0 g/g,however prolonged intake of even this low level of lead is hazardous to human beings.Occupational exposure also results in elevated blood lead levels.Increased blood levels are associated with delayed puberty in girl
32、s(Schoeters et al.,2008).There is no threshold value for the level of lead present in blood below which its concentration can be considered safe.Extremely low yet permanent levels of lead exposure were found to reduce the cognitive capacity of children(Needlemann et al.,1990).Dangers from lead poiso
33、ning due to paint pigments mainly in children have sharply reduced the use of lead in paints.However old houses may still contain substantial amounts of lead paint(Levin et al.2008).This sometimes causes an accidental contamination of lead in children.In industrialised countries white lead paint has
34、 been completely withdrawn from sale,however yellow lead chromate is still in use.Old paint should not be stripped by sanding,as this produces inhalable dust(Marino et al.,1990).Traditional medicines were also found to contain heavy metals including lead.A number of diseases have been reported due t
35、o consumption of traditional medicine(Karri et al.,2008).Ayurvedic medicines are considered to be heavily contaminated with heavy metals.In one recent study the blood lead levels were evaluated in consumers of ayurvedic medicines.Of the 115 participants 40%were found to have an elevated blood lead l
36、evels of 10 g/dL or above and 9.6%had blood lead levels above 50 g/dL(Breeher et al.,2015).Recently a patient taking Chinese folk remedies was reported to suffer from dysplastic changes in erythroid precursors due to lead poisoning(Lv et al.,2015).The Centers for Disease Control and Prevention also
37、issued guidelines about ingesting certain folk medicines which contain a high level of lead and may expose people to lead or lead compounds.For example Daw Tway is a digestive aid used in Thailand and Myanmar(Burma).Analysis of Daw Tway samples showed as much as 970 parts per million(ppm)of lead.The
38、 Daw Tway samples also contained high arsenic levels,as high as 7,100 ppm.Lead toxicity may be caused through fruits and vegetables contaminated with high lead levels from the soils where they were grown.The soil accumulates lead levels generally from pipes,lead paint and residual emissions from lea
39、ded gasoline that was used before the Environment Protection Agency issued the regulation around 1980.In order to prevent the general population from domestic lead poisoning,it is necessary to educate people about the major sources of lead poisoning.Lead from water pipes coming into homes is one of
40、the major sources(Moore,1977).For ingested lead,the rate of absorption by the body is very high with almost 2070%and in children it is even higher.However the rate of skin absorption for inorganic lead is low.Occupational exposureOccupational exposure is a major source for lead poison-ing in adults.
41、According to estimates made by the National Institute of Occupational Safety and Health(NIOSH),more than 3 million workers in the United States are potentially exposed to lead in the workplace(Staudinger&Roth,1998).Occupational exposure as the major concern and also the main cause of lead poisoning
42、was reported by Needleman(2004).The common working facilities that involve lead containing products are radiation shields,ammunition,certain surgical equipment,developing dental X-ray films prior to digital X-rays,fetal monitors,plumbing,circuit boards,jet engines,and ceramic glazes(Patrick,2006).Al
43、l these increase the chances of toxicity with increasing exposure.In addition,many other occu-pational workers like lead miners and smelters,plumbers and fitters,car mechanicians,glass manufacturers,con-struction workers,battery manufacturers and recyclers,firing range instructors,and plastic manufa
44、cturers are at risk for lead exposure.Occupations like welding and manufacture of battery recycling present also a risk for lead exposure(Sanborn et al.,2002).Parents who are exposed to lead at workplaces generally bring lead dust to their home with clothes or on their skin,thus increasing the chanc
45、es of exposure in their children(Watts,2009).The boom of industrialisation in the modern world makes use of lead and lead products.Thus due to the industrial use of lead in modern times,the routes by which exposure generally occurs in humans is difficult to trace exactly.58Ab Latif Wani,Anjum Ara,Ja
46、wed Ahmad UsmaniLead toxicityISSN:1337-6853(print version)|1337-9569(electronic version)Lead is a common environmental pollutant.Exposure to lead occurs mainly at occupational sites,production of lead-acid batteries or pipes,metal recycling and foundries(Woolf et al.,2007).Children living near such
47、places are also at risk of elevated blood lead levels.In August of 2009,2000 children living near zinc and manganese smelters were found to be poisoned with lead,an incident which resulted in riots(Watts,2009).Other common things which cause lead exposure are lead in the air,household dust,soil,wate
48、r,and commercial products(Rossi,2008).In cases of chronic exposure,lead often sequesters in the highest concentrations first in the bones then in the kidneys.According to the US Centres for Disease Control and Prevention and the World Health Organization,a blood lead level of 10 g/dL or above is a c
49、ause for con-cern.However there is no threshold value below which lead exposure can be considered safe.It has been found to impair development and have harmful effects even at lower levels(Rossi,2008;Barbosa et al.,2005).A variety of compounds formed by lead exists in the environment in different fo
50、rms(Grant,2009).Poisoning and its features also differ between organic and inorganic lead(Kosnett,2007).Organic lead poisoning is now very rare around the world because of withdrawal of organic lead compounds as gasoline additives.Nevertheless,such compounds are still used in industrial settings.Org