View source for Lead poisoning

{{DiseaseDisorder infobox |
  Name        = Lead poisoning |
  Image       = Lead PoisoningRadio.jpg |
  Caption     = An X ray demonstrating the characteristic finding of lead poisoning, dense [[metaphyseal]] lines.|
  ICD10       = {{ICD10|T|56|0|t|51}} |
  ICD9        = {{ICD9|984.9}} |
  DiseasesDB     = 7307 |
  eMedicineSubj  = article |
  eMedicineTopic = 815399 |
  MedlinePlus    = 002473 | 
   MeshID        = D007855
}}
<!-- DEFINITION, SIGNS AND SYMPTOMS, PATHOPHYSIOLOGY, COMPLICATIONS -->
'''Lead poisoning''' (also known as '''plumbism''', '''colica Pictonum''', '''saturnism''',  [[Devon colic]], or '''painter's colic''')  is a medical condition caused by increased levels of the [[Heavy metal (chemistry)|heavy metal]] [[lead]] in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the [[cardiovascular|heart]], [[bone]]s, [[intestine]]s, [[kidney]]s, and [[reproductive system|reproductive]] and [[nervous system|nervous]] systems.  It interferes with the development of the nervous system and is therefore particularly toxic to children, causing potentially permanent [[learning disorder|learning]] and behavior disorders.  Symptoms include abdominal pain, headache, [[anemia]], irritability, and in severe cases [[seizure]]s, [[coma]], and [[death]].  

<!-- EXPOSURE ROUTES, PREVENTION, EPIDEMIOLOGY --> 
Routes of exposure to lead include contaminated air, water, soil, food, and consumer products.<!--<ref name="Dart041423">[[#CITEREFDart04|Dart, Hurlbut, Boyer-Hassen (2004)]] pp. 1423</ref>-->  Occupational exposure is a common cause of lead poisoning in adults.  One of the largest threats to children is [[lead paint]] that exists in many homes, especially older ones; thus children in older housing with chipping paint are at greater risk.   Prevention of lead exposure can range from individual efforts (e.g. removing lead-containing items such as piping or blinds from the home) to nationwide policies (e.g. laws that ban lead in products or reduce allowable levels in water or soil).

<!-- Dx and Rx -->
Elevated lead in the body can be detected by the presence of changes in blood cells visible with a microscope and dense lines in the bones of children seen on X-ray.  However, the main tool for diagnosis is measurement of the [[blood lead level]]; different treatments are used depending on this level.  The major treatments are removal of the source of lead and [[chelation therapy]] (administration of agents that bind lead so it can be [[excretion|excreted]]). 

<!-- HISTORY --> 
Humans have been mining and using this heavy metal for thousands of years, poisoning themselves in the process.  Although lead poisoning is one of the oldest known work and environmental hazards,<!--<ref name="Flora08"/> --> the modern understanding of the small amount of lead necessary to cause harm did not come about until the latter half of the 20th&nbsp;century.  No safe threshold for lead exposure has been discovered—that is, there is no known amount of lead that is too small to cause the body harm.<!--<ref name="Merrill07861"/><ref name="Brodkin07-CMAJ"/>-->

==Classification==
<!-- DEFINITIONS -->
Classically, "lead poisoning" or "lead intoxication" has been defined as exposure to high levels of lead typically associated with severe health effects.<ref name="Grant09-785">[[#CITEREFGrant09|Grant (2009)]] pp. 785</ref>  Poisoning is a pattern of symptoms that occur with toxic effects from mid to high levels of exposure; toxicity is a wider spectrum of effects, including [[subclinical]] ones (those that do not cause symptoms).<ref name="Guidotti07-PedClin">{{Cite pmid|17448358 }}</ref>   However, professionals often use "lead poisoning" and "lead toxicity" interchangeably, and official sources do not always restrict the use of "lead poisoning" to refer only to symptomatic effects of lead.<ref name="Guidotti07-PedClin"/>  

The amount of lead in the blood and tissues, as well as the time course of exposure, determine toxicity.<ref name="Pearson03"/> 
<!-- ACUTE VS. CHRONIC -->
Lead poisoning may be acute  (from intense exposure of short duration) or chronic (from repeat low-level exposure over a prolonged period), but the latter is much more common.<ref name="Trevor07-479">[[#CITEREFTrevor07|Trevor, Katzung, Masters (2007)]] pp. 479</ref>  
<!-- BLOOD LEVELS -->
Diagnosis and treatment of lead exposure are based on blood lead level (the amount of lead in the blood), measured in [[microgram]]s of lead per [[deciliter]] of blood (μg/dL).  The US [[Centers for Disease Control and Prevention]] and the [[World Health Organization]] state that a blood lead level of 10&nbsp;μg/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level.<ref name="Rossi09"/><ref name="Barbosa">{{Cite pmid|16330345 }}</ref>  Authorities such as the American Academy of Pediatrics define lead poisoning as blood lead levels higher than 10&nbsp;μg/dL.<ref name="Ragan09-JAAPA"/>

<!-- ORGANIC VS. INORGANIC -->
Lead forms a variety of compounds and exists in the environment in various forms.<ref name="Grant09-761">[[#CITEREFGrant09|Grant (2009)]] pp. 761</ref>   Features of poisoning differ depending on whether the agent is an [[organic compound]] (one that contains carbon), or an [[inorganic]] one.<ref name="Katzung07-948"/>  Organic lead poisoning is now very rare, because countries across the world have phased out the use of organic [[gasoline#Lead|lead compounds as gasoline additives]], but such compounds are still used in industrial settings.<ref name="Katzung07-948"/>  Organic lead compounds, which cross the skin and respiratory tract easily, affect the [[central nervous system]] predominantly.<ref name="Katzung07-948"/>

==Signs and symptoms==

<!-- ABOUT S/S -->
Lead poisoning can cause a variety of [[symptom]]s and [[medical sign|signs]] which vary depending on the individual and the duration of lead exposure.<ref name="Karri08"/><ref name="Kosnett05-825"/>  Symptoms are nonspecific and may be subtle, and someone with elevated lead levels may have no symptoms.<ref name="Mycyk05-463"/>  Symptoms usually develop over weeks to months as lead builds up in the body during a chronic exposure, but acute symptoms from brief, intense exposures also occur.<ref name="Dart041426"/>  
<!-- ORGANIC LEAD -->
Symptoms from exposure to organic lead, which is probably more toxic than inorganic lead due to its lipid solubility, occur rapidly.<ref name="Timbrell08">{{cite book |author = |title= Principles of Biochemical Toxicology, 4th edition |chapter=Biochemical mechanisms of toxicity: Specific examples |editor= Timbrell, J.A. |year= 2008 |publisher=Informa Health Care |location= |isbn= 0849373026|page= |pages= |url= |accessdate= |quote= |ref= }}</ref>  Poisoning by organic lead compounds has symptoms predominantly in the central nervous system, such as [[insomnia]], [[delirium]], [[cognitive deficit]]s, [[tremor]], hallucinations, and convulsions.<ref name="Katzung07-948"/>

<!--
CHILDREN V. ADULTS-->
Symptoms may be different in adults and children; the main symptoms in adults are headache, [[abdominal pain]], [[memory loss]], [[kidney failure]], male reproductive problems, and weakness, pain, or tingling in the extremities.<ref name="Pearce07-EurNeurol">{{Cite pmid|17179719 }}</ref>  The classic signs and symptoms in children are [[anorexia (symptom)|loss of appetite]], abdominal pain, vomiting, weight loss, constipation, anemia, kidney failure, irritability, [[lethargy]], [[learning disabilities]], and behavior problems.<ref name="Pearce07-EurNeurol"/>  Children may also experience [[hearing loss]], delayed growth, drowsiness, clumsiness, or loss of new abilities, especially speech skills.<ref name="Mycyk05-463"/>  Symptoms may appear in children at lower blood lead levels than in adults.<ref name="Marshall08"/>

<!--
EARLY SIGNS -->
Early symptoms of lead poisoning in adults are commonly nonspecific and include [[depression (mood)|depression]], loss of appetite, intermittent abdominal pain, nausea, diarrhea, constipation, and [[myalgia|muscle pain]].<ref name="Merrill07"/>  Other early signs in adults include [[malaise]], fatigue, decreased [[libido]], and problems with sleep.<ref name="Karri08"/>  An unusual taste in the mouth and personality changes are also early signs.<ref name="Patrick06"/> 
<!--
BLL-ASSOCIATED SIGNS -->
In adults, symptoms can occur at levels above 40&nbsp;μg/dL, but are more likely to occur only above 50–60&nbsp;μg/dL.<ref name="Karri08"/> Symptoms begin to appear in children generally at around 60&nbsp;μg/dL.<ref name="Needleman04-AnnRev">{{Cite pmid|14746518 }}</ref>  However, the lead levels at which symptoms appear vary widely depending on unknown characteristics of each individual.<ref name="Bellinger04-Pedi"/>  At blood lead levels between 25 and 60&nbsp;μg/dL, [[neuropsychiatric]] effects such as delayed [[reaction time]]s, irritability, and difficulty concentrating, as well as slowed [[motor nerve]] conduction and headache can occur.<ref name="Kosnett06-240">[[#CITEREFKosnett06Pois|Kosnett (2006)]] pp.240</ref>  [[Anemia]] may appear at blood lead levels higher than 50&nbsp;μg/dL.<ref name="Merrill07"/>  In adults, Abdominal [[colic]], involving [[Paroxysmal attack|paroxysm]]s of pain, may appear at blood lead levels greater than 80&nbsp;μg/dL.<ref name="Kosnett05-825">[[#CITEREFKosnett05|Kosnett (2005)]] pp. 825</ref>  Signs that occur in adults at blood lead levels exceeding 100&nbsp;μg/dL include [[wrist drop]] and [[foot drop]], <!-- because of neuropathy --> and signs of [[encephalopathy]] (a condition characterized by [[cerebral edema|brain swelling]]), such as those that accompany increased [[intracranial pressure|pressure within the skull]], [[delirium]], [[coma]], [[seizures]], and [[headache]].<ref name="Henretig061314">[[#CITEREFHenretig06|Henretig (2006)]] pp. 1314</ref>  In children, signs of encephalopathy such as bizarre behavior, discoordination, and apathy occur at lead levels exceeding 70&nbsp;μg/dL.<ref name="Henretig061314"/>  For both adults and children, it is rare to be asymptomatic if blood lead levels exceed 100&nbsp;μg/dL.<ref name="Kosnett05-825"/>

===Acute poisoning===
In acute poisoning, typical neurological signs are pain, muscle weakness,  [[paraesthesia]], and, rarely, symptoms associated with [[encephalitis]].<ref name="Pearce07-EurNeurol"/> Abdominal pain, nausea, vomiting, diarrhea, and constipation are other acute symptoms.<ref name="Brunton07-31"/> Lead's effects on the mouth include [[astringent|astringency]] and a metallic taste.<ref name="Brunton07-31"/> [[Gastrointestinal]] problems, such as [[constipation]], [[diarrhea]], [[poor appetite]], or [[weight loss]], are common in acute poisoning.  Absorption of large amounts of lead over a short time can cause [[shock (medical)|shock]] (insufficient fluid in the [[circulatory system]]) due to loss of water from the gastrointestinal tract.<ref name="Brunton07-31"/>  [[Hemolysis]] (the rupture of [[red blood cells]]) due to acute poisoning can cause [[anemia]] and [[hemoglobinuria|hemoglobin in the urine]].<ref name="Brunton07-31"/>  Damage to kidneys can cause changes in urination such as [[oliguria|decreased urine output]].<ref name="Brunton07-31"/> People who survive acute poisoning often go on to display symptoms of chronic poisoning.<ref name="Brunton07-31"/>

===Chronic poisoning===
Chronic poisoning usually presents with symptoms affecting multiple systems,<ref name="Katzung07-948"/> but is associated with three main types of symptoms: [[gastrointestinal]], [[neuromuscular]], and [[neurological]].<ref name="Pearce07-EurNeurol"/>  [[Central nervous system]] and neuromuscular symptoms usually result from intense exposure, while gastrointestinal symptoms usually result from exposure over longer periods.<ref name="Brunton07-31"/>  Signs of chronic exposure include loss of [[short-term memory]] or concentration, [[depression (mood)|depression]], nausea, abdominal pain, loss of coordination, and numbness and tingling in the extremities.<ref name="Patrick06"/>  Fatigue, problems with sleep, headaches, stupor, slurred speech, and anemia are also found in chronic lead poisoning.<ref name="Pearce07-EurNeurol"/>  A "lead hue" of the skin with [[pallor]] is another feature<!--of chronic lead poisoning-->.<ref name="Andrews">James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. ISBN 0721629210. {{Rp|859}}</ref>  A blue line along the gum, with bluish black edging to the teeth is another indication of chronic lead poisoning.<ref name="Rambousek08-177">[[#CITEREFRambousek08|Rambousek (2008)]] pp.177</ref> Children with chronic poisoning may refuse to play or may have [[hyperkinetic]] or aggressive behavior disorders.<ref name="Pearce07-EurNeurol"/>

==Exposure routes==
<!-- ENVIRONMENT -->
Lead is a common environmental pollutant.<ref name="Ragan09-JAAPA">{{Cite pmid|19697571}}</ref>  Causes of environmental contamination include industrial use of lead, such as is found in plants that process lead-acid batteries or produce lead wire or pipes, and metal recycling and foundries.<ref name="Mañay08"/> Children living near facilities that process lead, such as smelters, have been found to have unusually high blood lead levels.<ref name="Sanborn"/>  In August 2009, parents rioted in China after [[2009 Chinese lead poisoning scandal|lead poisoning was found in nearly 2000 children]] living near zinc and manganese smelters.<ref name="Watts09-Lancet">{{Cite pmid|19757511}}</ref> Lead exposure can occur from contact with lead in air, household dust, soil, water, and commercial products.<ref name="Rossi09"/>  

===Occupational exposure===
[[File:Recycling lead in a lead-acid battery recovery facility.jpg|right|thumb|alt=A man in a hard hat with a clear face plate leans over a conveyor belt with a metal instrument. He is in a factory setting with heavy machinery in the background.|Battery recycling workers are at risk for lead exposure.<ref name="Brodkin07-CMAJ">{{Cite pmid|17200393 }}</ref> This worker ladles molten lead into billets in a lead-acid battery recovery facility.]]

In adults, occupational exposure is the main cause of lead poisoning.<ref name="Needleman04-AnnRev"/> People can be exposed when working in facilities that produce a variety of lead-containing products; these include [[radiation shield]]s, ammunition, certain surgical equipment, fetal monitors, plumbing, circuit boards, jet engines, and ceramic glazes.<ref name="Patrick06"/>  In addition, lead miners and smelters, plumbers and fitters, auto mechanics, glass manufacturers, construction workers, battery manufacturers and recyclers, firing range instructors, and plastic manufacturers are at risk for lead exposure.<ref name="Sanborn"/>  Other occupations that present lead exposure risks include welding, manufacture of rubber, printing, [[zinc]] and [[copper]] smelting, processing of [[ore]], combustion of [[solid waste]], and production of paints and pigments.<ref name="Dart041424">[[#CITEREFDart04|Dart, Hurlbut, Boyer-Hassen (2004)]] pp. 1424</ref>  Parents who are exposed to lead in the workplace can bring lead dust home on clothes or skin and expose their children.<ref name="Dart041424"/>

===Paint===
Some lead compounds are bright colors and are used widely in paints,<ref name="Henretig06">[[#CITEREFHenretig06|Henretig (2006)]] pp. 1310</ref> and [[lead paint]] is a major route of lead exposure in children.<ref name="Gilbert06">{{Cite pmid|16889836 }}</ref>  Deteriorating lead paint can produce dangerous lead levels in household dust and soil.<ref name="Dart041423">[[#CITEREFDart04|Dart, Hurlbut, Boyer-Hassen (2004)]] pp. 1423</ref>  Deteriorating lead paint and lead-containing household dust are the main causes of chronic lead poisoning.<ref name="Pearce07-EurNeurol"/> Many young children display [[Pica (disorder)|pica]], eating things that are not food. Even a small amount of a lead-containing product such as a paint chip or a sip of glaze can contain tens or hundreds of milligrams of lead.<ref name="Kosnett06-241"/>   Eating chips of lead paint presents a particular hazard to children, generally producing more severe poisoning than occurs from dust.<ref name="Chisolm04-222"/>  However, removing lead paint from dwellings, e.g. by sanding or torching, can create lead-containing dust and fumes.<ref name="Salvato03"/>  Therefore, special precautions must be taken when removing lead paint.<ref name="Salvato03">[[#CITEREFSalvato03|Salvato (2003)]] pp.116</ref>

===Soil===
[[File:Gas pump lead warning.jpg|thumb|right|A lead warning on a gas pump.  [[Tetra-ethyl lead|Tetraethyl lead]], which used to be added to gasoline, contributed to soil contamination.|alt=a closeup of a red gas pump with a warning label that reads, "for use as a motor fuel only" (in larger writing) "contains lead" (in smaller writing) "(tetraethyl)"]]

Residual lead in soil contributes to lead exposure in urban areas.<ref name="Guidotti07-PedClin"/>  Lead content in soil may be caused by broken-down lead paint, residues from lead-containing gasoline or [[pesticide]]s used in the past, contaminated landfills, or from nearby industries such as [[foundry|foundries]] or smelters.<ref name="Woolf07-PedClin"/>  Although leaded soil is less of a problem in countries that no longer have [[gasoline#Lead|leaded gasoline]], it remains prevalent, raising concerns about the safety of [[urban agriculture]];<ref>{{cite news|author=Murphy, K. |date=May 13, 2009 |url = http://www.nytimes.com/2009/05/14/garden/14lead.html?pagewanted=1&hpw |title= For urban gardeners, lead is a concern |publisher=New York Times |accessdate = September 18, 2009}}</ref> eating food grown in contaminated soil can present a lead hazard.<ref name="Yu05-188">[[#CITEREFYu05|Yu (2005)]] pp.188</ref>  

===Water===
Lead from the atmosphere or soil can end up in groundwater and surface water.<ref name="Yu05">[[#CITEREFYu05|Yu (2005)]] pp.187</ref>  It is also potentially in drinking water, e.g. from plumbing and fixtures that are either made of lead or have lead solder.<ref name="Chisolm04-222">[[#CITEREFChisolm04|Chisolm (2004)]] pp. 221–22</ref><ref name="Menkes06-703">[[#CITEREFMenkes06|Menkes (2006)]] pp.703</ref>  Since acidic water breaks down lead in plumbing more readily, chemicals can be added to municipal water to increase the [[pH]] and thus reduce the [[Corrosion|corrosivity]] of the public [[water supply]].<ref name="Chisolm04-222"/> [[Chloramine]]s, which were adopted as a substitute for [[chlorine]] [[disinfectant]]s due to fewer health concerns, increase corrositivity.<ref name="Maas2005" />  In the US, 14–20% of total lead exposure is attributed to [[drinking water]].<ref name="Maas2005">{{cite pmid|16134575}}</ref>  In 2004, a team of seven reporters from ''[[The Washington Post]]'' discovered [[Lead contamination in Washington, D.C. drinking water|high levels of lead in the drinking water in Washington, D.C.]] and won an award for [[investigative reporting]] for a series of articles about this contamination.<ref>{{cite web |title=Alum Wins Investigative Reporting Award with Post Team |publisher=[[University of Maryland College Park|University of Maryland]] |date=February 25, 2005 |url=http://www.journalism.umd.edu/newrel/05newrel/scohen05.html |doi= |accessdate=2007-11-07 }} {{Dead link|date=September 2010|bot=H3llBot}}</ref><ref>{{Cite news |last= |first= |author-link= |last2= |first2= |author2-link= |title=HONORS |newspaper=The Washington Post |pages= |year= |date=February 23, 2005 |url= |ref= harv |postscript= <!--None--> }}</ref>  

In Australia, collecting rainwater from roof runoff used as potable water may contain lead if there are lead contaminates on the roof or in the storage tank.<ref name="Rossi09"/> The Australian Drinking Water Guidelines allow a maximum of .01&nbsp;mg/L lead in water.<ref name="Rossi09">{{cite pmid|18787644 }}</ref>

===Lead-containing products===

Lead can be found in products such as [[kohl (cosmetics)|kohl]], a South Asian cosmetic, and from some toys.<ref name="Guidotti07-PedClin"/>  [[2007 Chinese export recalls|In 2007, millions of toys made in China were recalled]] from multiple countries owing to safety hazards including lead paint.<ref>{{cite news|url=http://www.cnn.com/2007/US/08/14/recall/index.html |author=|title=Mattel CEO: 'Rigorous standards' after massive toy recall|publisher=CNN|date=November 15, 2007|accessdate=September 26, 2009}}</ref>  Vinyl mini-blinds, found especially in older housing, may contain lead.<ref name="Ragan09-JAAPA"/>
<!--
MEDICINE-->
Lead is commonly incorporated into [[herbalism|herbal remedies]] such as Indian [[Ayurveda|Ayurvedic]] preparations and remedies of Chinese origin.<ref name="Rossi09"/><ref name="Karri08"/><ref name="Patrick06"/> There are also risks of elevated blood lead levels caused by folk remedies like ''azarcon'' and ''greta'', which each contain about 95% lead.<ref name="Karri08"/>  
<!--
FOOD -->
Ingestion of metallic lead, such as small lead fishing lures, increases blood lead levels and can be fatal.<ref>{{cite pmid|16625019}}</ref><ref>{{cite pmid|3190952}}</ref><ref>{{cite pmid|2869380}}</ref><ref>{{cite pmid|16572103 }}</ref>  Ingestion of lead-contaminated food is also a threat.  Ceramic glaze often contains lead, and dishes that have been improperly fired can leach the metal into food, potentially causing severe poisoning.<ref name="Salvato03-117"/>  In some places, the solder in cans used for food contains lead.<ref name="Patrick06"/>  People who eat animals hunted with lead bullets may be at risk for lead exposure.<ref>{{cite pmid|19390698}}</ref>  Bullets lodged in the body rarely cause significant levels of lead poisoning,<ref name ="Spitz08-ArqNeruo">{{cite pmid|18813727}}</ref><ref>{{cite pmid|6859004}}</ref> but bullets lodged in the joints are the exception, as they deteriorate and release lead into the body over time.<ref>{{cite pmid|2926538}}</ref>

==Pathophysiology==
[[File:Tera-ethyl-lead-chemical.png|right|thumb|[[Tetra-ethyl lead]], still used as an additive in some fuels, can be absorbed through the skin.<ref name="Patrick06"/> |alt=Two chemical diagrams of tetra-ethyl lead, or (CH3CH2)4Pb. On the left one, carbon and hydrogen are labeled, on the right they are shown as lines only.]]

<!-- MEANS OF ABSORPTION -->
Exposure occurs through [[inhalation]], [[ingestion]] or occasionally skin contact. Lead may be taken in through direct contact with mouth, nose, and eyes (mucous membranes), and through breaks in the skin.  [[Tetra-ethyl lead]], which was a gasoline additive and is still used in fuels such as aviation fuel, passes through the skin; however [[inorganic]] lead found in paint, food, and most lead-containing consumer products is only minimally absorbed through the skin.<ref name="Patrick06"/>  The main sources of absorption of inorganic lead  are from ingestion and inhalation.<ref name="Merrill07">[[#CITEREFMerrill07|Merrill, Morton, Soileau (2007)]] pp. 860</ref>  In adults, about 35–40% of inhaled lead dust is deposited in the lungs, and about 95% of that goes into the bloodstream.<ref name="Merrill07"/>  Of ingested inorganic lead, about 15% is absorbed, but this percentage is higher in children, pregnant women, and people with deficiencies of calcium, zinc, or iron.<ref name="Karri08"/> Children and infants may absorb about 50% of ingested lead, but little is known about absorption rates in children.<ref name="Grant09-767">[[#CITEREFGrant09|Grant (2009)]] pp. 767</ref> 

<!--
STORAGE -->
The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone.<ref name="Karri08"/> Lead in the bones, teeth, hair and nails is bound tightly and not available to other tissues, and is generally thought not to be harmful.<ref name="Rubin08">[[#CITEREFRubin08|Rubin, Strayer (2008)]] pp. 266</ref>  In adults, 94% of absorbed lead is deposited in the bones and teeth, but children only store 70% in this manner, a fact which may partially account for the more serious health effects on children.<ref name="Barbosa"/> The estimated half-life of lead in bone is 20–30&nbsp;years, and bone can introduce lead into the bloodstream long after the initial exposure is gone.<ref name="Patrick06"/>  The half-life of lead in the blood in men is about 40&nbsp;days, but it may be longer in children and pregnant women, whose bones are undergoing [[bone remodeling|remodeling]], which allows the lead to be continuously re-introduced into the bloodstream.<ref name="Barbosa"/>  Also, if lead exposure takes place over years, clearance is much slower, partly due to the re-release of lead from bone.<ref name="Hu07"/> Many other tissues store lead, but those with the highest concentrations (other than blood, bone, and teeth) are the brain, spleen, kidneys, liver, and lungs.<ref name="Dart041426">[[#CITEREFDart04|Dart, Hurlbut, Boyer-Hassen (2004)]] pp. 1426</ref>  
<!-- 
EXCRETION 
-->It is removed from the body very slowly, mainly through urine.<ref name="Pearson03"/>  Smaller amounts of lead are also eliminated through the feces, and very small amounts in hair, nails, and sweat.<ref name="Kosnett06-238"/>

<!--
HARMFUL EFFECTS -->
Lead has no known physiologically relevant role in the body,<ref name="Mañay08">{{Cite pmid|18418955 }}</ref><ref name="White07">{{Cite pmid|17904601 }}</ref> and its harmful effects are myriad.  Lead and other heavy metals create reactive [[free radical|radicals]] which damage cell structures including  [[DNA]] and [[cell membrane]]s.<ref name="Flora08">{{Cite pmid|19106443}}</ref>  Lead also interferes with [[Transcription (genetics)|DNA transcription]], [[enzyme]]s that help in the synthesis of [[vitamin D]], and enzymes that maintain the integrity of the [[cell membrane]].<ref name="Dart041426"/> Anemia may result when the cell membranes of [[red blood cell]]s become more fragile as the result of damage to their membranes.<ref name="Yu05-193">[[#CITEREFYu05|Yu (2005)]] pp.193</ref>  Lead interferes with metabolism of bones and teeth<ref name="Casarett07-946"/> and alters the permeability of blood vessels and [[collagen]] synthesis.<ref name="Needleman04-AnnRev"/>  Lead may also be harmful to the developing [[immune system]], causing production of excessive [[inflammation|inflammatory]] proteins; this mechanism may mean that lead exposure is a risk factor for [[asthma]] in children.<ref name="Casarett07-946">[[#CITEREFCasarett07|Casarett, Klaassen, Doull (2007)]] pp. 946</ref>  Lead exposure has also been associated with a decrease in activity of immune cells such as [[polymorphonuclear leukocyte]]s.<ref name="Casarett07-946"/>  Lead also interferes with the normal metabolism of [[calcium in biology|calcium in cells]] and causes it to build up within them.<ref name="Chisolm04-222"/>

===Enzymes===
The primary cause of lead's toxicity is its interference with a variety of enzymes because it binds to [[sulfhydryl group]]s found on many enzymes.<ref name="Pearson03"/>  Part of lead's toxicity results from its ability to mimic other metals that take part in biological processes, which act as [[cofactor (biochemistry)|cofactor]]s in many enzymatic reactions, displacing them at the enzymes on which they act.<ref name="Dart041426"/> Lead is able to bind to and interact with many of the same [[enzyme]]s as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme's ability to catalyze its normal reaction or reactions.  Among the essential metals with which lead interacts are calcium, iron, and zinc.<ref name="Kosnett06-238">[[#CITEREFKosnett06Pois|Kosnett (2006)]] pp.238</ref>

<!-- HEME -->
One of the main causes for the pathology of lead is that it interferes with the activity of an essential enzyme called [[delta-aminolevulinic acid dehydratase]], or ALAD, which is important in the biosynthesis of [[heme]], the cofactor found in [[hemoglobin]].<ref name="Patrick06"/>  Lead also inhibits the enzyme [[ferrochelatase]], another enzyme involved in the formation of heme.<ref name="Barbosa"/><ref name="Patrick06"/><ref name="pmid12498316">{{cite journal |author=Fujita H, Nishitani C, Ogawa K |title=Lead, chemical porphyria, and heme as a biological mediator |journal=Tohoku J. Exp. Med. |volume=196 |issue=2 |pages=53–64 |year=2002 |month=February |pmid=12498316 |doi= 10.1620/tjem.196.53|url=http://joi.jlc.jst.go.jp/JST.JSTAGE/tjem/196.53?from=PubMed |format={{dead link|date=June 2010}} |ref=harv}}</ref> Ferrochelatase catalyzes the joining of [[protoporphyrin]] and [[Iron|Fe<sup>2+</sup>]] to form heme.<ref name="Barbosa"/><ref name="Dart041426"/><ref name="Patrick06"/>  Lead's interference with heme synthesis results in production of [[zinc protoporphyrin]] and the development of [[anemia]].<ref name="Mycyk05-462">[[#CITEREFMycyk05|Mycyk, Hryhorczuk, Amitai (2005)]] pp. 462</ref>   Another effect of lead's interference with heme synthesis is the buildup of heme precursors, such as [[aminolevulinic acid]], which may be directly or indirectly harmful to neurons.<ref name="Kosnett05-822"/>

===Neurons===
[[File:Lead-exposed rat hippocampi.jpg|thumb|right|Lead exposure damages cells in the [[hippocampus]], a part of the brain involved in memory.  Hippocampi of lead-exposed rats (bottom) show structural damage such as irregular nuclei (IN) and denaturation of [[myelin]] (DNS) compared to controls (top).<ref name="Xu09"/>|alt=Two black and white photos; one shows dark, fairly regular rings on a lighter background, and the other shows irregular, smaller, and not as dark clusters.]]

<!-- NMDARS -->
Lead interferes with the release of [[neurotransmitter]]s, chemicals used by [[neuron]]s to send signals to other cells.<ref name="Dart041426"/><ref name="Needleman04-AnnRev"/>  It interferes with the release of [[glutamate]], a neurotransmitter important in many functions including learning, by blocking [[NMDA receptor]]s.  The targeting of NMDA receptors is thought to be one of the main causes for lead's [[neurotoxicity|toxicity to neurons]].<ref name="Xu09">{{Cite pmid|19374778 }}</ref>  A [[Johns Hopkins]] report found that in addition to inhibiting the NMDA receptor, lead exposure decreased the amount of the gene for the receptor in part of the brain.<ref>{{cite web |url=http://www.jhsph.edu/publichealthnews/press_releases/PR_2000/lead_change.html |title=How Lead Changes the Brain to Impair Learning and Memory, How Lead Changes the Brain to Impair Learning and Memory |accessdate=2007-08-14 |work=}}</ref>  In addition, lead has been found in animal studies to cause [[apoptosis|programmed cell death]] in brain cells.<ref name="Needleman04-AnnRev"/>

==Complications==
Lead affects every one of the body's organ systems, especially the nervous system, but also the bones and teeth, the kidneys, and the [[cardiovascular system|cardiovascular]], [[immune system|immune]], and [[reproductive system]]s.<ref name="White07"/>  [[Hearing loss]] and [[tooth decay]] have been linked to lead exposure,<ref name="Lanphear05EnvironHealth">{{cite pmid|16002379}}</ref> as have [[cataracts]].<ref name="Pokras08-Ecohealth"/>  Intrauterine and neonatal lead exposure promote tooth decay.<ref>{{cite journal |author=Brudevold F, Steadman LT  |title=The distribution of lead in human enamel |journal=J Dent Res |volume=35 |pages=430–437 |year=1956 |pmid=13332147 |url=http://jdr.sagepub.com/cgi/reprint/35/3/430.pdf |issue=3 |ref=harv }}</ref><ref>{{cite journal |author=Brudevold F, Aasenden R, Srinivasian BN, Bakhos Y |title=Lead in enamel and saliva, dental caries and the use of enamel bipsies for mesuring past exposure to lead. |journal=J Dent Res |volume=56 |pages=1165–1171 |year=1977 |pmid=272374 |url=http://jdr.sagepub.com/cgi/reprint/56/10/1165.pdf |issue=10 |ref=harv }}</ref><ref>{{cite journal |author=Goyer RA |title=Transplacental transport of lead |journal=Environ Health Perspect |volume=89 | pages=101–105 |year=1990 |pmid=2088735 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1567784/pdf/envhper00422-0101.pdf |doi=10.2307/3430905 |pmc=1567784 |jstor=3430905 |publisher=Environmental Health Perspectives, Vol. 89 |ref=harv}}</ref><ref>{{cite journal |author=Moss ME, Lamphear BP, Auinger P |title=Association of dental caries and blood lead levels |journal=JAMA |volume=281 |pages=2294–2298 |year=1999 |pmid=10386553 |url=http://jama.ama-assn.org/cgi/content/full/281/24/2294 |doi=10.1001/jama.281.24.2294 |issue=24 |ref=harv }}</ref><ref>{{cite journal |author=Campbell JR, Moss ME, Raubertas RF |title=The association between caries and childhood lead exposure |journal=Environ Health Perspect |volume=108 |pages=1099–1102 |year=2000 |pmid=11102303 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240169/pdf/ehp0108-001099.pdf |doi=10.2307/3434965 |issue=11 |pmc=1240169 |jstor=3434965 |publisher=Environmental Health Perspectives, Vol. 108, No. 11 |ref=harv}}</ref><ref>{{cite journal |author=Gemmel A, Tavares M, Alperin S, Soncini J, Daniel D, Dunn J,Crawford S, Braveman N, Clarkson TW, McKinlay S, Bellinger DC |title=Blood Lead Level and Dental Caries in School-Age Children |journal=Environ Health Perspect |volume=110 |pages=A625–A630 |year=2002 |pmid=12361944 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241049/pdf/ehp0110-a00625.pdf |issue=10 |pmc=1241049 |ref=harv }}</ref><ref>{{cite journal |author=Billings RJ, Berkowitz RJ, Watson G |title=Teeth |journal=Pediatrics |volume=113 |issue=4 |pages=1120–1127 |year=2004 |pmid=15060208 |url=http://pediatrics.aappublications.org/cgi/reprint/113/4/S1/1120.pdf |ref=harv }}</ref>  Aside from the developmental effects unique to young children, the health effects experienced by adults are similar to those in children, although the thresholds are generally higher.<ref>{{cite web |url=http://www.atsdr.cdc.gov/csem/lead/pbwhoisat_risk2.html |accessdate=August 25, 2009 |title=Lead Toxicity: Who Is at Risk of Lead Exposure? |publisher=United States Center for Disease Control: Agency for Toxic Substances and Disease Registry}}</ref>

=== Renal system ===
Kidney damage occurs with exposure to high levels of lead, and evidence suggests that lower levels can damage kidneys as well.<ref name="Grant09-789">[[#CITEREFGrant09|Grant (2009)]] pp. 789</ref>  The toxic effect of lead causes [[nephropathy]] and may cause [[Fanconi syndrome]], in which the [[proximal tubule|proximal tubular]] function of the kidney is impaired.<ref name="Rubin08-267">[[#CITEREFRubin08|Rubin, Strayer (2008)]] pp. 267</ref>  Long-term exposure at levels lower than those that cause lead nephropathy have also been reported as [[nephrotoxicity|nephrotoxic]] in patients from developed countries that had chronic kidney disease or were at risk because of hypertension or [[diabetes mellitus]].<ref name="Ekong06KidneyInt">{{cite pmid|17063179}}</ref>  
<!-- 
GOUT -->Lead poisoning inhibits excretion of the waste product [[uric acid|urate]] and causes a predisposition for [[gout]], in which urate builds up.<ref name="Wright83JReum">{{cite pmid|6434739}}</ref><ref name="pmid8035397">{{cite journal |author=Lin JL, Huang PT |title=Body lead stores and urate excretion in men with chronic renal disease |journal=J. Rheumatol. |volume=21 |issue=4 |pages=705–9 |year=1994 |month=April |pmid=8035397 |doi= |url= |ref=harv}}</ref><ref name="pmid10914856">{{cite journal |author=Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H |title=Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study |journal=J. Rheumatol. |volume=27 |issue=7 |pages=1708–12 |year=2000 |month=July |pmid=10914856 |doi= |url= |ref=harv}}</ref> This condition is known as ''saturnine gout''.

===Cardiovascular system===
Evidence suggests lead exposure is associated with [[hypertension|high blood pressure]], and studies have also found connections between lead exposure and [[coronary artery|coronary]] [[heart disease]], [[heart rate variability]], and death from [[stroke]], but this evidence is more limited.<ref name="Navas-Acien06">{{Cite pmid|17431501 }}</ref>  People who have been exposed to higher concentrations of lead may be at a higher risk for cardiac [[autonomic dysfunction]] on days when [[ozone]] and fine particles are higher.<ref name="Park09Epidem">{{cite pmid|18091001}}</ref>

===Reproductive system===
Lead affects both the male and female reproductive systems.  In men, when blood lead levels exceed 40&nbsp;μg/dL, [[sperm count]] is reduced and changes occur in volume of sperm, their [[motility]], and their [[Morphology (biology)|morphology]].<ref name="Grant09-792">[[#CITEREFGrant09|Grant (2009)]] pp. 792</ref> 
A pregnant woman's elevated blood lead level can lead to [[miscarriage]], [[prematurity]], low [[birth weight]], and problems with development during childhood.<ref name="Cleveland08"/>   Lead is able to pass through the [[placenta]] and into breast milk, and blood lead levels in mothers and infants are usually similar.<ref name="Dart041426"/>  A fetus may be poisoned ''in utero'' if lead from the mother's bones is subsequently mobilized by the changes in metabolism due to pregnancy; increased calcium intake in pregnancy may help mitigate this phenomenon.<ref name="Bellinger05BirthDef">{{Cite pmid|15880700 }}</ref> 

===Nervous system===

Lead affects the [[peripheral nervous system]] (especially [[motor nerve]]s) and the [[central nervous system]].<ref name="Dart041426"/>  Peripheral nervous system effects are more prominent in adults and central nervous system effects are more prominent in children.<ref name="Bellinger04-Pedi"/> Lead causes the [[axon]]s of [[neuron|nerve cells]] to degenerate and lose their [[myelin]] coats.<ref name="Dart041426"/>

[[File:Decreased Brain Volume from Lead Exposure.jpg|thumb|left|The brains of adults who were exposed to lead as children show decreased volume, especially in the [[prefrontal cortex]], on [[magnetic resonance imaging|MRI]].  Areas of volume loss are shown in color over a template of a normal brain.<ref name="Cecil08"/>|alt=Eight MRI views of a brain in black and white, with yellow, orange, and red areas overlaid in spots mainly toward the front.]]

<!-- CNS DEVELOPMENT -->
The brain is the organ most sensitive to lead exposure.<ref name="Cecil08">{{Cite pmid|18507499 }}</ref>  Lead poisoning interferes with the normal development of a child's brain and nervous system; therefore children are at greater risk of lead [[neurotoxicity]] than adults are.<ref name="Sanders09">{{Cite pmid|19476290 }}</ref>  In a child's developing brain, lead interferes with [[synapse]] formation <!-- "syaptic modeling" --> in the [[cerebral cortex]], [[neurochemical]] development (including that of neurotransmitters), and organization of [[ion channel]]s.<ref name="Mycyk05-462"/>  It causes loss of neurons' [[myelin]] sheaths, reduces numbers of neurons, interferes with neurotransmission, and decreases neuronal growth.<ref name="Pearson03"/>

<!-- 
COGNITIVE PERFORMANCE IN CHILDREN -->
Lead exposure in young children has been linked to [[learning disability|learning disabilities]],<ref name="Meyer-IntJHyge"/> and children with blood lead concentrations greater than 10&nbsp;μg/dL are in danger of [[developmental disability|developmental disabilities]].<ref name="Brunton07-31"/>   Increased blood lead level in children has been correlated with decreases in [[intelligence quotient|intelligence]], nonverbal reasoning, [[short-term memory]], attention, reading and arithmetic ability, [[fine motor skill]]s, [[emotional regulation]], and [[Social skill|social engagement]].<ref name="Cleveland08"/> <!--
LOW LEVELS -->
The effect of lead on children's cognitive abilities takes place at very low levels.<ref name="Lanphear05EnvironHealth"/><ref name="Cleveland08"/><ref name="Bellinger08"/>  There is apparently no lower threshold to the [[dose-response relationship]] (unlike other heavy metals such as [[mercury (element)|mercury]]).<ref>{{Cite pmid|2294437}}</ref>  Reduced academic performance has been associated with lead exposure even at blood lead levels lower than 5&nbsp;μg/dL.<ref name="Merrill07861"/><ref name="Casarett07-944">[[#CITEREFCasarett07|Casarett, Klaassen, Doull (2007)]] pp. 944</ref>  Blood lead levels below 10&nbsp;μg/dL have been reported to be associated with lower IQ and behavior problems such as aggression, in proportion with blood lead levels.<ref name="Guidotti07-PedClin"/>  Between the blood lead levels of 5 and 35&nbsp;μg/dL, an IQ decrease of 2–4 points for each μg/dL increase is reported in children.<ref name="Brunton07-31"/>

<!-- COGNITIVE PERFORMANCE IN ADULTS -->
High blood lead levels in adults are also associated with decreases in cognitive performance and with psychiatric symptoms such as depression and anxiety.<ref name="Shih07">{{cite pmid|17431502}}</ref>  It was found in a large group of current and former inorganic lead workers in Korea that blood lead levels in the range of 20–50&nbsp;μg/dL were correlated with neuro-cognitive defects.<ref name="Kosnett07EnvironHealthPers"/>  Increases in blood lead levels from about 50 to about 100&nbsp;μg/dL in adults have been found to be associated with persistent, and possibly permanent, impairment of central nervous system function.<ref name="Grant09-789"/> 

<!-- BEHAVIOR -->
Lead exposure in children is also correlated with neuropsychiatric disorders such as [[attention deficit hyperactivity disorder]] and [[antisocial]] behavior.<ref name="Bellinger08">{{Cite pmid|18332714 }}</ref>  Elevated lead levels in children are correlated with higher scores on aggression and delinquency measures.<ref name="Needleman04-AnnRev"/> A correlation has also been found between prenatal and early childhood lead exposure and violent crime in adulthood.<ref name="Cleveland08"/>  Countries with the highest air lead levels have also been found to have the highest murder rates, after adjusting for confounding factors.<ref name="Needleman04-AnnRev"/>  A May 2000 study by economic consultant [[Rick Nevin]] theorizes that lead exposure explains 65% to 90% of the variation in violent crime rates in the US.<ref>{{cite web |url=http://www.icfi.com/Markets/Community_Development/doc_files/LeadExposureStudy.pdf |title=Research Links Lead Exposure to Changes in Violent Crime Rates Throughout the 20<sup>th</sup> Century |publisher=ICF International |format=PDF}}</ref><ref>{{cite pmid|10845777 }}</ref> A 2007 paper by the same author claims to show a strong association between preschool blood lead and subsequent crime rate trends over several decades across nine countries.<ref>{{cite pmid|17451672 }}</ref><ref>{{cite news |url=http://www.washingtonpost.com/wp-dyn/content/article/2007/07/07/AR2007070701073_pf.html |title=Research links lead exposure, criminal activity |publisher=Washington Post |date=July 8, 2007 |accessdate=September 24, 2009 | first=Shankar | last=Vedantam}}</ref>

==Diagnosis==
Diagnosis includes determining the clinical signs and the medical history, with inquiry into possible routes of exposure.<ref name="Henretig061316">[[#CITEREFHenretig06|Henretig (2006)]] pp. 1316</ref>  [[medical toxicology|Clinical toxicologists]], medical specialists in the area of poisoning, may be involved in diagnosis and treatment.  <!-- BLOOD LEAD LEVEL -->
The main tool in diagnosing and assessing the severity of lead poisoning is laboratory analysis of the [[blood lead level]] (BLL).<ref name="Mycyk05-463">[[#CITEREFMycyk05|Mycyk, Hryhorczuk, Amitai (2005)]] pp. 463</ref>  
<!--
OTHER BLOOD -->
[[File:Lead poisoning - blood film.jpg|left|thumb|[[Basophilic stippling]] (arrows) of red [[blood cells]] in a 53-year-old who had elevated blood lead levels due to drinking repeatedly from glasses decorated with lead paint.<ref>{{cite web|url=http://cnx.org/content/m15003/latest/ |author=Fred HL, van Dijk HA|title=Images of Memorable Cases: Case 81|publisher=Connexions|date=|accessdate=August 25, 2009}}</ref>|alt=dozens of pink circular bodies with white centers on a white background.  Arrows point to three of the cells; two are speckled with dark purple dots, and the third has an irregular outer border]]

[[Blood film]] examination may reveal [[basophilic stippling]] of red [[blood cells]] (dots in red blood cells visible through a microscope),  as well as the changes normally associated with iron-deficiency anemia ([[microcytosis]] and [[hypochromic|hypochromasia]]).<ref name="Patrick06"/><ref name="Rubin08-267"/> However, basophilic stippling is also seen in unrelated conditions, such as megaloblastic anemia caused by [[vitamin]] B12 (colbalamin) and [[folate]] deficiencies.<ref>{{cite book |author=Fischer C |title=Kaplan Medical USMLE Steps 2 and 3 Notes: Internal Medicine, Hematology |pages=176–177 |year=2007}}</ref>

Exposure to lead also can be evaluated by measuring [[zinc protoporphyrin|erythrocyte protoporphyrin]] (EP) in blood samples.<ref name="Patrick06"/> EP is a part of red blood cells known to increase when the amount of lead in the blood is high, with a delay of a few weeks.<ref name="Kosnett05-825"/>  Thus EP levels in conjunction with blood lead levels can suggest the time period of exposure; if blood lead levels are high but EP is still normal, this finding suggests exposure was recent.<ref name="Kosnett05-825"/><ref name="Kosnett06-240"/>  However, the EP level alone is not sensitive enough to identify elevated blood lead levels below about 35&nbsp;μg/dL.<ref name="Patrick06"/>  Due to this higher threshold for detection and the fact that EP levels also increase in [[Iron deficiency (medicine)|iron deficiency]], use of this method for detecting lead exposure has decreased.<ref name="Grant09-784">[[#CITEREFGrant09|Grant (2009)]] pp. 784</ref> 

<!-- BONE -->
Blood lead levels are an indicator mainly of recent or current lead exposure, not of total [[body burden]].<ref name="Vaziri08-AmJPhys">{{Cite pmid|18567711 }}</ref>  Lead in bones can be measured [[Invasiveness of surgical procedures|noninvasively]] by [[X-ray fluorescence]]; this may be the best measure of cumulative exposure and total body burden.<ref name="Kosnett06-240"/>  However this method is not widely available and is mainly used for research rather than routine diagnosis.<ref name="Brodkin07-CMAJ"/>  Another radiographic sign of elevated lead levels is the presence of [[radiodensity|radiodense]] lines called lead lines at the [[metaphysis]] in the long bones of growing children, especially around the knees.<ref name="Mycyk05-464">[[#CITEREFMycyk05|Mycyk, Hryhorczuk, Amitai (2005)]] pp. 464</ref> These lead lines, caused by increased [[calcification]] due to disrupted metabolism in the growing bones, become wider as the duration of lead exposure increases.<ref name="Mycyk05-464"/> [[X-rays]] may also reveal lead-containing foreign materials such as paint chips in the gastrointestinal tract.<ref name="Katzung07-948">[[#CITEREFKatzung07|Kosnett (2007)]] pp. 948</ref><ref name="Mycyk05-464"/> 

<!-- FECES -->
Fecal lead content that is measured over the course of a few days may also be an accurate way to estimate the overall amount of childhood lead intake. This form of measurement may serve as a useful way to see the extent of oral lead exposure from all the diet and environmental sources of lead.<ref name="Gwiazda04">{{Cite pmid|15626656 }}</ref>

<!-- DIF DX -->
Lead poisoning shares symptoms with other conditions and may be easily missed.<ref name="Brunton07-31"/>  Conditions that present similarly and must be ruled out in diagnosing lead poisoning include [[carpal tunnel syndrome]], [[Guillain-Barré syndrome]], [[renal colic]], [[appendicitis]], [[encephalitis]] in adults, and [[viral gastroenteritis]] in children.<ref name="Henretig061316"/>  Other [[differential diagnosis|differential diagnoses]] in children include [[constipation]], abdominal colic, iron deficiency, [[subdural hematoma]], [[neoplasm]]s of the central nervous system, emotional and behavior disorders, and [[mental retardation]].<ref name="Mycyk05-463"/>

===Reference values===
The current reference range for acceptable blood lead concentrations in healthy persons without excessive exposure to environmental sources of lead is less than 10&nbsp;µg/dL for children and less than 25&nbsp;µg/dL for adults.<ref>A. Wu. ''Tietz Clinical Guide to Laboratory Tests'', 4th ed., Saunders Elsevier, St. Louis, MO, 2006, pp. 658-659.</ref> The current biological exposure index (a level that should not be exceeded) for lead-exposed workers in the U.S. is 30&nbsp;µg/dL in a random blood specimen. Blood lead concentrations in poisoning victims have ranged from 30->80&nbsp;µg/dL in children exposed to lead paint in older houses, 77-104&nbsp;µg/dL in persons working with pottery glazes, 90-137&nbsp;µg/dL in individuals consuming contaminated herbal medicines, 109-139&nbsp;µg/dL in indoor shooting range instructors and as high as 330&nbsp;µg/dL in those drinking fruit juices from glazed earthenware containers.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 823-826.</ref>

==Prevention==
[[File:Lead testing.jpg|thumb|right|Testing kits are commercially available for detecting lead. These swabs, when wiped on a surface, turn pink in the presence of lead.|alt=A box of cigarette-like white cylinders on the left, in the middle a white cylinder with a pink tip, on the right a paper with four circles, two blank and two pink]]

In most cases, lead poisoning is preventable;<ref name="Sanborn">{{cite pmid|12041847}}</ref>  the way to prevent it is to prevent exposure to lead.<ref name="Rossi09"/>  Prevention strategies can be divided into individual (measures taken by a family), preventive medicine (identifying and intervening with high-risk individuals), and public health (reducing risk on a population level).<ref name="Guidotti07-PedClin"/>

Recommended steps by individuals to reduce the blood lead levels of children include increasing their frequency of hand washing and their intake of calcium and iron, discouraging them from putting their hands to their mouths, vacuuming frequently, and eliminating the presence of lead-containing objects such as blinds and jewellery in the house.<ref name="Payne08"/>  In houses with lead pipes or plumbing solder, these can be replaced.<ref name="Payne08"/>  Less permanent but cheaper methods include running water in the morning to flush out the most contaminated water, or adjusting the water's chemistry to prevent corrosion of pipes.<ref name="Payne08"/> Lead testing kits are commercially available for detecting the presence of lead in the household.<ref name="Salvato03-117">[[#CITEREFSalvato03|Salvato (2003)]] pp.117</ref>

Screening is an important method in preventive medicine strategies.<ref name="Guidotti07-PedClin"/>  Screening programs exist to test the blood of children at high risk for lead exposure, such as those who live near lead-related industries.<ref name="Mycyk05-463"/>

Prevention measures also exist on national and municipal levels.  Recommendations by health professionals for lowering childhood exposures include banning the use of lead where it is not essential and strengthening regulations that limit the amount of lead in soil, water, air, household dust, and products.<ref name="Lanphear05EnvironHealth"/>  Regulations exist to limit the amount of lead in paint; for example, a 1978 law in the US restricted the lead in paint for residences, furniture, and toys to 0.06% or less.<ref name="Henretig06"/>  In October 2008, the [[United States Environmental Protection Agency‎|US Environmental Protection Agency‎]] reduced the allowable lead level by a factor of ten to 0.15 micrograms per cubic meter of air, giving states five years to comply with the standards.<ref>{{cite web|url=http://www.efluxmedia.com/news_EPA_Sets_Tightest_Lead_Air_Emission_Standard_In_Three_Decades_26899.html |author = Chisamera, D |title= EPA Sets Tightest Lead Air Emission Standard |date = October 19, 2008 |publisher = eFluxMedia}}</ref>  The European Union's [[Restriction of Hazardous Substances Directive]] limits amounts of lead and other toxic substances in electronics and electrical equipment. In some places, remediation programs exist to reduce the presence of lead when it is found to be high, for example in drinking water.<ref name="Payne08"/>  As a more radical solution, entire towns located near former lead mines have been "closed" by the government, and the population resettled elsewhere, as was the case with [[Picher, Oklahoma]] in 2009.<ref>{{cite news  | last =  | first =  | coauthors =  | title =Polluted Kansas Town Seeks Federal Buyout
  | work =[[All things considered]]  | pages =  | language =  | publisher =[[National Public Radio]]
  | date =August 25, 2009
  | url =http://www.npr.org/templates/story/story.php?storyId=112215626
  | accessdate =August 25, 2009  }}</ref><ref>[http://www.nytimes.com/2009/09/14/us/14kansas.html?hp Treece Journal: Welcome to Our Town. Wish We Weren’t Here]. Saulny, S. New York Times, September 13, 2009</ref>

==Treatment==
{| class="wikitable" style = "float:right; margin-left:15px;"
|+ ''' CDC management guidelines for children with elevated blood levels'''<ref name="Kosnett06-242">[[#CITEREFKosnett06Pois|Kosnett (2006)]] pp.242</ref> 
! Blood lead<br> level (μg/dL) !! Treatment
|-
! 10–14
| Education,<br> repeat screening
|-
! 15–19
| Repeat screening, case<br> management to abate sources
|-
! 20–44
| Medical evaluation,<br> case management
|-
! 45–69
| Medical evaluation,<br> chelation, case management
|-
! >69
| Hospitalization, immediate<br> chelation, case management
|}

The mainstays of treatment are removal from the source of lead and, for people who have significantly high blood lead levels or who have symptoms of poisoning, [[chelation therapy]].<ref name="Henretig061321">[[#CITEREFHenretig06|Henretig (2006)]] pp. 1321</ref>  Treatment of iron, [[Calcium deficiency|calcium]], and [[zinc deficiency|zinc deficiencies]], which are associated with increased lead absorption, is another part of treatment for lead poisoning.<ref name="Mycyk05-465">[[#CITEREFMycyk05|Mycyk, Hryhorczuk, Amitai (2005)]] pp. 465</ref>  When lead-containing materials are present in the gastrointestinal tract (as evidenced by abdominal X-rays), [[whole bowel irrigation]], [[Cathartic (medicine)|cathartic]]s, [[endoscopy]], or even surgical removal may be used to eliminate it from the gut and prevent further exposure.<ref name="Olson07">[[#CITEREFOlson07|Olson (2007)]] pp.1658</ref>  Lead-containing bullets and shrapnel may also present a threat of further exposure and may need to be surgically removed if they are in or near fluid-filled or [[Synovial membrane|synovial]] spaces.<ref name="Kosnett06-241">[[#CITEREFKosnett06Pois|Kosnett (2006)]] pp.241</ref> If lead encephalopathy is present, [[anticonvulsant]]s may be given to control seizures, and treatments to control [[cerebral edema|swelling of the brain]] include [[corticosteroids]] and [[mannitol]].<ref name="Katzung07-948"/><ref name="Kosnett05-832">[[#CITEREFKosnett05|Kosnett (2005)]] pp. 832</ref>  Treatment of organic lead poisoning involves removing the lead compound from the skin, preventing further exposure, treating seizures, and possibly chelation therapy for people with high blood lead concentrations.<ref name="Katzung07-949">[[#CITEREFKatzung07|Kosnett (2007)]] pp. 949</ref> 

<!--
CHELATION -->
[[File:Metal-EDTA.svg|thumb|left|EDTA, a [[Chelation|chelating agent]], binds a heavy metal, sequestering it.|alt=a chemical diagram of [CH2N(CH2CO2-)2]2 (shown in black) with the four O- tails binding a metal ion (shown in red).]]

<!--DEFINITION-->
A chelating agent is a molecule with at least two negatively charged groups that allow it to form complexes with metal ions with multiple positive charges, such as lead.<ref name="Trevor07-480">[[#CITEREFTrevor07|Trevor, Katzung, Masters (2007)]] pp. 480</ref> The [[chelate]] that is thus formed is nontoxic<ref name="Lightfoot08-VetClin"/>  and can be excreted in the urine, initially at up to 50 times the normal rate.<ref name="Kosnett05-822">[[#CITEREFKosnett05|Kosnett (2005)]] pp. 822</ref>  The chelating agents used for treatment of lead poisoning are edetate disodium calcium ([[EDTA|CaNa<sub>2</sub>EDTA]]), [[dimercaprol]] (BAL), which are injected, and  [[Dimercaptosuccinic acid|succimer]] and d-[[penicillamine]], which are administered orally.<ref name="Menkes06">[[#CITEREFMenkes06|Menkes (2006)]] pp.706</ref> 
<!-- 
INDICATIONS 
-->
[[Chelation therapy]] is used in cases of acute lead poisoning,<ref name="Patrick06">{{Cite pmid|16597190 }}</ref> severe poisoning, and encephalopathy,<ref name="Olson07"/> and is considered for people with blood lead levels above 25&nbsp;µg/dL.<ref name="Brunton07-31"/>   While the use of chelation for people with symptoms of lead poisoning is widely supported, use in asymptomatic people with high blood lead levels is more controversial.<ref name="Katzung07-948"/>  Chelation therapy is of limited value for cases of chronic exposure to low levels of lead.<ref name="Meyer08-MutatRes">{{Cite pmid|18436472 }}</ref>  Chelation therapy is usually stopped when symptoms resolve or when blood lead levels return to premorbid levels.<ref name="Katzung07-948"/>   When lead exposure has taken place over a long period, blood lead levels may rise after chelation is stopped because lead is leached into blood from stores in the bone;<ref name="Katzung07-948"/> thus repeated treatments are often necessary.<ref name="Needleman04-AnnRev"/>  
<!-- 
SIDE EFFECTS 
-->Chelating agents can have [[adverse medical effect|adverse effects]];<ref name="Brodkin07-CMAJ"/>  for example, chelation therapy can lower the body's levels of necessary nutrients like zinc.<ref name="Lightfoot08-VetClin"/><ref>{{cite pmid|19852620}}</ref> Chelating agents taken orally can increase the body's absorption of lead through the intestine.<ref name="Pearson03-370"/>

<!--
CHELATION CHALLENGE
-->
Chelation challenge, also known as provocation testing, is used to indicate an elevated and mobilizable body burden of heavy metals including lead.<ref name="Brodkin07-CMAJ"/> This testing involves collecting urine before and after administering a one-off dose of chelating agent to mobilize heavy metals into the urine.<ref name="Brodkin07-CMAJ"/>  Then urine is analyzed by a laboratory for levels of heavy metals; from this analysis overall body burden is inferred.<ref>{{cite pmid|7697134}}</ref>  Chelation challenge mainly measures the burden of lead in soft tissues, and may not accurately reflect long-term exposure or the amount of lead stored in bone.<ref name="Katzung07-948"/>  Although the technique has been used to determine whether chelation therapy is indicated and to diagnose heavy metal exposure, evidence does not support either of these uses as blood levels after chelation are not comparable to the reference range typically used to diagnose heavy metal poisoning.<ref name="Brodkin07-CMAJ"/> The single chelation dose could also redistribute the heavy metals to more sensitive areas such as central nervous system tissue.<ref name="Brodkin07-CMAJ"/>

==Prognosis==
<!--REVERSIBILITY-->  
Outcome is related to the extent and duration of lead exposure.<ref name="Chisolm04-223">[[#CITEREFChisolm04|Chisolm (2004)]] pp. 223</ref>  Effects of lead on the physiology of the kidneys and blood are generally reversible; its effects on the central nervous system are not.<ref name="Rubin08-267"/> While peripheral effects in adults often go away when lead exposure ceases, evidence suggests that most of lead's effects on a child's central nervous system are irreversible.<ref name="Bellinger04-Pedi">{{Cite pmid|15060194 }}</ref>  Children with lead poisoning may thus have adverse health, cognitive, and behavioral effects that follow them into adulthood.<ref name="Woolf07-PedClin">{{Cite pmid|17448360 }}</ref>

<!--
ENCEPHALOPATHY
-->
Lead encephalopathy is a medical emergency and causes permanent [[brain damage]] in 70–80% of children affected by it, even those that receive the best treatment.<ref name="Mycyk05-463"/>  The mortality rate for people who develop cerebral involvement is about 25%, and of those who survive who had lead encephalopathy symptoms by the time chelation therapy was begun, about 40% have permanent neurological problems such as [[cerebral palsy]].<ref name="Brunton07-31">[[#CITEREFBrunton07|Brunton (2007)]] pp. 1131</ref>

<!--
LONG-TERM
-->
Exposure to lead may also decrease lifespan and have health effects in the long term.<ref name="Needleman04-AnnRev"/> [[Mortality rate|Death rates]] from a variety of causes have been found to be higher in people with elevated blood lead levels; these include cancer, stroke, and heart disease, and general death rates from all causes.<ref name="Rossi09"/>  Lead is considered a possible human carcinogen based on evidence from [[animal experimentation|animal studies]].<ref name="Merrill07862">[[#CITEREFMerrill07|Merrill, Morton, Soileau (2007)]] pp. 862</ref>   Evidence also suggests that age-related mental decline and psychiatric symptoms are correlated with lead exposure.<ref name="Hu07"/>  Cumulative exposure over a prolonged period may have a more important effect on some aspects of health than recent exposure.<ref name="Hu07">{{Cite pmid|17431499 }}</ref>  Some health effects, such as [[high blood pressure]], are only significant risks when lead exposure is prolonged (over about one year).<ref name="Kosnett07EnvironHealthPers">{{Cite pmid|17431500 }}</ref>

==Epidemiology==

Since lead has been used widely for centuries, the effects of exposure are worldwide.<ref name="Payne08">{{Cite pmid|18663205}}</ref>  Environmental lead is ubiquitous, and everyone has some measurable blood lead level.<ref name="Karri08">{{Cite pmid|18690981 }}</ref><ref name="Hu07"/>  Lead is one of the largest [[environmental medicine]] problems in terms of numbers of people exposed and the public health toll it takes.<ref name="Pokras08-Ecohealth"/>  
<!--  
COUNTRY -->
Although regulation reducing lead in products has greatly reduced exposure in the developed world since the 1970s, lead is still allowed in products in many developing countries.<ref name="Pokras08-Ecohealth"/> In all countries that have banned leaded gasoline, average blood lead levels have fallen sharply.<ref name="Meyer08-MutatRes"/>  However, some developing countries still allow leaded gasoline,<ref name="Payne08"/> which is the primary source of lead exposure in most developing countries.<ref name="Meyer-IntJHyge"/>  Poor children in developing countries are at especially high risk for lead poisoning.<ref name="Meyer-IntJHyge">{{Cite pmid|12971691 }}</ref>  Of North American children, 7% have blood lead levels above 10 μg/dL, whereas among Central and South American children, the percentage is 33–34%.<ref name="Payne08"/>  About one fifth of the world's [[disease burden]] from lead poisoning occurs in the Western Pacific, and another fifth is in Southeast Asia.<ref name="Payne08"/> 

<!-- 
RACE AND SES -->
In developed countries, nonwhite people with low levels of education living in poorer areas are most at risk for elevated lead.<ref name="Pokras08-Ecohealth"/>  In the US, the groups most at risk for lead exposure are the impoverished, city-dwellers, and immigrants.<ref name="Cleveland08">{{Cite pmid|18827541 }}</ref> African-American children and those living in old housing have also been found to be at elevated risk for high blood lead levels in the US.<ref name="Jones09">{{Cite pmid|19254973 }}</ref>  Low-income people often live in old housing with lead paint, which may begin to peel, exposing residents to high levels of lead-containing dust.  

<!-- RISK FACTORS -->
Risk factors for elevated lead exposure include alcohol consumption and smoking (possibly because of contamination of tobacco leaves with lead-containing pesticides).<ref name="Hu07"/>  Adults with certain risk factors might be more susceptible to toxicity; these include calcium and iron deficiencies, old age, disease of organs targeted by lead (e.g. the brain, the kidneys), and possibly genetic susceptibility.<ref name="Kosnett07EnvironHealthPers"/>  <!--
SEX -->
Differences in vulnerability to lead-induced neurological damage between males and females have also been found, but some studies have found males to be at greater risk, while others have found females to be.<ref name="Bellinger04-Pedi"/>

<!-- AGE -->
In adults, blood lead levels steadily increase with increasing age.<ref name="Rossi09"/>  In adults of all ages, men have higher blood lead levels than women do.<ref name="Rossi09"/>  Children are more sensitive to elevated blood lead levels than adults are.<ref name="Murata">{{Cite pmid|18987427}}</ref>  Children may also have a higher intake of lead than adults; they breathe faster and may be more likely to have contact with and ingest soil.<ref name="Dart041423"/> Children ages one to three tend to have the highest blood lead levels, possibly because at that age they begin to walk and explore their environment, and they use their mouths in their exploration.<ref name="Bellinger04-Pedi"/>  Blood levels usually peak at about 18–24&nbsp;months old.<ref name="Pearson03"/> In many countries including the US, household paint and dust are the major route of exposure in children.<ref name="Dart041423"/>

==History==
[[File:Dioscorides01.jpg|thumb|[[Pedanius Dioscorides|Dioscorides]] noted lead's effect on the mind in the first century A.D.|alt=an ancient Greek black-and-white woodcut print of a middle aged bearded man.  His left hand rests on a book and in his right he holds a plant.]]
[[File:DSC00125 - Tubi di piombo romani - Foto di G. Dall'Orto.jpg|Roman lead water pipes with taps|thumb|right|alt=a block with two dull, dark gray metal spouts coming from the top. The spouts are chipped and very old-looking.]]
Lead poisoning was among the first known and most widely studied work and [[environmental hazard]]s.<ref name="Flora08"/>  One of the first metals to be [[smelting|smelt]]ed and used,<ref name="Henretig06"/> lead is thought to have been discovered and first [[mining|mine]]d in [[Anatolia]] around [[6500 BCE]].<ref name="Gilbert06"/> Its [[density]], [[workability]], and [[corrosion]]-resistance were among the metal's attractions.<ref name="Flora08"/>

<!-- GREEKS --> 
In the [[second century BCE]] the [[Greeks|Greek]] [[botanist]] [[Nicander]] described the [[colic]] and [[paralysis]] seen in lead-poisoned people.<ref name="Pearce07-EurNeurol">{{Cite pmid|17179719 }}</ref><ref name="Needleman04-AnnRev">{{Cite pmid|14746518 }}</ref>  [[Pedanius Dioscorides|Dioscorides]], a Greek [[physician]] who lived in the [[first century CE]], wrote that lead makes the mind "give way".<ref name="Henretig06"/><ref name="Needleman09-AnnEP">{{Cite pmid|19344860 }}</ref>

<!--ROMANS -->
Lead was used extensively in [[Roman aqueduct]]s from about [[500 BCE]] to [[300 CE]]<ref name="Gilbert06"/>  [[Julius Caesar]]'s engineer, [[Vitruvius]], reported, "water is much more wholesome from [[earthenware]] pipes than from lead pipes. For it seems to be made [[injury|injurious]] by lead, because [[white lead]] is produced by it, and this is said to be harmful to the human body."<ref name="Prioreschi98">{{cite book |title= A History of Medicine, Volume 3 Of Roman Medicine |chapter= |editor= |last= Prioreschi |first= P |authorlink= |coauthors= |year=1998 |publisher= Horatius Press |location= |isbn= 1888456035 |page= |pages=279 |url= |accessdate= |quote=}}</ref>  [[Gout]], prevalent in [[affluence|affluent]] Rome, is thought to be the result of lead, or leaded eating and drinking vessels.   [[lead(II) acetate|Sugar of lead]] (Lead II Acetate) was used to [[sweetener|sweeten]] [[wine]], and the gout that resulted from this was known as [[saturnine]] gout.<ref>{{cite journal |author=Couper RTL. |title=The Severe Gout of Emperor Charles V |journal=N Engl J Med |year=2006 |volume=355 |issue=18 |pages=1935–36 |doi=10.1056/NEJMc062352 |pmid=17079773 |last2=Fernandez |first2=P. L. |last3=Alonso |first3=P. L. |ref=harv}}</ref>  It is even [[hypothesis|hypothesized]] that lead poisoning may have contributed to the [[decline of the Roman Empire]],<ref name="Needleman04-AnnRev"/><ref name="Henretig06"/> a hypothesis thoroughly disputed:

{{quote|The great disadvantage of lead has always been that it is poisonous. This was fully recognised by the [[ancient history|ancients]], and [[Vitruvius]] specifically warns against its use. Because it was nevertheless used in [[profusion]] for carrying drinking water, the conclusion has often been drawn that the Romans must therefore have suffered from lead poisoning; sometimes conclusions are carried even further and it is inferred that this caused [[infertility]] and other unwelcome conditions, and that lead [[plumbing]] was largely responsible for the decline and fall of Rome.

In fact, two things make this otherwise attractive hypothesis impossible. First, the [[calcium carbonate]] deposit that formed so thickly inside the [[aqueduct]] channels also formed inside the pipes, effectively [[insulation|insulating]] the water from the lead, so that the two never touched. Second, because the Romans had so few [[faucet|tap]]s and the water was constantly running, it was never actually inside the pipes for more than a few minutes, and certainly not long enough to become [[water pollution|contaminated]]. The [[thesis]] that the Romans contracted lead poisoning from the lead pipes in their water systems must therefore be declared completely unfounded.<ref>{{harvnb|Hodge|1992|p=308}}</ref>}}

However, Romans also consumed highly unsafe quantities of lead through the consumption of [[defrutum|defrutum, carenum and sapa]], [[must]]s made by [[boiling]] down [[fruit]] in lead [[cookware]].  Defrutum and its relatives were widely used in [[Ancient Roman cuisine]] and [[cosmetics]], including as a [[food preservative]].<ref name="Brighton">{{cite video|title=Tales of the Living Dead: Poisoned Roman Babies|publisher=Brighton TV for National Geographic|people=Director: Chris Warren|medium=television|date=2004}}</ref><ref name="pmid6338384">{{cite journal |author=Nriagu JO |title=Saturnine gout among Roman aristocrats. Did lead poisoning contribute to the fall of the Empire?
|journal=[[N. Engl. J. Med.]] |volume=308|issue=11|pages=660–3|year=1983|month=March|pmid=17079773|url=http://content.nejm.org/cgi/content/extract/355/18/1935-a |doi=10.1056/NEJMc062352 |last2=Fernandez |first2=P. L. |last3=Alonso |first3=P. L.
}}</ref>

<!-- 16TH, 17TH, 18TH CENTURIES -->
After [[antiquity]], mention of lead poisoning was absent from [[medicine|medical]] [[literature]] until the end of the [[Middle Ages]].<ref name="Hernberg00">{{Cite pmid|10940962}}</ref>  In [[1656]] the [[Germany|German]] [[physician]] [[Samuel Stockhausen]] recognized [[dust]] and [[vapor|fumes]] containing lead compounds as the cause of disease, called since ancient Roman times ''morbi metallici'', that were known to afflict [[mining|miners]], [[smelting|smelter]] workers, [[pottery|potters]], and others whose work exposed them to the metal.<ref name="Eisinger-colic" /><ref name="Gochfeld-history">{{cite pmid|15706170}}</ref>

The [[painting|painter]] [[Caravaggio]] might have died of lead poisoning.  Bones with high lead levels were recently found in a grave likely to be Caravaggio's grave<ref>[http://www.guardian.co.uk/artanddesign/2010/jun/16/caravaggio-italy-remains-ravenna-art ''The mystery of Caravaggio's death solved at last &ndash; painting killed him''], Tom Kington, The Guardian, Wednesday, 16 June 2010.</ref>.  Paints used at the time contained high amounts of lead salts.  Caravaggio is known to have indulged in violent behavior, as caused by lead poisoning.

In 17th-century [[Germany]], the physician [[Eberhard Gockel]] discovered lead-contaminated [[wine]] to be the cause of an epidemic of [[colic]].<ref name="Eisinger-colic" /> He had noticed that [[monk]]s who did not drink wine were healthy, while wine drinkers developed colic,<ref name="Pearce07-EurNeurol"/> and traced the cause to [[sugar]] of lead, made by [[simmering]] [[litharge]] with [[vinegar]].<ref name="Eisinger-colic" /> As a result, [[Eberhard Ludwig, Duke of Württemberg]] issued an [[edict]] in [[1696]] banning the [[adulteration]] of wines with litharge.<ref name="Eisinger-colic">{{Cite pmid|6750289}}</ref>

In [[18th century]] [[Boston, Massachusetts|Boston]], lead poisoning was fairly frequent on account of the widespread drinking of [[rum]], which was made in [[still]]s with a lead component (the "worm").<ref>{{cite book |author=Brands, H. W. |authorlink=H. W. Brands |title=The First American: The Life and Times of Benjamin Franklin |city=New York |publisher=Anchor Books |year=2000 |isbn=970385495400}}</ref> Also in the 18th century, "[[Devonshire colic]]" was the name given to the [[symptom]]s suffered by people of [[Devon]] who drank [[cider]] made in [[fruit press|press]]es that were lined with lead.<ref name="Pearce07-EurNeurol"/>  Lead was added to cheap wine illegally in the 18th and early [[19th century|19th centuries]] as a [[sweetener]].<ref name="Mai06-JRColl"/>  The composer [[Ludwig van Beethoven|Beethoven]], a heavy wine drinker, suffered elevated lead levels (as later detected in his [[human hair|hair]]) possibly due to this; the cause of his death is controversial, but lead poisoning is a contender as a factor.<ref name="Mai06-JRColl">{{Cite pmid|17214130}}</ref>

<!-- 19TH AND 20TH CENTURIES -->
With the [[Industrial Revolution]] in the 19th century, lead poisoning became common in the work setting.<ref name="Henretig06"/>  The introduction of [[lead paint]] for residential use in the 19th century increased childhood exposure to lead; for millennia before this, most lead exposure had been [[occupation]]al.<ref name="Bellinger04-Pedi"/> An important step in the understanding of childhood lead poisoning occurred when [[toxicity]] in children from lead paint was recognized in [[Australia]] in [[1897]].<ref name="Henretig06"/>  [[France]], [[Belgium]] and [[Austria]] [[banning|banned]] [[white lead]] interior [[paint]]s in [[1909]]; the [[League of Nations]] followed suit in [[1922]].<ref name="Gilbert06"/> However, in the [[United States]], laws banning lead house paint were not passed until [[1971]], and it was phased out and not fully banned until [[1978]].<ref name="Gilbert06"/>

The [[20th century]] saw an increase in worldwide lead exposure levels due to the increased widespread use of the metal.<ref name="Grant09-757">[[#CITEREFGrant09|Grant (2009)]] pp. 757</ref> Beginning in the [[1920s]], [[Gasoline#Lead|lead was added to gasoline]] to improve its [[combustion]]; lead from this [[exhaust]] [[persistence|persist]]s today in [[soil]] and [[dust]] in buildings.<ref name="Rossi09"/>  [[Blood]] lead levels worldwide have been declining sharply since the [[1980s]], when leaded gasoline began to be phased out.<ref name="Rossi09"/>  In those countries that have banned lead in [[solder]] for food and drink [[canning|can]]s and have banned leaded gasoline [[additive]]s, blood lead levels have fallen sharply since the mid-1980s.<ref name="Mycyk05-467">[[#CITEREFMycyk05|Mycyk, Hryhorczuk, Amitai (2005)]] pp. 467</ref>  

The levels found today in most people are orders of magnitude greater than those of [[pre-industrial society]].<ref name="Patrick06"/><ref name="Merrill07861">[[#CITEREFMerrill07|Merrill, Morton, Soileau (2007)]] pp. 861</ref>  Due to reductions of lead in products and the workplace, acute lead poisoning is rare in most countries today; however, low level lead exposure is still common.<ref name="Chiras09">{{cite book |title= Environmental Science, 8th edition |chapter= |editor= |last= Chiras |first= DD |authorlink= |coauthors= |year= 2009 |publisher=Jones & Bartlett Publishers |location= |isbn=0763759252 |page= |pages=394 |url= |accessdate= |quote=}}</ref>  It was not until the second half of the 20th century that [[subclinical]] lead exposure became understood to be a problem.<ref name="Hernberg00"/>  During the end of the 20th century, the blood lead levels deemed acceptable steadily declined.<ref name="Grant09-758">[[#CITEREFGrant09|Grant (2009)]] pp. 758</ref> Blood lead levels once considered safe are now considered hazardous, with no known safe threshold.<ref name="Sanborn">{{cite pmid|12041847 }}</ref><ref>{{cite web |url=http://www.atsdr.cdc.gov/csem/lead/pbcover_page2.html |accessdate=2007-09-09 |title=Lead Toxicity Cover Page |publisher=United States Center for Disease Control}}</ref>

== Notable cases ==
15,000 people are being relocated from the Jiyuan in central Henan province to another location. This is the largest lead-smelting center. After 1000 children living around China's largest smelter plant owned by Yuguang Gold and Lead, were found to have excess lead in their blood. The total cost of this project is estimated to around 1 billion yuan ($150 million). 70% of the cost will be paid by local government and the smelter company, while rest be paid by the residents themselves. The government has suspended production at 32 of 35 lead plants.<ref name="China to relocate 15,000 from lead-poisoned area">{{cite news|url=http://news.yahoo.com/s/afp/20091016/hl_afp/healthchinaenvironmentpollutionlead|title=China to relocate 15,000 from lead-poisoned area|date=2009-10-16|publisher=AFP|accessdate=2009-10-20}} {{Dead link|date=September 2010|bot=H3llBot}}</ref> The affected area includes people from 10 different villages.<ref name="China to move residents from lead smelter base-report">{{cite news|url=http://www.reuters.com/article/rbssIndustryMaterialsUtilitiesNews/idUSPEK14546420091019|title=China to move residents from lead smelter base-report|date=2009-10-18|publisher=Reuters|accessdate=2009-10-20}}</ref>

[[Arthur Stayner]] a prominent citizen of [[Salt Lake City]] and a father of the [[sugar beet]] industry in [[Utah]], died on September 4, 1879 from lead poisoning stemming from a [[Lead shot|lead pellet]] which became embedded in his heel, causing irritation throughout the day and poisoning his blood.<ref name="news">{{cite news|url=http://news.google.com/newspapers?nid=336&dat=18990904&id=5oIxAAAAIBAJ&sjid=ZzADAAAAIBAJ&pg=4977,670193|title=Blood Poisoning Causes Fatality|date=September 4, 1899|publisher=The Deseret News |accessdate=13 February 2010}}</ref>

The [[Zamfara State lead poisoning epidemic]] occurred in Nigeria in 2010.{{Citation needed|date=June 2010}}

==In other species==
{{Main|Animal lead poisoning}}
Humans are not alone in suffering from lead's effects; plants and animals are also affected by lead toxicity to varying degrees depending on species.<ref name="Yu05-188"/>  Animals experience many of the same effects of lead exposure as humans do, such as abdominal pain, peripheral [[neuropathy]], and behavioral changes such as increased aggression.<ref name="Pokras08-Ecohealth"/>  Much of what is known about human lead toxicity and its effects is derived from animal studies.<ref name="Bellinger04-Pedi"/>  Animals are used to test the effects of treatments, such as chelating agents,<ref name="Redig08">{{Cite pmid|18406387 }}</ref> and to provide information the pathophysiology lead, such as how it is absorbed and distributed in the body.<ref name="Grant09-768-71">[[#CITEREFGrant09|Grant (2009)]] pp. 768, 771, 774</ref>  

Farm animals such as cows and horses<ref name="Neathery">{{cite pmid|1107364}}</ref> as well as pet animals are also susceptible to the effects of lead toxicity.<ref name="Lightfoot08-VetClin"/>  Sources of lead exposure in pets can be the same as those that present health threats to humans sharing the environment, such as paint and blinds, and there is sometimes lead in toys made for pets.<ref name="Lightfoot08-VetClin"/>  Lead poisoning in a pet dog may indicate that children in the same household are at increased risk for elevated lead levels.<ref name="Pokras08-Ecohealth"/>  

===Wildlife===
[[File:Condor de Calofornie.jpg|thumb|right|[[Critically endangered species|Critically endangered]] [[California Condor]] can be poisoned when they eat carcasses of animals shot with lead pellets.|alt=A large tan bird of prey with dark brown neck feathers and a bare red head sits on a dead cow in a desert with dead grass and scrub]]

Lead, one of the leading causes of toxicity in waterfowl, has been known to cause die-offs of wild bird populations.<ref name="Lightfoot08-VetClin">{{Cite pmid|18406386 }}</ref>  When hunters use [[lead shot]], [[waterfowl]] such as ducks can ingest the spent pellets later and be poisoned; predators that eat these birds are also at risk.<ref name="Ferreyra09">{{Cite pmid|19617495 }}</ref>  Lead shot-related waterfowl poisonings were first documented in the US in the 1880s.<ref name="Pokras08-Ecohealth"/>  By 1919, the spent lead pellets from waterfowl hunting was positively identified as the source of waterfowl deaths.<ref name="FedCartridge">Federal Cartridge Company Waterfowl and Steel Shot Guide. Volume I; 1988.</ref>  Lead shot has been banned for hunting waterfowl in several countries,<ref name="Pokras08-Ecohealth">{{Cite pmid|19165554 }}</ref> including the US in 1991 and 1997 in Canada.<ref name="Degernes08-VetClin">{{Cite pmid|18406388 }}</ref>  Other threats to wildlife include lead paint, sediment from lead mines and smelters, and lead weights from fishing lines.<ref name="Degernes08-VetClin">{{Cite pmid|18406388 }}</ref>  Lead in some fishing gear has been banned in several countries.<ref name="Pokras08-Ecohealth"/>

The [[Critically endangered species|critically endangered]] [[California Condor]] has also been affected by lead poisoning.  As [[scavenger]]s, condors eat carcasses of game that have been shot but not retrieved, and with them the fragments from lead bullets; this increases their lead levels.<ref name="Green08PLoS">{{Cite pmid|19107211 }}</ref>  Among condors around the [[Grand Canyon]], lead poisoning due to eating lead shot is the most frequently diagnosed cause of death.<ref name="Green08PLoS"/>  In an effort to protect this species, in areas designated as the California Condor's range the use of projectiles containing lead has been banned to hunt deer, wild pig, elk, pronghorn antelope, coyotes, ground squirrels, and other non-game wildlife.<ref name="leadout"/>  Also, conservation programs exist which routinely capture condors, check their blood lead levels, and treat cases of poisoning.<ref name="Green08PLoS"/>

==References==
{{Reflist|2|refs =
<ref name="leadout">{{cite web | url = http://www.dfg.ca.gov/wildlife/hunting/condor/ | title = Get the Lead Out (Protecting the Condor) | accessdate = 2009-07-28 | publisher = California Department of Fish and Game}}</ref>
<ref name="Pearson03">[[#CITEREFPearson03|Pearson, Schonfeld (2003)]] pp.369</ref> 
<ref name="Pearson03-370">[[#CITEREFPearson03|Pearson, Schonfeld (2003)]] pp.370</ref>
<ref name="Marshall08">{{cite book |author = |title= Clinical Chemistry, 6th edition |chapter= Therapeutic drug monitoring and chemical aspects of toxicology |editor= Marshall, W.J.; Bangert, S.K. |year= 2008 |publisher= Elsevier Health Sciences |location= |isbn= 0723434557 |page= 366 }}</ref>
}}

==Cited texts==
<div class="references-medium" style="-moz-column-count:2; column-count:2;">

<!-- B -->
*{{cite book |author = |title= Goodman and Gilman's Manual of Pharmacology and Therapeutics|chapter=Principles of toxicology |editor= Brunton, L.L.; Goodman, L.S.; Blumenthal, D.; Buxton, I.; Parker, K.L.  |year= 2007 |publisher= McGraw-Hill Professional |location= |isbn=0071443436  |page= |pages= |url= |accessdate= |quote= |ref=CITEREFBrunton07 }}
<!-- C -->
*{{cite book |author = |title=Casarett and Doull's Toxicology: The Basic Science of Poisons, 7th edition |chapter= Toxic effects of metals |editor= Casarett, LJ; Klaassen, CD; Doull, J  |year= 2007 |publisher= McGraw-Hill Professional |location= |isbn= 0071470514|page= |pages= |url= |accessdate= |quote= |ref= CITEREFCasarett07}}
*{{cite book |author = Chisolm, J.J. |title= Oski's Essential Pediatrics, 2nd edition |chapter= Lead poisoning |editor= Crocetti, M.; Barone, M.A.; Oski, F.A. |year= 2004 |publisher= Lippincott Williams & Wilkins |location= |isbn= 0781737702 |page= |pages= |url= |accessdate= |quote= |ref=CITEREFChisolm04 }}
<!-- D -->
*{{cite book |author= Dart, R.C.; Hurlbut, K.M.; Boyer-Hassen, L.V. |title= Medical Toxicology, 3rd edition |chapter= Lead |editor=Dart, RC |year= 2004 |publisher= Lippincott Williams & Wilkins |location= |isbn= 0781728452 |page= |pages= |url= |accessdate= |quote= |ref = CITEREFDart04}}
<!-- G -->
*{{cite book |author = Grant, L.D. |title= Environmental Toxicants: Human Exposures and Their Health Effects, 3rd edition |chapter= Lead and compounds |editor=  Lippmann, M. |year= 2009 |publisher=Wiley-Interscience |location= |isbn= 0471793353|page= |pages= |url= |accessdate= |quote= |ref=CITEREFGrant09 }}
<!-- H -->
*{{cite book |author = Henretig F.M. |title= Goldfrank's Toxicologic Emergencies, 8th edition |chapter= Lead |editor= Goldfrank, LR |year= 2006 |publisher= McGraw-Hill Professional |location= |isbn= 0071437630 |page= |pages= |url= |accessdate= |quote= |ref= CITEREFHenretig06}}
*{{Cite book
 | last = Hodge
 | first = A. Trevor
 | title = Roman Aqueducts & Water Supply
 | place = London
 | publisher = Duckworth
 | year = 1992
 | isbn = 0-7156-2194-7
 | ref = harv
 | postscript = <!--None-->
}}
<!-- K -->
*{{cite book |author = Kosnett M.J. |title=Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient |chapter= Lead|editor=   Brent, J |year= 2005 |publisher= Gulf Professional Publishing |location= |isbn= 0815143877|page= |pages= |url= |accessdate= |quote= |ref=CITEREFKosnett05 }}
*{{cite book |author = Kosnett, M.J. |title= Basic and Clinical Pharmacology |chapter=Heavy metal intoxication and chelators |editor=  Katzung, B.G. |year= 2007 |publisher= McGraw-Hill Professional |location= |isbn= 0071451536 |page= |pages= |url= |accessdate= |quote= |ref=CITEREFKatzung07 }}
*{{cite book |author = Kosnett, M.J. |title= Poisoning and Drug Overdose, 5th edition |chapter= Lead |editor= Olson, K.R.  |publisher= McGraw-Hill Professional |location= |isbn= 0071443339 |page= 2006 |pages= |url= |accessdate= |quote= |ref=CITEREFKosnett06Pois }}
<!-- M -->
*{{cite book |author = Menkes, J.H.|title= Child Neurology, 7th edition |chapter=Toxic and nutritional disorders |editor= Menkes, J.H.; Sarnat, H.B.; Maria, B.L.  |year= 2006 |publisher= Lippincott Williams & Wilkins |location= |isbn=0781751047 |page=706 |pages= |url= |accessdate= |quote=|ref= CITEREFMenkes06}}
*{{cite book |author = Merrill, J.C.; Morton, J.J.P.; Soileau, S.D. |title= Principles and Methods of Toxicology, 5th edition |chapter=Metals |editor= Hayes, A.W. |year= 2007 |publisher= CRC Press |location= |isbn= 084933778X |page= |pages= |url= |accessdate= |quote= | ref = CITEREFMerrill07}}
*{{cite book |author = Mycyk, M.; Hryhorczuk, D.; Amitai, Y.  |title= Pediatric Toxicology: Diagnosis and Management of the Poisoned Child |chapter= Lead |editor= Erickson, TB; Ahrens, WR; Aks, S; Ling, L |year= 2005 |publisher= McGraw-Hill Professional|location= |isbn=0071417362 |page= |pages= |url= |accessdate= |quote= |ref= CITEREFMycyk05}}
<!-- O -->
*{{cite book |author = Olson, K.R. |title= Current Medical Diagnosis and Treatment, 46th edition  |chapter= Poisoning |editor= McPhee, S.J.; Tierney, L.M.; Papadakis, M.A.  |year= 2007 |publisher= McGraw-Hill Professional |location= |isbn= 0071472479 |page= |pages= |url= |accessdate= |quote= |ref=CITEREFOlson07 }}
<!-- P -->
*{{cite book |author =Pearson H.A.; Schonfeld, D.J. |title= Rudolph's Pediatrics, 21st edition|chapter=Lead |editor=  Rudolph, C.D. |year= 2003|publisher= McGraw-Hill Professional |location= |isbn= 0838582850 |page= |pages= |url= |accessdate= |quote= |ref=CITEREFPearson03 }}
<!-- R -->
*{{cite book |author = |title= Industrial Poisoning from Fumes, Gases, and Poisons of Manufacturing Processes |chapter= The symptoms and treatment of industrial poisoning |editor=  Rambousek, A.J. |year= 2008 |publisher= READ BOOKS |location= |isbn= 1408670259 |page= |pages= |url= |accessdate= |quote= |ref=CITEREFRambousek08 }}
*{{cite book |author = |title=Rubin's Pathology: Clinicopathologic Foundations of Medicine, 5th edition|chapter= Environmental and nutritional pathology |editor= Rubin, R.; Strayer, D.S.  |year= 2008 |publisher= Lippincott Williams & Wilkins |location= |isbn= 0781795168 |page= |pages= |url= |accessdate= |quote= |ref=CITEREFRubin08 }}
<!-- S -->
*{{cite book |author = |title= Environmental Engineering, 5th edition |chapter= Noninfectious and noncommunicable diseases and conditions associated with the environment, including air, water, and food|editor= Salvato, J.A.;  Nemerow, N.L.; Agardy, F.J. |year= 2003 |publisher= John Wiley and Sons |location= |isbn=0471418137 |page= |pages= |url= |accessdate= |quote= |ref=CITEREFSalvato03 }}
<!-- T -->
*{{cite book |author =  |title= Katzung & Trevor's Pharmacology: Examination & Board Review, 8th edition |chapter= Heavy metals |editor= Trevor, A.J.; Katzung, B.G.; Masters, S.B. |year=2007 |publisher= McGraw-Hill Professional |location= |isbn= 0071488693 |page= |pages= |url= |accessdate= |quote= |ref= CITEREFTrevor07}}
<!-- Y -->
*{{cite book |author = Yu, M.H. |title= Environmental Toxicology: Biological and Health Effects of Pollutants |chapter=Soil and water pollution: Environmental metals and metalloids |editor=   |year=2005 |publisher= CRC Press |location= |isbn=156670670X |page= |pages= |url= |accessdate= |quote= |ref=CITEREFYu05 }}
</div>

==External links==
<!--
PREVENTION -->
* [http://www.ericdigests.org/2003-2/lead.html Helping Parents Prevent Lead Poisoning]
<!--
TREATMENT-->
* [http://www.atsdr.cdc.gov/csem/lead/ ATSDR - Case Studies in Environmental Medicine (CSEM): Lead Toxicity] U.S. [[Department of Health and Human Services]] (public domain)
<!--
GENERAL-->
* [http://www.npi.gov.au/database/substance-info/profiles/50.html National Pollutant Inventory - Lead and Lead Compounds Fact Sheet]
* [http://www.cdc.gov/niosh/topics/lead/ National Institute for Occupational Safety and Health - Lead Topic Page]
* [http://www.nydailynews.com/news/2007/06/26/2007-06-26_12m_for_toxic_hell.html City payout to Brooklyn family largest ever in lead poisoning]
* [http://escholarship.org/uc/item/6m68b873 eScholarship: Review: The Great Lead Water Pipe Disaster]

{{Poisoning and toxicity}}
{{Consumer Food Safety}}

{{good article}}

{{DEFAULTSORT:Lead poisoning}}
[[Category:Lead]]
[[Category:Element toxicology]]
[[Category:Occupational safety and health]]
[[Category:Disturbances of human pigmentation]]
[[Category:Occupational diseases]]
[[Category:Mental retardation]]
[[Category:Toxic effects of substances chiefly nonmedicinal as to source]]

[[ar:تسمم بالرصاص]]
[[bg:Сатурнизъм]]
[[ca:Saturnisme]]
[[de:Bleivergiftung]]
[[es:Saturnismo]]
[[eu:Saturnismo]]
[[fa:مسمومیت سرب]]
[[fr:Saturnisme]]
[[is:Blýeitrun]]
[[it:Saturnismo]]
[[nl:Loodvergiftiging]]
[[ja:鉛中毒]]
[[nds:Blievergiften]]
[[pl:Ołowica]]
[[pt:Saturnismo]]
[[ro:Saturnism]]
[[sv:Blyförgiftning]]
[[zh:鉛中毒]]
[[Category:2Fix]]