Laboratory Testing and Diagnosis for the Presence of Heavy Metals
The diagnosis of heavy metal toxicity requires observation of presenting symptoms, obtaining a thorough history of potential exposure, and the results of laboratory tests. Laboratory tests routinely used for seriously exposed persons include blood tests, liver and renal function tests, urinalysis, fecal tests, x-rays, and hair and fingernail analysis. Many of these tests are not routinely performed in a doctor's office. However, your physician can take blood samples and send them to the appropriate testing laboratory. Chest x-rays are recommended for persons with respiratory symptoms, and abdominal x-rays can detect ingested metals (refer to the ASTDR ToxFAQs for specific information).Arsenic.
Arsenic levels can be measured in blood, urine, hair, and fingernails. Because arsenic clears fairly rapidly from the blood, blood tests are not always useful (Dupler 2001). Therefore, urine tests are the most reliable for arsenic exposure within the past few days; hair and fingernail testing are used to measure exposure over the past several months (ASTDR ToxFAQs for Arsenic). Abdominal x-rays can reveal metallic fragments (Ferner 2001). Note: Hair treatments, including hair dyes, can contaminate hair samples. When testing for any heavy metal, the most accurate results are obtained from hair that has not been chemically treated for at least 2 months.Lead.
When there are presenting symptoms of lead toxicity, blood testing is done. Blood lead levels in children higher than 10 mcg/dL are considered to be of concern (Ferner 2001; ASTDR ToxFAQs for Lead). Symptoms in adults may not appear until blood lead levels exceed 80 mcg/dL (Dupler 2001). However, medical treatment is usually necessary in children who have levels of 45 mcg/dL. Significantly lower levels of 30 mcg/dL in children can cause mental retardation or cognitive and behavioral problems (ASTDR ToxFAQs for Lead). A complete blood count (CBC) is also done to check for abnormalities on red blood cells (basophilic stippling). In children, long-bone x-rays may reveal bands called "lead lines" that indicate failure of the bone to rebuild. These bands are not actual lead concentrations, but are bone abnormalities. Adults do not have lead lines. X-rays of the abdomen can reveal swallowed objects, such as paint chips, fishing sinkers, curtain weights, or bullets (Ferner 2001). A less common test is measurement of lead in teeth (ASTDR ToxFAQs for Lead). All children with brain-related symptoms should be considered for lead toxicity (Ferner 2001).Mercury.
A 24-hour urine specimen is collected for measurement of mercury levels. Chest x-rays can reveal a collection of mercury from exposure to elemental mercury or a pulmonary embolism containing mercury (Ferner 2001). Abdominal x-rays can reveal swallowed mercury as it moves through the gastrointestinal tract. Blood and urine samples are used to determine recent exposure, as well as exposure to elemental mercury and inorganic forms of mercury. Scalp hair is used in testing for exposure to methylmercury. Liver and kidney function tests are also important in severely exposed persons. Blood mercury levels should not exceed 50 mcg/L.Cadmium.
Laboratory testing procedures for cadmium toxicity include collection of a 24-hour urine specimen, CBC, and hair and fingernail clippings. Blood levels show recent exposure; urine levels show both recent and earlier exposure (ASTDR). Blood levels of cadmium above 5 mcg/dL and creatinine levels in urine above 10 mcg/dL suggest cadmium toxicity (Dupler 2001). Note: The ASTDR is unsure of the reliability of tests for cadmium levels.Aluminum.
Testing procedures measure aluminum levels in blood, urine, hair and fingernails, and feces (ASTDR ToxFAQs for Aluminum). According to a spokesperson at the ASTDR in spring 2002, levels of aluminum that are recognized as average are less than 0.01 mg/L. However, blood testing might underestimate the total body level of aluminum; postmortem brain, lung, and bone measurements reveal much higher levels of aluminum than blood tests.Significance of Individualized Treatment Regimens
It is very important to note that treatment regimens vary significantly and are tailored to each specific individual's medical condition and the circumstance of their exposure. Providing a complete history of the person, including their occupation, hobbies, recreational activities, and environment, is critical in diagnosing heavy metal toxicity. A possible history of ingestion often facilitates a diagnosis, particularly in children. Findings from physical examinations vary with the age of the person, health status of the person, amount or form of the substance, and time since exposure (absorption rate) (Ferner 2001).
Allopathic (conventional) and alternative medicine practitioners (and naturopathic practitioners to a lesser extent) treat heavy metal toxicity. Once toxicity is confirmed, all cases (even suspected) of heavy metal toxicity should be brought to the attention of a professional who is experienced in diagnosing and treating poisoning. Often professionals consult with regional poison control centers or medical toxicologists for added expertise. Emergency room personnel and first responders are trained in recognizing symptoms and in proper handling, decontamination, and treatment techniques in acute exposure cases.
Conventional and alternative medical treatment includes chelation therapy, supportive care (intravenous fluids, cardiac stabilization, exchange transfusion, dialysis), and decontamination (charcoal, cathartics, emesis, gastric lavage, surgery). These procedures typically require hospitalization or treatment in a health care or clinical setting (Dr. Joseph F. Smith Medical Library 2001). Follow-up is required with laboratory testing until reference levels are within and remain in the normal range, particularly when the exposure was acute or if the person continues to have symptoms after treatment (ASTDR Medical Management Guidelines; Wentz 2000). Additionally, if there is a suspected homicidal or suicidal association, proper medical and legal resources should be involved (Ferner 2001). Medical personnel should report exposures to the appropriate agency to prevent additional public health risks either in the workplace or in the home (ASTDR Medical Management Guidelines; Anon. 1993; WHO 1998; International Occupational Safety and Health Information Centre 1999; Roberts 1999; Dupler 2001; Ferner 2001; USNML/NIH 2001a; 2001b; 2001c; 2001d).Therapeutic Overview
- Chelation Therapy
- Chelating Agents
Therapies to remove heavy metals from humans include chelation and decontamination procedures, as well as supportive measures, often used in combination. The therapies can be very complex and highly individualized, tailored to the specific needs of each individual and requiring the expertise of trained and experienced professionals, sometimes a team of professionals. Self-diagnosis and treatment is not appropriate.Chelation Therapy
Chelation is a chemical process that has applications in many areas, including medical treatment, environmental site rehabilitation, water purification, and so forth. In the medical environment, chelation is used to treat cardiovascular disease, heavy metal toxicity, and to remove metals that accumulate in body tissues because of genetic disorders (hemochromatosis). This protocol will address the use of chelation therapy for the removal of heavy metals as a result of ingested or environmental exposure.
Chelation therapy, simply defined, is the process by which a molecule encircles and binds (attaches) to the metal and removes it from tissue (Dr. Joseph F. Smith Medical Library 2001). Depending on the drug used, chelating agents specific to the heavy metal involved are given orally, intramuscularly, or intravenously. Once the bound metal leaves the tissue, it enters the bloodstream, is filtered from the blood in the kidneys, and then is eliminated in the urine (Dupler 2001). The decision to chelate should be made only by professionals with experience using chelation therapy, preferably in consultation with a poison control center or a medical toxicologist.
Typically, a patient receives a programmed series of intravenous infusions, intramuscular injections, or oral administration of a chelating agent (possibly a combination of the three). The therapy is often lengthy (from a few hours in an emergency room to several days of in-patient treatment in a hospital). Sometimes repeated courses of treatment are required (Wentz 2000). Chelation may be uncomfortable because of the side effects of the medicine itself or from the route of administration (e.g., pain in the area surrounding an injection site) (Ferner 2001). Frequent follow-up testing is required to determine the amount of the metal that is being removed. Sometimes, as in the case of lead, testing may show a rapid decline initially, but then a leveling off occurs over time. In the case of lead, this leveling off is caused by lead that continues to enter the blood from the bones where it has been stored (the "rebound effect"). The leveling off effect is used as a guide for determining how long chelation therapy should be continued (Wentz 2000). As time passes following exposure, chelation therapy is less effective in reducing the severity of poisoning and the risk of serious delayed effects (see the ASTDR Medical Management Guidelines). It cannot reverse neurological damage that has already been sustained.
Acutely poisoned symptomatic persons or persons with a clear history of exposure to a toxic heavy metal may require chelation therapy to start before confirmation can be obtained from a laboratory (see the ASTDR Medical Management Guidelines). However, asymptomatic patients are not usually treated with chelation therapy until after test results reveal levels that require treatment. Interestingly, Goyer (1996) points out that there is growing interest in removing toxic metals from asymptomatic persons who are known to have received low-levels of environmental exposure to heavy metals.
This interest has been generated because of the toxic effects (or damage) that may occur at levels that were previously thought to be safe. According to Goyer, "It is clear that the margin between the levels of exposure for persons living in the industrialized nations of the world and levels of exposure currently recognized as producing the lowest adverse effect is small." Goyer listed low-level exposure to lead as possibly causing impaired cognitive and behavioral development in children, accumulation of cadmium being associated with renal tube dysfunction, and allegations that mercury vapor from dental amalgam may be a possible cause of chronic heath problems (Goyer 1996). Mercury vapor is released from amalgam in new fillings, when old amalgam fillings are replaced (Omura et al. 1996), and even when amalgam is scraped during cleaning.
Chelation is effective in treating arsenic, lead, iron, mercury, and aluminum poisoning. However, chelation is not considered to be particularly effective in treating cadmium poisoning, although it may be used to prevent further absorption in the gastrointestinal tract. To date there is no effective treatment for cadmium poisoning (ASTDR ToxFAQs for Cadmium1999; Wentz 2000; Dr. Joseph F. Smith Medical Library 2001).Chelating Agents
An agent frequently used in chelation therapy is dimercaprol (also known as BAL or British Anti-Lewisite). Oral chelating agents used as alternatives to BAL are 2,3-demercaptosuccinic acid (DMSA), dimercaptopropanesulfonate (DMPS), and D-penicillamine (ASTDR MMG). Another agent, deferoxamine, is often used to chelate iron. Ethylenediamintetraacetic acid (ETDA) also has an affinity for lead and was one of the first chelators developed.BAL (Dimercaprol).
BAL (British Anti-Lewisite) is a chelating agent administered by injection in the treatment of acute poisoning by certain heavy metals (e.g., arsenic, lead, mercury, gold, bismuth, and antimony). Contraindications to using BAL are preexisting kidney disease, pregnancy, hypertension, and current use of medicinal iron. BAL has significant side effects that are frequent and include pain at the injection site; hypertension and tachycardia; abdominal pain, nausea, and vomiting; headaches; burning sensation of the lips, excessive salivation, rhinorrhea, and tearing; fever; muscle pain, muscle spasms, and a feeling of chest constriction; and profuse sweating. It is considered to be the most toxic of the chelating agents (Wentz 2000). However, side effects can be medically managed and are seldom severe enough to cause treatment to be ended (Micromedex 1999).DMSA (Dimercaptosuccinic Acid).
DMSA is an oral chelating agent and an analogue of (similar to) BAL. DMSA is used in conjunction with or as an alternative to BAL for lead and mercury toxicity. DMSA is less toxic than BAL, and it is sometimes substituted for BAL when the patient's condition improves. It is also used when intolerance to BAL develops. Although DMSA is similar to BAL, it has fewer and milder side effects (e.g., nausea, vomiting, and diarrhea; rhinitis and cough; and rash) (see the ASTDR Medical Management Guidelines). An interesting study on thiol chelating substances showed that DMSA was more effective than DMPS and SAMe (S-adenosylmethionine) in protecting mice from acute hepatic or renal toxicity caused by arsenic, and that all three substances were nontoxic to the liver or kidneys of mice (Tripathi et al. 1998). Contraindications to using DMSA are preexisting kidney or liver disease and pregnancy. Hydration is essential. DMSA is not used in conjunction with ETDA or D-penicillamine (USNML/NIH 2001b).DMPS (Dimercaptopropanesulfonate).
DMPS is another analogue of BAL. It has been shown to be less effective and to have more side effects than DMSA (Aaseth et al. 1995). DMPS is the drug of choice in Europe and Asia; however, the FDA has not approved DMPS for chelating purposes in the United States. It does, however, appear on the FDA list of drugs that appear to be safe. In the United States, DMPS is distributed to pharmacists in bulk form for compounding and dispensing in oral and injection forms (FDA 1999; Marcus 2001).D-penicillamine.
D-penicillamine is an oral chelating agent used to treat heavy metal toxicity, particularly arsenic and mercury. Side effects are gastrointestinal intolerance, nausea and vomiting, and itchy skin (wheals). Contraindications are allergy to penicillin, possible interaction with other drugs (immunosuppressants, digoxin), severe blood disorders, kidney insufficiency, and pregnancy (USNML/NIH 2001d).Deferoxamine.
Deferoxamine is used to chelate iron, especially in acute iron poisoning in small children. It is also used to chelate aluminum. Deferoxamine is administered by injection or intravenously. Common side effects are blurred vision, wheezing, rapid heartbeat, seizures, itching, skin rash, bluish skin, and redness and pain at the injection site. Gastrointestinal discomfort, fever, cramping, and bruising are less common. Contraindications are allergies to certain foods or dyes, other medicines currently being taken, pregnancy or breast feeding, and kidney disease (USNML/NIH 2001a).EDTA (Ethylenediamintetraacetic Acid, Edetate Disodium).
EDTA is one of the oldest chelating agents, coming into prominence in the 1950s. EDTA has an affinity for lead. It is often used as a second-line of treatment in combination with BAL and given by IV infusion. Common side effects are gastrointestinal upset and headache. More serious side effects can include seizures, numbness or tingling in the hands and feet, irregular heartbeat, skin rashes, fever or chills, and blood in the urine (Ferner 2001). EDTA is contraindicated in pregnancy and if there is kidney disease. It can also interact with insulin and heart medicines (USNML/NIH 2001c).
The following table summarizes chelating agents, the heavy metals they are used to treat, their route of administration, and their brand name.
BAL in Oil
|Dimercaptosiccinic acid (DMSA)
(for compounding by pharmacists)
Ethylenediamintetra-acetic acid (EDTA) (Edetate disodium)||Lead||IV||Chealamide
*Not methylmercury poisoning.
**Under supervision of a physician: i.m., intramuscular; p.o., peroral or by mouth; IV, intravenous.
Source: Data from Beers et al. 1999; Micromedex 1999; Roberts 1999; Wentz 2000; Anon. 2001; Ferner 2001; Marcus 2001; USNML/NIH Drug Information 2001a; 2001b; 2001c; 2001d.Gastrointestinal Decontamination
- Gastric Lavage
- Whole Bowel Irrigation
- Supportive Measures
In addition to chelation therapy, decontamination procedures are often required: gastric lavage, whole bowel irrigation, emesis, charcoal, or cathartics.Gastric Lavage.
Gastric lavage is washing out of the stomach with sterile water or a salt solution to remove swallowed irritants or poisons (Dr. Joseph F. Smith Medical Library 2001). Gastric lavage is accomplished by placing a plastic tube into the stomach via the mouth and esophagus. Normal saline, water, or a combination is introduced into the stomach via the tube. Gastric lavage is not indicated if the substance ingested is an alkaline corrosive. It is done in a health care environment or hospital and is most effective within the first hour of ingestion. Gastric lavage is not effective in removing large tablets or large clumps of tablets or other material (Klein-Schwartz et al. 2000), but it is indicated for arsenic (Ferner 2001). Insertion of the tube may injure the esophagus. Gastric lavage is more effective in adults than in children because a larger tube can be used (Klein-Schwartz et al. 2000; James 2001).Whole Bowel Irrigation.
Bowel irrigation is emptying of the bowel with large volumes of solutions such as Golightly, Colyte, sterile water, or some other fluid to remove swallowed irritants or poisons from the bowel (e.g., arsenic and lead) (Ferner 2001; James 2001). The fluid may be administered orally or by gastric tube until the bowel fluid has the same appearance as the solution administered (Klein-Schwartz et al. 2000; James 2001). Whole bowel irrigation is indicated if some time has elapsed since ingestion of the toxin and if the toxin will not be effectively bound by charcoal. It can take several hours and has the side effects of nausea and vomiting, diarrhea, and cramping. Whole bowel irrigation is not indicated if mental status is impaired or bowel sounds are decreased (Anon. 2001).Emesis.
Emesis is forceful emptying (vomiting) of the stomach and is most effective for recent oral ingestion of noncorrosive substances. Ipecac Syrup USP is considered to be an essential emesis agent in many homes with young children and for years has been the cornerstone of poison management (Anon. 2001). If instructed by a physician, Ipecac may be given in the home prior to the arrival of emergency personnel or treatment in an emergency department, often preventing significant absorption from stomach contents (Klein-Schwartz et al. 2000). However, use of Ipecac is only effective when administered within the first 5-20 minutes after ingestion of a toxin. After a toxin has left the stomach, inducing emesis with Ipecac is useless. Administering it after the first few minutes may actually delay beginning further medical treatment (Anon. 2001). Ipecac may take 20 minutes to produce forceful vomiting (James 2001), and the vomiting may last for some time (2-4 hours). Emesis should not be induced if the patient is having difficulty maintaining consciousness, the toxin is caustic or might cause choking (e.g., a clump of pills), or if the person has gastrointestinal bleeding (Anon. 2001). When appropriate, emesis is induced in cases of acute arsenic or mercury poisoning (Dr. Joseph F. Smith Medical Library 2001).
Contact a physician, emergency department, or poison center before using emesis.Charcoal.
Charcoal is administered in single- or multiple-dose regimens, either intravenously or orally. Single doses are most effective if administered within the first hour after ingestion. Multiple-dose regimens are often used in complicated cases and in children because the smaller doses (half of a single dose) appear be better tolerated than the larger single dose (Anon. 2001). Charcoal should not be administered for caustic or corrosive materials, and bowel sounds must be present. Its usefulness is limited in certain pesticides and compounds that are poorly water soluble (e.g., iron and elemental metals) (Anon. 2001). Gastrointestinal decontamination with activated charcoal is indicated to aid in removal of mercury (Ferner 2001).Cathartics.
Cathartics are used to aid moving toxic material through the gastrointestinal tract, to remove and reduce concentrations, or to decrease absorption of toxic materials (Anon. 2001; James 2001). A cathartic agent increases intestinal action, increases the bulk of feces, makes feces soft, or adds water to the wall of the intestines, the term implying fluid bowel materials (Glanze 1996). Cathartics are often used in conjunction with charcoal in adults, particularly to prevent impaction or formation of charcoal "briquettes." Cathartics are not recommended for children under 1 year and should be used with caution in children under 3 years of age. Cathartics can produce significant diarrhea and electrolyte imbalance. They are not indicated if bowel sounds are absent (Anon. 2001).Supportive Measures.
IV fluids, dialysis, and drugs to treat complications resulting from heavy metal toxicity and treatments, such as shock, anemia, kidney failure, breathing difficulties, cardiac irregularities, infections, and so forth, may be required. Close monitoring of symptoms by medical personnel and immediate response to them are also required (Anon. 2001; Dr. Joseph F. Smith Medical Library 2001; James 2001; ASTDR Medical Management Guidelines).Treatment Regimes for Selected Heavy Metals
Chelation therapy shortens the distribution of arsenic in the blood and reduces the body burden. It can reduce the risks of serious delayed effects, but chelation does not reverse damage from the delayed effects of acute arsenic poisoning. BAL, DMSA, and D-penicillamine are the primary drugs used to remove arsenic. Chelation therapy with BAL by injection is the primary form of treatment for acute arsenic toxicity. The oral chelating agent DMSA is also an effective treatment choice.
Supportive care with abundant fluids to increase elimination of arsenic may be required. Exchange transfusion and hemodialysis may also be necessary in the event of kidney failure. However, these treatments are supportive and do not remove arsenic (Roberts 1999). Decontamination of the gastrointestinal system with gastric lavage aids in reducing continued absorption of arsenic. Whole bowel irrigation may also be necessary. Use supportive measures, such as correcting heart rhythm irregularities and hypotension (Ferner 2001).Mercury.
Chelation therapy is the usual treatment method for mercury poisoning, using BAL, DMSA, or D-penicillamine (Ferner 2001). BAL is widely used for inorganic mercury poisoning (Roberts 1999), with D-penicillamine used as an alternative. Other treatments are activated charcoal for gastrointestinal decontamination unless there is evidence of corrosive damage in the gastrointestinal tract (Ferner 2001), gastric and whole bowel lavage, and supportive measures. However, charcoal is not usually given when elemental mercury is ingested because elemental mercury is poorly absorbed in the gastrointestinal tract.Iron.
Chelation with deferoxamine is commonly used with blood serum levels greater than 500 mg/dL. (This level is only a guide. Much lower levels are known to produce cardiovascular difficulties, and some persons with higher levels exhibit no symptoms.) Deferoxamine is a drug that binds to absorbed iron very well and is eliminated in urine. Deferoxamine may be administered by injection or by intravenous administration; however, IV administration is less painful and more efficient. Supportive care with special attention to fluid balance and cardiovascular stabilization are essential in iron poisoning (Roberts 1999).
Blood levels are used as a guide to therapy, but the estimated ingested amount is often used to determine the initial course of action. If the person is symptomatic, however, or if the amount ingested exceeds 20 mg/kg (or as few as 5-9 30-mg tablets for a 30-pound child), gastrointestinal decontamination is recommended. Inducing emesis is an option within the first hour after ingestion. Gastric lavage may also remove fragments of tablets (Roberts 1999). Note: BAL chelation is contraindicated for iron toxicity, because BAL can combine with medicinal iron to become very toxic.Lead.
Chelation therapy with DMSA for children with blood lead levels of greater than 45 mcg/dL was approved in 1991 by the FDA (Wentz 2000). A major advantage of DMSA is that it can be given orally, which leads to better compliance by the patient. DMSA is relatively safe and significantly reduces blood levels of iron (Fournier et al. 1988). BAL, D-penicillamine, and EDTA are also used (Wentz 2000). Whole bowel irrigation is used if x-rays indicate the presence of lead (Ferner 2001). Follow-up blood testing is required because stored lead in bones may continue to release from the bones when the lead exposure has been long-term (Wentz 2000).Aluminum.
Although deferoxamine has not been approved by the FDA for aluminum chelation, deferoxamine has been used since 1980 as a first-line of treatment in cases of aluminum toxicity. (Important: Remember that deferoxamine is used to chelate iron. Therefore, during chelation treatment for aluminum, iron would also be chelated.) EDTA may also be used (Wentz 2000).Cadmium.
There is no known medical chelating method that is effective for the treatment of cadmium toxicity; however, DMSA may be used in cases of acute oral cadmium poisoning to help prevent additional absorption of cadmium in the gastrointestinal tract (Wentz 2000). Prevention or elimination of exposure is all that is available at this time for cadmium toxicity (ASTDR ToxFAQs for Cadmium).Preventing Heavy Metal Poisoning
Occupational exposure can be reduced by engineering solutions that address the manufacturing process, collecting and removing fumes, reducing dusts, and substituting other materials when possible. For example, in recent years, the pottery industry has replaced certain lead compounds in their products that are used as dishes or food containers. In most countries, laws have been passed to protect workers, setting limits of exposure, requiring monitoring in the workplace and medical surveillance of workers, and making recommendations (International Occupational Safety and Health Information Centre 1999):
- No smoking, eating, or drinking in work areas.
- Provide appropriate protective clothing that will remain at the facility.
- Provide showering facilities as needed.
- Work clothes and street clothes will not be kept in the same area.
Three agencies in the United States that provide information and guidance are the Occupational Safety and Health Administration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), and the Agency for Toxic Substances and Disease Registry (ASTDR). Local health departments, regional poison control centers, and clinics that specialize in occupational and environmental health conditions can also provide valuable resources and guidance.
In the home, practical measures include raising your awareness of possible sources of exposure and reducing the threat of exposure. Think carefully about the necessity of having products containing toxic metals around the house or in the garage (e.g., fertilizers, fungicides, insect or rodent poisons, lead-based paint, refinishing chemicals, household cleaning agents, hobby supplies, photographic chemicals, batteries, etc.). Use alternatives when possible. When these products are necessary, store them carefully and dispose of them properly. Medicines and personal health care products should be stored so that they are in a location well out of the creative and imaginative reach of children. Emphasize safety rules with children. If appropriate, before leaving the workplace, follow decontamination procedures to avoid bringing toxic materials into your house on your clothing and shoes or on your skin and hair. Consider cumulative exposures, such as from cookware, storage containers, medicines, water, foodstuffs, and the environment (National Medical Library 2001).
- Use the least harmful product possible.
- Buy only as much as you need.
- Read labels. Know the potential hazards of what you are buying.
- Store products in their original container. Read the label every time you use a product. Refer to the label in case of an accidental spill or ingestion. Never store household chemicals in a food container, even if the container has been relabeled.
- Support and use established disposal programs and facilities in your area.
- Become familiar with the symptoms of and first aid procedures for ingestion of substances containing toxic metals.
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