Toxic Metals PDF

Toxic Metals Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, or are toxic when in a certain form....

Toxic Metals Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, or are toxic when in a certain form. In the case of lead, any measurable amount may have negative health effects Often heavy metals are thought of as synonymous, but lighter metals may also be toxic in certain circumstances, such as beryllium and lithium. Not all heavy metals are particularly toxic, and some are essential, such as iron. The definition may also include trace elements when in abnormally high doses may be toxic. An option for treatment of metal poisoning may be chelation therapy, which is a technique which involves the administration of chelation agents to remove metals from the body. Toxic metals sometimes imitate the action of an essential element in the body, interfering with the metabolic process resulting in illness. Many metals, particularly heavy metals are toxic, but some heavy metals are essential, and some, such as bismuth, have a low toxicity. Most often the definition of toxic metals includes at least thallium, cadmium, manganese, lead, mercury and the radioactive metals. Metalloids (arsenic, polonium) may be included in the definition. Radioactive metals have both radiological toxicity and chemical toxicity. Metals in an oxidation state abnormal to the body may also become toxic: chromium(III) is an essential trace element, but chromium(VI) is a carcinogen. Heavy metals are dangerous because they tend to bioaccumulate. Bioaccumulation means an increase in the concentration of a chemical in a biological organism over time, compared to the chemical's concentration in the environment. Compounds accumulate in living things any time they are taken up and stored faster than they are broken down (metabolized) or excreted. Heavy metals can enter a water supply by industrial and consumer waste, or even from acidic rain breaking down soils and releasing heavy metals into streams, lakes, rivers, and groundwater. Heavy metal toxicity can result in damaged or reduced mental and central nervous function, lower energy levels, and damage to blood composition, lungs, kidneys, liver, and other vital organs. Long-term exposure may result in slowly progressing physical, muscular, and neurological degenerative processes that mimic Alzheimer's disease, Parkinson's disease, muscular dystrophy, and multiple sclerosis. Allergies are not uncommon and repeated long-term contact with some metals or their compounds may even cause cancer  Humans frequently encounter elemental toxins, with chronic, low-concentration exposure which may affect metal development especially in young. Some metals, even those essential, when it exceed a certain threshold, toxicity may happen. Elements in groups IB, IIB, IIIA, even IV in rows six and seven , which are referred to as heavy metals, usually have greater potential to induce toxicity. Analytical Methods Metals are measured in biological fluids using Atomic absorption spectrometry with flame (AAS-F), or electrothermal atomization furnace (AAS-ETA), inductively coupled plasma-optical emission spectrometry (ICP-OES), inductively coupled plasma-mass spectrometry (ICP-MS) and high performance liquid chromatography-mass spectrometry (LC-MS). Photometric assays are also possible but require large volumes of samples and have limited analytical performance. Beryllium It is an alkaline earth metal together with Mg, Ca, Sr, Ba and Ra Once called glucinum because of the sweet taste of its salts Differentiated from magnesium by adding quinalizarin + bromine water o Be: persistence of blue color o Mg: disappearance of blue color Regarded as the most toxic metal o Inhibits carbohydrate metabolic cycle by preventing breakdown of phosphorus compounds o Disturbs respiration, circulation, and temperature o No specific antidote is known Never used in medicine Used in the fluorescent lighting industry. Metallic, Alloys and ceramics of Be are widely used in dental appliances, wheelchairs, nuclear power and neutron modulator. Chronic Beryllium disease (CBD) is a chronic respiratory condition due to chronic beryllium exposure that is characterized by the formation of granulomas resulting from immune reaction to Be in the lungs. Aluminum It is most abundant metal and the 3rd most abundant element Pharmacological Action and Uses: may constrict the blood vessels when applied topically astringent (inherent) antiseptic antiperspirant Aluminum powder – used as inhalation in the treatment of silicosis; Used in burn treatment (aluminum foil): protects the burn and conserves fluid and stimulates tissue growth; Toxicity to aluminum has been linked with oral exposure to aluminum containing pharmaceutical products like antacids; Patients with renal failure have a high risk of aluminum toxicity. Aluminum accumulates in blood and binds tightly in protein (e.g. transferrin) and is rapidly distributed throughout the body. Aluminum overload may replace calcium in bone disrupting normal osteoid formation and may be reflected diagnostically with low parathyroid hormone (PTH). Note: Evacuated blood collection devices used in phlebotomy have rubber stoppers that are made of aluminum silicate that when punctured during blood collection may contaminate the sample with aluminum. Thallium a soft metal that quickly oxidizes upon exposure to air. It is a minor constituent in a variety of ores.  Thallium salts are used in the manufacture of jewelry, semiconductors, and optical devices. Thallium no longer is used in the United States as a depilatory or a rodenticide because of its high human toxicity. ○ From thallos meaning “green twig” ○ This can also be a by-product of lead smelting which can be very toxic ○ Mechanism of toxicity- The mechanism of thallium toxicity is not known. It appears to affect a variety of enzyme systems, resulting in generalized cellular poisoning. Thallium metabolism has some similarities to that of potassium, and it may inhibit potassium flux across biologic membranes by binding to Na-K ATP transport enzymes. ○ Primarily use as rodenticide ○ Clinical presentation. Symptoms do not occur immediately but are typically delayed 12 to 14 hours after ingestion. Acute effects include abdominal pain, nausea, vomiting, and diarrhea (sometimes with hemorrhage). Shock may result from massive fluid or blood loss. Within 2-3 days, delirium, seizures, respiratory failure, and death may occur. Chronic effects include painful peripheral neuropathy, myopathy, chorea, stomatitis, and ophthalmoplegia. Hair loss and nail dystrophy (Mees' lines) may appear after 2-4 weeks. ○ It is rapidly absorbed via ingestion, inhalation and skin contact. Sign and symptoms of poisoning includes loss of hair, peripheral neuropathy, seizures, renal failure and may also cause green tongue. ○ Diagnosis. Thallotoxicosis should be considered when gastroenteritis and painful paresthesia are followed by alopecia. Specific levels. Urinary thallium is normally less than 0.8 mcg/L. Concentrations higher than 20 mcg/L provide evidence of excessive exposure and may be associated with subclinical toxicity during workplace exposures. Blood thallium levels are not considered reliable measures of exposure except after large exposures. Hair levels are of limited value, used mainly in documenting past exposure and in forensic cases. Other useful laboratory studies include CBC, electrolytes, glucose, BUN, creatinine, and hepatic transaminases. Since thallium is radiopaque, plain abdominal x-rays may be useful after acute ingestion. ○ Treatment Emergency and supportive measures Maintain an open airway and assist ventilation if necessary (see Airway). Treat Seizures (see Seizures) and coma (Coma And Stupor) if they occur. Treat gastroenteritis with aggressive intravenous replacement of fluids (and blood if needed). Use pressors only if shock does not respond to fluid therapy (see Hypotension). Specific drugs and antidotes. There is currently no recommended specific treatment in the United States. 1. Prussian blue (ferric ferrocyanide) is the mainstay of therapy in Europe and received FDA approval for use in the United States in 2003. This compound has a crystal lattice structure that binds thallium ions and interrupts enterohepatic recycling. Insoluble Prussian blue (Radiogardase) is available as 500-mg tablets, and the recommended adult dose is 3 g orally three times per day.Prussian blue appears to be nontoxic at these doses. In the United States, Prussian blue should be available through pharmaceutical suppliers. 2. Activated charcoal is readily available and has been shown to bind thallium in vitro. Multiple-dose charcoal is recommended because thallium apparently undergoes enterohepatic recirculation. In one study, charcoal was shown to be superior to Prussian blue in eliminating thallium. 3. BAL (see BAL [Dimercaprol]) and other chelators have been tried with varying success. Penicillamine And diethyldithiocarbamate should be avoided because of studies suggesting that they contribute to redistribution of thallium to the brain. Decontamination. Administer activated charcoal orally if conditions are appropriate (see Table I–38). Ipecac- induced vomiting may be useful for initial treatment at the scene (eg,  children at home) if it can be given within a few minutes of exposure. Consider gastric lavage for large recent ingestions. Enhanced elimination. Repeat-dose activated charcoal may enhance fecal elimination by binding thallium secreted into the gut lumen or via the biliary system, interrupting enterohepatic orenteroenteric recirculation. Forced diuresis, dialysis, and hemoperfusion are of no proven benefit. Silicon It is the 2nd most abundant element next to oxygen but the most abundant elements in the environment. Compounds of Silicon 1. Colloidal silicon dioxide Used as adsorbent, desiccant, thickener 2. Amorphous oxide of silicon (e.g.Asbestos) Inhalation of asbestos-containing dust leads asbestosis, deposition of asbestos fiber in the pulmonary alveoli. 3. Methylated polymers of silicon (e.g. silicone) silicon implants have come to public attention. Silicon appears to induce a response from polymorphonuclear cells and macrophages that bind small particles of silicon and transport them to lymph nodes where they can accumulate. *Silicosis – a lung condition resembling chronic tuberculosis, developing after exposure to respirable silica dust. Lead is a soft, malleable metal that is obtained chiefly by the primary smelting and refining of natural ores or by the widespread practice of recycling and secondary smelting of scrap lead products. Recycling accounts for nearly 85% of domestic lead consumption, approximately 85% of which is used in the manufacture of lead acid batteries. Lead is used for weights and radiation shielding, and lead alloys are used in the manufacture of pipes; cable sheathing; brass, bronze, and steel; ammunition; and solder (predominantly electrical devices and automotive radiators). Lead compounds are added as pigments, stabilizers, or binders in paints, ceramics, glass, and plastic. Although the use of lead in house paint has been curtailed since the 1970s, industrial use of corrosion- resistant lead-based paint continues, and high-level exposure may result from renovation, sandblasting, torching, or demolition. Young children are particularly at risk from repeated ingestion of lead contaminated house dust, yard soil, or paint chips or from mouthing toy jewelry or other decorative items containing lead. Children may also be exposed to lead carried into the home on contaminated work clothes worn by adults. Lead exposure may occur from the use of lead-glazed ceramics or containers for food or beverage preparation or storage. Certain folk medicines (eg, the Mexican remedies azarcon and greta, the Dominican remedy litargirio, and some Indian Ayurvedic preparations) may contain high amounts of lead salts. ○ It is a metal commonly found in the environment (eg. Ceramics at home, paint, leaded gasoline, water pipes soldered with lead, soil) ○ Absorption is slow but action is cumulative; accumulates and stored in bones. ○ It can be ingested, inhaled or through dermal contact. ○ Toxicity will result to impaired growth and mental development, decrease vitamin D and hemoglobin synthesis, nephropathy, Encephalopathy and death. o Antidote: ▪ Chelation of BAL ▪ Dimercaprol Mechanism of Toxicity ○ A. The multisystem toxicity of lead is mediated by several mechanisms, including inactivation or alteration of enzymes and other macromolecules by binding to sulfhydryl, phosphate, or carboxyl ligands and interaction with essential cations, most notably calcium, zinc, and iron. Pathologic alterations in cellular and mitochondrial  membranes, neurotransmitter synthesis and function, heme synthesis, cellular redox status, and nucleotide metabolism may occur. Adverse impacts on the nervous, renal, GI, hematopoietic, reproductive, and cardiovascular systems can result. ○ B. Pharmacokinetics. Inhalation of lead fume or other fine, soluble particulate results in rapid and extensive pulmonary absorption, the major though not exclusive route of exposure in industry. Nonindustrial exposure occurs predominantly by ingestion, particularly in children, who absorb 45-50% of soluble lead compared with approximately 10-15% in adults. After absorption, lead is distributed via the blood (where 99% is bound to the erythrocyte) to multiple tissues, including transplacental transport to the fetus, and CNS transport across the blood- brain barrier. Clearance of lead from the body follows a multicompartment kinetic model, consisting of "fast" compartments in the blood and soft tissues (half-life of 1 to 2 months) and slow compartments in the bone (half-life of years to decades). Approximately 70% of lead excretion occurs via the urine, with smaller amounts eliminated via the feces and scant amounts via the hair, nails, and sweat. Greater than 90% of the lead burden in adults and more than two-thirds of the burden in young children occur in the skeleton. Slow redistribution of lead from bone to soft tissues may elevate blood lead concentrations for months to years after a patient with chronic high-dose exposure has been removed from external sources. In patients with high bone lead burden, pathologic states associated with rapid bone turnover or demineralization, such as hyperthyroidism and immobilization osteoporosis, have resulted in symptomatic lead intoxication. Toxic dose ○ Dermal absorption is minimal with inorganic lead but may be substantial with organic lead compounds, which may also cause skin irritation. ○ Ingestion. In general, absorption of lead compounds is directly proportional to solubility and inversely proportional to particle size. Gastrointestinal lead absorption is increased by iron deficiency and low dietary calcium and decreased by co-ingestion with food. 1.Acute symptomatic intoxication is rare after a single exposure but may occur within hours after ingestion of gram quantities of soluble lead compounds or days after GI retention of swallowed lead objects, such as fishing weights and curtain weights. 2. Studies have not established a low-dose threshold for adverse subclinical effects of lead. Recent epidemiologic studies in children have observed effects of lead on cognitive function at blood lead concentrations less than 5 mcg/dL, and other studies suggest that background levels of lead exposure in recent decades may have been associated with hypertension in some adults. The geometric mean blood lead concentration in the United States during 2001–2002 was estimated to be 1.45 mcg/dL; background dietary lead intake may be in the range of 1–4 mcg per day. 3. The US Environmental Protection Agency action level for lead in drinking water is 15 ppb (parts per billion). However, the Maximum Contaminant Level (MCL) goal for drinking water is zero ppb, and EPA has set no "reference dose" for lead because of the lack of a recognized low-dose threshold for adverse effects. ○ Inhalation. Unprotected exposure to the massive airborne lead levels (> 2500 mcg/m3) encountered during abrasive blasting, welding, or torch cutting metal surfaces coated with lead- based paint poses an acute hazard and has resulted in symptomatic lead intoxication from within a day to a few weeks. The OSHA workplace permissible exposure limit (PEL) for inorganic lead dust and fumes is 50 mcg/m3 as an 8-hour time-weighted average. The level considered immediately dangerous to life or health (IDLH) is 100 mg/m3. Clinical presentation. The multisystem toxicity of lead presents a spectrum of clinical findings ranging from overt, life- threatening intoxication to subtle, subclinical effects. o Acute ingestion of very large amounts of lead (gram quantities) may cause abdominal pain, anemia (usually hemolytic), toxic hepatitis, and encephalopathy. o Subacute or chronic exposure is more common than acute poisoning.  Constitutional effects include fatigue, malaise, irritability, anorexia, insomnia, weight loss, decreased libido, arthralgias, and myalgias. Hypertension may be associated with lead exposure in susceptible populations. Gastrointestinal effects include crampy abdominal pain (lead colic), nausea, constipation, or (less commonly) diarrhea. Central nervous system manifestations range from impaired concentration, headache, diminished visual- motor coordination, and tremor to overt encephalopathy (a life-threatening emergency characterized by agitated delirium or lethargy, ataxia, convulsions, and coma). Chronic low-level exposure in infants and children may lead to decreased intelligence and impaired neurobehavioral development, stunted growth, and diminished auditory acuity. Recent studies in adults suggest that lead may accentuate age-related decline in cognitive function. Peripheral motor neuropathy, affecting mainly the upper extremities, can cause severe extensor muscle weakness ("wrist drop"). Hematologic effects include normochromic or microcytic anemia, which may be accompanied by basophilic stippling. Hemolysis may occur after acute or subacute high-dose exposure. Nephrotoxic effects include reversible acute tubular dysfunction (including Fanconi-like aminoaciduria in children) and chronic interstitial fibrosis. Hyperuricemia and gout may occur. Adverse reproductive outcomes may include diminished or aberrant sperm production, increased rate of miscarriage, preterm delivery, decreased gestational age, low birth weight, and impaired neurologic development. o Repeated, intentional inhalation of leaded gasoline has resulted in ataxia, myoclonic jerking, hyperreflexia, delirium, and convulsions. Diagnosis. Although overt encephalopathy or abdominal colic associated with a suspect activity may readily suggest the diagnosis of severe lead poisoning, the nonspecific symptoms and multisystem signs associated with mild or moderate intoxication may be mistaken for a viral illness or another disorder. Consider lead poisoning in any patient with multisystem findings including abdominal pain, headache, and anemia and, less commonly, motor neuropathy, gout, and renal insufficiency. Consider lead encephalopathy in any child or adult with delirium or convulsions (especially with coexistent anemia) and chronic lead poisoning in any child with neurobehavioral deficits or developmental delays. o Specific levels. The whole-blood lead level is the most useful indicator of lead exposure. Relationships between blood lead levels and clinical findings generally have been based on subacute or chronic exposure and not on transiently high values that may result immediately after acute exposure. In addition, there may be considerable interindividual variability. Note: Blood lead samples must be drawn and stored in lead-free syringes and tubes ("trace metals" tube or royal blue stopper tube containing heparin or EDTA). 1. Blood lead levels are less than 5 mcg/dL in populations without occupational or specific environmental exposure. Levels between 5 (or lower) and 25 mcg/dL have been associated with subclinical decreases in intelligence and impaired neurobehavioral development in children exposed in utero or in early childhood. Studies in adults suggest that long-term blood lead concentrations in the range of 10-25 mcg/dL may pose a risk for hypertension and might possibly contribute to age-related decline in cognitive function. 2. Blood lead levels of 25-60 mcg/dL may be associated with headache, irritability, difficulty concentrating, slowed reaction time, and other neuropsychiatric effects. Anemia may occur, and subclinical slowing of motor nerve conduction may be detectable. 3. Blood levels of 60–80 mcg/dL may be associated with GI symptoms and subclinical renal effects.  4. With blood levels in excess of 80 mcg/dL, serious overt intoxication may occur, including abdominal pain (lead colic) and nephropathy. Encephalopathy and neuropathy usually are associated with levels over 100 mcg/dL. o Elevations in free erythrocyte protoporphyrin (FEP) or zinc protoporphyrin (ZPP) (> 35 mcg/dL) reflect lead-induced inhibition of heme synthesis. Because only actively forming and not mature erythrocytes are affected, elevations typically lag lead exposure by a few weeks. High blood lead in the presence of a normal FEP or ZPP therefore suggests very recent exposure. Protoporphyrin elevation is not specific for lead and may also occur with iron deficiency. Protoporphyrin levels are not sensitive for low-level exposure (blood lead < 30 mcg/dL). o Urinary lead excretion increases and decreases more rapidly than blood lead. In the CDC's Third National Report on Human Exposure to Environmental Chemicals, the geometric mean urinary lead concentration of subjects age 6 and older was 0.7 mcg/L. Normal, baseline urinary lead excretion for the general population is less than 10 mcg/day. Several empiric protocols that measure 6- or 24-hour urinary lead excretion after calcium EDTA challenge have been developed to identify persons with elevated body lead burdens. However, since chelatable lead predominantly reflects lead in soft tissues, which in most cases already correlates satisfactorily with blood lead, chelation challenges are seldom indicated in clinical practice. o Noninvasive in vivo x-ray fluorescence measurement of lead in bone, a test predominantly available in research settings, may provide the best index of long-term cumulative lead exposure and total body lead burden. o Other tests. Nonspecific laboratory findings that support the diagnosis of lead poisoning include anemia (normocytic or microcytic) and basophilic stippling of erythrocytes, a useful but insensitive clue. Acute high-dose exposure sometimes may be associated with transient azotemia (elevated BUN and serum creatinine) and mild to moderate elevation in serum transaminases. Recently ingested lead paint, glazes, chips, or solid lead objects may be visible on abdominal x-rays. CT or MRI of the brain often reveals cerebral edema in patients with lead encephalopathy. Because iron deficiency increases lead absorption, iron status should be evaluated. Treatment o Emergency and supportive measures ▪ Treat seizures (see Seizures) and coma (Coma And Stupor) if they occur. Provide Adequate Fluids To Maintain urine flow (optimally 1–2 mL/kg/h) but avoid overhydration, which may aggravate cerebral edema. Avoid phenothiazines for delirium, as they may lower the seizure threshold. o Patients with increased intracranial pressure may benefit from corticosteroids (eg, dexamethasone, 10 mg IV) and mannitol (0.25–1.0 g/kg IV as a 20–25% solution). o Specific drugs and antidotes. Treatment with chelating agents decreases blood lead concentrations and increases urinary lead excretion. Although chelation has been associated with improvement in symptoms and decreased mortality, controlled clinical trials demonstrating efficacy are lacking, and treatment recommendations have been largely empiric. Encephalopathy. Administer intravenous calcium EDTA [see EDTA, Calcium (Calcium Disodium EDTA, Calcium Disodium Edetate, Calcium Disodium Versenate)]. Some clinicians initiate treatment with a single dose of BAL (BAL), followed 4 hours later by concomitant administration of calcium EDTA and BAL. Symptomatic without encephalopathy. Administer oral succimer (DMSA, Succimer [DMSA]) or parenteral calcium EDTA [EDTA, Calcium (Calcium Disodium EDTA, Calcium Disodium Edetate, Calcium Disodium Versenate)]. Calcium EDTA is preferred as initial treatment if the patient has severe GI toxicity (eg, lead colic) or if the blood lead concentration is extremely  elevated (eg, > 150 mcg/dL). Unithiol (Unithiol [DMPS]) may be considered as an alternative to DMSA. Asymptomatic children with elevated blood lead levels. The Centers for Disease Control and Prevention (CDC) recommend treatment of children with levels of 45 mcg/dL or higher. Use oral succimer (DMSA, Succimer [DMSA]). A large randomized, double-blind, placebo-controlled trial of DMSA in children with blood lead concentrations between 25 and 44 mcg/dL found no evidence of clinical benefit. Asymptomatic adults. The usual treatment is removal from exposure and observation. Consider oral succimer (DMSA, Succimer [DMSA]) for patients with markedly elevated levels (eg,> 80-100 mcg/dL). Although D-penicillamine (see Penicillamine) is an alternative oral treatment, it may be associated with more side effects and less efficient lead diuresis. Blood lead monitoring during chelation. Obtain a blood lead measurement immediately prior to chelation and recheck the measurement within 24-48 hours after starting chelation to confirm that levels are declining. Recheck measurements 1 and 7 to 21 days after chelation to assess the extent of rebound in blood lead level associated with redistribution of lead from high bone stores and/or the possibility of reexposure. Additional courses of treatment and further. Silver Also called noble metal because of its use in making articles of value (e.g. coins, ornaments, jewelry) May be precipitated by HCl Pharmacological Action and Uses ○ Protein precipitant ○ Antiseptic, astringent, and corrosive to tissues ○ Possesses oligodynamic action ○ Treatment of burn (silver sulfadiazine) Toxicity: Discolors skin (argyria) which may result in growth retardation, hemopoiesis, cardiac enlargement, degeneration of the liver, destruction of renal tubules. Antidote: 6% Na2S2O3 + 1% K4Fe(CN)6 subcutaneously but requires several injections into the affected area. Arsenic compounds are found in a select group of industrial, commercial, and pharmaceutical products. Use of arsenic as a wood preservative in industrial applications (such as marine timbers and utility poles) accounts for two-thirds of domestic consumption, but former widespread use in new lumber sold for residential purposes (eg, decks, fencing, play structures) ended with a voluntary ban effective at the end of 2003. Arsenic-treated lumber used in residential structures and objects created prior to 2004 has not been officially recalled or removed. Arsenic-impregnated gels are used as ant baits, and a few organo arsenicals, such as methane arsonates and cacodylic acid, continue to be used as herbicides and defoliants. Phenyl Arsenic compounds are used as feed additives for poultry and swine, and intravenous arsenic trioxide, reintroduced to the US pharmacopoeia in 2000, is used as a drug for cancer chemotherapy. Inorganic arsenic is used in the production of nonferrous alloys, semiconductors, and certain types of glass. Inorganic arsenic is sometimes found in folk remedies and tonics, particularly from Asian sources. Artesian well water can be contaminated by inorganic arsenic from natural geologic deposits, and elevated levels of arsenic may be encountered in mine tailings and sediments and coal fly ash. Arsine, a hydride gas of arsenic, is discussed in Arsine. ○ Steel-gray brittle solid with a distinct metallic luster ○ It is widely known to be toxin that gained notoriety from its extensive use by Renaissance and was known as Poison of Kings and King of Poisons; ○ It is listed as the number one toxicant in the US.  ○ It is also a known carcinogenic agent Mechanism of toxicity. Arsenic compounds may be organic or inorganic and may contain arsenic in either a pentavalent (arsenate) or a trivalent (arsenite) form. Once absorbed, arsenicals exert their toxic effects through multiple mechanisms, including inhibition of enzymatic reactions vital to cellular metabolism, induction of oxidative stress, and alteration in gene expression and cell signal transduction. Although arsenite and arsenate undergo in vivo biotransformation to less toxic pentavalent monomethyl and dimethyl forms, there is evidence that the process also forms more toxic trivalent methylated compounds. o A. Soluble arsenic compounds, which are well absorbed after ingestion or inhalation, pose the greatest risk for acute human intoxication. o B. Inorganic arsenic dusts (such as arsenic trioxide) may exert irritant effects on the skin and mucous membranes. Contact dermatitis has also been reported. Although the skin is a minor route of absorption for most arsenic compounds, systemic toxicity has resulted from industrial accidents involving percutaneous exposure to highly concentrated liquid formulations. o C. The chemical warfare agent lewisite (dichloro [2-chlorovinyl] arsine) is a volatile vesicant liquid that causes immediate severe irritation and necrosis to the eyes, skin, and airways. o D. Arsenate and arsenite are known human carcinogens by both ingestion and inhalation. Toxic dose. The toxicity of arsenic compounds varies considerably with the valence state, chemical composition, and solubility. Humans are generally more sensitive than other animals to the acute and chronic effects of arsenicals. o A. Inorganic arsenic compounds. In general, trivalent arsenic (As3+) is 2–10 times more acutely toxic than pentavalent arsenic (As5+). However, overexposure to either form produces a similar pattern of effects, requiring the same clinical approach and management. 1.Acute ingestion of as little as 100–300 mg of a soluble trivalent arsenic compound (eg,sodium arsenite) could be fatal. 2. The lowest observed acute effect level (LOAEL) for acute human toxicity is approximately 0.05mg/kg, a dose associated with gastrointestinal distress in some individuals. 3. Death attributable to malignant arrhythmias has been reported after days to weeks of cancer chemotherapy regimens in which 0.15 mg/kg/day of arsenic trioxide was administered intravenously. 4. Repeated ingestion of approximately 0.04 mg/kg/day can result in gastrointestinal distress and hematologic effects after weeks to months and peripheral neuropathy after 6 months to several years. Lower chronic exposures, approximately 0.01 mg/kg/day, can result in characteristic skin changes (initially spotted pigmentation, followed within years by palmar-plantar hyperkeratosis) after intervals of 5–15 years. 5. The US National Research Council (2001) estimated that chronic ingestion of drinking water containing arsenic at a concentration of 10 mcg/L could be associated with an excess lifetime cancer risk greater than 1 in 1000. The latency period for development of arsenic-induced cancer is probably a decade or longer. o B. Organic arsenic. In general, pentavalent organoarsenic compounds are less toxic than either trivalent organoarsenic compounds or inorganic arsenic compounds. Marine organisms may contain large quantities of arsenobetaine, an organic trimethylated compound that is excreted unchanged in the urine and produces no known toxic effects. Arsenosugars (dimethylarsinoyl riboside derivatives) are present in some marine and freshwater animals (eg, bivalve mollusks) and marine algae (eg,seaweeds often used in Asian foods). Clinical presentation o A. Acute exposure most commonly occurs after accidental, suicidal, or deliberate poisoning by ingestion. A single, massive dose produces a constellation of multisystemic signs and symptoms that emerge over the course of hours to weeks. 1. Gastrointestinal effects. After a delay of minutes to hours, diffuse capillary damage results in hemorrhagic gastroenteritis. Nausea, vomiting, abdominal pain, and watery diarrhea are common. Although prominent gastrointestinal (GI) symptoms may subside within 24 to 48 hours, severe multisystemic effects may still ensue.  2. Cardiovascular effects. In severe cases, extensive tissue third spacing of fluids combined with fluid loss from gastroenteritis may lead to hypotension, tachycardia, shock, and death. Metabolic acidosis and rhabdomyolysis may be present. After a delay of 1–6 days, there may be a second phase of congestive cardiomyopathy, cardiogenic or noncardiogenic pulmonary edema, and isolated or recurrent cardiac arrhythmias. Prolongation of the QT interval may be associated with torsade de pointes ventricular arrhythmia. 3. Neurologic effects. Mental status may be normal, or there may be lethargy, agitation, or delirium. Delirium or obtundation may be delayed by 2–6 days. Generalized seizures may occur but are rare. Symmetric, sensorimotor axonal peripheral neuropathy may evolve 1–5 weeks after acute ingestion, beginning with painful distal dysesthesias, particularly in the feet. Ascending weakness and paralysis may ensue, leading in severe cases to quadriplegia and neuromuscular respiratory failure. 4. Hematologic effects. Pancytopenia, particularly leukopenia and anemia, characteristically develops within 1–2 weeks after acute ingestion. A relative eosinophilia may be present, and there may be basophilic stippling of red blood cells. 5. Dermatologic Effects. Findings that occasionally appear after a delay of 1-6 weeks include desquamation (particularly involving palms and soles), a diffuse maculopapular rash, periorbital edema, and herpes zoster or herpes simplex. Transverse white striae in the nails (Aldrich-Mees lines) may become apparent months after an acute intoxication. o B. Chronic intoxication is also associated with multisystemic effects, which may include fatigue and malaise, gastroenteritis, leukopenia and anemia (occasionally megaloblastic), sensory predominant peripheral neuropathy, hepatic transaminase elevation, noncirrhotic portal hypertension, and peripheral vascular insufficiency. Skin disorders and cancer may occur (see below), and a growing body of epidemiologic evidence links chronic arsenic ingestion with an increased risk of hypertension, cardiovascular mortality, diabetes mellitus, and chronic non- malignant respiratory disease. 1. Skin lesions, which emerge gradually over a period of 1–10 years, typically begin with a characteristic pattern of spotted ("raindrop") pigmentation on the torso and extremities, followed after several years by the development of hyperkeratotic changes on the palms and soles. Skin lesions may occur after lower doses than those causing neuropathy or anemia. Arsenic-related skin cancer, which includes squamous cell carcinoma, Bowen's disease, and basal cell carcinoma, is characteristically multicentric and occurs in non- sun-exposed areas. 2. Cancer. Chronic inhalation increases the risk of lung cancer. Chronic ingestion is an established cause of cancer of the lung, bladder, and skin. Diagnosis usually is based on a history of exposure combined with a typical pattern of multisystemic signs and symptoms. Suspect acute arsenic poisoning in a patient with abrupt onset of abdominal pain, nausea, vomiting, watery diarrhea, and hypotension, particularly when followed by an evolving pattern of delayed cardiac dysfunction, pancytopenia, and peripheral neuropathy. Metabolic acidosis and elevated CPK may occur early in the course of severe cases. Some arsenic compounds, particularly those of lower solubility, are radiopaque and may be visible on a plain abdominal x-ray. o A. Specific levels. In the first 2–3 days after acute symptomatic poisoning, total 24-hour urinary arsenic excretion is typically in excess of several thousand micrograms (spot urine greater than 1000 mcg/L) and, depending on the severity of poisoning, may not return to background levels (less than 50 mcg in a 24-hour specimen or less than 30 mcg/L in a spot urine) for several weeks. Spot urine analyses are usually sufficient for diagnostic purposes. 1. Ingestion of seafood, which may contain very large amounts of nontoxic organoarsenicals such as arsenobetaine and arsenosugars, can "falsely" elevate measurements of total urinary arsenic for up to 3 days. Speciation of urinary arsenic by a laboratory capable of reporting the concentration of inorganic arsenic and its primary human metabolites, monomethylarsinic acid (MMA) and dimethylarsinic acid (DMA), may sometimes be helpful: Background urine concentration of the sum of urinary inorganic arsenic, MMA, and DMA is usually less than 20 mcg/L in the absence of recent seafood ingestion. It should be noted that although arsenobetaine is excreted unchanged in the  urine, arsenosugars, which are abundant in bivalve mollusks and seaweed, are metabolized in part to DMA. 2.Blood levels are highly variable and are rarely of value in the diagnosis or management in patients capable of producing urine. Although whole-blood arsenic, normally less than 5 mcg/L, may be elevated early in acute intoxication, it may decline rapidly to the normal range despite persistent elevated urinary arsenic excretion and continuing symptoms. 3.Elevated concentrations of arsenic in nails or hair (normally less than 1 ppm) may be detectable in certain segmental samples for months after urine levels normalize but should be interpreted cautiously owing to the possibility of external contamination. o B. Other useful laboratory studies include CBC with differential and smear for basophilic stippling, electrolytes, glucose, BUN and creatinine, liver enzymes, CPK, urinalysis, ECG and ECG monitoring (with particular attention to the QT interval), and abdominal and chest x-rays. Treatment o A. Emergency and supportive measures 1.Maintain an open airway and assist ventilation if necessary (seeAirway) 2. Treat coma (see Coma and stupor), shock (Anaphylactic and anaphylactoid reactions), and arrhythmias (Ventricular arrhythmias) if they occur. Because of the association of arsenic with prolonged QT intervals, avoid quinidine, procainamide, and other type Ia antiarrhythmic agents. Phenothiazines should not be given as antiemetics or antipsychotics because of their ability to prolong the QT interval and lower the seizure threshold. 3. Treat hypotension and fluid loss with aggressive use of intravenous crystalloid solutions, along with vasopressor agents if needed, to support blood pressure and optimize urine output. 4. Prolonged inpatient support and observation are indicated for patients with significant acute intoxication, because cardiopulmonary and neurologic complications may be delayed for several days. Continuous cardiac monitoring beyond 48 hours is warranted in patients with persistent symptoms or evidence of toxin-related cardiovascular disturbance, including electrocardiographic abnormalities, or any degree of congestive heart failure. o B. Specific drugs and antidotes. Treat seriously symptomatic patients with chelating agents, which have shown therapeutic benefit in animal models of acute arsenic intoxication when administered promptly (ie, minutes to hours) after exposure. Treatment should not be delayed during the several days often required to obtain specific laboratory confirmation. 1. Unithiol [2, 3 - dimercaptopropanesulfonic acid, DMPS, Dimaval; see Unithiol], a water-soluble analog of dimercaprol (BAL) that can be administered intravenously, has the most favourable pharmacologic profile for treatment of acute arsenic intoxication. Although published experience is sparse, 3-5 mg/kg every 4 hours by slow intravenous infusion over 20 minutes is a suggested starting dose. In the United States, the drug is available through compounding pharmacists. 2. Dimercaprol (BAL, British anti-Lewisite, 2-3 dimercaptopropanol; see BAL) is the chelating agent of second choice if unithiol is not immediately available. The starting dose is 3-5 mg/kg by deep intramuscular injection every 4-6 hours. Lewisite burns to the skin and eyes can be treated with topical inunctions of dimercaprol. 3. Once patients are hemodynamically stable and GI symptoms have subsided, parenteral chelation may be changed to oral chelation with either oral unithiol, or oral succimer (DMSA, 2-3 dimercaptosuccinic acid; see Succimer [DMSA]). A suggested dose of unithiol is 4-8 mg/kg orally every 6 hours. Alternatively, give succimer, 7.5 mg/kg orally every 6 hours or 10 mg/kg orally every 8 hours. 4. The therapeutic endpoints of chelation are poorly defined. For chelation instituted to treat symptomatic acute intoxication, one empiric approach would be to continue treatment (initially parenterally, then orally) until total urinary arsenic levels are less than 500 mcg/24 hours (or spot urine < 300 mcg/L), levels below those associated with overt symptoms in acutely poisoned adults. Alternatively, oral chelation could be continued until total urinary arsenic levels reach background levels (< 50 mcg/24 hours or spot urine < 30 mcg/L). The value of chelation for treatment of an established neuropathy (or prevention of an incipient neuropathy) has not been proved.  Pharmacological Action and Uses ○ Protoplasmic poison ○ Effective in polycythemia vera (represses the bone marrow which overproduces RBC) Was once used as antisyphilitic agent and still currently present in some insecticides. Note: Hair analysis use to document time of arsenic exposure; Axillary or pubic hair is use to document long term exposure to arsenic. Antidotes: ○ Freshly prepared Iron (III) and Magnesium hydroxide (if still in the GI tract) ○ Dimercaprol (aka 2,3-dimercaptopropanol, British Anti-Lewisite or BAL) via IM injection Special Tests to determine the presence of Arsenic ○ 1. Gutzeit test ○ 2. Marsh test ○ 3. Reinsch test ○ “Lewisite” Antimony Is widely used as a hardening agent in soft metal alloys and alloys of lead; for compounding rubber; as a major flame retardant component of plastics and as a coloring agent in dyes and varnishes, paints and glazes. Exposure to antimony dusts and fumes may also occur during mining and refining of ores and from the discharge of firearms. Organic antimony compounds are used as antiparasitic drugs. Foreign or folk remedies may contain antimony potassium tartrate (Tartar emetic). ○ Compared to arsenic, it is less readily absorbed and produces topical irritation ○ More caustic to the skin than arsenic causing papular eruptions which develop into vesicular and pustular sores ○ Exhibits expectorant and nauseant action orally in small quantities ○ Exposure to Sb dust over a period of years leads to pneumoconiosis; It may also cause cardiac arrhythmias, spontaneous abortion, and dermatitis and inability of the blood to clot. ○ Mechanism of toxicity – Compounds probably act by binding to sulfhydryl groups, enhancing oxidative stress, and inactivating key enzymes. Ingested antimonials are also corrosive to mucosal membranes. ○ Toxic dose – The lethal oral dose of metallic antimony in rats is 100mg/kg body weightl the trivalent and pentavalent oxides are less toxic, with a Lethal Dose 50 (LD50) in rats ranging from 3200-4000mg.kg of body weight. The recommended workplace limit for antimony is 0.5mg/m3 as an 8-hour-time-weighted average. The air level considered immediately dangerous to life and health (ILDH) is 50mg/m3. ○ Clinical presentation (acute ingestion of antimony)- causes nausea, vomiting, hemorrhagic gastritis, and diarrhea ("cholera stibie"). Hepatitis and renal insufficiency may occur. Death is rare if the patient survives the initial gastroenteritis. Cardiac dysrhythmias (including torsade), pancreatitis, and arthralgias have been associated with the use of the organic antimonial compounds for treatment of parasitic infections (e.g. leishmaniasis). ○ Clinical presentation (Chronic exposure to antimony dust and fumes) - in the workplace is the most common type of exposure and may result in headache, anorexia, pneumonitis, peptic ulcers, and dermatitis (antimony spots). Sudden death presumably resulting from a direct cardiotoxic effect has been reported in workers exposed to antimony trisulfide. Based on evidence of in vitro genotoxicity and limited rodent carcinogenicity testing, antimony trioxide is a suspected carcinogen. ○ Diagnosis is based on a history of exposure and typical clinical presentation. A. Specific levels. Urine antimony levels are normally below 2 mcg/L. Serum and whole-blood levels are not reliable and are no longer used. Urine concentrations correlate poorly with workplace exposure, but exposure to air concentrations greater than the TLV-TWA will increase urinary levels. Urinary antimony is increased after firearm discharge exposure. There is no established toxic antimony level after stibine exposure. B. Other useful investigations include CBC, plasma-free hemoglobin, serum lactate dehydrogenase (LDH), free haptoglobin, electrolytes, BUN, creatinine, urinalysis for free  hemoglobin, liver transaminases, bilirubin, prothrombin time, and 12-lead ECG. Chest radiography is recommended for chronic respiratory exposures. ○ Treatment Large-volume intravenous fluid resuscitation may be necessary for shock caused by gastroenteritis (see Hypotension). Electrolyte abnormalities should be corrected, and intensive supportive care may be necessary with multiple organ failure. ○ Official Compound 1. Antimony potassium tartrate (KSbOC4H4O6) aka Tartar Emetic formerly used as emetic and expectorant used as anti-schistosomal agent (IV) Cadmium is found in sulfide ores, along with zinc and lead. Exposure is common during the mining and smelting of zinc, copper, and lead. The metallic form of Cd is used in electroplating because of its anticorrosive properties, the metallic salts are used as pigments and stabilizers in plastics, and Cd alloys are used in soldering and welding and in nickel-cadmium batteries. Cd solder in water pipes and Cd pigments in pottery can be sources of contamination of water and acidic foods. ○ It is a member of volatile metal group ○ Mechanism of toxicity. Inhaled Cd is at least 60 times more toxic than the ingested form. Fumes and dust may cause delayed chemical pneumonitis and resultant pulmonary edema and hemorrhage. Cd is a known human carcinogen (IARC Group 1). Ingested Cd is a GI tract irritant. Once absorbed, Cd is bound to metallothionein and filtered by the kidney, where renal tubule damage may occur. ○ Toxic dose A. Inhalation. The ACGIH-recommended threshold limit value (TLV-TWA) for air exposure to Cd dusts and fumes, established in 1993, is 0.01 (inhalable fraction) to 0.002 (respirable dusts) mg/m3 as an 8-hour time-weighted average. Exposure to 5 mg/m3 inhaled for 8 hours may be lethal. The level considered immediately hazardous to life or health (IDLH) for Cd dusts or fumes is 9 mg Cd/m3. B. Ingestion. Cd salts in solutions of greater than 15 mg/L may induce vomiting. The lethal oral dose ranges from 350 to 8900 mg. C. Water. The US Environmental Protection Agency has established a safe limit of 0.005 mg/L in drinking water. ○ Clinical Presentation A. Direct contact may cause local skin or eye irritation. There are no data on dermal absorption of Cd in humans. B. Acute inhalation may cause cough, wheezing, headache, fever, and, if severe, chemical pneumonitis and noncardiogenic pulmonary edema within 12–24 hours after exposure. C. Chronic inhalation at high levels is associated with lung cancer. D. Acute ingestion of Cd salts causes nausea, vomiting, abdominal cramps, and diarrhea, sometimes bloody, within minutes after exposure. Deaths after oral ingestion result from shock or acute renal failure. E. Chronic ingestion results in accumulation of Cd in bones, causing painful itai-itai ("ouch-ouch") disease, and in kidneys, causing renal disease. *Itai-itai disease (“ouch-ouch disease”) – first documented occurrence of mass cadmium poisoning in the world due to mining in Toyama Prefecture; contracted from drinking water and eating rice contaminated with cadmium ○ Symptoms: Weak and brittle bones Spinal and leg pain Anemia Kidney failure ○ Diagnosis is based on a history of exposure and the presence of respiratory complaints (after inhalation) or gastroenteritis (after ingestion).  A. Specific levels. Whole-blood Cd levels may confirm the exposure; normal levels are less than 1 mcg/L. Very little Cd is excreted in the urine until binding of Cd in the kidney is exceeded and renal damage occurs. Urine Cd values are normally less than 1 mcg/g of creatinine. Measures of tubular microproteinuria (beta-microglobulin, retinol- binding protein, albumin, and metallothionein) are used to monitor the early and toxic effects of Cd on the kidney. B. Other useful laboratory studies include CBC, electrolytes, glucose, BUN, creatinine, arterial blood gases or oximetry, and chest x-ray. ○ Treatment A. Emergency and supportive measures 1. Inhalation. Monitor arterial blood gases and obtain chest x-ray. Observe for at least 6-8 hours and treat wheezing and pulmonary edema (see Hypoxia and Bronchospasm) if they occur. After significant exposure, it may be necessary to observe for 1–2 days for delayed-onset noncardiogenic pulmonary edema. 2.Ingestion.Treatfluidlosscausedbygastroenteritiswithintravenouscrystalloidfluids B. Specific drugs and antidotes. There is no evidence that chelation therapy (eg, with BAL, EDTA,or penicillamine) is effective, although various chelating agents have been used. ○ Pharmacological Action Closely resembles zinc in action but is more toxic Behaves like mercury systemically and after absorption, produces death by arresting respiration; -its toxicity results to renal dysfunction with proteinuria with slow onset. Mercury (Hg) is a naturally occurring metal that is mined chiefly as HgS in cinnabar ore. It is converted to three primary forms, each with a distinct toxicology: elemental (metallic) mercury (Hgo), inorganic mercury salts (eg, mercuric chloride [HgCl2]), and organic (alkyl and aryl) mercury (eg,methylmercury). Approximately one-half to one-third of commercial mercury use is in the manufacture of chlorine and caustic soda, one-half to one third in electrical equipment, and the remainder in various applications, such as dental amalgam, fluorescent lamps, switches, thermostats, and artisanal gold production. In the United States, mercury use in batteries and paints has been discontinued. Previous use in pharmaceuticals and biocides has declined sharply, although mercuric chloride is still used as a stool fixative, and some organomercury compounds (such as mercurochrome, phenylmercuric acetate, and thimerosal) are still used as topical antiseptics or preservatives. Some folk medicines contain inorganic mercury compounds, and some Latin American and Caribbean communities have used elemental mercury in religious or cultural rituals. Aquatic organisms can convert inorganic mercury into methylmercury, with resulting bioaccumulation in large carnivorous fish such as swordfish. Also called liquid silver or quicksilver with low boiling point and melting point ○ Cinnabar (HgS) is a mineral source of mercury; aka Aethrop’s mineral ○ Mercury that falls into cracks and difficult to clean places is removed best by covering with powdered sulfur, allowing several days for conversion to sulfide then vacuumed. ○ Elemental mercury (Hg 0) can be converted chemically or biologically to its toxic form (Hg +,2+ ) and or the methylated or alkyl Hg which will result in kidney failure. ○ Mercury and its compounds are inherently toxic ○ Mechanism of toxicity - Mercury reacts with sulfhydryl (SH) groups, resulting in enzyme inhibition and pathologic alteration of cellular membranes. Elemental mercury and methylmercury are particularly toxic to the CNS. Metallic mercury vapour is also a pulmonary irritant. Methylmercury is associated with neurodevelopmental disorders. Inorganic mercuric salts are corrosive to the skin, eyes, and GI tract and are nephrotoxic. o Inorganic and organic mercury compounds may cause contact dermatitis. ○ Toxic dose. The pattern and severity of toxicity are highly dependent on the form of mercury and the route of exposure, mostly because of different pharmacokinetic profiles. Chronic exposure to any form may result in toxicity. See Table II–34 for a summary of absorption and toxicity. A. Elemental (metallic) mercury is a volatile liquid at room temperature. Hgo vapor is absorbed rapidly by the lungs and distributed to the CNS. Airborne exposure to 10 mg/m3 is considered immediately dangerous to life or health (IDLH), and chemical pneumonitis may occur at levels in excess of 1 mg/m3. In occupational settings, overt signs and symptoms of elemental mercury intoxication generally have required months to years of sustained daily exposure to airborne mercury levels of 0.05–0.2 mg/m3. The recommended workplace limit (ACGIH TLV-TWA) is 0.025 mg/m3 as an 8-hour time- weighted average; however, some studies suggest that subclinical effects on the CNS and kidneys may occur below this level. Liquid metallic mercury is poorly absorbed from GI tract, and acute ingestion has been associated with poisoning only in the presence of abnormal gut motility that markedly delays normal fecal elimination or after peritoneal contamination. B. Inorganic mercuric salts. The acute lethal oral dose of mercuric chloride is approximately 1 to 4 g. Severe toxicity and death have been reported after use of peritoneal lavage solutions containing mercuric chloride concentrations of 0.2-0.8%. C. Organic mercury 1. Mercury-containing antiseptics such as mercurochrome have limited skin penetration; however, in rare cases, such as topical application to an infected omphalocele, intoxication has resulted. Oral absorption is significant and may also pose a hazard. 2. Methylmercury is well absorbed after inhalation, ingestion, and probably dermal exposure. Ingestion of 10 to 60 mg/kg may be lethal, and chronic daily ingestion of 10 mcg/kg may be associated with adverse neurologic and reproductive effects. The US Environmental Protection Agency reference dose (RfD), the daily lifetime dose believed to be without potential hazard, is 0.1 mcg/kg/day. The RfD was derived from studies of neuropsychologic deficits arising from in utero exposure in humans. To minimize neurodevelopmental risk, the US EPA and FDA have advised pregnant women, women who might become pregnant, nursing mothers, and young children to avoid consumption of fish with high levels of mercury (such as swordfish) and to limit consumption of fish and shellfish with lower mercury levels to no more than 12 ounces (two average meals) perweek (www.epa.gov/waterscience/fishadvice/advice.html). 3.Dimethylmercury, a highly toxic synthetic liquid used in analytic chemistry, is well absorbed through the skin, and cutaneous exposure to only a few drops has resulted in a delayed but fatal encephalopathy. Causes Minamata disease (acquired through ingestion of contaminated fish, shellfish and sea mammals in Minamata Bay, Japan) Symptoms of poisoning: Initial: burning metallic taste, thirst, sore throat, visual field constriction, hearing loss, Latter: salivation, sore gums, bloody diarrhea, severe gastric pain, and cerebral cortex necrosis. Antidote: Egg white or milk – to inactivate mercury ions by coagulation followed by extensive gastric lavage Sodium formaldehyde sulfoxylate – for the bichloride Dimercaprol – agent of choice; given via IM or Penicillamine that would mobilize and excrete Hg in the urine. ○ Aside from being toxic, Mercury still has Therapeutic Uses Diuretic – mercurial diuretics bring about sodium and water diuresis by inhibiting the reabsorption of sodium  Antiseptic – mercuric ion is a protein precipitant Antisyphilitic – mercury and its salts have been used in the prophylaxis and treatment of syphilis (Calomel ointment) Cathartic Parasiticide and fungicide – used in the treatment of impetigo and ringworm infections in the form of Ammoniated Mercury Ointment Nickel It is was once known as “Old Nick’s copper” or “Kupfernickel” It is use favorably as alloying metal (eg. jewelry) due to its anticorrosive and hardness property. It can be used in nickel-based batteries, a catalyst in the hydrogenation of oil. Alloys: ○ Raney Nickel – nickel-aluminum alloy ○ German Silver – nickel, zinc, and copper alloy Nickel carbonyl (Ni[CO]4) – used in petroleum refining is the most toxic chemical known to humans. Exposure and toxicity may cause contact dermatitis, pulmonary congestion, inability to oxygenate hemoglobin especially if lesions are present in liver, kidney, adrenal gland, and speen.