Gloved hand holding labeled urine sample in test tube.

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Below you will find information regarding tests for both individual elements and trace element panels. Click through to learn more about details such as general information, sources/routes of exposure, treatment and cost.

Element Sample Types Availble Panels
Aluminum Erythrocytes
Hair
Plasma
Tissue
Urine
Whole Blood
Plasma Toxic Panel
Urine Toxic Panel
Hair Toxic Panel
Antimony Erythrocytes
Hair
Urine
Whole Blood
Urine Toxic Panel
Hair Toxic Panel
Arsenic (Inorganic) Urine
Arsenic (Total) Erythrocytes
Hair
Nail
Urine
Whole Blood
Erythrocyte Toxic Panel
Hair Toxic Panel
Urine Toxic Panel
Whole Blood Toxic Panel
Barium Hair
Urine
Hair Toxic Panel
Urine Toxic Panel
Beryllium Hair
Urine
Urine Toxic Panel
Bismuth Hair
Urine
Hair Toxic Panel
Urine Toxic Panel
Boron Hair
Urine
Hair Essential Panel
Urine Essential Panel
Cadmium Erythrocytes
Hair
Tissue
Urine
Whole Blood
Erythrocyte Toxic Panel
Hair Toxic Panel
Urine Toxic Panel
Whole Blood Toxic Panel
Calcium Erythrocytes
Hair
Urine
Whole Blood
Erythrocyte Essential Panel
Hair Essential Panel
Urine Essential Panel
Chromium Erythrocytes
Hair
Plasma
Serum
Tissue
Urine
Whole Blood
Erythrocyte Essential Panel
Plasma Essential Panel
Hair Essential Panel
Urine Essential Panel
Cobalt Erythrocytes
Hair
Plasma
Serum
Tissue
Urine
Whole Blood
Erythrocyte Essential Panel
Plasma Essential Panel
Hair Essential Panel
Urine Essential Panel
Copper Erythrocytes
Hair
Plasma
Tissue
Urine
Whole Blood
Erythrocyte Essential Panel
Plasma Essential Panel
Hair Essential Panel
Urine Essential Panel
Iodine Hair
Plasma
Urine
Hair Essential Panel
Iron Hair
Tissue
Urine
Hair Essential Panel
Urine Essential Panel
Lead Erythrocytes
Hair
Tissue
Urine
Whole Blood
Erythrocyte Toxic Panel
Hair Toxic Panel
Urine Toxic Panel
Whole Blood Toxic Panel
Magnesium Erythrocytes
Hair
Tissue
Urine
Whole Blood
Erythrocyte Essential Panel
Hair Essential Panel
Urine Essential Panel
Manganese Erythrocytes
Hair
Plasma
Urine
Whole Blood
Erythrocyte Essential Panel
Hair Essential Panel
Plasma Essential Panel
Urine Essential Panel
Mercury Erythrocytes
Hair
Urine
Whole Blood
Erythrocyte Toxic Panel
Hair Toxic Panel
Urine Toxic Panel
Whole Blood Toxic Panel
Molybdenum Erythrocytes
Hair
Plasma
Urine
Whole Blood
Erythrocyte Essential Panel
Hair Essential Panel
Plasma Essential Panel
Urine Essential Panel
Nickel Erythrocytes
Hair
Plasma
Tissue
Urine
Whole Blood
Erythrocyte Toxic Panel
Hair Toxic Panel
Plasma Toxic Panel
Urine Toxic Panel
Whole Blood Toxic Panel
Niobium Erythrocytes
Whole Blood
Palladium Hair Hair Toxic Panel
Phosphorus Hair Hair Essential Panel
Potassium Hair
Urine
Hair Essential Panel
Urine Essential Panel
Selenium Erythrocytes
Hair
Plasma
Tissue
Urine
Whole Blood
Erythrocyte Essential Panel
Hair Essential Panel
Plasma Essential Panel
Urine Essential Panel
Silver Erythrocytes
Hair
Urine
Whole Blood
Hair Toxic Panel
Urine Toxic Panel
Sodium Hair
Urine
Hair Essential Panel
Urine Essential Panel
Strontium Hair
Urine
Hair Essential Panel
Urine Essential Panel
Sulfur Hair
Urine
Hair Essential Panel
Urine Essential Panel
Thallium Erythrocytes
Hair
Urine
Whole Blood
Erythrocyte Toxic Panel
Hair Toxic Panel
Urine Toxic Panel
Whole Blood Toxic Panel
Tin Hair
Urine
Hair Essential Panel
Urine Essential Panel
Titanium Erythrocytes
Hair
Plasma
Serum
Whole Blood
Hair Toxic Panel
Uranium Hair
Urine
Hair Toxic Panel
Urine Toxic Panel
Vanadium Erythrocytes
Hair
Plasma
Urine
Whole Blood
Erythrocyte Essential Panel
Hair Essential Panel
Plasma Essential Panel
Urine Essential Panel
Zinc Erythrocytes
Hair
Plasma
Tissue
Urine
Whole Blood
Erythrocyte Essential Panel
Hair Essential Panel
Plasma Essential Panel
Urine Essential Panel
Zinc-Protoprophyrin (ZPP) Whole Blood

Erythrocyte Essential Panel

Specimen Types: BD Royal Blue K2-EDTA Vacutainer.
Included Elements: Calcium
Chromium
Cobalt
Copper
Magnesium
Manganese
Molybdenum
Selenium
Vanadium
Zinc
Uses: To monitor steady-state levels of the nutritional elements.
Shipping Instructions: Click here for shipping instructions
Price: $60

Erythrocyte Toxic Panel

Specimen Types: BD Royal Blue K2-EDTA Vacutainer.
Included Elements: Arsenic
Cadmium
Lead
Mercury
Nickel
Thallium
Uses: To assess on-going or recent exposure to toxic elements.
Shipping Instructions: Click here for shipping instructions
Price: $60

Whole Blood Toxic Panel

Specimen Types: BD Royal Blue K2-EDTA Vacutainer.
Included Elements: Arsenic
Cadmium
Lead
Mercury
Nickel
Thallium
Uses: To assess on-going or recent exposure to toxic elements.
To evaluate patients with metallic orthopedic implants such as Aluminum, Chromium, Cobalt, Molybdenum, Nickel, Titanium and Vanadium.
Shipping Instructions: Click here for shipping instructions
Price: $60

Plasma Essential Panel

Specimen Types: BD Royal Blue K2-EDTA Vacutainer.
Included Elements: Chromium
Cobalt
Copper
Manganese
Molybdenum
Selenium
Vanadium
Zinc
Uses: To assess nutritional status.

Plasma levels of essential trace elements changes more quickly that erythrocyte levels, thus plasma levels are better indicators of recent intake or deficiency.
Shipping Instructions: Click here for shipping instructions
Price: $60

Plasma Toxic Panel

Specimen Types: BD Royal Blue K2-EDTA Vacutainer.
Included Elements: Aluminum
Nickel
Uses: To assess exposure to Nickel and Aluminum. Plasma Aluminum testing is routinely used for monitoring patients with renal failure on dialysis.
Shipping Instructions: Click here for shipping instructions
Price: $40

Urine Essential Panel

Specimen Types: 24-hour urine collected in an unused 24-hour urine container or random urine collected in an unused 100 ml container.
Included Elements: Boron
Calcium
Chromium
Cobalt
Copper
Iron
Magnesium
Manganese
Molybdenum
Potassium
Selenium
Sodium
Strontium
Sulfur
Tin
Vanadium
Zinc
Uses: To assess nutritional status.
Shipping Instructions: Click here for shipping instructions
Price: $60

Urine Toxic Panel

Specimen Types: 24-hour urine collected in an unused 24-hour urine container or random urine.
Included Elements: Aluminum
Antimony
Arsenic (Total)
Barium
Beryllium
Bismuth
Cadmium
Lead
Mercury
Nickel
Silver
Thallium
Uranium
Uses: To assess on-going occupational exposure.

To monitor recent exposure to toxic elements such as total and inorganic Arsenic, organic Lead, elemental Mercury and inorganic Mercury.
Shipping Instructions: Click here for shipping instructions
Price: $60

Hair Essential Panel

Specimen Types: Hair should be collected closet to the scalp and cut at the nape of the neck.
Included Elements: Boron
Calcium
Chromium
Cobalt
Copper
Iodine
Iron
Magnesium
Manganese
Molybdenum
Phosphorus
Potassium
Selenium
Sodium
Strontium
Sulfur
Tin
Vanadium
Zinc
Uses: To assess nutritional status.
Shipping Instructions: Click here for shipping instructions
Price: $60

Hair Toxic Panel

Specimen Types: Hair should be collected closest to the scalp and cut at the nape of the neck.
Included Elements: Aluminum
Antimony
Arsenic
Barium
Bismuth
Cadmium
Lead
Mercury
Nickel
Palladium
Silver
Thallium
Titanium
Uranium
Uses: To assess long term exposure to heavy metals such of inorganic Arsenic and organic Mercury.
Shipping Instructions: Click here for shipping instructions
Price: $60

Aluminum

TITLE Aluminum (Al)
SYNONYMS/FORMS Silver-grey metal, Aluminum oxide Al2O3, Bauxite AlO(OH), Gibbsite Al(OH)3
GENERAL INFORMATION: Aluminum is a non-essential metal. It has no known physiological function in the human body. Because of its atomic size and electric charge, it is sometimes a competitive inhibitor of several essential elements of similar characteristics, such as magnesium, calcium, and iron (1).

Because of the ubiquitous distribution of aluminum compounds, natural human exposure is unavoidable, and moderate amounts of the element enter the body constantly through inhalation of atmospheric dusts and ingestion of food and drink. Despite an oral intake ranging from 5 to 10 mg daily, <1% of aluminum is absorbed. After absorption, about 95% of aluminum becomes bound to transferrin and albumin. With normal renal function, aluminum is readily excreted in the urine. Tissue aluminum levels are very low. However, if the patient has renal dysfunction, or if aluminum bypasses the GI tract and enters the blood directly, e.g., by iv infusion, aluminum has the potential to accumulate in the body (1).

Aluminum is mainly deposited in the brain and bone. Increased tissue content of aluminum appears to be the major factor in the aetiology of dialysis dementia and dialysis osteodystrophy (2, 3).
SOURCES/ROUTE OF EXPOSURE Patients with chronic renal failure on long term haemodialysis treatment have high risk of aluminum overload. This increased tissue load of aluminum may be derived from the following sources:

1. Intestinal absorption may follow the administration of aluminum hydroxide gels used to control the high plasma phosphate levels in chronic renal failure. Because of the risk of aluminum toxicity, aluminum-containing phosphate binders have largely been abandoned.

2. Water used for haemodialysis may contain aluminum which will dialyse across the dialysis membrane and enter the blood.

The prevention of iatrogenic aluminum poisoning involves regular monitoring of (i) the aluminum content of the dialysate, (ii) the domestic tap water used to prepare the dialysate, and (iii) plasma aluminum levels in patients on long term haemodialysis treatment.

According to the guidelines provided by The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI), the dialysate concentration of aluminum should not exceed 370 nmol/L (10 µg/L) (4).

Other sources of aluminum include cookware, some baking powders, some fluoridated drinking water, antacid medications, and from occupational exposure.

TOXICITY Acute intoxication is extremely rare. Long-term exposure may increase chances of developing Alzheimer-like disease (3), kidney and liver problems, neuromuscular disorders, hemolysis, porphyria, anemia, and osteoporosis.

Symptoms and signs of aluminum toxicity are usually nonspecific. Some symptoms include flatulence, headaches, weak/aching muscles, bone pain, premature osteoporosis, multiple nonhealing fractures, proximal muscle weakness, and acute or subacute alteration in mental status, dry skin, cavities, excessive perspiration. These patients typically have some degree of renal disease.
MONITORING/CLINICAL INTERPRETATION Routine monitoring of plasma, urine and water (dialysis use) is used to assess the risk from chronic aluminum exposure in dialysis patients, occupational workers, and the general population.

NKF KDOQI guidelines for Chronic Kidney Disease:
  • Baseline levels of plasma aluminum should be <740 nmol/L (20 µg/L).
  • Plasma aluminum levels from 2220 nmol/L to 7400 nmol/L (60 to 200 µg/L) along with clinical signs and symptoms of aluminum toxicity, a deferoxamine (DFO) test should be performed.
  • A DFO test should not be performed if the plasma aluminum levels are > 7400 nmol/L (200 µg/L) to avoid DFO-induced neurotoxicity.
MATRIX CHOICE Plasma is the sample of choice for patients with chronic renal failure. Note: The BD K2-EDTA Royal Blue Vacutainer must be used. Serum samples are unacceptable for Aluminum analysis, due to high levels of contamination in the BD Non Additive Royal Blue Vacutainer.

Urine is preferred for occupational exposure. Hair is easily contaminated with aluminum from hair treatment, wash water if it contains a high content of aluminum and from dust.
TREATMENT Aluminum toxicity can be treated by chelating agent deferoximine (3).
REFERENCES 1. Toxicity, Aluminum http://emedicine.medscape.com/article/165315-overview
2. Toxicological Profile for Aluminum, ATSDR September 2008 http://www.atsdr.cdc.gov/toxprofiles/tp22.html
3. Am J Epidemiol 2000;152:50-66.
4. KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease, 2003 http://www.kidney.org/professionals/KDOQI/guidelines_bone/Guide11.htm

Antimony

TITLE Antimony (Sb)
SYNONYMS/FORMS Antimony metal, Antimony powder, Stibium
GENERAL INFORMATION: Antimony has no known function in the human body and has a low toxicity. The Greek derivative of the word antimony means "a metal rarely found alone." In nature, antimony has a strong affinity for sulphur, oxygen and some metallic elements, including lead, copper and silver. Antimony trioxide is one of the most important Sb compounds and used as a flame retardant in markets such as firefighters’ uniforms, children's clothing, toys, aircraft, and car seat covers (1).

The element antimony is found in the periodic table directly below arsenic, and shares many of the characteristics of arsenic, but is less toxic. It exerts its activity by binding to sulfhydryl (SH) groups on many enzymes. Unlike arsenic, antimony is not methylated in vivo, but is excreted in the bile and in the urine. In normal subjects, Sb is four-fold higher in erythrocytes than in plasma.
SOURCES/ROUTE OF EXPOSURE Natural sources of Sb are found in over 100 minerals. It is sometimes found in its native form, but most frequently found as sulfide stibnite (2).

Antimony trioxide is widely used in flame-retardants for textiles, plastics, building materials, adhesives and other materials. This use accounts for 60-65% of its consumption in the US. It is also used in battery components (lead antimony), paints, chemicals, ceramics, glass, friction bearings, ammunition and other applications. Antimony compounds are used as Antileishmaniasis agents such as sodium stibogluconate (3).

Exposure is most likely to occur in industrial settings. As it is associated in ores with arsenic, lead and copper, toxic exposure occurs in the mining and ore extraction industries.
TOXICITY Short-term Exposure
Skin and eye irritant: may develop "antimony spots" (a rash consisting of pustules around sweat and sebaceous glands) after repeated exposure (4).

Ingestion: abdominal pain, nausea, vomiting - in substantial ingestion, other features such as myocardial depression, vasodilation and fluid loss may cause shock with hypotension, electrolyte disturbances and acute renal failure. Cerebral oedema, coma and convulsions are possible. A fatality occurred following ingestion of a soluble antimony trioxide derivative (4).

Inhalation: Irritant to the respiratory tract and mucous membranes causing conjunctivitis, laryngitis, pharyngitis, tracheitis, rhinitis bronchitis and rarely non-cardiogenic pulmonary oedema (4).

Long-term Exposure
Chronic occupational inhalation may cause pneumoconiosis with cough, wheeze and diffuse, punctate opacities in the middle and lower lung zones (4).
MONITORING/CLINICAL INTERPRETATION Antimony containing drugs for treatment of leishmaniasis produced increased hair Sb levels in patients (5).
MATRIX CHOICE Erythrocytes and urine are used to monitor antimony in occupational workers or subjects suspected of toxic poisoning. Trivalent Sb is bound to RBC with lower amounts in plasma. Elevated levels in RBC indicate recent or chronic exposure.

Blood samples must be collected in a BD glass tube. Samples collected in plastic tubes yield elevated antimony results due to leaching from the tube walls.

Hair testing is not recommended for antimony analysis because external contamination can be caused by antimony-containing substances that stick to hair such as ash or hair treatment products.
TREATMENT Dermal: Wash well with soap and water. Steroids may be used for contact dermatitis.

Ingestion: Monitor urine and blood antimony. May require chelation with dimercaprol, DMSA or DMPS.

Inhalation: Remove from exposure, if significant respiratory symptoms occur, investigate toxicity with urine and blood antimony.
REFERENCES 1. http://minerals.usgs.gov/minerals/pubs/commodity/antimony/
2. http://www.corrosionsource.com/handbook/periodic/51.htm
3. De Wolff, FA. Antimony and Health. BMJ 1995;310:1216-1217.
4. http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Antimonytrioxide.pdf
5. Dorea, JG, Costa HM, Holzbecher J, Ryan DE, Marsden PD. Antimony accumulation in hair during treatment of leishmaniasis. Clin Chem 1987;33:2081-2082

Arsenic

TITLE Arsenic (As)
SYNONYMS/FORMS Arsen, Arsenic-75, Grey Arsenic, Metallic Arsenic
GENERAL INFORMATION: Arsenic (As) exists in nature in several forms: inorganic, organic compounds, and arsine gas. Inorganic As poisoning, usually occurring from occupational exposure, is more toxic than organic As. The most toxic form is Arsine gas (AsH3) that is much less common and the least toxic is Arsenobetaine as found in shellfish and fish (1, 2).

Over 90% of the ingested inorganic arsenic is absorbed from the GI tract. After absorption, arsenic is rapidly cleared from the blood (90% within 2 hours) and widely distributed to the tissues (2). It concentrates in hair, nails and skin within 2 weeks of exposure. Inorganic As is methylated to monomethylarsonic acid and dimethylarsinic acid (75%) for excretion into the urine. The half-life of inorganic As in humans is estimated to be up to 40 days. Organic arsenic compounds in seafood are also readily absorbed (75–85%) and excreted unchanged in urine within a few days. Total urine As is increased between 2 and 7 times from ingestion of seafood above those not consuming these products (1.2).
SOURCES/ROUTE OF EXPOSURE Arsenic is used in wood preservation, pesticides, hide tanning, glass production, and smelting of copper, lead and zinc. It may be present in seafood, tobacco, coal dust, and contaminated well water. Fish and shellfish contain predominately organic arsenic. The major form is arsenobetaine that is much less toxic (1).

Arsenic can be absorbed into the body through inhalation, ingestion and skin contact. Inhalation exposure to inorganic arsenic occurs mainly at the workplace. In general population, seafood ingestion represents the major source of arsenic exposure.

The normal body burden for As is 0.01 - 0.46 mg/kg. The WHO tolerable daily intake is 0.05 mg As/kg body weight from food and 50ug/L in drinking water (3).
TOXICITY Arsenic covalently binds to sulfhydryl groups (SH) in enzymes, inhibiting enzyme activity and uncoupling of oxidative phosphorylation to reduce high-energy phosphate in ATP.

After oral intake, explosive gastroenteritis develops in 30 minutes to 2 hours, giving rise to the GI erosion symptoms, such as violent abdominal pain, vomiting, and bloody diarrhea. Garlic-like smell to breath can occur from high As intake. Loss of fluids and electrolytes can result in shock and death.

Chronic signs of toxicity to As are insidious and difficult to diagnose. The most sensitive endpoint from arsenic exposure is dermal effects. Repeated or prolonged contact with skin may cause dermatitis, skin pigmentation, and white stria (Mees lines) in nails. Arsenic exposure can result in neuropathy and is carcinogenic to humans (IARC-Group 1). Arsenic found in tobacco smoke may be a causative factor in lung cancer (1, 3).
MONITORING/CLINICAL INTERPRETATION Total As in urine includes inorganic, mono- and di-methylated As, and trimethylated As such as arsenobetaine. Inorganic As includes mono- and di-methylated As which represents the group monitored for occupational exposure (American Conference of Governmental Industrial Hygienist, ACGIH), and the Biological Exposure Index (BEI).

Organic, trimethylated species such as arsenobetaine, arising from seafood contamination, are not measured in inorganic As testing.

BEI (4) for Inorganic As plus methylated metabolites in urine (end of work week)

35 ug/L (0.47 umol/L)
MATRIX CHOICE Due to the rapid clearance of As from blood, urine is the preferred specimen for analysis. Blood can be used if it is drawn within a couple of hours of acute exposure.

If urine or blood samples are not collected, then hair or nails can be used.

For more information please see our newsletter Which Test to Order for Arsenic.
TREATMENT Remove subject from As source. After acute ingestion, gastric decontamination is indicated with gastric lavage, not induced emesis. Supportive measures include isotonic IV fluids. Chelation may be required with agents such as British anti-Lewisite (BAL), Penicillamine, Dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonate (DMPS) (5, 6).

Precautions: Subjects must have adequate urine flow, and used with caution in those with renal insufficiency. Proper supplementation is required with nutritional mineral and trace elements to replace those lost by chelation (8).
REFERENCES 1. 1. ATSDR Toxicological profile for arsenic http://www.atsdr.cdc.gov/toxprofiles/tp2.pdf
2. Rev Environ Contam Toxicol 2001;169:165-214.
3. Arsenic: Public health information http://www.prn.usm.my/old_website/sites/arsenic.html
4. ACGHI (American Conference of Governmental Industrial Hygienists). Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, 2008
5. Human Exp Toxicol 1997;16:460-465.
6. Toxicity, Arsenic. eMedicine http://emedicine.medscape.com/article/812953-treatment
7. J Nutritional & Environ Med 2002;12:53-67

Arsenic (Total)

TITLE Arsenic (As)
SYNONYMS/FORMS Arsen, Arsenic-75, Grey Arsenic, Metallic Arsenic
GENERAL INFORMATION: Arsenic (As) exists in nature in several forms: inorganic, organic compounds, and arsine gas. Inorganic As poisoning, usually occurring from occupational exposure, is more toxic than organic As. The most toxic form is Arsine gas (AsH3) that is much less common and the least toxic is Arsenobetaine as found in shellfish and fish (1, 2).

Over 90% of the ingested inorganic arsenic is absorbed from the GI tract. After absorption, arsenic is rapidly cleared from the blood (90% within 2 hours) and widely distributed to the tissues (2). It concentrates in hair, nails and skin within 2 weeks of exposure. Inorganic As is methylated to monomethylarsonic acid and dimethylarsinic acid (75%) for excretion into the urine. The half-life of inorganic As in humans is estimated to be up to 40 days. Organic arsenic compounds in seafood are also readily absorbed (75–85%) and excreted unchanged in urine within a few days. Total urine As is increased between 2 and 7 times from ingestion of seafood above those not consuming these products (1.2).
SOURCES/ROUTE OF EXPOSURE Arsenic is used in wood preservation, pesticides, hide tanning, glass production, and smelting of copper, lead and zinc. It may be present in seafood, tobacco, coal dust, and contaminated well water. Fish and shellfish contain predominately organic arsenic. The major form is arsenobetaine that is much less toxic (1).

Arsenic can be absorbed into the body through inhalation, ingestion and skin contact. Inhalation exposure to inorganic arsenic occurs mainly at the workplace. In general population, seafood ingestion represents the major source of arsenic exposure.

The normal body burden for As is 0.01 - 0.46 mg/kg. The WHO tolerable daily intake is 0.05 mg As/kg body weight from food and 50ug/L in drinking water (3).
TOXICITY Arsenic covalently binds to sulfhydryl groups (SH) in enzymes, inhibiting enzyme activity and uncoupling of oxidative phosphorylation to reduce high-energy phosphate in ATP.

After oral intake, explosive gastroenteritis develops in 30 minutes to 2 hours, giving rise to the GI erosion symptoms, such as violent abdominal pain, vomiting, and bloody diarrhea. Garlic-like smell to breath can occur from high As intake. Loss of fluids and electrolytes can result in shock and death.

Chronic signs of toxicity to As are insidious and difficult to diagnose. The most sensitive endpoint from arsenic exposure is dermal effects. Repeated or prolonged contact with skin may cause dermatitis, skin pigmentation, and white stria (Mees lines) in nails. Arsenic exposure can result in neuropathy and is carcinogenic to humans (IARC-Group 1). Arsenic found in tobacco smoke may be a causative factor in lung cancer (1, 3).
MONITORING/CLINICAL INTERPRETATION Total As in urine includes inorganic, mono- and di-methylated As, and trimethylated As such as arsenobetaine. Inorganic As includes mono- and di-methylated As which represents the group monitored for occupational exposure (American Conference of Governmental Industrial Hygienist, ACGIH), and the Biological Exposure Index (BEI).

Organic, trimethylated species such as arsenobetaine, arising from seafood contamination, are not measured in inorganic As testing.

BEI (4) for Inorganic As plus methylated metabolites in urine (end of work week)

35 ug/L (0.47 umol/L)
MATRIX CHOICE Due to the rapid clearance of As from blood, urine is the preferred specimen for analysis. Blood can be used if it is drawn within a couple of hours of acute exposure.

If urine or blood samples are not collected, then hair or nails can be used.

For more information please see our newsletter Which Test to Order for Arsenic.
TREATMENT Remove subject from As source. After acute ingestion, gastric decontamination is indicated with gastric lavage, not induced emesis. Supportive measures include isotonic IV fluids. Chelation may be required with agents such as British anti-Lewisite (BAL), Penicillamine, Dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonate (DMPS) (5, 6).

Precautions: Subjects must have adequate urine flow, and used with caution in those with renal insufficiency. Proper supplementation is required with nutritional mineral and trace elements to replace those lost by chelation (8).
REFERENCES 1. 1. ATSDR Toxicological profile for arsenic http://www.atsdr.cdc.gov/toxprofiles/tp2.pdf
2. Rev Environ Contam Toxicol 2001;169:165-214.
3. Arsenic: Public health information http://www.prn.usm.my/old_website/sites/arsenic.html
4. ACGHI (American Conference of Governmental Industrial Hygienists). Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, 2008
5. Human Exp Toxicol 1997;16:460-465.
6. Toxicity, Arsenic. eMedicine http://emedicine.medscape.com/article/812953-treatment
7. J Nutritional & Environ Med 2002;12:53-67

Barium

TITLE Barium (Ba)
SYNONYMS/FORMS none
GENERAL INFORMATION: A barium compound such as barium sulfate that does not dissolve well in water is generally not harmful. It is used as a contrast media for x-ray examination of the gastrointestinal (GI) tract. As this compound is extremely insoluble, very little is absorbed in the GI tract in routine medical procedures. However, barium sulfate may potentially be toxic when it is introduced into the GI tract under conditions where there is colon cancer or perforations of the GI tract and barium is able to enter the bloodstream.

Water soluble barium compounds such as barium chloride, barium nitrate and barium hydroxide are well-known toxicants. Barium inhibits the passive efflux of potassium from extracellular to intracellular compartments, resulting in decreased blood levels of potassium (hypokalemia).
SOURCES/ROUTE OF EXPOSURE Occupational exposure primarily occurs in barium mining or processing industries which produce paint, bricks, tiles, glass, pesticides, fuel additives and rubber.

The general population is exposed to low levels of barium present in drinking water and food.
TOXICITY Ingestion of large amounts of soluble barium compounds may cause rapid onset of gastrointestinal symptoms (nausea, vomiting, abdominal cramps and watery diarrhea) and hypokalemia that can result in ventricular tachycardia, hypertension and/or hypotension, muscle weakness and paralysis.
MONITORING/CLINICAL INTERPRETATION none
MATRIX CHOICE Urine
TREATMENT none
REFERENCES 1. BARIUM AND BARIUM COMPOUNDS, https://www.atsdr.cdc.gov/ToxProfiles/tp24-c2.pdf
2. Medical Management Guidelines for barium (Elemental) and Selected barium Compounds. Agency for Toxic Substances and Disease Registry (ATSDR)

Beryllium

TITLE Beryllium
SYNONYMS/FORMS none
GENERAL INFORMATION: Beryllium can inhibit a variety of enzyme systems at high concentrations. This includes alkaline phosphatase, hexokinase, lactate dehydrogenase, and others. However the blockage of these enzyme systems has never been shown to play a role in human disease.

The major toxic effect of Beryllium in humans is thought to be due to the strongly acidic solution that is the result of dissolving Beryllium salts in water. These solutions will be toxic to tissues and are thought to be the cause of acute chemical pneumonitis that results from the inhalation of high concentrations of Beryllium. Beryllium appears to have a unique place in immunological reaction in that itis the smallest element known that can be involved in an immune response.
SOURCES/ROUTE OF EXPOSURE Beryllium is a metal widely used in industry because of its important properties including light weight, high melting point, high strength, and good electrical conductivity. The beryllium-containing materials that Canadian industry commonly use are the metal itself, beryllium oxide, and beryllium alloys. Industrial uses include the manufacture of thermal coating, nuclear reactors,rocket heat shields, brakes, x-ray tubes, and dental plates. The occupations listed below involve exposure to beryllium. (1)

Industrial processes that use beryllium or products that contain the metal include:
  • extraction of beryllium (smelting and refining)
  • beryllium metallurgy (production of beryllium metal and compounds)
  • precision machining
  • nuclear applications
  • microcircuits
  • stamping/cutting
  • die casting
  • stamping/cutting
  • plastic moulding
  • welding electrodes
  • handling/assembly
  • dental plates manufacturing
  • thermal castings
  • x-ray tube window manufacturing
  • guidance and navigation systems manufacturing
  • rocket parts and heat shields.
TOXICITY none
MONITORING/CLINICAL INTERPRETATION none
MATRIX CHOICE none
TREATMENT none
REFERENCES 1. ATSDR Toxicological profile for arsenic http://www.atsdr.cdc.gov/toxprofiles/tp2.pdf
2. Rev Environ Contam Toxicol 2001;169:165-214.
3. Arsenic: Public health information http://www.prn.usm.my/old_website/sites/arsenic.html
4. ACGHI (American Conference of Governmental Industrial Hygienists). Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, 2008
5. Human Exp Toxicol 1997;16:460-465.
6. Toxicity, Arsenic. eMedicine http://emedicine.medscape.com/article/812953-treatment
7. J Nutritional & Environ Med 2002;12:53-67

Bismuth

TITLE Bismuth (Bi)
SYNONYMS/FORMS none
GENERAL INFORMATION: Bismuth is a heavy metal that is not an essential element. It is mainly used in the production of alloys especially of those with low melting points. Bismuth is also used in paint pigments. Toxicity in industry has not been reported.

All lethal intoxications are attributed to the medical uses of bismuth compounds. These compounds include formulations which are used as antiseptics, astringents, and antacids and preparations for the treatment of duodenal ulcers and peptic diseases (Helicobacter pylori infections).

Most (90%) bismuth absorbed in the body is excreted in urine. The half-life in the body is approximately 20 days.
SOURCES/ROUTE OF EXPOSURE Medical uses of bismuth compounds are largely responsible for excessive exposure to bismuth. Some compounds include bismuth subsalicylate (Pepto-Bismol) to control GI upset, diarrhea and irritable bowel syndrome, and bismuth subgallate (Colo-fresh) to control fecal odours associated with colostomies, ileostomies and fecal incontinence.
TOXICITY Excessive use of bismuth compounds may result in renal damage, encephalopathy, peripheral neuropathy, joint pain and muscle spasm.
MONITORING/CLINICAL INTERPRETATION none
MATRIX CHOICE Levels in urine and hair have been used to monitor excessive exposure.
TREATMENT none
REFERENCES none

Boron

TITLE Boron (B)
SYNONYMS/FORMS None
GENERAL INFORMATION: Boron is a non-metallic mineral that is found in igneous rocks, sandstones, limestones, water and soil (2). At first, Boron was thought to be essential for plant function and by the 1980s, Boron was proven to be critical for animal growth (11). Only since 1990, has boron gained acceptance as an essential element for humans (2).

Boron plays a role in magnesium and calcium homeostasis; increased boron supplementation was shown to reduce the urinary excretion of both Mg and Ca (11). This is especially true for postmenopausal women where Boron supplementation will prevent calcium loss and bone demineralization, which means that it reduces the incidence of osteoporosis (11). Boron has numerous other health benefits: it helps prevent arthritis, aids in the production of estrogen, reduces severity of rheumatoid arthritis, ensures proper development and growth, alleviates heart disease and fungal infections (9). In addition, boron has a lot of involvement in glycogen synthesis in the liver so it is involved in carbohydrate and lipid metabolism. It also plays a role in steroid hormone synthesis such as estrogen, testosterone and vitamin D (2).
SOURCES/ROUTE OF EXPOSURE Boron is rapidly absorbed and quickly excreted in the urine.

The general population is exposed to Boron through fruit, vegetables, water, air and consumer products (1). Out of these, the primary exposure for most people is through food and water (6).

Occupational exposure to Boron occurs in various industries: borate mines, processing plants, glass manufacturing, cleaning products, fertilizers, pesticides and cosmetics (13). In the workplace, inhalation of borate dust is the major route of exposure, though dermal contact can also occur (1).
DEFICIENCY/TOXICITY Boron deficiency is not very common. It is most likely to be seen in individuals who do not consume a wholesome diet. There is currently no recommended daily intake value for Boron. Postmenopausal women are more at risk of boron deficiency and benefitting with boron supplementation since boron plays a role in bone metabolism, vitamin D and estrogen synthesis (8). The fact that boron supplementation improves magnesium and calcium retention in postmenopausal women suggests that many of these women may be boron deficient and supplementation would help to prevent osteoporosis (11).

When a large amount of boron-containing foods or water is consumed, symptoms of toxicity may appear. To reduce boron toxicity, the World Health Organization has banned the addition of boric acid as a preservative (2). Those that are at risk for toxicity also include people who work in occupational settings where boron is being manufactured (1).

Toxicity may also occur in those that overdose on Boron supplements. Many athletes may choose to take boron supplements as it increases testosterone levels and thus builds body muscle mass (5).
MONITORING/CLINICAL INTERPRETATION Symptoms of boron deficiency include an imbalance in sex hormones, anxiety, depression, cognitive difficulties, hyperthyroidism, arthritis, osteoporosis, pale skin, rash development and allergies (4). Those that present with these symptoms and have a history of a poor diet or have undergone menopause should be evaluated further for a boron deficiency.

Boron toxicity presents with non-specific symptoms such as nausea, vomiting, weakness, diarrhea and dermatitis (9). Neurotoxic effects can be seen with boron toxicity including dizziness, muscle tremors and incoordination (10). In some cases, skeletal abnormalities are also seen. Boron toxicity is more concerning in patients with kidney disease because usually, B is eliminated in the urine and when the kidney is unable to do so, boron accumulates in organs and tissues (9).

There is some evidence of reproductive toxicity in humans with chronic industrial exposure to boron, this is especially seen with men (3).

It is important to monitor for toxicity in those that are taking boron supplements, those that work in an environment that exposes them to boron and also in those that have recently consumed boron-rich products. Small doses of boron over time could also lead to toxicity so it is important to screen those at risk.
MATRIX CHOICE Hair levels are indicative of long-term ingestion of Boron. Ingested boron is quickly absorbed and can be deposited in the tissues (10). Elemental boron has low toxicity while borates and boranes have neurotoxic effects (10). However, Boron levels are sensitive to contamination from hair preparation products. Increased body levels of toxic elements are also shown to raise hair boron levels without there actually being an excess of boron levels itself (10).

Urinary boron excretion rate changes rapidly depending on the amount of boron ingested, which suggests that urine levels are a good marker since the kidney is the major site of homeostasis for boron (7). Therefore, urinary levels of boron are a strong indicator of boron intake (8). However, urine levels are not very effective for chronic exposure as they have no correlation in chronic cases with signs of toxicity (12).
TREATMENT Individuals that are Boron deficient can be treated by increasing intake of food products that contain boron such as fruits, vegetables and nuts. Supplements of Boron are also available, though care should be taken with this so as not to overdose.

Treatment for toxicity involves identifying the source of the toxicity and removing the patient from the source of exposure. Dietary supplements should be withdrawn if the patient is on boron supplementation (6). Boron toxicity can be avoided in most patients with a few precautions. In patients on oral contraceptives or hormone replacement therapy, boron should not be indicated as a supplement because it may lead to increased estrogen levels. It should also be avoided in patients with impaired renal function as it is primarily excreted via the kidneys. Boron overdose has rarely resulted in death so removing the source of the exposure and providing symptomatic treatment should aid with many of the symptoms of boron toxicity.
REFERENCES 1. Boron. Lenntech. http://www.lenntech.com/periodic/elements/b.htm
2. Boron - General Discussion http://www.dcnutrition.com/minerals/detail.cfm?RecordNumber=47
3. Boron as a Medicinal Ingredient in Oral Natural Health Products. Health Canada. http://www.hc-sc.gc.ca/dhp-mps/pubs/natur/boron-bore-eng.php#a14
4. Boron- Deficiency Symptoms, Health Benefits and Important Food Sources. Vigour Health and Sport Nutrition.http://www.vigour.co.uk/blog/?p=853
5. Boron. http://jctonic.com/include/minerals/boron.htm
6. Boron. IPCS INCHEM. http://www.inchem.org/documents/ehc/ehc/ehc204.htm#PartNumber:11
7. Boron. Life & Health Library. http://findarticles.com/p/articles/mi_m0FDN/is_4_9/ai_n9479460/
8. Boron. Vitamins & Herb University. http://www.vitaminherbuniversity.com/topic.asp?categoryid=2&topicid=1016#subcatid16
9. Health and Fitness News: Benefits of Boron. True Healthy Products. http://www.truehealthyproducts.com/tag/natural-sources-of-boron
10. Kaslow, J. E. Hair Analysis. http://www.drkaslow.com/html/hair_analysis.html
11. Nielsen, F. H. (1988). Boron - An Overlooked Element of Potential Nutritional Importance. Nutrition Today.
12. Robbins, W. A., Xun, L., Jia, J., Kennedy, N., Elashdoff, D. A., & Ping, L. (2010). Chronic Boron Exposure and Human Semen Parameters. Reproductive Toxicology, 29(2), 184-190. http://www.ncbi.nlm.nih.gov/pubmed/19962437
13. Summary Article from the Health Advisory for Boron. Environmental Protection Agency. Summary Article from the Health Advisory for Boron

Cadmium

TITLE Cadmium (Cd)
SYNONYMS/FORMS Silver-white metal, Salt forms as oxide, carbonate, chloride, sulfate and sulfide.
GENERAL INFORMATION: Cadmium has no essential biological function, and is extremely toxic to humans. Cadmium occurs naturally with zinc and is a byproduct in the smelting of zinc and some lead ores.

Cadmium is well absorbed by inhalation but poorly by ingestion. In the blood, ~90% of Cd binds to red blood cells and travels to the liver where it binds to metallothionein (MT). Cd-metallothionein complexes are then transported to the kidneys. In the kidneys, Cd is filtered at the glomerulus, but reabsorbed by the tubular cells. Since urine excretion is very limited, Cd accumulates in the kidneys, causing kidney damage. Cadmium is built up in the kidneys with a half-life of 15 to 30 years. Average Cd levels in the kidney are near zero at birth, and rise with age roughly linearly to a peak (around 40-50 ug/g wet weight) between 50 and 60, after which kidney concentration plateau or decline (1).
SOURCES/ROUTE OF EXPOSURE Cadmium is used in electroplating, in alloys, as a deoxidizer in nickel plating, in Cd-Ni batteries, as pigments in glazes and enamel paints, in plastics, and fertilizers. Occupational exposure may occur from the manufacture of these products and from smelting of lead, zinc and copper in mixed ores with Cd and welding.

In general population, the major source of Cd intake is food, including livers and kidneys of adult animals, saltwater fish, shellfish, and black tea. Cadmium is also present in cigarettes and cigarette fumes. Although there is less Cd in cigarettes than in food, Cd is absorbed much more efficiently by the lungs than the stomach. Smokers tend to have higher Cd concentrations than non-smokers.
TOXICITY Cadmium inactivates enzymes with sulphydryl groups, and also uncouples oxidative phosphorylation in mitochondria. The three main target organs for Cd are the lungs, kidneys and bone, although the kidney is generally considered the critical organ.

Acute inhalation may cause flu-like “fume fever”, pneumonitis, and pulmonary edema and even death after several hours.

Chronic exposure by inhalation or ingestion can result in a build-up of Cd in the kidneys and cause kidney diseases. Increased urinary excretion of the beta2-microglobulin or tubular proteinuria is the early sign of kidney damage. Chronic exposure also can cause pulmonary emphysema and bone diseases (osteomalcia and osteoporosis). The bone disease caused by Cd, also termed the itai-itai (“ouch-ouch”) disease was first observed in Japan where residents were exposed to Cd in rice crops irrigated with Cd-contaminated water. The most serious consequence of chronic Cd poisoning is cancer (lung and prostate) (2).
MONITORING/CLINICAL INTERPRETATION Biological Monitoring of Cadmium Workers

ACGIH Biological Exposure Index (3)
Cadmium in blood: 5 ug/L (44.5 nmol/L)
Cadmium in urine: 5 ug/g creatinine (5.0 umol/mol creatinine)

OSHA Threshold (4)
Cadmium in blood >5 & ≤10 ug/L (>44.5 & ≤ 89.0 nmol/L)
Cadmium in urine >3 & ≤ 7ug/g creatinine (>3.0 & ≤7.0 umol/mol)
Action: Medical removal is discretionary (If proteinuria also exists, removal is required)

Cadmium in blood >10 ug/L (>89.0 nmol/L)
Cadmium in urine >7 ug/g creatinine (>7.0 umol/mol)
Action: Medical removal is mandatory

Ontario Ministry of Labour Threshold(5, 6)
Cadmium in blood >11 ug/L (97.9 nmol/L): Suggest medical assessment
Cadmium in urine > 5 umol/mol: Suggest review of work practices
Cadmium in urine > 10 umol/mol: Suggest medical assessment
MATRIX CHOICE Urine sample shows both recent and past exposure and can be used in occupational workers (acute and chronic exposure).

Whole blood is the recommended sample for acute exposure.
TREATMENT There is no effective chelation treatment. It has been shown that Cd absorption is decreased by zinc, calcium, and selenium. Vitamin D has been used to treat cadmium induced bone disease.
REFERENCES

Calcium

TITLE Calcium (Ca)
SYNONYMS/FORMS none
GENERAL INFORMATION: Calcium is the most abundant mineral in the body. Approximately 99% of the total body calcium is located in the bones and teeth to provide structural support. The remaining 1% is present in the extracellular fluid and soft tissues and plays a role in blood clotting, signal transduction, muscle contraction, activation of enzyme reactions and hormone secretion. Reduced blood calcium levels can result in low tissue calcium presenting with mental changes, cardiac abnormalities and skeletal muscle cramping (tetany).
SOURCES/ROUTE OF EXPOSURE none
DEFICIENCY A deficiency of calcium can result from decreased intake, poor absorption, increased excretion or hormonal imbalance. Bones are affected with poor mineralization and result in rickets during the growing years in children, and osteomalacia in adults. If mobilization from the skeletal bone exceeds deposition, the bone becomes porous and develops osteoporosis. Osteoporosis in older women due to loss of total bone mass is caused by a multiple etiology of low calcium, estrogen and lack of exercise.
MONITORING/CLINICAL INTERPRETATION Hair calcium is determined as part of the panel of 38 elements available in hair. Reference values have been established (400-1500 ug/g) which show a wide range, in contrast to serum calcium which has a fairly narrow range. Calcium accumulation in hair can reflect its chronic mobilization from the bone with calcium loss. High concentrations of hair calcium can be seen in older women with indications of osteoporosis. Hair calcium concentrations are inversely correlated to that of the aorta. In adults, low concentrations of calcium in hair have been seen in cases of myocardial infarction, with increased aortic calcium levels. During the active growing years in children, there is a rapid uptake of calcium by osteocytes of the bone with lower hair calcium. This may not directly be related to dietary intake of calcium.
MATRIX CHOICE none
TREATMENT none
REFERENCES 1. none

Chromium

TITLE Chromium (Cr)
SYNONYMS/FORMS Metal Chromium (Cr), Compounds of Cr (III) and Cr (VI)
GENERAL INFORMATION: Chromium exists primarily in two valence states, trivalent Cr(III) and hexavalent Cr(VI). Cr(III) is an essential nutrient necessary for glucose and lipid metabolism. It enhances insulin activity by forming a complex with insulin (1). Cr(III) deficiency has been shown to lead to symptoms similar to that of diabetes with an impaired glucose tolerance. The estimated safe and adequate daily dietary intake (ESADDI) for 7 years-adults is 50 to 200 µg and for children 0-6 years is 10 to 40 µg (2). There is no evidence of detrimental effects of supplemental chromium at intakes up to 1000 ug/day (2).

Cr(VI) is a toxic form and certain Cr(VI) compounds produced industrially have been recognized as lung carcinogens (2). Cr(VI) is better absorbed than Cr(III). Once absorbed into blood, Cr(VI) enters the red blood cells where it is reduced to Cr(III) which binds to hemoglobin. After exposure, Cr concentrations in red blood cells remain elevated for weeks, while plasma concentrations return to baseline values within days. About 80% of absorbed Cr is excreted in urine and its excretion is rather rapid.
SOURCES/ROUTE OF EXPOSURE Principle industrial users of Cr compounds are the metallurgical processors of ferrochromium and stainless steel, electroplating, wood tanalising, pigment production and leather tanning. The major routes of occupational exposure are inhalation and skin contact of industrial hexavalent chromium (CrO3). Non-occupational exposure occurs mainly by ingestion of foods containing Cr(III) supplements and drinking well-water contaminated with chromium picolinate.
TOXICITY Most toxic effects occur in an occupational setting when workers are exposed to Cr(VI) compounds that can be absorbed by the lung and GI tract and to a less extent by skin contact. Symptoms include cough, chest tightness, wheeze, irritation of mucous membranes and skin, ulceration and nasal septum perforation and kidney damage. Cr(VI) is a known carcinogen implicated in lung cancer (4).
MONITORING/CLINICAL INTERPRETATION Chromium (III) is provided as a supplement in total parenteral nutrition (TPN). Patients on long-term TPN should be monitored regularly to avoid TPN overload.

Chromium concentrations in erythrocytes, whole blood, plasma and urine may be elevated in individuals with metallic prosthetic joints due to wear and corrosion of orthopaedic implants. The clinical significance of elevated metal ion levels has not been fully understood. However, evidence has shown that highly elevated blood levels are probably associated with high wear at the bearing, implant dysfunction, and adverse tissue reactions to metal debris.

Blood or Serum Chromium Levels
Cr (VI) enters red blood cells, but Cr (III) does not. Therefore, it is possible to distinguish sources and types of exposure, Cr (VI) versus other forms of Cr by measuring RBC versus serum Cr. This can beespecially helpful if urine Cr levels are elevated and one wants to know if this indicates a toxic Cr (VI) exposure or an essentially benign Cr (III) exposure (7). Chromium rapidly clears from the blood, and measurements relate only to recent exposure (7).

UK MHRA Threshold for individuals with metallic hip replacement (5)
Cobalt in blood: 7 ug/L (134.6 nmol/L)

ACGIH Biological Exposure Index (6)
Chromium in urine (end of shift at end of workweek): 25 ug/L (222.5 nmol/L)
MATRIX CHOICE For monitoring Cr levels following orthopedic arthroplasty, whole blood is the recommended sample because it does not need to be separated or transferred into a secondary tube after draw, and the primary collection tube can be sent directly for testing. This avoids possible sample contaminations from additional sample process steps.

Plasma and erythrocyte Cr concentrations can be used for nutritional assessment in patients on TPN. Plasma concentration reflects day-to-day Cr variations. The measurement of Cr in erythrocytes provides a better index of body content than the measurement of Cr in plasma.

Note: If serum is requested for analysis, the sample must be spun and separated from blood cells within 30 minutes. Because Cr concentration is much higher in erythrocytes than in serum, Cr will be released from erythrocytes resulting in falsely elevated levels in serum if not separated within 30 minutes or hemolysis occurs.

Random urine is recommended for occupational monitoring.

Hair can be used for chronic exposure.
TREATMENT No proven antidote is available for chromium poisoning.
Remove from exposure in industrial setting, and rely on the urinary and fecal clearance of the body burden.
REFERENCES 1. http://www.atsdr.cdc.gov/tfacts7.html
2. National Research Council: Recommended Dietary Allowance, 10th ed. Washington, DC. National Academy Press, 1989.
3. Anderson, R.A. Chromium as an Essential Nutrient, The Chromium File (1999) Issue No. 6 http://www.chromium-asoc.com/publications/crfile6sep99.htm
4. Aw, T-C. Biological Monitoring and Health Surveillance for Workers Exposed to Chromium Chemicals in Chromate Ore Processing, The Chromium File (2004) Issue No.10 http://www.chromium-asoc.com/publications/crfile10apr04.htm
5. Metal-on-metal hip replacement and hip resurfacing arthroplasty. What does the MHRA medical device alert mean? http://www.jisrf.org/pdf_files/MoM_BOA-BHS_AdvicetoSurgeons_1.pdf
6. ACGHI (American Conference of Governmental Industrial Hygienists). Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, 2008.
7. http://www.atsdr.cdc.gov/csem/csem.asp?csem=10&po=12

Cobalt

TITLE Cobalt (Co)
SYNONYMS/FORMS none
GENERAL INFORMATION: Cobalt is an essential element. The only known function is as an integral part of vitamin B12 (Cobalamin) which is essential for folate and fatty acid metabolism (1). Cobalt is obtained primarily as a by-product of the mining and processing of copper and nickel ores. Cobalt compounds are used mainly as oxidation catalysts in chemical reactions and pigments in the production of glass and ceramics.

The absorption rate by the lungs and GI tract is dependent on the solubility of Co compounds. About 30% of Co inhaled as Co oxide can be absorbed and the oral absorption rate varies from 5 to 45%. Cobalt is mainly excreted in urine; most being eliminated rapidly (a few days), with a small fraction eliminated slowly (a couple of years) (2).
SOURCES/ROUTE OF EXPOSURE Cobalt is normally associated with copper or nickel. The major sources of environmental cobalt include mining and smelting of cobalt-bearing ores, the use of cobalt-containing sludge or phosphate fertilizers on soil, and the disposal of cobalt-containing waste. Occupational exposure to Co occurs mainly by inhalation of fumes and dusts containing cobalt.

Dietary sources include meats, fish, cheese and brewer’s yeast and yeast extracts. Cobalt is also added in multivitamin pills.
TOXICITY In the past, Co salts used to be added to beer as foam stabilizers which lead to an epidemic of cardiomyopathy among heavy beer drinkers. Cobalt and alcohol may have an additive effect in reducing coronary blood flow and thus causing anoxia and damage to the heart muscle (1, 3).
MONITORING/CLINICAL INTERPRETATION Cobalt deficiency is not a major problem in humans as long as the body has sufficient amounts of vitamin B12 (1).

Individuals with metallic prostheses made from cobalt and chromium may have significantly elevated concentrations of cobalt and chromium in blood and urine due to wear and corrosion of orthopaedic implants. The clinical significance of elevated metal ion levels has not been fully understood. However, evidence has shown that highly elevated blood levels are probably associated with high wear at the bearing, implant dysfunction, and adverse tissue reactions to metal debris.

UK MHRA Threshold for individuals with metallic hip replacement (4) Cobalt in blood: 7 ug/L (118.8 nmol/L)

ACGIH Biological Exposure Index (5)
Cobalt in blood (end of shift at end of workweek): 1 ug/L ( 16.97 nmol/L)
Cobalt in urine (end of shift at end of workweek): 15 ug/L (254.5 nmol/L)
MATRIX CHOICE Analysis of Co in urine samples collected at the end of the work week is recommended for assessing exposure to soluble cobalt compounds.

For metal ion analysis following orthopedic arthroplasty, whole blood is the recommended sample because it does not need to be separated or transferred into a secondary tube after draw, and the primary collection tube can be sent directly for testing. This avoids possible sample contaminations from additional sample process steps.

If urine is to be tested, 24-hour urine is the preferred sample.
TREATMENT No proven antidote is available for chromium poisoning.
Remove from exposure in industrial setting, and rely on the urinary and fecal clearance of the body burden.
REFERENCES 1. http://www.food.gov.uk/multimedia/pdfs/evm_cobalt.pdf
2. Industrial Chemical Exposure. Guidelines for Biochemical Monitoring, Robert Lauwerys and Perrine Hoet, 3rd Edition, 2001
3. WHO International Programme on Chemical Safety (IPCS). Concise International Chemical Assessment Document 69. Cobalt and Inorganic Cobalt Compounds. 2006
4. Metal-on-metal hip replacement and hip resurfacing arthroplasty. What does the MHRA medical device alert mean? http://www.jisrf.org/pdf_files/MoM_BOA-BHS_AdvicetoSurgeons_1.pdf
5. ACGHI (American Conference of Governmental Industrial Hygienists). Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, 2008.

Copper

TITLE Copper(Cu)
SYNONYMS/FORMS none
GENERAL INFORMATION: Copper is an essential trace element that plays a key role in the formation of red blood cells and maintenance of normal brain function. It is a constituent of numerous metallo-enzymes required in cytochrome oxidation, free radical detoxification and catecholamine production, and in the crosslinking of collagen, elastin and keratin (1).

Copper is mainly absorbed through the GI tract. Copper can be a very toxic ion and must be transported efficiently after absorption. Approximately 90% plasma Cu is bound firmly to ceruloplasmin and the rest is bound loosely to albumin. The primary route of Cu excretion is through the bile, with a small proportion excreted in the urine (1).

In patients with Wilson's disease, biliary excretion of Cu and incorporation into ceru-loplasmin are both severely impaired. Copper accumulates in the liver, causing pro-gressive liver damage and subsequently overflows to the brain, causing involuntary movements and loss of co-ordination. Deposition of Cu in the cornea produces Kay-ser Fleischer rings (2, 3).

Menkes disease (kinky hair syndrome) is a rare Cu deficiency disease caused by a genetically determined X-chromosomal defect in Cu absorption from the intestinal mucosa to the blood. The defect prevents Cutransport across most other body cells, making correction by parenterally administered Cu impossible. It is character-ized by subnormal Cu levels in blood, liver and hair, progressive mental deterioration, hypothermia, defective keratinization of hair and degenerative changes in aortic elas-tin. Death usually occurs before 2 years of age (4).
SOURCES/ROUTE OF EXPOSURE Copper ores are mined, smelted and refined to produce many industrial and commercial products. Copper is widely used in cooking utensils and water distribution systems, as well as fertilizers, bactericides, fungicides and antifouling paints. Copper is also used in production of wood preservatives, electroplating, azo-dye manufacture, as a mordant for textile dyes, in petroleum refining and the manufacture of Cu compounds.

For non-occupationally exposed population the major route of exposure to Cu is oral. The average daily oral intakes of Cu (food plus drinking water) are between 1 and 2 mg. Women using Cu IUDs are exposed to only 80 µg or less of Cu per day from this source (5).
TOXICITY/DEFICIENCY The liver stores significant amounts of Cu, so Cu deficiency is unlikely in general population without a prolonged inadequate dietary intake. Severe diarrhea may lead to intestinal malabsorption of Cu. Copper deficiency is associated with microcytic hypochromic anaemia, neutropenia, and bone abnormalities.

Acute poisoning may cause nausea, vomiting, diarrhea, circulatory collapse, and in-tramuscular hemolysis. Chronic Cu poisoning can lead to liver diseases.
MONITORING/CLINICAL INTERPRETATION 1. Deficiency
2. Wilson’s disease and other hepato-biliary disorders
3. Toxicity
Copper levels are monitored in subjects on prolonged TPN to ensure adequate nutri-tional intake. Plasma Cu levels are useful measures of moderate to severe deficiency but less
sensitive measures of marginal deficiency.

In Wilson's disease, plasma levels of Cu and ceruloplasmin may be decreased, but the body's burden of Cu as found in the liver is elevated. Urine levels of Cu are usu-ally increased.

In cases of acute ingestion of Cu salts, such as Cu sulfate solutions, plasma Cu will be high and ceruloplasmin levels will be normal.

Ceruloplasmin is an acute phase reactant, increasing in response to infection, in-flammation, and trauma, so plasma Cu levels are expected to rise in these condi-tions. Steroid hormones stimulate ceruloplasmin synthesis. Plasma Cu levels can be two to three-fold higher in pregnancy and with the use of oral contraceptives because of estrogen action (6, 7). Raised Cu levels are also seen in lymphoma and Hodgkin's disease, where an early response to treatment can be judged by the fall in serum Cu to normal levels.
MATRIX CHOICE Plasma/serum: copper deficiency, Wilson’s disease and other hepato-biliary disor-ders, and toxicity.

Urine: 24-hour urine is required for investigating Wilson’s disease. Random urine is acceptable for investigating occupational exposure and acute poisoning.

Liver biopsy: Measuring copper in liver tissue has been used in the diagnosis of Wil-son's disease in which concentrations of over 250 µg/g dry weight are usually found. However, values below this level donot exclude the diagnosis and high levels may also be found in obstructive liver disease.
TREATMENT Toxicity: The mainstay of treatment for Wilson disease is removal of Cu from the body with chelating agents. Zinc, which can block Cu absorption in the stomach, has been used to treat patients with Wilson’s disease (2).
REFERENCES 1. http://www.inchem.org/documents/ehc/ehc/ehc200.htm
2. National Digestive Diseases Information Clearinghouse: Wilson’s Disease http://digestive.niddk.nih.gov/ddiseases/pubs/wilson/
3. Fatemi N and Sarkar B. Molecular mechanism of copper transport in Wilson disease. Environmental Health Perspectives. 110 (supplement) 5: 695-698, 2002
4. http://emedicine.medscape.com/article/1180460-overview
5. WHO-IPCS (International Programme on Chemical Safety Environmental Health Criteria. 2: Copper, World Health Organization, Geneva, 1998.
6. Scheinberg IH, et al. Concentration of copper and ceruloplasmin in maternal and infant plasma at delivery. J Clin Invest. 33:963, 1954.
7. Liukko P, et al. Trace elements during 2 years’ oral contraception with low-estrogen peparations. Gynecol Obstet Invest. 25:113-117,1988.

Copper Liver

TITLE Copper(Cu)
SYNONYMS/FORMS none
GENERAL INFORMATION: Copper is an essential trace element that plays a key role in the formation of red blood cells and maintenance of normal brain function. It is a constituent of numerous metallo-enzymes required in cytochrome oxidation, free radical detoxification and catecholamine production, and in the crosslinking of collagen, elastin and keratin (1).

Copper is mainly absorbed through the GI tract. Copper can be a very toxic ion and must be transported efficiently after absorption. Approximately 90% plasma Cu is bound firmly to ceruloplasmin and the rest is bound loosely to albumin. The primary route of Cu excretion is through the bile, with a small proportion excreted in the urine (1).

In patients with Wilson's disease, biliary excretion of Cu and incorporation into ceru-loplasmin are both severely impaired. Copper accumulates in the liver, causing pro-gressive liver damage and subsequently overflows to the brain, causing involuntary movements and loss of co-ordination. Deposition of Cu in the cornea produces Kay-ser Fleischer rings (2, 3).

Menkes disease (kinky hair syndrome) is a rare Cu deficiency disease caused by a genetically determined X-chromosomal defect in Cu absorption from the intestinal mucosa to the blood. The defect prevents Cutransport across most other body cells, making correction by parenterally administered Cu impossible. It is character-ized by subnormal Cu levels in blood, liver and hair, progressive mental deterioration, hypothermia, defective keratinization of hair and degenerative changes in aortic elas-tin. Death usually occurs before 2 years of age (4).
SOURCES/ROUTE OF EXPOSURE Copper ores are mined, smelted and refined to produce many industrial and commercial products. Copper is widely used in cooking utensils and water distribution systems, as well as fertilizers, bactericides, fungicides and antifouling paints. Copper is also used in production of wood preservatives, electroplating, azo-dye manufacture, as a mordant for textile dyes, in petroleum refining and the manufacture of Cu compounds.

For non-occupationally exposed population the major route of exposure to Cu is oral. The average daily oral intakes of Cu (food plus drinking water) are between 1 and 2 mg. Women using Cu IUDs are exposed to only 80 µg or less of Cu per day from this source (5).
TOXICITY/DEFICIENCY The liver stores significant amounts of Cu, so Cu deficiency is unlikely in general population without a prolonged inadequate dietary intake. Severe diarrhea may lead to intestinal malabsorption of Cu. Copper deficiency is associated with microcytic hypochromic anaemia, neutropenia, and bone abnormalities.

Acute poisoning may cause nausea, vomiting, diarrhea, circulatory collapse, and in-tramuscular hemolysis. Chronic Cu poisoning can lead to liver diseases.
MONITORING/CLINICAL INTERPRETATION 1. Deficiency
2. Wilson’s disease and other hepato-biliary disorders
3. Toxicity
Copper levels are monitored in subjects on prolonged TPN to ensure adequate nutri-tional intake. Plasma Cu levels are useful measures of moderate to severe deficiency but less
sensitive measures of marginal deficiency.

In Wilson's disease, plasma levels of Cu and ceruloplasmin may be decreased, but the body's burden of Cu as found in the liver is elevated. Urine levels of Cu are usu-ally increased.

In cases of acute ingestion of Cu salts, such as Cu sulfate solutions, plasma Cu will be high and ceruloplasmin levels will be normal.

Ceruloplasmin is an acute phase reactant, increasing in response to infection, in-flammation, and trauma, so plasma Cu levels are expected to rise in these condi-tions. Steroid hormones stimulate ceruloplasmin synthesis. Plasma Cu levels can be two to three-fold higher in pregnancy and with the use of oral contraceptives because of estrogen action (6, 7). Raised Cu levels are also seen in lymphoma and Hodgkin's disease, where an early response to treatment can be judged by the fall in serum Cu to normal levels.
MATRIX CHOICE Plasma/serum: copper deficiency, Wilson’s disease and other hepato-biliary disor-ders, and toxicity.

Urine: 24-hour urine is required for investigating Wilson’s disease. Random urine is acceptable for investigating occupational exposure and acute poisoning.

Liver biopsy: Measuring copper in liver tissue has been used in the diagnosis of Wil-son's disease in which concentrations of over 250 µg/g dry weight are usually found. However, values below this level donot exclude the diagnosis and high levels may also be found in obstructive liver disease.
TREATMENT Toxicity: The mainstay of treatment for Wilson disease is removal of Cu from the body with chelating agents. Zinc, which can block Cu absorption in the stomach, has been used to treat patients with Wilson’s disease (2).
REFERENCES 1. http://www.inchem.org/documents/ehc/ehc/ehc200.htm
2. National Digestive Diseases Information Clearinghouse: Wilson’s Disease http://digestive.niddk.nih.gov/ddiseases/pubs/wilson/
3. Fatemi N and Sarkar B. Molecular mechanism of copper transport in Wilson disease. Environmental Health Perspectives. 110 (supplement) 5: 695-698, 2002
4. http://emedicine.medscape.com/article/1180460-overview
5. WHO-IPCS (International Programme on Chemical Safety Environmental Health Criteria. 2: Copper, World Health Organization, Geneva, 1998.
6. Scheinberg IH, et al. Concentration of copper and ceruloplasmin in maternal and infant plasma at delivery. J Clin Invest. 33:963, 1954.
7. Liukko P, et al. Trace elements during 2 years’ oral contraception with low-estrogen peparations. Gynecol Obstet Invest. 25:113-117,1988.

Iodine

TITLE Iodine (I)
SYNONYMS/FORMS none
GENERAL INFORMATION: Iodine is an essential trace element that is required for the synthesis of thyroid hormones by the thyroid gland. Thyroid hormones (T3 and T4) stimulate many metabolic processes and increase the basal metabolic rate. These hormones are essential for normal growth and development. Iodine is especially important in pregnant women. In the early stages of pregnancy, the fetus is entirely dependent on the maternal thyroid hormones for normal development of the brain. Iodine deficiency during pregnancy can result in mental retardation and other developmental problems in fetus.

The recommended daily iodine intake is 90-120 ug for children (1-12 years) and 150 ug for adults. In pregnancy there is an increased requirement for iodine, and a daily intake of 200 μg is recommended (1).

Iodine is absorbed through the GI trace from food, water, or medication. Dietary iodine is converted to the iodide ion before absorption. Once absorbed, it enters the extracellular iodine pool. The thyroid gland extracts amount required for hormone synthesis and the kidney excretes excess iodide (approximately 90% of ingested iodine) into urine (2). Because urinary iodine excretion directly reflects dietary iodine intake, urine iodine analysis is the best test for biochemical assessment of iodine status. It is most commonly used to diagnose Iodine deficiency in a population. The test is also useful to monitor iodine levels in patients taking iodine-containing drugs such as Amiodarone, iodine supplements or radioiodine therapy.
SOURCES/ROUTE OF EXPOSURE Seaweed and marine fish are rich sources of iodine.
Dairy products, eggs, and meat are also rich in iodine.
Many multivitamin preparations contain 150 ug of iodine per tablet.
Iodized salt: In Canada, salt iodization is mandatory (1g of iodized salt contains about 77 ug of iodine).

Excess Iodine Intake:
Medication, such as Amiodaron containing 75 mg iodine per 200 mg capsule.
Iodine-containing dyes for radiological procedures.
TOXICITY Deficiency
Iodine deficiency can lead to enlargement of thyroid gland (known as a goiter) and impaired thyroid hormone synthesis. The thyroid gland enlarges to maximize the amount of iodine to be extracted from the blood, and if this problem is not corrected, a shortage of thyroid hormone in the body may lead to weakness, weight gain, cold intolerance, dry skin, constipation, and depression (3).

Iodine deficiency during pregnancy has been associated with miscarriages, stillbirth, preterm delivery, and mental retardation, short stature, and impaired hearing and speech in children (4).

Toxicity
Most people can tolerate fairly large amounts of iodine without problems. However, excess iodine intake in some people, especially those who were previously iodine deficient, may lead to hyperthyroidism (Jod-Basedow phenomenon). Paradoxically, rapid excess uptake of iodine may inhibit thyroid hormone synthesis, a condition known as “Wolff-Chaikoff effect”.

The upper limit of safe daily iodine intake is 1 mg for adults, and it is lower for children. (5).
MONITORING/CLINICAL INTERPRETATION Urinary iodine excretion can be used as an index of dietary iodine intake. Value <100 ug/day suggests dietary deficiency. Values >460 ug/day may indicate dietary excess, but more frequently suggest recent drug or contrast media exposure.

Patients exposed to large amounts of radiographic contrast media or iodine rich drug, such as Amiodarone need to have their iodine levels monitored.
MATRIX CHOICE The 24-hour urine collection is preferred. If a 24-hour urine collection is not practical, a random urine sample can be used instead. The result of random urine iodine is reported as a ratio of iodine to creatinine.

Plasma iodine includes free inorganic iodide and organic iodine bound to the thyroid hormones. Measurement of iodine in plasma was used in history for indirect assessment of the concentration of thyroid hormones. This test has been replaced by direct measurement of the thyroid hormones, TSH, T4 and T3.
TREATMENT Goiter due to iodine deficiency can be treated with iodine supplementation. Long term dietary supplementation of iodine includes iodized salt, iodine rich diet (saltwater fish, milk, and eggs) and iodine in multivitamins.
REFERENCES 1. WHO, UNICEF, ICCIDD. Assessment of iodine deficiency disorders and monitoring their elimination. A guide for program managers, 3rd ed. 2007 http://whqlibdoc.who.int/publications/2007/9789241595827_eng.pdf
2. Iodine. Vitamin and mineral requirements in human nutrition. 2nd ed, 1998. http://whqlibdoc.who.int/publications/2004/9241546123_chap16.pdf
3. Iodine deficiency. eMedicine. http://emedicine.medscape.com/article/122714-overview
4. Iodine deficiency. American Thyroid Association. http://www.thyroid.org/patients/patient_brochures/iodine_deficiency.html
5. Iodine and health. Eliminating iodine deficiency disorders safely through salt iodination. Geneva, World health Organization, 1994.
6. Hollowell JG et al. 1998 Iodine nutrition in the United Stages. Trends and public health implications: Iodine excretion data from national health and nutrition examination surveys I and III (1971-1974 and 1998-1994). J Clin Endocrinol Metab 83:3401-3408, 1998.

Inorganic Arsenic

TITLE Arsenic (As)
SYNONYMS/FORMS Arsen, Arsenic-75, Grey Arsenic, Metallic Arsenic
GENERAL INFORMATION: Arsenic (As) exists in nature in several forms: inorganic, organic compounds, and arsine gas. Inorganic As poisoning, usually occurring from occupational exposure, is more toxic than organic As. The most toxic form is Arsine gas (AsH3) that is much less common and the least toxic is Arsenobetaine as found in shellfish and fish (1, 2).

Over 90% of the ingested inorganic arsenic is absorbed from the GI tract. After absorption, arsenic is rapidly cleared from the blood (90% within 2 hours) and widely distributed to the tissues (2). It concentrates in hair, nails and skin within 2 weeks of exposure. Inorganic As is methylated to monomethylarsonic acid and dimethylarsinic acid (75%) for excretion into the urine. The half-life of inorganic As in humans is estimated to be up to 40 days. Organic arsenic compounds in seafood are also readily absorbed (75–85%) and excreted unchanged in urine within a few days. Total urine As is increased between 2 and 7 times from ingestion of seafood above those not consuming these products (1.2).
SOURCES/ROUTE OF EXPOSURE Arsenic is used in wood preservation, pesticides, hide tanning, glass production, and smelting of copper, lead and zinc. It may be present in seafood, tobacco, coal dust, and contaminated well water. Fish and shellfish contain predominately organic arsenic. The major form is arsenobetaine that is much less toxic (1).

Arsenic can be absorbed into the body through inhalation, ingestion and skin contact. Inhalation exposure to inorganic arsenic occurs mainly at the workplace. In general population, seafood ingestion represents the major source of arsenic exposure.

The normal body burden for As is 0.01 - 0.46 mg/kg. The WHO tolerable daily intake is 0.05 mg As/kg body weight from food and 50ug/L in drinking water (3).
TOXICITY Arsenic covalently binds to sulfhydryl groups (SH) in enzymes, inhibiting enzyme activity and uncoupling of oxidative phosphorylation to reduce high-energy phosphate in ATP.

After oral intake, explosive gastroenteritis develops in 30 minutes to 2 hours, giving rise to the GI erosion symptoms, such as violent abdominal pain, vomiting, and bloody diarrhea. Garlic-like smell to breath can occur from high As intake. Loss of fluids and electrolytes can result in shock and death.

Chronic signs of toxicity to As are insidious and difficult to diagnose. The most sensitive endpoint from arsenic exposure is dermal effects. Repeated or prolonged contact with skin may cause dermatitis, skin pigmentation, and white stria (Mees lines) in nails. Arsenic exposure can result in neuropathy and is carcinogenic to humans (IARC-Group 1). Arsenic found in tobacco smoke may be a causative factor in lung cancer (1, 3).
MONITORING/CLINICAL INTERPRETATION Total As in urine includes inorganic, mono- and di-methylated As, and trimethylated As such as arsenobetaine. Inorganic As includes mono- and di-methylated As which represents the group monitored for occupational exposure (American Conference of Governmental Industrial Hygienist, ACGIH), and the Biological Exposure Index (BEI).

Organic, trimethylated species such as arsenobetaine, arising from seafood contamination, are not measured in inorganic As testing.

BEI (4) for Inorganic As plus methylated metabolites in urine (end of work week)

35 ug/L (0.47 umol/L)
MATRIX CHOICE Due to the rapid clearance of As from blood, urine is the preferred specimen for analysis. Blood can be used if it is drawn within a couple of hours of acute exposure.

If urine or blood samples are not collected, then hair or nails can be used.

For more information please see our newsletter Which Test to Order for Arsenic.
TREATMENT Remove subject from As source. After acute ingestion, gastric decontamination is indicated with gastric lavage, not induced emesis. Supportive measures include isotonic IV fluids. Chelation may be required with agents such as British anti-Lewisite (BAL), Penicillamine, Dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonate (DMPS) (5, 6).

Precautions: Subjects must have adequate urine flow, and used with caution in those with renal insufficiency. Proper supplementation is required with nutritional mineral and trace elements to replace those lost by chelation (8).
REFERENCES 1. 1. ATSDR Toxicological profile for arsenic http://www.atsdr.cdc.gov/toxprofiles/tp2.pdf
2. Rev Environ Contam Toxicol 2001;169:165-214.
3. Arsenic: Public health information http://www.prn.usm.my/old_website/sites/arsenic.html
4. ACGHI (American Conference of Governmental Industrial Hygienists). Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, 2008
5. Human Exp Toxicol 1997;16:460-465.
6. Toxicity, Arsenic. eMedicine http://emedicine.medscape.com/article/812953-treatment
7. J Nutritional & Environ Med 2002;12:53-67

Iron

TITLE Iron (Fe)
SYNONYMS/FORMS Ferrum
GENERAL INFORMATION: Iron plays a key role in the human body. It is needed as the functional ion in the porphyrin ring of heme in hemoglobin, myoglobin, catalase, peroxidases and cytochromes. Iron interacts reversibly with oxygen, and in electron transfer reactions. Iron is a necessary trace element for nearly all organisms. Daily requirements for iron vary depending on sex, age and physiological status (i.e. the iron requirements are higher during adolescence, pregnancy, nursing or menstruation) (5).
SOURCES/ROUTE OF EXPOSURE Iron is found in many dietary foods such as meat, fish, poultry, beans, peas, lentils and some fruits. Food products (such as grain) are also fortified with iron in Canada (2). There are also many iron supplements available for purchase over the counter. Other sources of iron include drinking water, iron pipes and cookware (2).
TOXICITY/DEFICIENCY Iron deficiency is often seen in individuals and it can be due to increased iron needs or due to decreased iron intake or absorption. For example, with children, since they are rapidly growing, they are at risk of iron deficiency because they have increased iron requirements (5). Another common cause of iron deficiency is menstrual bleeding. There can also be a decrease in iron absorption and this can be either due to a lack of iron sources in the diet or due to low absorption. There are two forms of iron that are available in the diet: heme and non-heme (5). Heme iron is found mainly in meat, poultry and fish and while non-heme iron is found in vegetables and fruit. Non-heme iron is not absorbed as well as heme iron and a higher bioavailability of dietary non-heme iron can be achieved by increasing the intake of food compounds containing vitamin C (4). Additionally, iron deficiency anemia can be related to cofactor deficiencies, which include pyridoxine, vitamin B12, and folic acid.

Iron overload can occur from excess intake or from genetic causes; the commonest genetic reason being hemochromatosis. Since iron is rapidly absorbed in the gastrointestinal tract, most iron toxicity casesoccur due to ingestion. Iron overload is also associated with an elevated risk of several malignancies.
MONITORING/CLINICAL INTERPRETATION In children, iron deficiency is the most common nutritional deficiency (1). It is associated with adverse outcomes such as impaired psychomotor and mental development. It is recommended that all children at the age of 12 months get universally screened for iron deficiency (1). Additionally, children at high risk for iron deficiency anemia or children with other special health needs (such as chronic infection or gastrointestinal dysfunction) should undergo screening as well. In many clinical settings, a Complete Blood Count (CBC) is ordered for infants and children. Any hemoglobin value below 11 g/dL is abnormal. With regards to adults, any adult at risk of iron deficiency should be screened. Similarly, any adult or child with symptoms such as abdominal pain, vomiting, diarrhea, metabolic acidosis, hematemesis, melena should be screened for iron toxicity (1).

There are a number of ways to get a measure of iron stores in the body and below is a brief discussion of the different methods.

Serum iron ranges are very variable due to diurnal changes. A low result could indicate chronic disease whereas a high value may suggest iron overload (6).

Transferrin transports iron and a low transferrin value could be indicative of chronic disease, while a high result may suggest iron deficiency or pregnancy (6).

Transferrin saturation is an assessment of how much serum iron is bound to transferrin. A low percentage bound could be due to iron deficiency or chronic disease, while a high percentage may be due to iron overload or iron therapy (6).

Ferritin stores and releases iron in a controlled manner. A low ferritin result almost certainly points towards iron deficiency, but a high result could be due to a number of things including iron overload, liver disease and malignancies.
MATRIX CHOICE There are various methods of measuring the body’s iron status such as measuring transferrin saturation, transferrin and serum iron values. The gold standard of measuring the body’s iron status is to measure serum or plasma ferritin. However, ferritin might be falsely elevated as an acute-phase reactant (11).

Hair iron is not a good measure of the body’s iron status itself, however, low hair iron can be suggestive of lead exposure. There is also evidence that high levels of iron in the hair can be correlated to some cancers (3).

Measuring iron levels in liver tissue is extremely useful in aiding with the diagnosis of iron-overload diseases as the liver is the first organ to be affected. In hemachromatosis, a hepatic iron concentration > 10,000 mcg/g is diagnostic (8).

Iron elimination is extremely diurnal so random urine collections can be very misleading. A 24-hour sample can be useful for the diagnosis for a variety of disorders such as hemochromatosis and hemolytic anemia. With anemia, urinary excretion of iron will be less than normal and the opposite will be observed in patients with iron overload conditions (8).
TREATMENT For the treatment of iron deficiency, consider transfusion if there is severe anemia. Oral iron supplementation can be initiated and continued until iron stores are replenished and increasing intake of iron-rich foods is of benefit.

With regards to acute iron toxicity, many patients require fluid resuscitation since they have lost a lot of volume to vomiting and hemorrhage. A gastric lavage or medications such as deferoxamine (which enhances iron elimination in urine) may also be indicated (10).

Chelation is another treatment that can reduce the adverse effects of iron deposition in organs in patients with iron overload, especially in those subjects where phlebotomy cannot be used (7). Phlebotomy is not an option for patients who are transfusion-dependent such as those with thalassemia, sickle cell anemia or myelodysplastic syndrome (7).
REFERENCES 1. Children's Health. Mayo Clinic. http://www.mayoclinic.com/health/iron-deficiency/MY01654/
2. Food Sources of Iron. Dietitians of Canada. http://www.dietitians.ca/Nutrition-Resources-A-Z/Factsheets/Minerals/Food-Sources-of-Iron.aspx
3. Hall, A. Hair Test Interpretation: Finding Hidden Toxicities. http://www.noamalgam.com/hairtestbook.html
4. Hallberg, L., Brune, M., & Rossander, L. (1989). The role of vitamin C in iron absorption. Internation Journal for Vitamin and Nutrition Research, 103-8.
5. Iron and Iron Deficiency. Centers for Disease Control and Prevention. http://www.cdc.gov/nutrition/everyone/basics/vitamins/iron.html
6. Iron Deficiency: Investigations and Management. Guidelines and Protocols. bcguidelines.ca/pdf/iron_deficiency.pdf
7. Iron Toxicity: Onset and Emergency Treatment. EMS World. http://www.emsworld.com/article/10322675/iron-toxicity-onset-and-emergency-treatment
8. Iron, Random Urine. Mayo Medical Laboratories. http://www.mayomedicallaboratories.com/test-catalog/print/88970
9. Protective Foods. The Cancer Project. http://www.cancerproject.org/protective_foods/building_strength/iron.php
10. Reynolds, L. G. (1989). Diagnosis and management of acute iron poisoning. Bailleres Clinical Hematology, 2(2), 423-33. Diagnosis & Management of acute iron poisoning
11. Ward, S. Interpretation of Iron Studies. Interpretation of Iron studies: Dr Steven Ward

Iron Liver

TITLE Iron (Fe)
SYNONYMS/FORMS Ferrum
GENERAL INFORMATION: Iron plays a key role in the human body. It is needed as the functional ion in the porphyrin ring of heme in hemoglobin, myoglobin, catalase, peroxidases and cytochromes. Iron interacts reversibly with oxygen, and in electron transfer reactions. Iron is a necessary trace element for nearly all organisms. Daily requirements for iron vary depending on sex, age and physiological status (i.e. the iron requirements are higher during adolescence, pregnancy, nursing or menstruation) (5).
SOURCES/ROUTE OF EXPOSURE Iron is found in many dietary foods such as meat, fish, poultry, beans, peas, lentils and some fruits. Food products (such as grain) are also fortified with iron in Canada (2). There are also many iron supplements available for purchase over the counter. Other sources of iron include drinking water, iron pipes and cookware (2).
TOXICITY/DEFICIENCY Iron deficiency is often seen in individuals and it can be due to increased iron needs or due to decreased iron intake or absorption. For example, with children, since they are rapidly growing, they are at risk of iron deficiency because they have increased iron requirements (5). Another common cause of iron deficiency is menstrual bleeding. There can also be a decrease in iron absorption and this can be either due to a lack of iron sources in the diet or due to low absorption. There are two forms of iron that are available in the diet: heme and non-heme (5). Heme iron is found mainly in meat, poultry and fish and while non-heme iron is found in vegetables and fruit. Non-heme iron is not absorbed as well as heme iron and a higher bioavailability of dietary non-heme iron can be achieved by increasing the intake of food compounds containing vitamin C (4). Additionally, iron deficiency anemia can be related to cofactor deficiencies, which include pyridoxine, vitamin B12, and folic acid.

Iron overload can occur from excess intake or from genetic causes; the commonest genetic reason being hemochromatosis. Since iron is rapidly absorbed in the gastrointestinal tract, most iron toxicity casesoccur due to ingestion. Iron overload is also associated with an elevated risk of several malignancies.
MONITORING/CLINICAL INTERPRETATION In children, iron deficiency is the most common nutritional deficiency (1). It is associated with adverse outcomes such as impaired psychomotor and mental development. It is recommended that all children at the age of 12 months get universally screened for iron deficiency (1). Additionally, children at high risk for iron deficiency anemia or children with other special health needs (such as chronic infection or gastrointestinal dysfunction) should undergo screening as well. In many clinical settings, a Complete Blood Count (CBC) is ordered for infants and children. Any hemoglobin value below 11 g/dL is abnormal. With regards to adults, any adult at risk of iron deficiency should be screened. Similarly, any adult or child with symptoms such as abdominal pain, vomiting, diarrhea, metabolic acidosis, hematemesis, melena should be screened for iron toxicity (1).

There are a number of ways to get a measure of iron stores in the body and below is a brief discussion of the different methods.

Serum iron ranges are very variable due to diurnal changes. A low result could indicate chronic disease whereas a high value may suggest iron overload (6).

Transferrin transports iron and a low transferrin value could be indicative of chronic disease, while a high result may suggest iron deficiency or pregnancy (6).

Transferrin saturation is an assessment of how much serum iron is bound to transferrin. A low percentage bound could be due to iron deficiency or chronic disease, while a high percentage may be due to iron overload or iron therapy (6).

Ferritin stores and releases iron in a controlled manner. A low ferritin result almost certainly points towards iron deficiency, but a high result could be due to a number of things including iron overload, liver disease and malignancies.
MATRIX CHOICE There are various methods of measuring the body’s iron status such as measuring transferrin saturation, transferrin and serum iron values. The gold standard of measuring the body’s iron status is to measure serum or plasma ferritin. However, ferritin might be falsely elevated as an acute-phase reactant (11).

Hair iron is not a good measure of the body’s iron status itself, however, low hair iron can be suggestive of lead exposure. There is also evidence that high levels of iron in the hair can be correlated to some cancers (3).

Measuring iron levels in liver tissue is extremely useful in aiding with the diagnosis of iron-overload diseases as the liver is the first organ to be affected. In hemachromatosis, a hepatic iron concentration > 10,000 mcg/g is diagnostic (8).

Iron elimination is extremely diurnal so random urine collections can be very misleading. A 24-hour sample can be useful for the diagnosis for a variety of disorders such as hemochromatosis and hemolytic anemia. With anemia, urinary excretion of iron will be less than normal and the opposite will be observed in patients with iron overload conditions (8).
TREATMENT For the treatment of iron deficiency, consider transfusion if there is severe anemia. Oral iron supplementation can be initiated and continued until iron stores are replenished and increasing intake of iron-rich foods is of benefit.

With regards to acute iron toxicity, many patients require fluid resuscitation since they have lost a lot of volume to vomiting and hemorrhage. A gastric lavage or medications such as deferoxamine (which enhances iron elimination in urine) may also be indicated (10).

Chelation is another treatment that can reduce the adverse effects of iron deposition in organs in patients with iron overload, especially in those subjects where phlebotomy cannot be used (7). Phlebotomy is not an option for patients who are transfusion-dependent such as those with thalassemia, sickle cell anemia or myelodysplastic syndrome (7).
REFERENCES 1. Children's Health. Mayo Clinic. http://www.mayoclinic.com/health/iron-deficiency/MY01654/
2. Food Sources of Iron. Dietitians of Canada. http://www.dietitians.ca/Nutrition-Resources-A-Z/Factsheets/Minerals/Food-Sources-of-Iron.aspx
3. Hall, A. Hair Test Interpretation: Finding Hidden Toxicities. http://www.noamalgam.com/hairtestbook.html
4. Hallberg, L., Brune, M., & Rossander, L. (1989). The role of vitamin C in iron absorption. Internation Journal for Vitamin and Nutrition Research, 103-8.
5. Iron and Iron Deficiency. Centers for Disease Control and Prevention. http://www.cdc.gov/nutrition/everyone/basics/vitamins/iron.html
6. Iron Deficiency: Investigations and Management. Guidelines and Protocols. bcguidelines.ca/pdf/iron_deficiency.pdf
7. Iron Toxicity: Onset and Emergency Treatment. EMS World. http://www.emsworld.com/article/10322675/iron-toxicity-onset-and-emergency-treatment
8. Iron, Random Urine. Mayo Medical Laboratories. http://www.mayomedicallaboratories.com/test-catalog/print/88970
9. Protective Foods. The Cancer Project. http://www.cancerproject.org/protective_foods/building_strength/iron.php
10. Reynolds, L. G. (1989). Diagnosis and management of acute iron poisoning. Bailleres Clinical Hematology, 2(2), 423-33. Diagnosis & Management of acute iron poisoning
11. Ward, S. Interpretation of Iron Studies. Interpretation of Iron studies: Dr Steven Ward

Lead

TITLE Lead (Pb)
SYNONYMS/FORMS Plumbum, lead (IV) hydride
GENERAL INFORMATION: Lead poisoning is one of the most common environmental health problems today, especially in children. Lead can severely damage all parts of the body. The most sensitive organ is the central nervous system, particularly in children. Even short term exposure can cause developmental delays in children (1, 2).

Lead will affect many enzymes systems; those involving ligands with sulfhydryl groups are especially vulnerable. The best-known effect is inhibiting heme production and causing anemia (3). Lead also damages the GI trace, kidneys and the reproductive system. The effects are the same whether it is breathed or swallowed.

Lead is eliminated from the body mainly through the kidneys. Half-life in blood is 30 days, and in bone 20-30 years (3). Lead absorbed in childhood accumulates in bone. Years later, lead stored in bone may be released into blood during pregnancy. Lead can cross the placenta and affect the fetus.
SOURCES/ROUTE OF EXPOSURE Occupational Exposure:
Lead mining and refining, smelters, welders, glassmakers, scrap metal workers, lead battery manufacturing and recycling, plastic manufacturing, auto repair, and construction work. Lead workers can carry lead back home on hands, clothes and hair, exposing family members.

Non-occupational Exposure:
  • Drinking water, due to lead solder in water pipes
  • Paints, dust and soil
  • Plastic window blinds, ceramic ware, solder in tin cans
  • Food – plants that absorb lead from air
  • Asian or Hispanic folk remedies contain high concentration of lead
  • Hobbies such as pottery, stained glass, preparing lead shot or fishing sinkers
  • Houses built before 1978 may have lead-based paints, especially those built 1920 -1950.
TOXICITY Short-term Exposure:
Vomiting, diarrhea, convulsions, coma or even death. Severe cases of lead poisoning are rare in Canada.

Long-term Exposure:
Damage to the nervous system causing impaired mental function, anemia, loss of appetite, abdominal pain, constipation, fatigue, sleeplessness, irritability and headache. Continued excessive exposure, as in an industrial setting, can affect renal and reproductive systems.

No specific group-of symptoms exist. Consider lead poisoning whenever peculiar symptoms that do not match any one particular disease develop, especially in small children. These may include, irritability, excess lethargy, poor appetite, abdominal pain with or without vomiting (without diarrhea), and headaches.
MONITORING/CLINICAL INTERPRETATION Screening of Children
The CDC guidelines recommend universal screening for virtually all young children, maximizing screening of children at high-risk and reducing screening of children and low-risk (4). Children living in the old houses (built before 1950) are at high risk of lead exposure due to the lead paint and should be screened with a blood lead test.

No lead levels in children are deemed safe. In 1991 the CDC defined the blood lead level of 0.48 umol/L (10 ug/dL) was the threshold. However, accumulated evidence shows that blood lead levels greater than 0.12 umol/L (2.5 ug/dL) can affect a child’s cognitive skills (5,6). Recently, we established the pediatric reference range for blood lead as <0.10 umol/L (0-16 years old) and defined the alert value and action value as follows:

Whole Blood
  • Alert value for children: >0.12 umol/L
  • Action value for children: >0.48 umol/L
  • Action value for adults: >1.00 umol/L
Erythrocytes
  • Alert value for children: >0.26 umol/L
  • Action value for children: >1.26 umol/L
  • Action value for adults: >2.2 umol/L
Recommend actions to be taken according to Blood lead level (7)
Whole Blood Lead (umol/L) Action
0.30 - 0.50 Above average in Canadian population: take exposure history
0.50 - 0.75 Repeat blood test now and in 3-6 months; locate source to reduce exposure
>0.75 - 1.00 Refer patient to a pediatrician for lead poisoning assessment
>1.00 - 2.10 Refer patient to a pediatrician immediately. Chelation considered
>2.10 Urgent case management: hospital admission

Recommend actions to be taken according to Erythrocyte lead level
Erythrocyte Lead (umol/L) Action
0.66 - 1.10 Above average in Canadian population: take exposure history
1.10 - 1.65 Repeat blood test now and in 3-6 months; locate source to reduce exposure
>1.65 - 2.20 Refer patient to a pediatrician for lead poisoning assessment
>2.20 - 4.62 Refer patient to a pediatrician immediately. Chelation considered
>4.62 Urgent case management: hospital admission

Biological Monitoring of Lead Workers

Biological Exposure Index (8)
Lead in Blood: 30 ug/100 mL (1.45 umol/L)

The aim of blood lead monitoring of workers exposed to lead is to maintain a whole blood lead level below 1.5 µmol/L.
A pre-employment screen is recommended to exclude sources of lead other than occupational exposure.

The Occupational Safety and Health Administration (OSHA) has published standards for employees working in industry. Employees with whole blood lead >2.41 umol/L (50 ug/dL) averaged over six months must be removed from workplace exposure (9).
MATRIX CHOICE
  • Whole blood lead is the best screening and diagnostic test for lead poisoning. It is commonly used for industrial and environmental monitoring (for both acute and chronic exposure).
  • Erythrocyte lead is a very sensitive marker of lead exposure since over 93% of the lead is bound to hemoglobin in the blood.
  • Urine, random or 24-h, is commonly used for occupational monitoring.
  • Hair lead may be used for chronic exposure. However, it is difficult to distinguish whether the lead being measured is from endogenous or exogenous sources, such as from hair treatment products, strong alcohol intake, and tobacco smoke (10) or exposure from the workplace such as the plastics industry and plumbers working with lead solder.
TREATMENT 1. Remove from source of exposure.
2. Chelation therapy with ethylenediaminetetraacetic acid (EDTA).

Precautions: Chelation is not specific to lead and may reduce levels of other trace elements within the body.
REFERENCES 1. http://www.nlm.nih.gov/medlineplus/leadpoisoning.html
2. Effects of lead on human health. http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/environ/lead-plomb-eng.php
3. Toxicity, Lead. http://emedicine.medscape.com/article/815399-overview
4. Preventing lead poisoning in young children. Atlanta, GA: US Department of Health and Human Services, 1991.
5. Canfield RL, et al. N Eng J Med 2003;348:1517-1526.
6. Lanphear BP, et al. Public Health Report 2000;115:521529
7. Sanborn MD et al. CMAJ 2002; 166:1287-1292
8. ACGHI (American Conference of Governmental Industrial Hygienists). Threshold Limit Values for Chemical Substances andPhysical Agents & Biological Exposure Indices, 2008
9. OSHA Lead Standard - Requirements from the General Industry Standards Lead. http://www.osha.gov/SLTC/lead/standards.html
10. Strumylaite, L, et al.. Content of lead in human hair from people with various exposure levels in Lithuania. Int. J. Hyg. and Environ Health, 2004; 207:345-351

Magnesium

TITLE Magnesium (Mg)
SYNONYMS/FORMS None
GENERAL INFORMATION: Magnesium is a silvery-grey essential element that serves as a cofactor for over 300 cellular enzymes involving energy metabolism (3). Mg has a role in both protein and nucleic acid synthesis. In the body, it is the fourth most abundant cation overall, but in intracellular fluid, it is the second most common cation (3). With regards to body distribution, more than half of the body’s magnesium isfound in bone, 27% in muscle, 19% in soft tissue, 0.5% in erythrocytes and only 0.3% in serum (6). Magnesium has also shown to improve the outcome for a number of conditions including the following: asthma, depression, fibromyalgia, noise induced hearing loss, arrhythmia, heart failure, hypertension, migraines, osteoporosis, preeclampsia, premenstrual syndrome and restless leg syndrome (2).
SOURCES/ROUTE OF EXPOSURE Magnesium can either be inhaled or ingested. In nature, magnesium is found in many leafy foods such as whole grains, nuts, and green vegetables (2). Magnesium from dietary sources does not result in toxicity, however, pharmacological Mg supplements can cause toxicity (2). Magnesium is also added to certain medications such as laxatives. Another source of magnesium exposure for the general public is from drinking water, which contains Mg salts (4). Magnesium can also be found in the environment as discharge from industrial plants. Occupations that are at higher risk for magnesium exposure include those who work in mining and those that process or produce magnesium alloys, which are used for aircrafts, vehicles and machinery (4).
TOXICITY/DEFICIENCY Magnesium is absorbed in the gastrointestinal tract (mostly the small intestine) and excreted mainly via the kidneys (3). Magnesium deficiency could result from insufficient dietary intake or due to gastrointestinal or renal impairments (5). In terms of gastrointestinal causes, both diarrhea and vomiting can result in Mg losses (11). Medical conditions such as Crohn’s disease that impair absorption in the gastrointestinal tract also can result in a deficiency (5). Kidney disease can exacerbate magnesium losses in the urine so conditions such as diabetes can result in Mg deficiency as well. There are many drugs that can cause hypomagnesemia; some of these include proton pump inhibitors, diuretics, alcohol and antibiotics (5). Low potassium, calcium, parathyroid hormone levels may also be suggestive of an underlying magnesium deficiency (5).

Magnesium toxicity could occur through workplace exposure.

Another common cause of magnesium toxicity is due to renal failure since the kidney’s ability to filter the magnesium is impaired (10). Magnesium infusion can also result in magnesium toxicity and this canbe seen in women with pre-eclampsia where magnesium is infused to decrease neuromuscular excitability (6). Toxicity could also occur with patients who take Mg supplements or medications that contain magnesium (i.e. laxatives, antacids).
MONITORING/CLINICAL INTERPRETATION Normal values of Mg in the blood should be between 1.7 – 2.2 mg/dL (2). Magnesium deficiency is much more common in those that are admitted in the intensive care unit (6). It is important to monitor hospital inpatients for Mg deficiencies. Deficiency presents with symptoms such as nausea, vomiting, fatigue and weakness (5). As the deficiency gets worse, it can present with neuromuscular hyperactivity, psychiatric disturbances, calcium or potassium abnormalities and cardiac issues (6). Patients that complain of these symptoms should be screened for electrolyte imbalances. Specifically, patients who are diabetic, consume high levels of alcohol, have gastrointestinal or renal problems are more at risk for Mg deficiency and therefore should be monitored (5).

Patients at risk for occupational exposure or that have kidney failure should be monitored for Mg toxicity. Patients that take Mg supplements or medications such as laxatives or antacids should also be screened (10).

Magnesium toxicity can result by inhalation or ingestion. Inhalation of magnesium fumes can cause irritation and metal fume fever with symptoms such as fever, chills, nausea, vomiting, muscle pain and fatigue (4). Magnesium toxicity through ingestion can result in nausea, vomiting, flushing, muscle weakness and a reduction in the deep tendon reflexes. The cutaneous flushing is more commonly seen with a rapid infusion of Mg (6).
MATRIX CHOICE Serum magnesium level does not relate directly to body’s stores since only 0.3% of the body’s magnesium is located in the serum (6). The serum level has been shown to correlate well with bone stores of magnesium (3). For patients with chronic issues with their Mg concentrations, the serum concentration levels are not valuable (3). In patients with toxicity, monitoring physical signs of toxicity such as deep tendon reflexes can be more valuable than measuring serum levels (9).

Erythrocyte magnesium levels have been proven to be inversely related to hypertension, premenstrual syndrome and chronic fatigue syndrome, but the conclusion about whether or not they effectively measure the body’s magnesium stores are undetermined (3).

Urine magnesium levels could be helpful in determining deficiency, but it is important to collect a 24 hr urine sample due to circadian variability (6).

Hair analysis of magnesium could provide important information about the bioavailability of magnesium (12). Usually, hair magnesium levels are at approximately 60 parts per million, but at levels over 90 parts per million, the bioavailability of magnesium in the body is lessened (12). For example, in patients with fibromyalgia, they have high levels of magnesium levels in the hair, but benefit greatly from magnesium supplementation (8).
TREATMENT If the patient is magnesium deficient, usually Mg supplementation is a good treatment choice either orally or intravenously depending on the severity of the deficiency (1). If the Mg deficiency is mild, dietary changes can be adopted by the patient (1).

Treatment for overexposure to magnesium includes removing the source of exposure. If Mg is on the skin or in the eyes, wash the affected area with water and soap for 10-15 minutes (4).

When renal function is normal, removing the Mg therapy should be sufficient (7). If renal function is abnormal, consider hemodialysis to normalize Mg levels. Calcium gluconate can be administered to treat toxicity (7).
REFERENCES

Manganese

TITLE Manganese (Mn)
SYNONYMS/FORMS none
GENERAL INFORMATION: Manganese is an essential trace element, which plays an important role as a cofactor for many enzyme systems. At high levels, however, it is toxic to humans and can cause damage to the brain (7).

Human body contains about 10 mg of manganese, most of which is found in the bones, liver, kidney, and pancreas. The estimated safe and adequate daily dietary intake is 2-5 mg (7), However, manganese supplements up to 20 mg have been administered without adverse effects (5). Cationic manganese compounds are more toxic than anionic and manganese2+ is more toxic than manganese3+ (9). Under physiologic conditions, inorganic manganese exists in the oxidation states manganese2+, manganese3+ and manganese4+. Organic manganese usually exists in forms such as methylcyclopentadienyl manganese tricarbonyl (MMT). MMT is used as a gasoline additive (9).

Manganese toxicity is unlikely to happen due to diet. The most probable cause of toxicity is due to industrial exposure to high levels of manganese (8). In the occupational setting, inhalation of manganese fumes is the major route of absorption.

The GI absorption of manganese is low (3-5%). manganese and iron share the common absorption pathway, and in iron deficient diets more manganese is absorbed. On the other hand, excess manganese interferes with the absorption of dietary iron (7).

In blood, manganese is mainly present in red blood cells, bound to hemoglobin, in which the manganese concentration is about 25-fold higher than in serum. Through the blood stream, manganese is rapidly distributed to the tissues, particularly the liver. The half-life is ~30 hours with its removal from the body from 6 -10 days. The main route for excretion is through the bile to the feces with little excreted in the urine (7).
SOURCES/ROUTE OF EXPOSURE People who are most likely subjected to manganese toxicity are those who work in jobs that produce high levels of manganese fumes. Occupational exposure may occur in the following industries: mining and refining of manganese ore, iron and steel industries, arc welding, dry-cell battery manufacture, pulp/paper/newsprint mills, manufacturing of heating and commercial refrigeration equipment, pesticide handling (8).

High levels of manganese are also found in some foods, such as beets, pineapple, nuts, beans, whole grains, tea and cereals. Manganese may be added to nutritional supplements. Other sources of manganese include wood preservation, fertilizer and water (8).
TOXICITY Manganese deficiency is very rare in humans and only seen in those with extremely restricted diets. Manganese deficits in studies have been associated with a scaly dermatitis and dyslipidemia. In animals, manganese deficiencies are associated with poor growth, fertility and metabolism problems (7).

Short-term exposure to heated manganese fumes may cause irritation of the lungs and could lead to "metal fume fever" which results in fever, chills and aching that lasts up to 24-hours. In addition, manganese fume exposure could also cause a specific kind of pneumonia that causes shortness of breath, congestion in the chest and coughing. It does not respond to antibiotics (7).

Those who work with manganese on a daily basis are most at risk of manganese poisoning. Long-term overexposure to manganese can lead to a disease known as Manganism. Manganism presents with symptoms that are somewhat similar to Parkinson's disease. The symptoms include gait disturbances, postural instability, mask-like facial expression, tremor and psychiatric problems. The reason for this presentation could be because of the build-up of manganese in the basal ganglia (7). Exposure to air concentrations in excess of 5 mg manganese/m3 can cause this condition.

Another concerning source for manganese toxicity includes the possibility of toxicity from parenteral nutrition. This is true especially for those who are chronically reliant on parenteral nutrition. Very little manganese is absorbed from food; however, nearly all intravenously administered manganese is absorbed readily. Manganese is one of the trace elements that is added to parenteral nutrition solutions. It is especially worrisome for neonates who should not be receiving manganese levels greater than 1 mcg/kg/day. However, it is hard to maintain that level while ensuring that all other trace minerals are being received at target levels since there are only so many formulations available (1).
MONITORING/CLINICAL INTERPRETATION Patients should be monitored for hypermanganesmia if they receive total parenteral nutrition. Also, those that have a high risk of exposure to manganese occupationally should also be screened for toxicity.
MATRIX CHOICE Whole blood or erythrocytes is the recommended specimen for assessment of manganese status and long-term occupational exposure.

Avoid hemolysis with plasma collections.

Note: Concentrations of manganese are much higher in erythrocytes than in plasma or serum. The results in plasma or serum may be falsely elevated if not separated within 30 minutes and/or hemolysis is present.

Urine is NOT recommended for monitoring manganese exposure.

TREATMENT Presently, there are no curative treatments available for manganese toxicity. The neurological effects of toxicity are rarely reversible. Studies have successfully used calcium EDTA for the treatment of acute manganese poisoning (6). Treatment of chronic manganese toxicity involves removal of the patient from the high manganese environment, as well as lifelong doses of the drug L-dopa (6). Parkinson's-like symptoms have been treated with some success with Levadopa and other anti-Parkinson drugs.

Manganese chelation is not as easily managed as lead or mercury poisoning, as it has less of an affinity for the chelator compounds (6).
REFERENCES 1. Aschner, J. L., & Aschner, M. (2005). Nutritional aspects of manganese homeostasis. Molecular aspects of Medicine. http://www.ncbi.nlm.nih.gov/pubmed?term=16099026
2. Blaurock-Busch, E. The Clinical Effects of manganese http://www.tldp.com/issue/180/Clinical%20Effects%20of%20manganese.html
3. Manganese. Linus Pauling Institute. http://lpi.oregonstate.edu/infocenter/minerals/manganese/
4. Manganese and its Compounds. InChem. http://www.inchem.org/documents/cicads/cicads/cicad12
5. Manganese in Drinking Water. WHO Guidelines for Drinking Water Quality. http://www.who.int/water_sanitation_health/dwq/chemicals/manganese.pdf
6. Manganese Poisoning Treatment. Retrieved June 13, 2012, from http://www.manganese-wilsons-parkinsons-disease.com/manganese/manganese_poisoning_treatment.html
7. Manganese Toxicity. The Analyst. http://www.digitalnaturopath.com/cond/C686313.html
8. McMillan, D. E. (1999). A brief history of the neurobehavioral toxicity of manganese: some unanswered questions. Neurotoxicology, 20, 499-507. http://www.ncbi.nlm.nih.gov/pubmed?term=10385908
9. PDR Health.http://www.pdrhealth.com/drugs

Mercury

TITLE Mercury (Hg)
SYNONYMS/FORMS Quicksilver
GENERAL INFORMATION: Mercury exists in three forms: elemental, inorganic, and organic mercury. Each has its own toxicologic profile. Elemental or metallic mercury is a liquid at room temperature and vaporizes easily. The most dangerous route of exposure is inhalation of mercury vapour through the respiratory tract, where ~ 80 % of elemental mercury is absorbed into the blood, and then it readily crosses the blood-brain barrier. Liquid metallic mercury is poorly absorbed (<0.1% absorbed) when ingested (1). Inorganic mercury salts, such as mercurous chloride (calomel) and mercuric oxide, are not well absorbed through the GI tract (less than 10% absorbed). It is trapped mainly in the kidney and excreted through the urine. Organic mercury is most easily absorbed through the GI tract (~95% absorbed). As it is lipid soluble, it readily enters the brain, and can also cross the placenta. Organic mercury is eliminated primarily in the feces (2).

The half-life of elemental and inorganic mercury in the blood is 40–60 days, and the half-life of organic mercury in the blood is about 70 days (3).
SOURCES/ROUTE OF EXPOSURE Coals plants make up for most of the mercury in the atmosphere. From here, atmospheric mercury contaminates lakes, rivers, oceans and streams. Elemental Hg in these bodies of water is converted to organic Hg by bacteria and then can accumulate in the fatty tissues of fish, which makes them a large source of long-term organic mercury exposure (4).

Medical waste combustion is among the top sources of mercury. Various devices and products contain elemental mercury, such as thermometers, barometers, blood-pressure cuffs, fluorescent light bulbs, switches, and batteries. Some folk remedies also contain elemental or inorganic mercury. Dental amalgam is composed of 50% elemental mercury with silver. Very small amount of mercury is slowly released from the surface of the tooth fillings due to chewing or corrosion.
TOXICITY Elemental Mercury
The severity of elemental Hg vapour exposure depends on amount of mercury spilled, air temperature, air flow in the room, and the size of the person being exposed. Acute exposure to high concentrations of mercury vapor can damage respiratory system, causing chest pain, cough, dyspnea, and inflammation of lungs. In severe cases, respiratory distress, pulmonary edema, and pneumonia may occur. Long-term exposure to mercury vapour mainly affects the central nervous system (CNS). The symptoms include insomnia, weak appetite, tremors, and memory impairment and may be misdiagnosed as psychiatric disorders.

Inorganic Mercury
Although poorly absorbed by ingestion, if ingested, inorganic mercury salt is extremely caustic. Gastrointestinal ulceration and hemorrhage develop rapidly followed by circulatory collapse. After absorption, inorganic Hg is trapped mainly in the kidneys and can lead to severe kidney damage.

Organic Mercury
The primary target organ is the CNS, especially the brain. Long-term ingestion of methylmercury (e.g. through fish) can lead to personality changes (irritability, shyness, nervousness), loss of sensation, constricted visual field, deafness, muscle incoordination, and ataxia. Organic mercury can readily pass the placental barrier and adversely affect fetal development, leading to developmental problems such as delayed onset of walking and talking, cerebral palsy, altered muscle tone and deep tendon reflexes, and reduced neurological test scores (5, 6).
MONITORING/CLINICAL INTERPRETATION Elevated blood mercury levels suggest a recent exposure to mercury.

Biological Exposure Index (7)
Total inorganic Hg in blood: 15 ug/L (74.8 nmol/L)
Total inorganic Hg in urine: 35 ug/g creatinine (19.74 umol/mol creatinine)

Alert Value
Blood Hg ≥50 nmol/L or Erythrocyte Hg ≥110 nmol/L: suggests investigation of possible source of exposure (3). In general population, the primary source of exposure to mercury is fish consumption.

Action Value
Blood Hg ≥200 nmol/L or Erythrocyte Hg ≥440 nmol/L: suggests consultation with a clinical toxicologist for advice about clinical management, such as chelation therapy (3).
MATRIX CHOICE Blood samples are useful for acute and chronic exposure to mercury. In blood, organic Hg concentrates in erythrocytes and inorganic Hg concentrates in plasma. Whole blood mercury will measure the inorganic and organic mercury as total mercury.

Urine samples provide the best indicator of body burden from long-term exposure to metallic mercury vapor and inorganic mercury. Because organic mercury is excreted mainly in the feces rather than in the urine, urine test is not useful for assessing exposure to organic mercury.

Hair sample is useful only for exposures to methylmercury.

For more information, please see our newsletter Mercury testing and the alert value for whole blood mercury.
TREATMENT Chelating agents such as d-penicillamine, succimer, or dimercaptopropane sulfonate (DMPS) can be used for elemental and inorganic mercury toxicity, however efficacy is uncertain. There is no FDA approved chelator for treatment of organic mercury toxicity; however in severe cases of toxicity, the chelator shown to be most effective is succimer (6).
REFERENCES

Molybdenum

TITLE Molybdenum (Mo)
SYNONYMS/FORMS None
GENERAL INFORMATION: Molybdenum is a silvery-white metal that has many commercial uses. Most importantly, it is an essential nutrient for humans that is required for normal functioning (5). It is important in nitrogen metabolism and is a cofactor for three essential enzymes: sulfite oxidase, xanthine oxidase and aldhehyde oxidase (5). These enzymes play a role in the breakdown of nucleotides and partake in the metabolism of amino acids and drugs (10). Out of the three enzymes, sulfite oxidase deficiency has the most severe effects that can lead to neurological deficits and even result in early death (3). Molybdenum concentrations in the tissue are not very high; the highest concentrations are found in the liver, kidney, adrenal glands and bone (5). Likely, molybdenum also has antioxidant properties and has been associated with preventing anemia and cancers (5).
SOURCES/ROUTE OF EXPOSURE Molybdenum is readily absorbed in the gastrointestinal tract and excreted mostly in urine (11). Intake of airborne molybdenum is usually not of significance in people, but those that work in occupations that use molybdenum could be at increased risk of toxicity (6).

Primarily, Molybdenum enters the body through the diet. Food sources that have molybdenum include legumes, cereal products and leafy vegetables (3).

Commercially, molybdenum is used in many industries; it is used to manufacture metal alloys, spark plugs, chemical reagents in laboratories, lubricants and pigments (6). People that work in these occupations may be exposed to more molybdenum than the average individual.

Molybdenum is also present in varying amounts in water, depending on geographical location (6).
DEFICIENCY/TOXICITY Molybdenum deficiency is quite rare. It has been seen in those who are on total parenteral nutrition when molybdenum is not added to the formulation (10). There are also those who are born with very rare errors of metabolism that result in a molybdenum deficiency. There are two ways in which this can present; it can either be a molybdenum cofactor deficiency, which affects all three of the enzymes that molybdenum plays a role in as cofactor, or it can be an isolated sulfite oxidase deficiency, which only affects the functioning of sulfite oxidase (10).

Interestingly, copper and molybdenum have a well-established relationship. Elevated molybdenum levels result in a copper deficiency, while molybdenum deficiency results in copper toxicity (2). There also appears to be a relationship between molybdenum and other metals, but these are not well established.

Molybdenum toxicity can result from increased intake of molybdenum (over 10-15 mg/day). Those that were exposed to molybdenum over long periods of time in an occupational setting are also at risk of toxicity, though it has been determined that unlike other metals, a very large amount of Mo exposure is required to elicit toxic effects (10).
MONITORING/CLINICAL INTERPRETATION Patients on total parenteral nutrition should be monitored for molybdenum deficiency.
Signs of molybdenum deficiency include tachycardia, tachypnea, headache, night blindness and coma (10).

Inborn errors of metabolism where there is a cofactor deficiency are usually inherited in a recessive manner, so if there is a family history of these conditions, monitoring for neurological signs or symptoms in an infant is important as these neonates are at risk for an early death (5). Along with the deficiency, the metabolic conditions are also associated with low sulfate excretion and low uric acid concentrations (5).

In addition, patients with abnormalities of copper levels could also have underlying problems with molybdenum so it is imperative to monitor patients with conditions such as Wilson’s Disease, where copper accumulates in the body.

Toxicity studies of molybdenum in animals have demonstrated that after high levels of exposure to molybdenum, symptoms of diarrhea, growth retardation, infertility and gout could develop (1). In humans, it has been shown that those that take more than 10-15 mg/day of molybdenum are at increased risk for gout (3). Chronic exposure to molybdenum in the workplace can cause symptoms of fatigue, headaches and joint pain – if these symptoms are occurring in someone that may have occupational exposure to molybdenum, further investigations may be necessary (9).
MATRIX CHOICE Serum and urine levels are useful for monitoring molybdenum levels in the body. They can be of use for monitoring deficiencies including the cofactor deficiencies (7). However, molybdenum levels are also known to rise in patients with prosthetic joints.

Hair levels of molybdenum reflects ingestion and tissue levels, but not levels of molybdenum as a cofactor (4).
TREATMENT Molybdenum deficiency can be treated by ensuring adequate intake of molybdenum through the diet or with supplementation.

There are no successful treatments available for molybdenum cofactor deficiency.

Cases of acute toxicity in humans with molybdenum is extremely rare and unlikely. It may still important to address the issue of chronic toxicity especially in those who work in industries that manufacture with molybdenum. Removing the patient from the source of exposure is usually sufficient (3).
REFERENCES

Nickel

TITLE Nickel (Ni)
SYNONYMS/FORMS None
GENERAL INFORMATION: Elemental Nickel is a non-essential element. It plays an important role in catalyzing bacterial and plant enzymes, but its activity in humans is not as well defined (4). Nickel is very useful because it combines with other metals to form alloys and these alloys are used in many industries. They are also used to make coins and jewelry (7). Nickel is extremely useful for making stainless steel (6).

10% of women and 2% of men are highly sensitive to Ni. (8). The most common reaction of exposure to nickel containing alloys is a skin rash that is called nickel dermatitis. These reactions do not correlate to blood concentrations of nickel (4). However, the most serious health effects occur when nickel is inhaled, often in the form of nickel carbonyl (Ni(CO)4).

Nickel exists in our environment at 1000 times the concentration found in biological samples. It is very easy to contaminate samples, therefore, strict collection precautions must be observed while obtaining samples.

Average Ni intake for adults is estimated to be approximately 100 to 300 micrograms per day (µg/d) (3).
SOURCES/ROUTE OF EXPOSURE Nickel is absorbed by inhalation and ingestion; a very limited amount of nickel is absorbed via dermal exposure (5). Nickel is excreted primarily via the urine, but nickel that is unabsorbed by the gastrointestinal tract is excreted in the feces.

Nickel is found in naturally in many substances such as in air, water, vegetation, soil, volcanic and meteoric dust (5). In the general population, smoking and food sources are the largest sources of exposure to nickel (5). In food, nickel is found in shellfish, canned vegetables and fruits, cocoa, wheat products and various nuts (4).

Since nickel is used in many industries, occupational exposure is a concern. Workers who mine and refine ores, manufacture nickel containing products, manufacture products with stainless steel, electroplate and weld may be at risk for nickel exposure (6).

Higher levels of nickel have been reported in polluted areas, thus, living in more industrialized areas is a risk factor for nickel exposure (5).

People who own inexpensive jewelry, belts or wristwatches could be exposed to nickel through prolonged dermal contact with the skin (5).
TOXICITY The commonest adverse health effect of nickel is an allergic dermatitis because of a sensitivity reaction to nickel products that are in contact with the skin.

When nickel is inhaled, as nickel carbonyl, it binds avidly to hemoglobin with the resultant inability of hemoglobin to bind to oxygen, leading to pulmonary congestion. The affinity nickel carbonyl has for hemoglobin is higher than carbon monoxide. This is the most severe and serious form of nickel toxicity (5). Nickel carbonyl is found in industries that work with nickel and also in cigarette smoke (5).

Toxicity can also occur through the ingestion of nickel compounds accidently. Toxicity as a result of food ingestion is extremely rare (7).
MONITORING/CLINICAL INTERPRETATION Those who have allergic dermatitis in response to the nickel products have symptoms that include burning, itching, redness and bumps (7).

Inhalation of nickel can lead to very severe symptoms such as shortness of breath, cough, pulmonary edema. These can result from inhaling heated fumes of nickel and can occur with just one incident of exposure. Patients who may have a history of occupational exposure to nickel, with these symptoms, should be immediately monitored and treated. There may also be accompanying neurological symptoms. The pulmonary symptoms, in these cases, could resemble those of pneumonia (5). With more chronic inhalation of nickel, lung function can be adversely affected; patients can develop bronchitis, reduced lung function, scarring of lung tissue. Chronic exposure can also affect the heart, liver and kidney (7). It is extremely important to monitor workers who have contact with nickel for symptoms of nickel toxicity.

Acute ingestion of nickel is very rare, and include symptoms of nausea, vomiting, headache, cough and shortness of breath. There is no data on the effects of chronic ingestion of nickel (5).

It is extremely important to be aware of signs of cancer developing in patients exposed to nickel, especially those that are exposed in an occupational setting and also those that may smoke (7). Cancers ofthe lung, nasal sinus and throat have resulted in those that have inhaled dust containing nickel compounds (7). These products may also be damaging reproductive organs and developing fetuses (7).
MATRIX CHOICE For chronic occupational exposure, urine is the sample of choice. Urine is also the specimen of choice for acute inhalation of nickel carbonyl exposure (4). Hair analysis correlates with chronic exposures and ingestions of nickel (1).

Serum levels could reflect a recent exposure while erythrocytes may reflect a more extended exposure (4).
TREATMENT The first step of treatment would be to remove the patient from the source of exposure. Most mild cases resolve with conservative treatment. However, in more severe scenarios, such as those caused by inhalation of nickel, supplemental oxygen and hydrocortisone may be indicated to reduce pulmonary complications. Chelation therapy with oral or intravenous diethyldithiocarbamate can be used in patients who are in more serious conditions (2).
REFERENCES

Palladium

TITLE Palladium (Pd)
SYNONYMS/FORMS none
GENERAL INFORMATION: Palladium is a heavy metal which has low toxicity. It occurs together with other platinum group metals (PGMs) at very low concentrations (<1 μg/kg) in the Earth’s crust. Palladium and its alloys are mainly used in automotive emission control catalysts. It is also used in electronics, jewelry and dental appliances.

For use in dentistry, palladium is alloyed with mercury, silver, gold, and copper. Metal ions such as mercury and palladium are continuously released and accumulated in various organs which may or may not be sufficient to pose a significant health risk. In Switzerland, palladium containing dental alloys have been banned. In Germany, dentists have been advised not to use palladium-copper alloys.

Due to the low dissolution rate of palladium ions, the risk of using palladium in dental alloys appears to be extremely low. Reported reactions to palladium, including sensitivity to contact with palladium in dental and jewelry alloys, are very infrequent, palladium containing dental alloys continue to be employed.
SOURCES/ROUTE OF EXPOSURE Most occupational exposures occur during palladium refining and catalyst manufacture. The general population may come into contact with palladium through dental alloys, jewelry and emissions from automobile catalytic converters.
TOXICITY Laboratory tests have shown the following toxic effects:
  • Allergic reactions in people with nickel allergy
  • Inhibition of enzyme activity
  • Disturbance of collage synthesis
  • Damage of DNA
MONITORING/CLINICAL INTERPRETATION A major health concern is allergic reactions to palladium in susceptible individuals. People with a known nickel allergy may be especially susceptible.
MATRIX CHOICE Hair analysis can be used to monitor exposure to palladium.
TREATMENT none
REFERENCES 1. Melber C et al. Environmental Health Criteria 226: palladium. 2001 Germany.
2. Immunotoxicology of metals. Zur Deutshcen Auszahe, 1996
3. Schedle A1 et al. Response of L-929 fibroblasts, human gingival fibroblasts, and human tissue mast cells to various metal cations. J Dent Res 1995;74:1513-1520.
4. Liu TZ et al. Palladium and platinum exacerbates hydroxyl radical mediated DNA damage. Free Radic Biol Med 1997;23:155-161.
5. Wataha JC and Hanks CT. Biological effects of palladium and risk of using palladium in dental casting alloys. J. Oral Rehabil 1996, 23:309-320.
6. Johnson DE, et al. Levels of platinum, palladium, and lead in populations of Southern California. Environ Health Perspect. 1975,12:27-33.

Phosphorus

TITLE Phosphorus (P)
SYNONYMS/FORMS none
GENERAL INFORMATION: Phosphorus is the second most abundant mineral in the body. It is essential for normal bone and tooth formation and plays an important role during skeletal development. About 85% of phosphorus in the human body is present in the bone and the remaining part is in the extracellular fluid or in nuclear acids, phospholipids, phosphoproteins and high energy compounds. It is an essential component in most of the energy producing reactions in the cells
SOURCES/ROUTE OF EXPOSURE Major dietary sources of phosphorus are protein-rich foods and cereal grains.
TOXICITY/DEFICIENCY Phosphorus deficiency may occur in patients receiving long term total parenteral nutrition (TPN) not supplemented with phosphorus and in patients with keto-acidosis treatment with insulin not supplemented with phosphorus. Phosphorus deficiency may also occur in patients taking large amounts of aluminum-containing antacids, because high intake of aluminum impairs phosphate absorption.
MONITORING/CLINICAL INTERPRETATION Phosphorus depletion results in failure of muscle contractility, impaired oxygen delivery, muscle weakness and heart failure.
MATRIX CHOICE Hair
TREATMENT none
REFERENCES none

Potassium

TITLE Potassium (K)
SYNONYMS/FORMS none
GENERAL INFORMATION: Potassium is the major intracellular ion. The total body potassium of an adult is approximately 3500 mmol (40-60 mmol/kg) of which only 2% is present in the extracellular fluid. Its concentrations in tissue cells and in erythrocytes are 150 mmol/L and 105 mmol/L respectively. The concentration in plasma is 3.5-4.5 mmol/L which is a relatively good indicator of the total body potassium with a few exceptions. Because plasma concentrations of potassium are maintained at the expense of the intracellular supply, plasma potassium concentrations can be normal and belie a total body deficit of up to 200 mmol.

Cellular uptake of potassium is stimulated by insulin. A fall in plasma potassium occurs following insulin therapy. There is a relationship between plasma concentrations of potassium and hydrogen. In metabolic acidosis, intracellular potassium ions move to plasma in exchange for hydrogen ions, leading to hyperkalemia. The opposite can occur in metabolic alkalosis. Generally, acidosis is associated with hyperkalemia while alkalosis with hypokalemia.

The main functions of potassium include regulation of neuromuscular excitability, maintenance of osmotic pressure, adrenal and kidney function, and protein synthesis. Hyperkalemia causes mental confusion, muscle weakness and cardiac arrest. The causes of hyperkalemia include renal failure, Addison’s disease, acidosis and potassium release from damaged tissues as occurs in rhabdomyolysis, trauma and malignancy. Hypokalemia causes severe muscle weakness, cardiac arrhythmias and mental confusion. The causes of hypokalemia include gastrointestinal loss due to vomiting, diarrhea or a surgical fistula; renal loss due to kidney diseases, diuretic therapy or increased aldosterone production; and alkalosis.
SOURCES/ROUTE OF EXPOSURE none
TOXICITY none
MONITORING/CLINICAL INTERPRETATION In hair analysis, a significant increase has been related to patients with acute celiac disease and cystic fibrosis, and is decreased after prolonged alcohol abuse.
MATRIX CHOICE Erythrocyte potassium is a more useful index of nutritional and tissue content than plasma measurement.
TREATMENT none
REFERENCES none

Selenium

TITLE Selenium (Se)
SYNONYMS/FORMS None
GENERAL INFORMATION: Selenium is a non-metallic element, naturally occurring in the earth's crust at concentrations of approximately 0.09 mg/kg (1). Se is present in the environment in elemental form, or in its inorganic forms, which are selenide (Se2-), selenate (SeO42-), or selenite (SeO32-). The most absorbable organic forms of Se are selenomethionine and selenocystiene. (9)

Selenium is an element that is essential nutritionally and the recommended daily intake of Se is 1 mg/kg of body weight per day. There is a small margin of safety between deficient levels and toxic levels of Se (8). Se incorporated into proteins to make selenoproteins, which are essential antioxidant enzymes (5). Se plays an important role in immune function and thyroid function; since it is an antioxidant, it helps prevent damage to cells caused by free radicals. Free radicals play a role in the development of various chronic conditions such as heart disease and cancer (5), which is why the antioxidant properties of Se are important. With regards to its antioxidant properties, Selenium is involved with the glutathione-peroxidase antioxidant system and the effectiveness of selenium can be increased by intake of vitamin E and other antioxidant nutrients that are involved in glutathione-peroxidase function. Se function is decreased with high doses of vitamin C.
SOURCES/ROUTE OF EXPOSURE Most Canadians are exposed to Se compounds from the air, drinking water, soil, and mostly from food - more than 98% of daily Se intake is from food (8). Plants are the major source of selenium from dietary sources and the amount of selenium varies depending on the selenium content of the soil where the plants were grown (5). Meats, breads and nuts are also a source of selenium (5).

Selenium is also used in various industries: electronics, glass, pigments, paints, rubber and in the preparation of anti-dandruff shampoos (2).
TOXICITY/DEFICIENCY Selenium is absorbed mainly via the gastrointestinal tract, mostly in the duodenum, and is excreted in both the urine and feces (4).

Selenium deficiency is quite rare in Canada, and it is more prevalent in locations where Se levels in soil are quite low such as China. There are certain diseases are also associated with Se deficiencies: Keshan Disease, Kashin-Beck Disease and Myxedematous Endemic Cretinism. Selenium deficiency is also noted in people who rely on total parenteral nutrition because Se may not be part of their TPN feed (5). Any gastrointestinal problem that prevents normal absorption of Se can also result in deficiency (Se).

Selenium toxicity can occur due to inhalation or ingestion. Toxicity could occur due to occupational exposure, but it is mostly well controlled in industrial settings (7). Intoxication can also occur by ingesting excessive amounts of Se-rich foods or due to Se supplement overdose. The use of selenium containing shampoos has also been shown to cause toxicity, but this is exceedingly rare (7). Chronic exposure could occur in areas where there is a high amount of Se in the soils (7).
MONITORING/CLINICAL INTERPRETATION Common signs of Selenium deficiency include fatigue, hypothyroidism, reproductive disorders and muscle weakness. Se deficiency can also be noted in those with acute illness so it is important to monitor Se levels in people presenting with any acute illness. In addition, people on prolonged TPN nutrition must be monitored for Se deficiency and also must receive Se supplementation. People from geographical areas that have historically been known to have low levels of Se in their soil, such as China, should also be monitored for Se deficiency.

Selenium toxicity presents with symptoms such as discolouration of skin, brittle nails, gastrointestinal disorders, decay of teeth, hair loss. With more severe intoxication, more neurological symptoms suchas peripheral anesthesia are present (7). A very characteristic finding in Se toxicity, especially in chronic cases, is a garlicky odour of the breath (7). Overall, toxicity is quite rare and has been seenin relation more often due to manufacturing error that resulted in inaccurately high doses of Se in supplements and also due to industrial accidents (5). Therefore, it may be most important to monitor those who may have been exposed to selenium in an occupational setting and those that take Se supplements.
MATRIX CHOICE To measure Selenium levels, urine, plasma and blood concentrations of Se have been shown to be reliable measures (7). Measurement of Se erythrocyte levels are not as useful for indication of excessive Se exposure (7). Hair Selenium is a good method to monitor occupational exposure, especially in cases of chronic exposure (6).

Also, Selenium is a negative acute phase reactant and concomitant measurement of C-reactive protein may be useful in some circumstances as an aid to interpreting low Se concentrations.
TREATMENT Treatment for Se deficiency involves ensuring that the patient receives the daily recommended intake levels of Se. If the patient is on TPN, it is important to ensure that they are receiving Se as part of the preparation.

There is no specific treatment for selenium toxicity and treatment involves removing the patient from the excess source of Selenium and treating symptoms, when possible. Oftentimes, symptoms of toxicity such as discolouration of skin, brittle nails and hair loss reverse once the source of exposure is removed (3).
REFERENCES 1. Environmental and Workplace Health. (n.d.). Retrieved June 21, 2012, from http://www.hc-sc.gc.ca/ewh-semt/pubs/eval/environ_assess-eval/index-eng.php
2. Selenium Compounds. (n.d.). Air Toxics Website. Retrieved June 21, 2012, from http://www.epa.gov/ttn/atw/hlthef/selenium.html
3. Selenium FAQs. (n.d.). Virigina Department of Health. Retrieved June 21, 2012, from http://www.vdh.state.va.us/news/Alerts/Selenium/SeleniumFAQs.htm
4. Selenium. Retrieved June 21, 2012, from http://www.exrx.net/Nutrition/Antioxidants/Selenium.html
5. Selenium. (n.d.). Office of Dietary Supplements. Retrieved June 21, 2012, from http://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/
6. Srivastava, A. K., Gupta, B. N., Bihari, V., Gaur, J. S., & Mathur, N. (1997). Hair selenium as a monitoring tool for occupational exposures in relation to clinical profile. Journal of Toxicology and Environmental Health, 51(5), 437-45. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9233378
7. Thomas, D. J. (1998). Chapter 88. In Selenium. (pp. 911 - 14).
8. Retrieved June 21, 2012, from 1. http://www.hc-sc.gc.ca/hecs-sesc/water/pdf/dwg/selenium.pdf
9. Retrieved June 21, 2012, from 3. http://www.vitaminherbuniversity.com/topic.asp?categoryid=2 &topicid=1028#subcatid130

Silver

TITLE Silver (Ag)
SYNONYMS/FORMS none
GENERAL INFORMATION: Clinical interest in silver analysis includes 1) monitoring burn patients being treated with silver sulfadiazine, and 2) monitoring patients treated with silver containing nasal decongestants. In both cases, silver deposits in many organs, including the sub epithelium of skin and mucous membranes producing a syndrome called argyria. It is associated with growth retardation hemopoiesis, cardiac enlargement, degeneration of the liver, and destruction of renal tubules.

Silver can enter the body by ingestion, inhalation or absorption by the skin. After ingestion, silver is eliminated primarily in the feces, with small amounts eliminated in the urine. The rate of excretion is rapid (within a week).
SOURCES/ROUTE OF EXPOSURE Exposure to silver can occur in workers in the metallurgical industry, patients who take silver-containing medications and individuals who accidentally or intentionally ingest silver salts.
TOXICITY Silver compounds can cause the skin to turn gray or blue-gray. This condition is called argyria and can occur in people who eat or breathe in silver compounds over a long period (several months to several years).
MONITORING/CLINICAL INTERPRETATION none
MATRIX CHOICE Whole blood is the recommended sample for monitoring exposure to silver. Urine can be used to measure silver but the metal may not always be detected in the urine samples because silver is eliminated primarily through the feces.
TREATMENT none
REFERENCES 1. TOXICOLOGICAL PROFILE FOR SILVER, Agency for Toxic Substances and Disease Registry, U.S. Public Health Service December1990

Sodium

TITLE Sodium (Na)
SYNONYMS/FORMS none
GENERAL INFORMATION: Sodium is the most important extracellular ion and functions to maintain normal osmotic pressure of plasma and acid-base and water balance. The amount of sodium is a reflection of the dietary intake, and the output is through the GI tract, skin and urine.
SOURCES/ROUTE OF EXPOSURE none
TOXICITY none
MONITORING/CLINICAL INTERPRETATION Hypernatremia occurs from loss of water (dehydration) or from sodium retention (infusion of hypertonic saline or ingestion). Sodium retention may cause an increase in extracellular water retention in tissues (edema). Hyponatremia occurs with nephrotic syndrome, syndrome of inappropriate antidiuresis (SIAD), diuretic therapy and cystic fibrosis. Levels below 115 mmol/L can lead to significant neurological dysfunction, cerebral edema and increased intra cranial pressure.
MATRIX CHOICE Hair sodium concentrations generally do not reflect dietary status, but very high concentrations may be diagnostic in cystic fibrosis. Retention of sodium in hair tissue may be caused by disturbances in renal function and electrolyte balance. Chronic stress syndrome can result in depressed hair sodium as a result of inadequate renal response to adrenal hormones.
TREATMENT none
REFERENCES none

Strontium

TITLE Strontium (Sr)
SYNONYMS/FORMS none
GENERAL INFORMATION: Strontium is a common trace element in the lithosphere. It has physiological and chemical properties similar to calcium. Approximately 99% of strontium in the body is found in bone (1). Studies in animals have shown that low doses of oral Strontium stimulate bone formation (2). Strontium ranelate, a new oral drug has shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis (3,4).

The radioactive form (90Sr) was of considerable concern when atomic weapons were being tested in the atmosphere, as the radioactive element taken up into bone was considered a potential health hazard.
SOURCES/ROUTE OF EXPOSURE Strontium is present in seawater and some other forms of water. Generally, Strontium concentrations are higher in seawater than in freshwater.

In general, plant foods are better sources of Strontium than animal foods. Brazil nuts are an especially rich source of Strontium.
TOXICITY There have been no reported cases of Strontium intoxication or deficiency symptoms in humans.
MONITORING/CLINICAL INTERPRETATION Low blood levels of Strontium and Calcium may be suggestive of a Calcium deficient diet or Vitamin D insufficiency.

The blood level of Strontium has been used in forensic medicine to diagnose seawater and freshwater drowning (5).
MATRIX CHOICE Hair levels correlate well with bone levels and are considered a good indicator of Strontium exposure.
TREATMENT none
REFERENCES 1. Haas EM. Minerals: Strontium http://www.healthy.net/Author_Biography/Elson_M_Haas_MD/96
2. Marie PJ et al. Effect of low doses of stable strontium on bone metabolism in rats. Miner Electrolyte Metab. 1985; 11(1):5-13.
3. Reginster JY et al. Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study. J. Clin. Endocrinol. Metab. 90(5):2816–2822. 4. Reginster JY. Strontium ranelate in osteoporosis. Curr Pharm Des. 2002;8(21):1907-16. 5. Pérez-Cárceles et al. Strontium levels in different causes of death: diagnostic efficacy in drowning. Biol Trace Elem Res. 2008;126 (1-3):27-37.

Sulfur

TITLE Sulfur (S)
SYNONYMS/FORMS Sulphur
GENERAL INFORMATION: Sulfur is an essential nutrient for humans and performs a number of functions mainly as an important component of various substances.

As a part of four amino acids (cysteine, cystine, methionine and taurine), sulfur has important functions in enzyme reactions. For example, the sulfhydryl (SH) group is a part of the active centre of various enzymes that help the body eliminate and deactivate many kinds of toxins. Cysteine and methionine have shown some benefits against heavy metal poisoning. Keratin present in the skin, hair and nails contains particularly high amounts of cysteine. The sulfur-sulfur bond in keratin gives it shape and strength. Sulfur is a component of glucosamine and chondroitin sulfates that present in high amounts in the cartilage to support the joint tissue. In patients with arthritis, adequate sulfur intake through supplementation can help repair the cartilage. Sulfur is a part of glutathione which is a detoxifying substance.

Sulfur is absorbed from the GI tract mainly as the sulfur-containing amino acids or from sulfates in water or fruits and vegetables. Sulfur is stored in all body cells, especially the skin, hair and nails. Excess amounts are eliminated through the urine and in the feces.
SOURCES/ROUTE OF EXPOSURE Sulfur is widely available in foods and people can easily get adequate amounts from the diet. Sulfur-rich foods include eggs, legumes, garlic, onions, brussel sprouts and cabbage.
TOXICITY none
MONITORING/CLINICAL INTERPRETATION Skin and nail disease have been associated with inadequate intakes of sulfur-containing amino acids. Psoriasis and rheumatic condition often respond well to increased intakes of these amino acids.
MATRIX CHOICE Hair and urine
TREATMENT none
REFERENCES none

Thallium

TITLE Thallium (Th)
SYNONYMS/FORMS none
GENERAL INFORMATION: Thallium is a heavy metal which is extremely toxic, and ingestion of more than 10-20 mg per kg of body weight can be lethal.

Thallium and its salts can enter the body by ingestion, inhalation, or absorption through the skin. In blood, about 70% thallium is present in erythrocytes (1). Soluble thallium salts are widely distributed in the body, the highest concentration being found initially in the kidneys. It is mainly excreted by the kidneys and to a less extent by the intestine, hair, and saliva. The half-life of thallium in the body is 15-30 days (2). Thallium can cross the placenta and lead to fetal abnormalities.
SOURCES/ROUTE OF EXPOSURE Thallium is widely distributed in low concentration in the earth’s crust. It enters the environment mainly from coal burning and cement manufacture. It was used in rodenticide and insecticide, but was banned in the US and other countries in 1980s. It is still used in the manufacture of electronic components, optical lenses, imitation jewelry, semiconductor materials, alloys, low-temperature thermometers and green fireworks.
TOXICITY Thallium poisonings are generally due to ingestion of thallium salts, but can also occur by inhalation of dusts or fumes and skin absorption. Thallium toxic effect is due to its ability to inhibit a number of intracellular potassium-mediated processes. It can also bind to sulfhydryl groups of enzymes and inhibit enzyme activities.

The classic symptoms of acute thallium poisoning are:
  • Poisoning starts in the GI system and symptoms include abdominal pain, nausea, vomiting, and bloody diarrhea (12-48 hours)
  • Followed by neurologic symptoms such as sensory and motor changes, peripheral neuropathy, and loss of reflexes (2-5 days)
  • Hair loss (2-3 weeks)
Other problems such as arrhythmias and kidney disease may occur in 2-3 weeks and may last up to 2 months. Severe thallium poisoning can lead to seizures, coma, respiratory failure and death (3, 4).

Chronic poisoning due to lower level intake mainly affects the nervous system. Symptoms include tiredness, fatigue, headaches, depression, numbness of fingers and toes, muscle pains, hair loss, and disturbances of vision.
MONITORING/CLINICAL INTERPRETATION Thallium testing is used for industrial and environmental monitoring. The test is also used to diagnose criminal and unintentional thallium poisonings.
MATRIX CHOICE Thallium can be measured in the blood, erythrocytes or urine. The determination of thallium in urine is probably a more reliable indicator of exposure than its determination in blood (5). Although a 24-hour urine thallium concentration is the most accurate way to assess thallium toxicity, a spot urine level is likely to provide a more rapid and reasonably reliable result.
TREATMENT Thallium can be treated with a specific antidote, Prussian Blue (potassium ferric hexacyanoferrate). This reagent can prevent thallium absorption from the GI tract and enhance fecal excretion.
REFERENCES 1. Rauws, A. G. Thallium pharmacokinetics and its modification by Prussian Blue, Naunyn Schmiedeberg’s Arch. Pharmacol. 1974;284(3):294-306.
2. Barclay, R et al, Distribution and excretion of radioactive thallium in the chick embryo, rat, and man. J. Pharmacol. Exp. Ther.1953;107(2):178-87
3. Metals as Toxins -Thallium. http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/group29/thaltox.htm
4. Thallium Poisoning. http://patient.info/doctor/thallium-poisoning
5. Schaller, K. H. et al. Investigation of thallium-exposed workers in cement factories. Int. Arch. Occup. Environ. Health, 1980 47, 223-231.

Tin

TITLE Tin (Sn)
SYNONYMS/FORMS none
GENERAL INFORMATION: Tin (Sn, from the Latin word Stannum) is a soft and silver white metal which has no known biological function and is toxic to humans. Due to its relatively low melting point and outstanding corrosion resistance, tin has been widely used in coating other metals. Elemental tin is used to line cans for food and beverages. Tin can combine with other elements to form various compounds. It combines with chlorine, sulfur or oxygen to form inorganic tin compounds. These compounds are present in toothpaste, perfumes, soaps, coloring agents, food additives and dyes. Tin also can combine with carbon to form organic tin compounds. These compounds are used in making plastics, food packages, plastic pipes, pesticides, paints, wood preservatives and rodent repellants. In general, organic tin compounds are more toxic than inorganic forms.

Elemental tin and inorganic tin compounds are poorly absorbed when ingested, which explains its relatively low toxicity. Hydrophobic organic tin compounds are toxic to a variety of organs due to their high solubility in the cell membrane.
SOURCES/ROUTE OF EXPOSURE The main source for tin in humans is food. High levels of tin may be found in some processed foods due to the addition of tin-based preservatives and stabilizers such as stannous chloride. Tin coated cans may also contaminate processed foods through corrosion of the tin plating.
TOXICITY/DEFIENCY Organic tin inhibits heme oxygenase synthesis, leading to anemia. It also causes severe irritation and burning to the skin.
MONITORING/CLINICAL INTERPRETATION Chronic exposure to tin dusts and fumes in foundries results in its deposition in the lungs and may cause a benign pneumoconiosis known as stannosis. There are no symptoms attributable to it, but x-ray exam shows very opaque nodular shadows.
MATRIX CHOICE Urine is the sample of choice for monitoring exposure to inorganic compounds.
TREATMENT none
REFERENCES 1. Tin and Compounds. Agency for Toxic Substances and Disease Registry. http://www.atsdr.cdc.gov/PHS/PHS.asp?id=541&tid=98
2. Tin and inorganic tin compounds. World Health Organization. Geneva, 2005
3. Handbook on the Toxicology of Metals. Nordberg GF et al. Fourth Edition, 2015

Titanium

TITLE Titanium (Ti)
SYNONYMS/FORMS Titanate
GENERAL INFORMATION: Titanium is a grey metal that is very resistant to corrosion and when it is a dust or a powder, it is extremely flammable. Titanium is a relatively modern metal that was not made commercially until the 1940s (9). It is very strong, not very heavy and also resistant to corrosion (1). It has the ability to withstand extreme temperatures and for this reason, titanium is combined with many alloys in many industries, especially in the aerospace industry (1).

There is no evidence that Ti is an essential element for any species (11).
SOURCES/ROUTE OF EXPOSURE In its metallic form, Ti is lightweight and strong along with a rust-resistant property and so, it is used for a variety of purposes (9). Titanium metal containing alloys are used as a medical and dental prosthesis such as for joint replacements. It is believed to be very inert and safe (3). In this form, titanium is also used for aircraft engines, spacecrafts, missiles, cars, wrist watches and in other industrial materials (9). People who have medical implants or those working in industries that produce titanium alloys are exposed to Ti.

Titanium dioxide is a white pigment and its reflective property adds richness to colours. Additionally, it also provides UV protection (9). It is used in paints, paper, ink, cosmetics, sunscreen, leather, food colouring and ceramics (9). Exposure to Titanium dioxide could occur through any of these sources.

Of all the forms of Ti, the one that is well-known to cause toxicity is Titanium tetrachloride. Titanium tetrachloride is used for smokescreens and skywriting because it makes a dense white smoke. It is also used to make titanium metal and other titanium compounds (7). Workplace exposure to titanium tetrachloride occurs in industries where titanium compounds are being produced. Toxicity could occur by all routes of exposure, though inhalation and dermal are the commonest (7). It is unlikely that the general population will be exposed to titanium tetrachloride (8).

Most Titanium that is ingested is not absorbed and is excreted by urine (10).
TOXICITY Overall, in the general population, Ti toxicity is not seen.

Unlike original belief that Titanium is completely non-toxic in its metallic form, there is new evidence emerging that titanium toxicity can occur due to medical prosthetics due to corrosive by-products that can cause damage (3). However, Ti is still widely used in medical and dental settings. Overall though, the toxicity of metallic and Titanium dioxide is not commonly reported. Inhaled Titanium dioxide has been shown to cause changes in the lung in both animal and human studies (4).

Titanium seems to accumulate in the lungs (10) with time and even with the forms of Titanium that have been regarded as non-toxic, cases of pulmonary fibrosis has been seen in subjects that are exposed to the metal (10). Since only about 3% of Ti is absorbed by the gastrointestinal tract, ingestion of Ti has not been shown to cause any toxicity (10).

Titanium toxicity is most likely to occur in occupational settings where individuals are working in places where Ti is produced and manufactured. Commonly, toxicity is due to Titanium tetrachloride and this is due to inhalation or dermal contact of the substance (7).
MONITORING/CLINICAL INTERPRETATION When removing medical or dental implants from a patient, great care should be taken by both the health care professional for their own safety and also to avoid leakage for the patient’s safety (3). Medical and dental equipment that contain titanium can cause alterations in the spleen and affected functioning of the immune system (3).

It is important to monitor patients who are at occupational risk of exposure to Ti for toxicity symptoms as these are the people who are most likely to encounter Ti toxicity due to titanium tetrachloride. Dermal contact could cause burns since this compound reacts with water to produce hydrochloric acid (7). Inhalation of large amounts could result in enough respiratory damage to cause death (6).

Acute symptoms of toxicity include irritation to skin, eyes and the respiratory tract (8). It could also damage the cornea. Chronic exposure results in decreased pulmonary function, pulmonary edema, chronic bronchitis and other respiratory conditions (8). There are no current associations between titanium tetrachloride exposure and cancer risk (8).
MATRIX CHOICE Titanium levels can be detected in RBC, urine and hair from environmental and occupational exposure. In patients with joint replacements, it was shown that there was an increase in serum and urine levels of Ti over time (10). It is useful to have these levels for knowing whether the implant is breaking down even though toxicity was not seen with the rising Ti levels (10). Hair levels may be falsely elevated with Ti since many people may use products that contain titanium dioxide pigments on their hair (2).
TREATMENT Firstly, prevention of workers from inhalation of Titanium fumes should be attempted in all workplaces. The patient should be removed from the source of exposure. If there is dermal exposure, the patient should wash all hair and contaminated skin for 10-15 minutes and see a specialist if there are burns (5). For ocular exposure, the patients should irrigate the eye for 10-15 minutes. If inhalation has occurred, the patient should be given oxygen and treated symptomatically (5). In the rare cases of an ingestion toxicity, it is important to maintain the airway. It is advised not to attempt a gastric lavage or give neutralizing chemicals as the chemicals may increase injury (5).
REFERENCES

Uranium

TITLE Uranium (U)
SYNONYMS/FORMS none
GENERAL INFORMATION: Uranium is a radioactive heavy metal which is a mixture of three isotopes, 234U, 235U and 238U (the most common isotope). It is used mainly as fuel for nuclear power reactors. Canada is the world’s largest producer of uranium.

Uranium can enter the body by inhalation, ingestion, absorption by the skin or contamination of the wounds. Overall, absorption of uranium in the body is low, regardless of the route of exposure.

After absorption into blood, most of the uranium is rapidly cleared, mainly in urine. Approximately 65% is removed during the first day and another 10% removed during the first week.
SOURCES/ROUTE OF EXPOSURE Occupational exposure may occur in workers involved in
  • using armor-piercing weapons
  • decommissioning uranium-contaminated areas
  • processing nuclear fuel
  • maintenance and/or repair activities at applicable U.S. government facilities
  • mining or milling of uranium, silver, phosphorus and coal
  • producing phosphate fertilizer
  • operating power plants
  • repairing, storing, transporting and using uranium weapons
  • working with gyroscope, helicopter rotor counterbalances, or control surfaces of aircraft containing uranium metal weights
  • using uranium-containing glazes as artists, hobbyists and glass workers
Non-occupational exposure occurs in communities living near Department of Energy facilities and mining sites and living in areas where naturally occurring uranium levels are high.
TOXICITY Uranium is primarily a chemical toxicant with radiation playing a minor role. The primary target of uranium exposure is the kidney. High level acute exposures to uranium can cause kidney damage which usually resolves after exposure ends.
MONITORING/CLINICAL INTERPRETATION none
MATRIX CHOICE Urine is the preferred sample for evaluation of exposure to uranium.
TREATMENT none
REFERENCES 1. Uranium Toxicity. Agency for Toxic Substances and Disease Registry (ATSDR)
2. Canadian Soil Quality Guidelines for Uranium:
3. Environmental and Human Health http://www.ccme.ca/files/Resources/supporting_scientific_documents/Uranium_ssd_soil_1.2.pdf
4. Briner W. The Toxicity of Depleted Uranium. Int J Environ Res Public Health. 2010 Jan; 7(1): 303–313.
5. Dewar D. Uranium mining and health. Can Fam Physician. 2013;59:469-71

Vanadium

TITLE Vanadium (V)
SYNONYMS/FORMS None
GENERAL INFORMATION: Vanadium is a naturally occurring metallic element (7). Vanadium is not readily absorbed by the body from the stomach, gut, or through contact with the skin. Therefore it is generally considered non-toxic as only very minor amounts are actually absorbed in to the bloodstream and the rest is breathed out, or excreted though urine or feces. There is a very minor amount of vanadium in the human body, however, it does not serve any biological purpose in higher organisms. In lower organisms, it has been found that vanadium is required for the function of vanadium-dependent enzymes.

Studies have tested various vanadium compounds as potential treatment for type I and type II diabetes. Vanadium salts have been shown to improve hyperglycemia and hyperinsulinemia in several animal studies (6). As a dietary supplement, it has been marketed to improve blood sugar control, increase muscle strength and improve osteoporosis (7).
SOURCES/ROUTE OF EXPOSURE The uptake of vanadium by humans mainly takes place through foodstuffs, such as buckwheat, soya beans, olive oil, sunflower oil, apples and eggs. Seafood contains higher portions of Vanadium (4). For the general population, food is the main source of exposure (6). Since most of a person's V intake is from food, one can eat about 10-20 µg daily (4).

Airborne sources of vanadium and its compounds come from industrial areas, such as burning of high vanadium fossil fuels, and production of vanadium-containing metal alloys. In the UK, high vanadium exposure was linked to cleaning of oil-fired boilers and furnaces (6). People who are exposed to Vanadium in the occupational setting are actually exposed to vanadium oxides in the dust (6).
TOXICITY/DEFICIENCY Vanadium deficiency has not been seen in humans (7).

Vanadium toxicity depends on its oxidation state. Elemental vanadium could be oxidized to vanadium pentoxide (V2O5) during welding. The pentoxide form is more toxic than the elemental form. Occupational exposure is mainly due to vanadium peroxide dust (4).
MONITORING/CLINICAL INTERPRETATION Very rarely does Vanadium toxicity occur in those that are not exposed to the element through the workplace. However, it may be important to monitor those that may be taking V supplements.

Those that are at occupational risk of exposure to vanadium peroxide dust should be monitored. Acute signs of V exposure include severe irritation of the eyes, skin, upper respiratory tract. Over time, these symptoms become more chronic and persistent inflammations of the trachea and bronchi, pulmonary edema, and systemic poisoning can be seen. Cough, rapid heart beat, lung changes, skin pallor, chronic bronchitis, conjunctivitis, nasopharyngitis, labored breathing, greenish-black tongue and an allergic skin rash are some of the other findings to monitor for in a patient that may be exposed to vanadium pentoxide through their workplace (4).
MATRIX CHOICE Urine is an appropriate medium to monitor V levels (1). Measurements in blood can give information about whether one has been exposed to larger than normal amounts of V (5). Blood and urine are good indicators of occupational exposure to V. Hair measurements of V are not a good indicator of occupational exposure.
TREATMENT Treatment of V toxicity involves removing the patient from the source of the Vanadium and providing symptomatic treatment for the respiratory, cardiovascular and neurovascular manifestations.
REFERENCES

Zinc

TITLE Zinc
SYNONYMS/FORMS none
GENERAL INFORMATION: Zinc is an essential trace element for normal growth and development, wound healing and immunocompetence. It is also necessary for the activity of more than 70 metalloenzymes, eg carbonic anhydrase, alkaline phosphatase, RNA & DNA polymerases, thymidine kinase and carboxypeptidases and is involved in virtually all metabolic pathways.

Zinc is actively absorbed from the gut into epithelial cells, where it is stored as mucosal metallothionen or released into the plasma, where 80% is mainly bound to albumin. It is then transported to the liver, where it is stored by hepatocytes in metallothionen. Zinc is mainly stored in muscle, with bone, liver and plasma forming a small exchangeable pool. Twenty percent of body zinc is found in the skin, nails and hair. Regulation of zinc absorption is thought to be controlled by the amount of metal free albumin. Zinc absorption decreases in the presence of dietary phytate, high dietary phosphate and excessive calcium. Coffee, dairy products and high fibre bread also reduce zinc absorption. Zinc is mainly excreted in the faeces, with small amounts being lost via the kidneys; urinary zinc increases in nephrosis, postalcoholic hepatic cirrhosis and hepatic porphyria. Increased excretion also occurs in total starvation and on administration of chelation agents. Large amounts of zinc can also be lost in sweat. Increased zinc intake depresses copper absorption and conversely copper absorption is greatly increased in zinc deficiency. Metabolic interactions occur between zinc and cadmium, zinc and iron, and zinc and chromium. Cadmium and iron uptake are depressed by high zinc levels, while chromium and zinc are metabolised by a common pathway in the intestine and are mutually antagonistic.

In blood approximately 80% of zinc is in the red blood cells. Almost all of this is in carbonic anhydrase. About 3% is found in leucocytes. The rest, approximately 20%, is found in the plasma. In the new-born, erythrocyte zinc levels are about half that of the adult, with levels progressively increasing until about 12 years of age.
SOURCES/ROUTE OF EXPOSURE Zinc is used in galvanising iron and steel, and as an alloy of brass and bronze. Inhalation of zinc oxide fumes produced during welding can cause metal fume fever characterised by nausea, headaches, muscular and joint pain, shortness of breath, thirst and a cough. These symptoms develop 4-12 hours after exposure and last for 1-2 days. Zinc chloride fumes, which are highly corrosive to skin, eyes and mucous membranes, are produced from welding flux, wood preservatives and the manufacture of high quality paper, dyes and deodorants. It is also used in smoke screens.
DEFICIENCY Deficiency results in a variety of symptoms such as poor wound healing, skin disorders, poor growth and sexual development in infants and children, and impaired immune function. It is monitored in patients on admission for adequate dietary intake, and during TPN therapy. Deficiency causes failure to grow, skin rashes, impaired cell mediated immunity, failure of sexual maturation, taste abnormalities, abnormalities of fetal development, poor wound healing, and impaired vitamin A metabolism.

In zinc deficiency a reduction in plasma zinc levels reflects a loss of zinc from the bone and liver, with a consequent increase in the risk for development of metabolic and clinical signs of zinc deficiency. Alkaline phosphatase levels also decrease. Growth retardation is often the first sign of zinc deficiency.

Apart from zinc deficiency, plasma zinc levels decrease after meals and during acute infections. They are also associated with liver disease, malignant tumours, pernicious anaemia or short term fasting. Plasma zinc levels are also lower in late pregnancy. The drop in plasma zinc in these conditions (except fasting) is caused by redistribution to other tissues in response to metabolic need.

Acrodermatitis enteropathica is a genetic disorder of zinc metabolism that manifests as zinc deficiency, with retarded growth, hypogonadism, gastrointestinal disturbances and skin lesions. It appears in early infancy but with oral zinc therapy a total recovery occurs.
MONITORING/CLINICAL INTERPRETATION Haemolysed samples are unsuitable for plasma zinc estimation because the red cells contain 80% of circulating zinc. Zinc levels in serum are approximately 16% higher than those in plasma due to the release of zinc from platelets during the clotting process.

Plasma zinc levels are thought to follow a circadian pattern, with the highest values occurring in the morning at approximately 10.00 am.

If a nonheparinized (no additive) vacutainer is used, serum zinc will be up to 16% higher, due to release of zinc from platelets during clotting.
MATRIX CHOICE none
TREATMENT none
REFERENCES none

Zinc Protoprophyrin

TITLE Zinc Protoporphyrin (ZPP)
SYNONYMS/FORMS none
GENERAL INFORMATION: Zinc protoporphyrin (ZPP) is a normal metabolite in the heme biosynthetic pathway that is present in trace amounts in erythrocytes. Increases in the concentration of ZPP may occur in several pathological conditions that inhibit the heme synthesis, including lead poisoning and iron deficiency (1).

Heme is synthesized in the erythrocyte through a series of reactions. In the last reaction, Ferrochelatase catalyzes the incorporation of Fe2+ into protoporphyrin molecule to form heme. When the enzyme activity is inhibited by lead or iron supply is insufficient, Fe2+ cannot be inserted into protoporphyrin. Consequently, Zn2+ takes the place of Fe2+ to be inserted into protoporphyrin nonenzymatically to yield ZPP. Once formed, ZPP is stable and remains bound in erythrocytes during their 120-day life span (2). ZPP levels rise and decline to baseline more slowly than blood lead levels, a ZPP determination along with the blood lead testing can help differentiate acute from chronic exposure. However, the ZPP test has its disadvantages in monitoring lead toxicity. It is not sufficiently sensitive for low level lead exposure. In 1991, the CDC defined lead poisoning in children as a blood lead level of 0.48 µmol/L (100 µg/L) (3). At this blood lead level, ZPP has poor diagnostic sensitivity, so it should not be used as a screening test for lead poisoning in children. In addition, ZPP is not specific for lead exposure because it may also be elevated in iron deficiency anemia.

The ZPP level is determined by a ProtoFluor-Z Hematofluorometer.
SOURCES/ROUTE OF EXPOSURE none
DEFICIENCY none
MONITORING/CLINICAL INTERPRETATION Elevated ZPP levels may indicate long-term lead exposure or iron deficiency anemia.

An increase in the concentration of ZPP may occur at blood lead levels of 200-300 µg/L. Increases in ZPP become more significant once the blood lead level has reached 400 µg/L. Increases in blood lead levels beyond 400 µg/100 g are associated with exponential increases in ZPP (4).
MATRIX CHOICE Whole blood
TREATMENT none
REFERENCES 1. National Committee on Clinical Laboratory Standards. C42-P. Erythrocyte protoporphyrin testing: approved guideline. Villanova, PA: NCCLS, 1996
2. Stanton NV, et al: Empirically determined lead-poisoning screening cutoff for the Protofluor-Z hematofluorometer. Clin Chem 1989;35(10):2104-2107
3. Centers of disease control. Preventing lead poisoning in young children. A statement of the centers for disease control. Atlanta: CDC, 1991.
4. OSHA Medical Surveillance Guidelines: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10644

Niobium

TITLE Niobium (Nb)
SYNONYMS/FORMS none
GENERAL INFORMATION: Niobium (Nb) is a soft, gray-white, ductile metal that has a high resistance to corrosion and high temperatures. Niobium alloys are used in heat-resistant equipment in the field of rocket technology, in the supersonic aircraft industry, and in satellites. Niobium is also used as a corrosion-proof material for heat exchangers, filters, grids, electrolytic condensers, rectifiers, needle valves, and cutting tools.

Niobium and its alloys have been used as biomaterials for orthopedic implants due to its resistance to wear and the ability to promote osseointegration - the process whereby the bone tissue adheres firmly to the surface of a metallic implant.

Metallic Niobium is not absorbed from the GI tract. Intravenous and intraperitoneal injections of radioactive Niobium tend to accumulate in the liver, kidneys, spleen, and bone. It is mainly excreted into the feces rather than urine.
SOURCES/ROUTE OF EXPOSURE During the mining of Niobium ore and processing of its products, the workers may be exposed to Niobium dust and fumes. After inhalation, Niobium is retained mainly in the lungs and can be absorbed into the bones.
TOXICITY In the occupational setting, exposure to Niobium dust causes eye and skin irritation. No other adverse health effects have been reported.
MONITORING/CLINICAL INTERPRETATION Blood Niobium analysis is available, but its usefulness in monitoring implant wear is uncertain. The precision of our method is 15%-20% of the CV at the low end of the reference range.
MATRIX CHOICE Whole blood
TREATMENT none
REFERENCES 1. http://www.ilo.org/safework_bookshelf/english?content&nd=857170741
2. http://www.lenntech.com/periodic/elements/nb.htm
3. http://en.wikipedia.org/wiki/Niobium
Schulich School of Medicine and Dentistry London Health Sciences CentreSt. Joseph's Health Care LondonWestern University