Lead poisoning

Overview
Lead poisoning is a medical condition, also known as saturnism, plumbism, or painter's colic caused by increased blood lead levels. Lead may cause irreversible neurological damage as well as renal disease, cardiovascular effects, and reproductive toxicity.

Humans have been mining and using this heavy metal for thousands of years, poisoning themselves in the process due to accumulation and exposure. These dangers have long been known, though the modern understanding of their full extent and the small amount of lead necessary to produce them is relatively recent; blood lead levels once considered safe are now considered hazardous, with no known threshold. Reducing these hazards requires both individual actions and public policy regulations.

History
Lead was first mined in Asia Minor (today Turkey) about 6500 BC. A 6000- to 8000-year-old lead necklace was found in the ancient city site of Anatolia. Lead's easy workability, low melting point and corrosion resistance were among its attractions.

Lead toxicity was first recognized as early as 200 BC. Nicander of Colophon wrote of lead-induced anemia and colic in 250 BC. Gout, prevalent in affluent Rome, is thought to be the result of lead, or leaded eating and drinking vessels. Lead was used in makeup. Sugar of lead (lead(II) acetate) was used to sweeten wine, and the gout that resulted from this was known as saturnine gout.

Aulus Cornelius Celsus, writing ca. 30 AD, listed white lead on a list of poisons with antidotes (beside cantharides, hemlock, hyoscyamus, poisoned mushrooms, and a swallowed leech), and claimed it could be remedied by mallow or walnut juice rubbed up in wine. Despite his awareness of lead's toxicity, citing many contemporary authorities, Celsus recommended its use in a wide range of ointments applied to wounds to stop bleeding and reduce infection or inflammation.

Julius Caesar's engineer, Vitruvius, who also served his successor Caesar Augustus, reported, "Water is much more wholesome from earthenware pipes than from lead pipes. For it seems to be made injurious by lead, because white lead, a pigment base produced by soaking lead in vineger until a soft paste, is produced from it; and this is said to be harmful to the human body." It should be noted that the prevalence of lead poisoning, at least that caused by drinking water containing lead, in ancient Rome is far less than what is traditionally believed. The hardness of Rome's water caused heavy deposits of calcium carbonate to form on pipes and in turn prevented the lead of the pipes from coming into contact with the water, thus reducing the chance of getting lead poisoning from drinking water. The calcium deposits takes some time to collect. Older homes have the potential for less lead exposure where new homes with fresh pipes, connections and construction residue have a good potential for lead poisoning of occupants.

In 17th-century Germany, an Ulm physician noticed that monks who did not drink wine were healthy, while wine drinkers developed colic. The culprit was sugar of lead, made by simmering litharge with vinegar.

In 18th-century Boston, lead poisoning was fairly frequent on account of the widespread drinking of rum in that city, which was distilled in stills with one component (the "worm") made of lead.

Chinese alchemists found that lead could be rendered harmless by soaking it in blood and firing it. When this process was repeated several times it provided a protective coat that lead could not pass. The only notable use of this measure was by martial artists so they could use the heavy metal as weights for training.

Today, most exposure in developed countries is the result of occupational hazards, leaded paint, and leaded gasoline (which continues to be phased out in most countries). Lead poisoning interferes with the normal development of the brain.

The term "lead poisoning" is sometimes used as a euphemism for gunshot wounds, as almost all bullets are mainly composed of lead. Despite this, bullets lodged in the body rarely cause significant levels of lead poisoning. Bullets lodged in the joints are the exception, as they deteriorate and release lead into the body over time.

Symptoms and effects
The symptoms of chronic lead poisoning include neurological problems, such as reduced cognitive abilities, or nausea, abdominal pain, irritability, insomnia, metal taste in oral cavity, excess lethargy or hyperactivity, chest pain, headache and, in extreme cases, seizure and coma. There are also associated gastrointestinal problems, such as constipation, diarrhea, vomiting, poor appetite, weight loss, which are common in acute poisoning. Other associated effects are anemia, kidney problems, and reproductive problems.

In humans, lead toxicity sometimes causes the formation of a bluish line along the gums, which is known as the "Burton's line", although this is very uncommon in young children. Blood film examination may reveal "basophilic stippling" of red blood cells, as well as the changes normally associated with iron deficiency anemia (microcytosis and hypochromia). However, basophillic stippling is also seen in unrelated conditions, such as megaloblastic anemia caused by vitamin B12 (colbalamin) and folate deficiencies.

Lead affects the peripheral and central nervous system. The most common sign of peripheral neuropathy due to chronic lead poisoning is painless wristdrop (weakness of the extensor muscles of hand) which usually develops after many weeks of exposure.

A direct link between early lead exposure and extreme learning disability has been confirmed by multiple researchers and child advocacy groups.

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 U.S. . A July 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 different countries. These results were discussed in a July 2007 Washington Post article, reviving interest in the subject. Nevin's results are somewhat supported by Dartmouth Political Scientist Roger D. Masters' work, and similar work is being done by other researchers. Amherst economist Jessica Reyes' working paper and Masters' work are both pre-publication and available online.

Biological role
Lead has no known physiologically relevant role in the body. The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc which act as cofactors in many enzymatic reactions. Lead is able to bind to and interact with many of the same enzymes 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(s).

Most lead poisoning symptoms are thought to occur by interfering with an essential enzyme Delta-aminolevulinic acid dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the cofactor found in hemoglobin. Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form a Heme. Genetic mutations of ALAD cause the disease porphyria, a disease which was highlighted in the movie The Madness of King George. Lead poisoning is sometimes mistaken for porphyria but the distinction is that lead poisoning usually causes anemia while true porphyria does not.

An article on Lead Encephalopathy on Emedicine states:

Lead also interferes with excitatory neurotransmission by glutamate, which is the transmitter at more than half the synapses in the brain and is critical for learning. The glutamate receptor thought to be associated with neuronal development and plasticity is the N-methyl-D-aspartate (NMDA) receptor, which is blocked selectively by lead. This disrupts long-term potentiation, which compromises the permanent retention of newly learned information.

The January 2004 edition of Scientific American magazine contained an article on schizophrenia that said the latest research:

... implies that their brain circuits reliant on NMDA receptors are out of kilter. If reduced NMDA receptor activity prompts schizophrenia's symptoms, what then causes this reduction? The answer still remains unclear.

However, a Johns Hopkins report by Tomas Guilarte stated:

It has been known for some time that lead is a potent inhibitor of the NMDA receptor, a protein known to play an important role in brain development and cognition. In this study we demonstrate that lead exposure decreased the amount of NMDA receptor gene and protein in a part of the brain called the hippocampus.

Ezra Susser and his colleagues at Columbia University in New York followed 12,000 children born in Oakland, California, between 1959 and 1966, whose mothers had given samples of blood serum while they were pregnant, which were frozen and stored for later analysis. They found that children who had been exposed to high levels of lead in the womb were more than twice as likely to go on to develop schizophrenia. Their research was presented at the 2004 annual meeting of the American Association for the Advancement of Science in Seattle, Washington.

Lead poisoning can also be fatal.

Occurrence
Outside of occupational hazards, the majority of lead poisoning occurs in children under age twelve. The main sources of poisoning are from ingestion of lead contaminated soil (this is less of a problem in countries that no longer have leaded gasoline) and from ingestion of lead dust or chips from deteriorating lead-based paints. This is particularly a problem in older houses where the sweet-tasting lead paint is likely to chip, but deteriorating lead-based paint can also powder and be inhaled. Small children also tend to teethe and suck on painted windowsills as they look outside. In most American states, landlords and those selling such houses are required to inform the potential residents of the danger.

Lead has also been found in drinking water. It can come from plumbing and fixtures that are either made of lead or have trace amounts of lead in them. In 2004, seven reporters from The Washington Post discovered high levels of lead in the drinking water in Washington, D.C. The team won an award for investigative reporting for a series of articles about this contamination.

Exposure to metallic lead such as small lead objects, can rarely lead to an increase in blood lead levels if the lead is retained in the gastrointestinal tract or appendix.

Lead can also be found in some imported cosmetics such as Kohl, from the Middle East, India, Pakistan, and some parts of Africa, and Surma from India and from imported toys, such as many made in China. There are also risks of elevated blood lead levels caused by folk remedies like Azarcon which contains 95 percent lead and is used to "cure" empacho. For more information about less common causes of elevated blood lead levels, see footnote.

Lead may be contracted through the mucous membranes through direct contact to mouth, nose, eyes, and breaks in skin.

Measurement
One measure of lead in the body is the blood lead level (BLL), measured in micrograms of lead per deciliter of blood (μg/dL). Nearly everyone has a measurable BLL. The Centers for Disease Control and Prevention (CDC) states that a BLL of 10 μg/dL or above is a cause for concern. However, lead can impair development even at BLLs below 10 μg/dL. However, BLL measures current exposure to lead, but lead may also be incorporated into bone from prior exposures that will not show in BLLs until this bone-lead becomes "mobilized" through pregnancy or fracture healing. A fetus can be poisoned in utero if its mother had high bone-lead from either childhood exposure or a later occupational or other exposure that is subsequently mobilized by the fetal need for calcium. K-fluorescent X-ray metering can measure bone-lead.

Portable X-ray fluorescence (XRF) equipment can be used to measure lead concentrations and exposures in the field, from lead paint, children's toys, etc. Simple inexpensive test kits are available, which show color changes based on chemical reactions, but they are inexact.

Exposures and demographics
The average person has less than 10 micrograms per deciliter, or 100 parts per billion, ppb, of lead in their blood. People who have been exposed to an unusual amount of lead will have blood lead levels higher than 200 ppb&mdash;most clinical symptoms of lead poisoning begin at around 100 ppb. The effect on children's mental/cognitive abilities has been noted at very low levels. The levels found today in most people are orders of magnitude greater than that of ancient times. These levels are within an order of magnitude of levels that have resulted in adverse health effects. Blood lead levels once considered safe are now considered hazardous, with no known threshold. Although many people are exposed to lead through household products, workplace, and lead paint, studies show that people of color and recent immigrants are at a much greater risk for high levels of exposure than whites. Low income people often live in rental housing with lead paint, and unless the landlord conducts regular inspections, paint may begin to peel and residents will be exposed to high levels of lead paint dust, thus greatly increasing their chance of lead poisoning.

Pathways
Today almost everyone is exposed to environmental lead. Exposure to lead and lead chemicals can occur through inhalation, ingestion or occasionally dermal contact. Lead mining and lead smelting are common in many countries, where children and adults can receive substantial lead exposure from sources uncommon today in the U.S. Most countries will have phased out use of leaded gasoline by 2007. Lead exposure in the general population (including children) occurs primarily through ingestion, although inhalation also contributes to lead body burden and may be the major contributor for workers in lead-related occupations. Inhalation is the second major pathway of exposure. Almost all inhaled lead is absorbed into the body, whereas from 20% to 70% of ingested lead is absorbed (with children generally absorbing a higher percentage than adults do). Dermal exposure plays a role for exposure to organic lead among workers, but is not considered a significant pathway for the general population, except in areas where leaded gasoline is used. Organic lead from gasoline additives may be absorbed directly through the skin.

Children
Lead-contaminated household dust is the major source of lead exposure to children in the U.S. A 2006 study in New York City found lead levels in settled outdoor dust, which is a source of household dust, of 175 to 730 μg/ft2, and noted that these levels exceed the HUD/EPA lead in indoor dust standard of 40 μg/ft2. In 1978 there were 13.5 million children in the United States with elevated blood lead levels (i.e., 10µg/dl). By 2002, that number had dropped to 310,000 children. The U.S. incurs $43.4 billion annually in the costs of all pediatric environmental disease, with childhood lead poisoning alone accounting for the vast majority of it.

Adults
Although children are at greater risk from lead exposure, adult exposures can also result in harmful health effects. Most adult exposures are occupational and occur in lead-related industries such as lead smelting, refining, and manufacturing industries. One frequent source of lead exposure to adults is home renovation that involves scraping, remodeling, or otherwise disturbing lead-based paint. Adults can also be exposed during certain hobbies and activities where lead is used. Workers may inhale lead dust and lead oxide fumes, as well as eat, drink, and smoke in or near contaminated areas, thereby increasing their probability of lead ingestion. Between 0.5 and 1.5 million US workers are exposed to lead in the workplace (ATSDR, 1999). Other than the developmental effects unique to young children, the health effects experienced by adults from adult exposures are similar to those experienced by children, although the thresholds are generally higher.

US Rules and Regulations
See United States Environmental Protection Agency: Rules and Regulations for its jurisdiction and regulations.

"In 1998, the US Government instituted regulations which limit the amount of lead in toys and other consumer products which are expected to be used by infants to 0.06% (or 600 ppm)."

Ten µg/dL (micrograms /deciliter) was adopted by CDC in 1991 as an action level for children, an advisory level for environmental and educational intervention. There are requirements that children receiving Medicaid be screened. Most states ask or require primary care physicians and persons in charge of screening programs to report both presumptive and confirmed cases of lead toxicity to the appropriate health agency. This is to ensure abatement of the lead source, education of the patient, and remediation steps are undertaken. In some states, the clinical laboratories performing blood lead testing are required to report cases of lead toxicity.

In early 2008, the watchdog Food and Drug Administration ordered several US retail stores and malls to remove bindi and sindoor from their shelves due to concerns over high lead and other harmful chemical contents.

Workplace Air
The OSHA Lead Standard specifies the permissible exposure limit (PEL) of lead in the workplace, the frequency and extent of medical monitoring, and other responsibilities of the employer. OSHA has set a PEL (enforceable) of lead in workplace air at 50 µg/m3 averaged over an 8-hour workday for workers in general industry. NIOSH at CDC has set a Recommended Exposure Limit (REL) of 50 µg/m3 to be maintained so that worker blood lead remains < 60 µg/dL of whole blood. The ACGIH has set a threshold limit value for a time-weighted average (TLV/TWA) of 50 µg/m3 for lead in workplace air (except for lead arsenate).

The NIOSH Adult Blood Lead Epidemiology and Surveillance (ABLES) program, a state-based surveillance program of laboratory-reported adult blood lead levels works to reduce the rate of adults (age 16 or older) who have blood lead levels of 25 micrograms per deciliter (mcg/dL) or greater.

Lead contaminated soil can pose a risk through direct ingestion, uptake in vegetable gardens, or tracking into homes. Uncontaminated soil contains lead concentrations less than 50 ppm but soil lead levels in many urban areas exceed 200 ppm. (AAP 1993) The EPA’s standard for lead in bare soil in play areas is 400 ppm by weight and 1200 ppm for non-play areas. This regulation applies to cleanup projects using federal funds. The soil screening level (SSL) for lead represents a conservative estimate for a level that would be protective of public health in residential soils based on an analysis of the direct ingestion pathway for children.

EPA has set drinking water standards with two levels of protection. The maximum contaminant level goal (MCLG) is zero. This is the level determined to be safe by toxicological and biomedical considerations, independent of feasibility. EPA’s final rule establishes an action level is set at 15 µg/L. The use of lead solder and other lead-containing materials in connecting household plumbing to public water supplies was banned by EPA as of June 1988.

FDA has set a number of action levels (enforceable) and levels of concern for lead in various food items. These levels are based on FDA calculations of the amount of lead a person can consume without ill affect. FDA has set an action level of 0.5 µg/mL for lead in products intended for use by infants and children and has banned the use of lead-soldered food cans.

House paint contained up to 50% lead before 1955. Federal law lowered the amount of lead allowable in paint to 1% in 1971. The CPSC has limited since 1977 the lead in most paints to 0.06% (600 ppm by dry weight). Paint for bridges and marine use may contain greater amounts of lead.

Both the federal government and the state of Massachusetts are considering (as of September 2007) action against lead in children’s jewelry. "But Mr. Durbin said he was disappointed with Ms. Nord and the safety commission, which he said did not appear to be attacking the problem aggressively enough, including moving too slowly to institute and enforce a ban on lead in children’s jewelry. He also mocked a new agreement with Chinese officials to block lead in toys, saying that the Chinese government told his office the policy had long been in place."

Less regulated countries
Dermatologists have concluded that the internal effects of lead are dangerous, as it has effects on the central nervous system, kidney and heart. Nevertheless, the emergence of synthetic dye industry has led to a variety of chemical dyes and salts being produced at a cheaper price in India.

Treatment
Although the most important part of treating lead poisoning is decreasing exposure to lead, there are some forms of chelation therapy that can be used to reduce existing BLL levels:
 * DMSA
 * EDTA
 * British anti-Lewisite

Additionally, a comparative study of chelating agents showed that vitamin C (ascorbic acid), along with DMSA, CDTA and DMPS increased survival in an animal model of lead intoxication, while EGTA, N-acetyl-L-cysteine (NAC) and various other agents did not. High serum levels of vitamin C have been associated with a decreased prevalence of elevated blood lead levels and intervention with supplemental vitamin C was shown to markedly decrease lead levels in smokers (mean: 81 %). Authors hypothesize, however, that this effect might be due to an inhibition of lead absorption.

Other meanings
The phrase "lead poisoning" is sometimes used as slang for death by shooting, as bullets and shot are usually made of lead.