Lead poisoning

• 1. Introduction

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  Lead poisoning, also known as plumbism and saturnism, was blamed for an estimated 1.5 million deaths around the world in 2021. People have mined and used the metal for thousands of years. Written descriptions of its poisonous effects date back to at least 200 BC, and efforts to limit its use reach back to at least the 16th century. Yet concern about small, everyday doses is surprisingly recent. It began in the 1970s, once the bioaccumulative nature of lead came to be understood.

  Lead has no known necessary role in the body, so the first question is what it does once it gets inside. Why do toddlers pay the heaviest price? How did an additive meant for car engines carry lead across the planet? Why do turmeric, noodles, tap water and old paint keep turning up in the story? And once lead is in a person, can anything undo the damage?

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• 2. Anatomy of a Poison

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  Calcium, iron and zinc all do essential work inside the body's enzymes, and lead causes harm largely by impersonating them. It binds to sulfhydryl groups found on many enzymes and takes the place of those metals. Its chemistry is different, so it cannot do their job as a helper molecule. The enzyme then fails to carry out its normal reaction. Lead and other heavy metals also create reactive radicals that damage DNA and cell membranes.

  One enzyme, delta-aminolevulinic acid dehydratase, or ALAD, sits at the center of the damage. It helps build heme, the part of hemoglobin that holds iron. Lead also blocks ferrochelatase, the enzyme that joins protoporphyrin to iron to form heme. The result is zinc protoporphyrin and anemia. Precursor molecules such as aminolevulinic acid pile up, and these may harm neurons directly or indirectly. That pile-up gives lead poisoning symptoms that resemble acute porphyria.

  Calcium ions are also lead's passport into the brain, the organ most sensitive to the metal. Lead can stand in for calcium and be taken up by calcium-ATPase pumps, which carries it across the blood brain barrier. In a child's developing brain it disrupts synapse formation in the cerebral cortex, the development of neurotransmitters and the organization of ion channels. It strips neurons of their myelin sheaths, reduces their numbers and slows their growth. Lead ions, like magnesium ions, also block NMDA receptors. That suppresses long-term potentiation and drives an abnormal rise in long-term depression, which feeds on itself in a positive feedback loop. Targeting these receptors is thought to be one of the main reasons lead is toxic to neurons.

  In adults, 94% of absorbed lead ends up in the bones and teeth. Children store only 70% of it that way, which may partly explain why they suffer more serious effects. Lead locked in bone is tightly bound and generally thought to be harmless. But bone can release it into the bloodstream long after the original exposure is gone. In men, the half-life of lead in blood is about 40 days, compared with months in soft tissue and years to decades in bone. Pregnant women and children, whose bones are being remodeled, keep returning lead to the blood. The body clears it very slowly, mainly in urine, with smaller amounts in feces and traces in hair, nails and sweat.

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• 3. Reading the Signs

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  A bluish line along the gums, edged in bluish black where it meets the teeth, is called a Burton line. It is one marker of chronic lead poisoning. Another is a "lead hue" of the skin, a pallor or lividity. Chronic poisoning is the far more common form, and it falls into three broad groups of symptoms: gastrointestinal, neuromuscular and neurological. Intense exposure tends to produce nerve and brain symptoms, while longer exposure tends to produce stomach problems.

  At a blood lead level of 40 micrograms per deciliter, adults may begin to notice symptoms, though they more often appear only above 50-60. Children generally begin to show symptoms at around 60. Between 25 and 60, reaction times slow and irritability and poor concentration set in. Anemia can appear above 50, and attacks of abdominal colic above 80. Above 100, adults can develop wrist drop and foot drop, along with brain swelling, delirium, coma and seizures. In children, bizarre behavior, poor coordination and apathy appear above 70.

  Hemoglobin in the urine can be a sign of acute poisoning, when red blood cells rupture in large numbers. A large dose absorbed over a short time can also cause shock, because water drains out of the gastrointestinal tract. The kidneys may develop acquired Fanconi syndrome and produce less urine. Many people who survive an acute episode go on to show chronic symptoms.

  The main diagnostic tool is a laboratory measurement of the blood lead level, counted in micrograms per deciliter. Under a microscope, a blood film may show basophilic stippling, which are dots inside red blood cells. The same dots appear in vitamin B12 and folate deficiency, so they prove nothing alone. A blood lead level mainly reflects recent or current exposure rather than the total body burden. X-ray fluorescence can measure lead in bone noninvasively, and may be the best gauge of cumulative exposure, but it is used mostly in research. In growing children, X-rays can show dense lead lines at the ends of the long bones, especially around the knees. These lines widen the longer exposure lasts.

  Carpal tunnel syndrome, Guillain-Barre syndrome, renal colic, appendicitis, adult encephalitis and, in children, viral gastroenteritis can all look similar, so poisoning is easily missed. The CDC's blood lead reference value for children is 3.5 micrograms per deciliter, lowered from 5 in October 2021. For adults, the CDC and its partner agencies designated 5 as the reference level in November 2015, replacing a case definition of 10 that had stood since 2009. Recorded poisonings show how wide the range runs. Children living with lead paint in older houses have measured 30 to 80, and people drinking fruit juice from glazed earthenware containers have reached as high as 330.

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• 4. Small Bodies

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  Children aged one to three tend to carry the highest blood lead levels, and the peak usually arrives at about 18-24 months. That is the age of crawling, walking and exploring with the mouth. Toddlers spend their days on the floor, where they breathe in and swallow contaminated dust. Many also show pica, the habit of eating things that are not food. A single paint chip can hold tens or hundreds of milligrams of lead.

  Young children absorb 4 to 5 times as much lead as an adult does from the same source. Adults absorb about 15% of ingested inorganic lead, while infants may absorb about 50%. Deficiencies of calcium, zinc or iron push absorption higher still.

  Between blood lead levels of 5 and 35 micrograms per deciliter, studies report an IQ drop of 2-4 points for every unit of increase. Higher levels in children also correlate with weaker nonverbal reasoning, short-term memory, attention, reading, arithmetic, fine motor skills, emotional regulation and social engagement. Unlike mercury, lead shows no apparent lower threshold in its dose-response relationship. Reduced academic performance has been tied to blood lead below 5. Some researchers caution that confounding factors may cause studies of low-level exposure to overstate the effect.

  Blood lead in mothers and their infants is usually similar, because lead crosses the placenta and passes into breast milk. A fetus can be poisoned when lead stored in the mother's bones is released by the metabolic changes of pregnancy. Extra calcium during pregnancy may help limit this. Elevated lead in a pregnant woman raises the risk of miscarriage, prematurity and low birth weight.

  Lead encephalopathy causes permanent brain damage in 70-80% of the children it affects, even with the best treatment. About 25% of people who develop cerebral involvement die. Among survivors who already had encephalopathy symptoms when chelation therapy began, about 40% have lasting neurological problems such as cerebral palsy. Effects on the kidneys and blood are generally reversible, but most effects on a child's central nervous system are not. Among boys, childhood lead exposure also appears to increase school suspensions and juvenile detention.

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• 5. Petrol and Crime

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  Tetraethyllead was first added to gasoline in 1923 because it helped prevent engine knocking. Car exhaust became a major route by which lead was inhaled, entered the bloodstream and reached the brain. Use of the additive peaked in the 1970s, and by the next decade most high-income countries had prohibited leaded petrol. As late as 2002, almost all low- and middle-income countries still used it. The UN Environment Programme launched a campaign that year to end the practice, and Algeria became the last country to stop, in July 2021.

  Half the US population was exposed to substantially harmful lead levels in early childhood, mainly from car exhaust. Lead pollution from that source peaked in the 1970s and caused widespread loss of cognitive ability. Aviation gasoline still uses tetraethyllead, and removing it from airplane fuel would keep about 450 tons of lead out of the environment every year.

  In May 2000, the economic consultant Rick Nevin theorized that lead exposure explains 65% to 90% of the variation in violent crime rates in the US. A 2007 paper by the same author claimed a strong association between preschool blood lead and later crime trends across nine countries. Countries with the highest air lead levels have also had the highest murder rates, after adjusting for confounding factors. Researchers link the traits of childhood exposure, namely low IQ, impulsivity and aggression, to crimes of passion such as aggravated assault in young adults.

  An increase in childhood lead exposure was linked to a rise in aggravated assault rates 22 years later. The peak in leaded gasoline use in the late 1970s lines up with a peak in aggravated assault in the late 1990s. It is believed that the US ban on lead paint in buildings in the late 1970s, together with the phaseout of leaded gasoline in the 1970s and 1980s, helped drive the fall in violent crime since the early 1990s. Man-made lead pollution of the air, however, was already elevated long before any engine existed, and has been for the past 2000 years.

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• 6. Pipes and Paint

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  In 2004, a team of seven reporters from The Washington Post found high levels of lead in the drinking water of Washington, DC, and won an award for investigative reporting. In Flint, Michigan, a switch to a more corrosive municipal water source pushed up lead in household taps. Acidic water dissolves lead from plumbing more readily, so utilities can add chemicals to raise the pH. Chloramines, adopted in place of chlorine disinfectants because of fewer health concerns, make water more corrosive. In the US, 14-20% of total lead exposure is attributed to drinking water.

  Wisconsin faces estimates of up to 176,000 underground lead service lines to replace. The City of Madison replaced all of its lines, but other cities have not followed. Homeowners must replace the pipes on their own property, at an average cost of $3,000. Partial replacement can dislodge lead in the parts left behind and raise concentrations in the water. Congress authorized the EPA to fund line removal under Section 50105 of the Safe Drinking Water Act. In the meantime, only cold tap water should be used for drinking, cooking and making baby formula, since hot water is likelier to carry more lead.

  A study conducted in 1998-2000 found 38 million US housing units with lead-based paint, down from a 1990 estimate of 64 million. Deteriorating paint breaks down into dust, and eating the chips themselves generally causes more severe poisoning than the dust does. Sanding or torching old paint creates lead dust and fumes, so it is usually safer to seal it under new paint. A 1978 US law limited lead in paint for residences, furniture and toys to 0.06% or less.

  Lead white was the main white of oil painters until compounds containing zinc or titanium replaced it in the mid-20th century. It is speculated that Caravaggio, and possibly Francisco Goya and Vincent Van Gogh, suffered lead poisoning from overexposure or carelessness with this colour.

  Soil holds a legacy of its own. In the Montevideo neighborhood of La Teja, former industrial sites became important sources of exposure in the early 2000s. Interfacial solar evaporation, which draws heavy metal ions out of moist soil as vapor, has recently been studied as a way to clean such sites.

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• 7. Hidden Sources

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  In Bangladesh, lead chromate was added to turmeric to make it a brighter yellow, a practice believed to have started in the 1980s. A 2019 report named the adulterated spice as the main cause of lead poisoning in the country. The government launched a rapid crackdown and a public campaign. By 2021, leaded turmeric had vanished from the market, and blood lead in workers at turmeric mills had fallen by a median of 30%.

  In 2007-29 young adults in Leipzig, Germany, spent months in hospital after smoking marijuana tainted with small lead particles. Police suspected the lead was added for its weight, since dealers sell by the gram. Researchers estimated it raised profit by as much as $1,500 per kilogram. Cannabis plants also absorb heavy metals from soil naturally. In 2022, around 40% of cannabis products from unlicensed storefronts in New York City contained heavy metals, pesticides and bacteria.

  In May 2015, food safety regulators in Uttar Pradesh found Maggi 2 Minute Noodles with lead up to 17 times beyond permissible limits. On the 3rd of June 2015, the New Delhi Government banned the noodles in the city's stores for 15 days. The Gujarat food regulator followed on the 4th of June 2015 with a 30-day ban, after 27 of 39 samples showed objectionable levels. Retailers including Future Group, Big Bazaar, Easyday and Nilgiris imposed nationwide bans.

  In 2007, millions of toys made in China were recalled from several countries, partly over lead paint. Kohl, an ancient cosmetic from the Middle East, South Asia and parts of Africa, can contain lead. So can Ayurvedic and Chinese herbal remedies. The folk remedies azarcon and greta are powders of lead tetroxide and lead oxide, each about 95% lead. Lead-contaminated opium has poisoned people in Iran and other Middle Eastern countries. In December 2022, Consumer Reports tested 28 dark chocolate brands and found cadmium, lead or both in 23 of them.

  Ammunition is the second-largest use of lead in the US, at over 84,800 metric tons in 2013, behind only storage batteries. A 2008 study found that 1.1% of 736 people who ate wild game had blood lead of 5 micrograms per deciliter or more. Copper, steel, bismuth-tin and tungsten-polymer blends are among the alternatives. Bullets lodged in the body rarely raise lead significantly, but those lodged in joints deteriorate and release it over time.

  Dental X-ray film packets once carried a lead liner, so developing them was a hazard of the job. Lead miners, plumbers, auto mechanics, glass manufacturers, battery recyclers and firing range workers also face exposure. Indoor shooting range instructors have shown blood lead of 109-139 micrograms per deciliter, and pottery glaze workers 77-104. Workers can also carry lead dust home on their clothes or skin and expose their children.

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• 8. Cleanup and Cure

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  In 2009, about 15,000 people were slated for relocation from Jiyuan, in China's Henan province. About 1000 children near the country's largest smelter had excess lead in their blood. The project was estimated to cost around 1 billion yuan, or $150 million, with 70% to come from local government and the smelter company. Production was suspended at 32 of 35 lead plants. In August 2009, parents in another part of China rioted after nearly 2000 children near zinc and manganese smelters were found to be poisoned. Picher, Oklahoma, was bought out the same year and its people resettled. In Zamfara State, Nigeria, at least 400 children had died by the 5th of October 2010.

  When a patient is already poisoned, the first step is removal from the source. For significantly high blood lead or symptoms, doctors add chelation therapy. A chelating agent is a molecule that grips multivalent metal ions such as lead, forming a nontoxic complex that can be excreted in urine at up to 50 times the normal rate. Dimercaprol and edetate calcium disodium are injected, while succimer and d-penicillamine are taken by mouth. Before these agents existed, doctors in the 19th and early 20th centuries gave iodide salts, popularized by Louis Melsens.

  The agents carry risks. Dimercaprol's commercial formulation contains peanut oil, so patients must be checked for peanut allergy. Calcium EDTA can damage the kidneys, and it should be given four hours after dimercaprol. Succimer is the preferred agent in mild to moderate cases, and its most reported side effect is stomach upset. Chelation lowers blood lead but may not prevent the cognitive problems tied to lead in tissue. Under CDC guidelines for children, a level of 45-69 calls for chelation, and anything above 69 calls for hospitalization and immediate chelation.

  The World Health Organization reported in June 2022 that only 45% of countries had confirmed legally binding controls on lead paint. Prevention efforts receive about $0.31 of funding per year of healthy life affected, roughly six hundred times less than for HIV. On the 30th of July 2020, a report by UNICEF and Pure Earth said lead poisoning was affecting children on a "massive and previously unknown scale." It found that one in three children, up to 800 million worldwide, have blood lead levels at or above 5 micrograms per deciliter.

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