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Biomedical subjects

D G Barceloux

Publications and source records attributed to D G Barceloux.

10 recordsLinked to original sources

Selenium.

The 4 natural oxidation states of selenium are elemental selenium (0), selenide (-2), selenite (+4), and selenate (+6). Inorganic selenate and selenite predominate in water whereas organic selenium compounds (selenomethionine, selenocysteine) are the major selenium species in cereal and in vegetables. The principal applications of selenium include the manufacture of ceramics, glass, photoelectric cells, pigments, rectifiers, semiconductors, and steel as well as use in photography, pharmaceutical production, and rubber vulcanizing. High concentrations of selenium in surface and in ground water usually occur in farm areas where irrigation water drains from soils with high selenium content (Kesterson Reservoir, California) or in lakes receiving condenser cooling water from coal-fired electric power plants (Belews Lake, North Carolina). For the general population, the primary pathway of exposure to selenium is food, followed by water and air. Both selenite and selenate possess substantial bioavailability. However, plants preferentially absorb selenates and convert them to organic compounds. Aquatic organisms (e.g., bivalves) can accumulate and magnify selenium in the food chain. Selenium is an essential component of glutathione peroxidase, which is an important enzyme for processes that protect lipids in polyunsaturated membranes from oxidative degradation. Inadequate concentrations of selenium in the Chinese diet account, at least in part, for the illness called Keshan disease. Selenium deficiency occurs in the geographic areas where Balkan nephropathy appears, but there is no direct evidence that selenium deficiency contributes to the development of this chronic, progressive kidney disease. Several lines of scientific inquiry suggest that an increased risk of cancer occurs as a result of low concentrations of selenium in the diet; however, insufficient evidence exists at the present time to recommend the use of selenium supplements for the prevention of cancer. The toxicity of most forms of selenium is low and the toxicity depends on the chemical form of selenium. The acute ingestion of selenious acid is almost invariably fatal, preceded by stupor, hypotension, and respiratory depression. Chronic selenium poisoning has been reported in China where changes in the hair and nails resulted from excessive environmental exposures to selenium. Garlic odor on the breath is an indication of excessive selenium exposure as a result of the expiration of dimethyl selenide. The US National Toxicology Program lists selenium sulfide as an animal carcinogen, but there is no evidence that other selenium compounds are carcinogens.

Animals

Chromium.

Chromium occurs primarily in the trivalent state (III), which is the most stable form, or in the hexavalent state (VI), which is a strong oxidizing agent. Elemental chromium (0) does not occur naturally on earth. Trivalent chromium (III) is an essential trace metal necessary for the formation of glucose tolerance factor and for the metabolism of insulin. Commercial applications of chromium compounds include tanning (III), corrosion inhibition, plating, glassware-cleaning solutions, wood preservatives (VI), manufacture of safety matches, metal finishing (VI), and the production of pigments (III, VI). Hexavalent chromium (VI) contaminated local soil when chromium waste slag was part of the fill material present in residential, public, and industrial areas. In some urban areas, about two-thirds of the chromium in air results from the emission of hexavalent chromium from fossil fuel combustion and steel production. The remaining chromium in air is the trivalent form. The residence time of chromium in air is < 10 days, depending on the particle size. Trivalent compounds generally have low toxicity and the gastrointestinal tract poorly absorbs these compounds. Hexavalent chromium is a skin and mucous membrane irritant and some of these hexavalent compounds are strong corrosive agents. Hexavalent chromium compounds also produce an allergic contact dermatitis characterized by eczema. Sensitivity to trivalent compounds is much less frequent, but some workers may react to high concentrations of these compounds. Hexavalent chromium is recognized by the International Agency for Research on Cancer and by the US Toxicology Program as a pulmonary carcinogen. The increased risk of lung cancer occurs primarily in workers exposed to hexavalent chromium dust during the refining of chromite ore and the production of chromate pigments. Although individual studies suggest the possibility of an excess incidence of cancer at sites outside the lung, the results from these studies are inconsistent.

Animals

Cobalt.

Cobalt is a relatively rare magnetic element with properties similar to iron and nickel. The two valance states are cobaltous (II) and cobaltic (III) and the former is the most common valance used in the chemical industry. Cobalt occurs in nature primarily as arsenides, oxides, and sulfides. Most of the production of cobalt involves the metallic form used in the formation of cobalt superalloys. The term "hard metal" refers to compounds containing tungsten carbide (80-95%) combined with matrices formed from cobalt (5-20%) and nickel (0-5%). For the general population, the diet is the main source of exposure to cobalt. In the occupational setting, exposure to cobalt alone occurs primarily during the production of cobalt powders. In other industrial exposures (e.g., hard metal, diamond polishing), additional agents (tungsten) modulate the toxicity of cobalt. Cobalt is an essential element necessary for the formation of vitamin B12 (hydroxocobalamin); however, excessive administration of this trace element produces goiter and reduced thyroid activity. In 1966, the syndrome "beer drinker's cardiomyopathy" appeared in Quebec City, Canada, and was characterized by pericardial effusion, elevated hemoglobin concentrations, and congestive heart failure. An interstitial pulmonary fibrosis has been associated with industrial exposure to hard metal dust (tungsten and cobalt), but not to cobalt alone. Exposure to cobalt alone produces an allergic contact dermatitis and occupational asthma. Treatment of cobalt toxicity is primarily supportive.

Animals

Copper.

Copper is an essential trace element, which is an important catalyst for heme synthesis and iron absorption. Following zinc and iron, copper is the third most abundant trace element in the body. Copper is a noble metal, like silver and gold. Useful industrial properties include high thermal and electrical conductivity, low corrosion, alloying ability, and malleability. Most of the metallic copper appears in electrical applications. Copper is a constituent of intrauterine contraceptive devices and the release of copper is necessary for their contraceptive effects. The average daily intake of copper in the US is about 1 mg Cu with the primary source being the diet. The bioavailability of copper from the diet is about 65-70% depending on a variety of factors including chemical form, interaction with other metals, and dietary components. The biological half-life of copper from the diet is 13-33 days with bilary excretion being the major route of elimination. Copper sulfate is a gastric irritant that produces erosion of the lining of the gastrointestinal tract. Chronic copper toxicity is rare and primarily affects the liver. Wilson's disease and Indian childhood cirrhosis are examples of severe chronic liver disease that results from the genetic predisposition to the hepatic accumulation of copper. The serum copper concentration ranges up to approximately 1.5 mg/L in healthy persons. Gastrointestinal symptoms occur at whole blood concentrations near 3 mg Cu/L. Chelating agents (CaNa2EDTA, BAL) are recommended in severe poisoning, but there are little pharmacokinetic data to evaluate the effectiveness of these agents.

Animals

Molybdenum.

Molybdenum does not exist naturally in the pure metallic form and of the 5 oxidation states (2-6) the predominant species are Mo(IV) and Mo(VI). Molybdenum rapidly polymerizes to a wide variety of complex polymolybdate compounds in solution. The vast majority of molybdenum is used in metallurgical applications (stainless steel, cast-iron alloys). Ammonium tetrathiomolybdate is an experimental chelating agent for Wilson's disease. For the general population, the diet is the most important source of molybdenum and concentrations in water and air usually are negligible. The average daily dietary intake is about 0.1-0.5 mg m.o. Molybdenum is an essential element with relatively low toxicity. Enzymes containing molybdenum catalyze basic metabolic reactions in the carbon, sulfur, and nitrogen cycles. Elimination of molybdenum occurs via the kidney and usually is complete within several weeks. Molybdenosis (teart) is a form of molybdenum toxicity that produces a disease in ruminants similar to copper-deficiency. Little data are available on the human toxicity of molybdenum. A gout-like syndrome and pneumoconiosis have been associated with excessive concentrations of molybdenum, but the inadequate design of the studies prevents an adequate determination of the etiology of these effects.

Animals

Nickel.

Nickel is an essential element for at least several animal species. These animal studies associate nickel deprivation with depressed growth, reduced reproductive rates, and alterations of serum lipids and glucose. Although there is substantial evidence of an essential status for nickel in animals, a deficiency state in humans has not been clearly defined. Nickel is a silver-white metal with siderophilic properties that facilitate the formation of nickel-iron alloys. In contrast to the soluble nickel salts (chloride, nitrate, sulfate), metallic nickel, nickel sulfides, and nickel oxides are poorly water-soluble. Nickel carbonyl is a volatile liquid at room temperature that decomposes rapidly into carbon monoxide and nickel. Drinking water and food are the main sources of exposure for the general population with the average American diet containing about 300 micrograms Ni/d. Nickel is highly mobile in soil, particularly in acid soils. There is little evidence that nickel compounds accumulate in the food chain. Nickel is not a cumulative toxin in animals or in humans. Almost all cases of acute nickel toxicity result from exposure to nickel carbonyl. The initial effects involve irritation of the respiratory tract and nonspecific symptoms. Patients with severe poisoning develop intense pulmonary and gastrointestinal toxicity. Diffuse interstitial pneumonitis and cerebral edema are the main cause of death. Sodium diethyldithiocarbamate is an investigational drug used to chelate nickel following exposure to nickel carbonyl. Nickel is a common sensitizing agent with a high prevalence of allergic contact dermatitis. Nickel and nickel compounds are well-recognized carcinogens. However, the identity of the nickel compound or compounds, which cause the increased risk of cancer, remains unclear. Currently, there are little epidemiological data to indicate that exposure to metallic nickel increases the risk of cancer, or that exposure to the carcinogenic forms of nickel causes cancer outside the lung and the nasal cavity.

Animals

Vanadium.

Vanadium is a steel-grey, corrosion-resistant metal, which exists in oxidation states ranging from -1 to +5. Metallic vanadium does not occur in nature, and the most common valence states are +3, +4, and +5. The pentavalent form (VO3-) predominates in extracellular body fluids whereas the quadrivalent form (VO+2) is the most common intracellular form. Because of its hardness and its ability to form alloys, vanadium (i.e., ferrovanadium) is a common component of hard steel alloys used in machines and tools. Although most foods contain low concentrations of vanadium (< 1 ng/g), food is the major source of exposure to vanadium for the general population. High air concentrations of vanadium occur in the occupation setting during boiler-cleaning operations as a result of the presence of vanadium oxides in the dust. The lungs absorb soluble vanadium compounds (V2O5) well, but the absorption of vanadium salts from the gastrointestinal tract is poor. The excretion of vanadium by the kidneys is rapid with a biological half-life of 20-40 hours in the urine. Vanadium is probably an essential trace element, but a vanadium-deficiency disease has not been identified in humans. The estimated daily intake of the US population ranges from 10-60 micrograms V. Vanadyl sulfate is a common supplement used to enhance weight training in athletes at doses up to 60 mg/d. In vitro and animal studies indicate that vanadate and other vanadium compounds increase glucose transport activity and improve glucose metabolism. In general, the toxicity of vanadium compounds is low. Pentavalent compounds are the most toxic and the toxicity of vanadium compounds usually increases as the valence increases. Most of the toxic effects of vanadium compounds result from local irritation of the eyes and upper respiratory tract rather than systemic toxicity. The only clearly documented effect of exposure to vanadium dust is upper respiratory tract irritation characterized by rhinitis, wheezing, nasal hemorrhage, conjunctivitis, cough, sore throat, and chest pain. Case studies have described the onset of asthma after heavy exposure to vanadium compounds, but clinical studies to date have not detected an increased prevalence of asthma in workers exposed to vanadium.

Animals

Zinc.

The use of zinc in metal alloys and medicinal lotions dates back before the time of Christ. Currently, most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. Some studies support the use of zinc gluconate lozenges to treat the common cold, but there are insufficient data at this time to recommend the routine use of these lozenges. Zinc is an essential co-factor in a variety of cellular processes including DNA synthesis, behavioral responses, reproduction, bone formation, growth, and wound healing. Zinc is a relatively common metal with an average concentration of 50 mg/kg soil and a range of 10-300 mg/kg soil. Meat, seafood, dairy products, nuts, legumes, and whole grains contain relatively high concentrations of zinc. The mobility of zinc in anaerobic environments is poor and therefore severe zinc contamination occurs primarily near points sources of zinc release. The recommended daily allowance for adults is 15 mg zinc. The ingestion of 1-2 g zinc sulfate produces emesis. Zinc compounds can produce irritation and corrosion of the gastrointestinal tract, along with acute renal tubular necrosis and interstitial nephritis. Inhalation of high concentrations of zinc chloride from smoke bombs detonated in closed spaces may cause chemical pneumonitis and adult respiratory distress syndrome. In the occupational setting inhalation of fumes from zinc oxide is the most common cause of metal fume fever (fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, salivation). Zinc compounds are not suspected carcinogens. Treatment of zinc toxicity is supportive. Calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) is the chelator of choice based on case reports that demonstrate normalization of zinc concentrations, but there are few clinical data to confirm the efficacy of this agent.

Animals

Manganese.

Manganese is a very hard, brittle metal, which is used to increase the strength of steel alloys. Absorption from the gastrointestinal tract occurs in the divalent and tetravalent forms. Permanganates, which are strong oxidizing agents, have a +7 valence. The principal organomanganese compound is the anti-knock additive, methylcyclopentadienyl manganese tricarbonyl. Manganese is a ubiquitous constituent of the environment comprising about 0.1% of the earth's crust. For the general population, food is the most important source of manganese with daily intake ranging from 2-9 mg Mn. Combustion of gasoline containing methylcyclopentadienyl manganese tricarbonyl releases submicron particles of Mn3O4 that are potentially respirable. Biomagnification of manganese in the food chain probably does not occur. The lungs and gastrointestinal tract absorb some manganese, but the relative amounts absorbed from each site are not known. Homeostatic mechanisms limit the absorption of manganese from the gastrointestinal tract. Elimination of manganese occurs primarily by excretion into the bile. Animal studies indicate that manganese is an essential co-factor for enzymes, such as hexokinase, superoxide dismutase, and xanthine oxidase. However, no case of manganese deficiency in humans has been identified. Manganism is a central nervous system disease first described in the 1800s following exposure to high concentrations of manganese oxides. Manganese madness was the term used to describe the initial psychiatric syndrome (compulsive behavior, emotional lability, hallucinations). More commonly, these workers developed a Parkinson's-like syndrome. Currently, the risks of exposure to low concentrations of manganese in the industrial and in the environmental settings (e.g., methylcyclopentadienyl manganese tricarbonyl in gasoline) are being evaluated with regards to the development of subclinical neuropsychological changes. The American Conference of Governmental and Industrial Hygienists recently lowered the TLV-TWA for manganese compounds and inorganic manganese compounds to 0.2 mg Mn/m3.

Animals

American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee.

Fomepizole (4-methylpyrazole, 4-MP, Antizol) is a potent inhibitor of alcohol dehydrogenase that was approved recently by the US Food and Drug Administration (FDA) for the treatment of ethylene glycol poisoning. Although ethanol is the traditional antidote for ethylene glycol poisoning, it has not been studied prospectively. Furthermore, the FDA has not approved the use of ethanol for this purpose. Case reports and a prospective case series indicate that the intravenous (i.v.) administration of fomepizole every 12 hours prevents renal damage and metabolic abnormalities associated with the conversion of ethylene glycol to toxic metabolites. Currently, there are insufficient data to define the relative role of fomepizole and ethanol in the treatment of ethylene glycol poisoning. Fomepizole has clear advantages over ethanol in terms of validated efficacy, predictable pharmacokinetics, ease of administration, and lack of adverse effects, whereas ethanol has clear advantages over fomepizole in terms of long-term clinical experience and acquisition cost. The overall comparative cost of medical treatment using each antidote requires further study.

Antidotes