Heavy Metals

Heavy metals

'Heavy metals' is a somewhat ambiguous term used to describe chemical elements that have metallic or metalloid properties with a specific gravity that is around five times or more than the specific gravity of water. Specific gravity is a measure of density, which compares a given amount of a solid substance to an equal amount of water. The specific gravity of water is 1 at 4 C (39 F). Some well-known toxic metallic elements with a specific gravity that is five or more times that of water are arsenic (5.7), cadmium (8.65), iron (7.9), lead (11.34), and mercury (13.546) (Lide 1992). There are approximately 23 heavy metals that are important or relevant to health protection and toxicology. Small amounts of some of these heavy metals are necessary for normal body function and good health, and are known as 'trace elements' (see below), e.g. iron, copper, and cobalt. Trace elements are present in the environment and in our diet. However, they can be toxic at higher doses. Other metals such...

Heavy metal toxicity

In general, heavy metal toxicity is rare in clinical practice. However, when it does occur, diagnosis may be delayed, compounding the clinical effects with delayed or inappropriate treatment and resulting in serious ill-health (Ferner 2001). Symptoms of acute heavy metal toxicity may be more easily recognized if there is a sufficient degree of suspicion and awareness of potential sources of exposure. Following acute toxic exposures, symptoms usually appear rapidly, thus diagnosis and treatment are often prompt (Ferner 2001). However, symptoms of chronic toxicity can be vague, so the establishment of a cause and effect relationship becomes difficult and symptoms may be misdiagnosed as those of a non-toxicological illness. The symptoms of chronic toxicity, e.g. impairment of brain function (cognitive dysfunction), learning difficulties, nervousness, insomnia, lethargy, and general malaise, also tend to vary in intensity with time. Heavy metal toxicity usually needs to be confirmed by...

David Baker Virginia Murray Norman HT Parkinson

A Review of Some Toxic Agents addresses in detail a selection of important toxic agents carbon monoxide pesticides heavy metals and trace elements as well as the emerging issues of traditional medicines and the deliberate release of toxic agents in warfare and terrorism. There are new chapters covering the toxic products of combustion and the increasingly important area of nanotoxicology.

The Supplement Shambles

Government Accountability Office (GAO) conducted an investigation. The GAO 2010 report indicated that dietary supplement products often were still promoted with deceptive and unfounded disease-related claims, encouraging consumers to use the products to prevent or treat diabetes, cancer, heart disease, Alzheimer's disease, and other serious conditions. The GAO investigation also found that most of the herbal supplement products tested were contaminated with heavy metals such as lead or pesticide residues, but usually at low levels.

Evaluation Guidelines Table95

Thyroid function testing is important to identify patients with thyroid orbitopathy, but it must be remembered that nearly a half of patients have normal thyroid function at the time they present with orbital manifestations. Patients with lead and other heavy metal poisoning can present with elevated intracranial pressure and false-localizing cranial nerve VI palsy. Urine screen for heavy metals is an important adjunct to the workup of these patients.

The Atomic Case The 3d Doubleshell Effect

An important conclusion to be drawn from the data in Table 1 is that the double-shell effect seems to vanish when moving down to the second-row (and presumably also third-row) transition series. Indeed, for Rh+ the difference between the CASPT2 results obtained with the small and large active space is never larger than 0.1 eV. Of course, this does not mean that radial 4d correlation effects do not affect the relative energies of configurations with a varying number of 4d electrons. The effect is still manifested at the CASSCF level, giving results for the d7dl-d8 splitting that are increased by up to 0.5 eV in CAS(11) as compared to CAS(6). However, the fact that the CASPT2 relative energies are virtually indifferent to the altered reference wavefunctions indicates that the differential 4d correlation effect can in a satisfactory manner be described by second-order perturbation theory. The 4d 4d transitions care even less about the presence of the 4d' shell than the 4d 5s transitions...

Physical Outcomes of Long Term Survivors

The Children's Oncology Group (2008) document titled Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers details the specific problems that have been seen following treatments with radiation, heavy metals, antimetabolites, alkylating agents, antitumor antibiotics, corticosteroids, anthracycline antibiotics, enzymes, plant alkaloids, and epipo-dophyllotoxins. The guide addresses the potential damage to each organ system and the follow-up needed. Treatments may affect the eye, ear, neuroendocrine system, oral cavity, thyroid, breast, heart, lungs, spleen, liver, gastrointestinal system, muscu-loskeletal system, urinary tract, and reproductive system.

As low as reasonably practicable

Once absorbed into the body heavy metals may partition between the blood, soft tissue, liver, kidney, bone, and teeth, although this varies dependent on the properties of the metal under consideration. Elimination of heavy metals from the body may take months or even years. For example, absorbed lead has an elimination half-life of 27 years from bone and is excreted primarily in urine. Numerous chelating agents exist that are able to bind to and enhance the rate of excretion of heavy metals from the body following acute and chronic poisoning. Table 14.1 lists those chelating agents currently recommended to be kept by emergency departments in the UK for heavy metal poisoning (College of Emergency Medicine 2008). The following sections contain a brief introduction to the toxicity of some of the more common heavy metals.

Agents affecting tissue respiration cyanides

Cyanide agents include the gas hydrogen cyanide (HCN) and the cyanogens. Following inhalation they act very quickly (short latency) and in high concentrations cause death by interfering with the normal function of oxygen at the mitochondria in the body cells. Early antidote therapy is essential for management. This involves either producing a variant of haemoglobin in the red cells of the blood (methaemoglobin), which binds to cyanide and renders it ineffective, or accelerating the breakdown of HCN by the enzyme rhodonase, which can be achieved by providing sodium thiosulphate. Another approach is to use dicobalt edetate. HCN combines with heavy metals and the cobalt ions in this compound act to remove HCN. The properties of cyanide are described in Box 17.7.

Classification Of Inorganic Pharmaceuticals

Here, the entire complex, metal ion, and ligands, determines the action. Many coordination compounds act as neurotoxins by blocking acetylcholine receptors. Cisplatin and other uncharged Pt(II) and Ru(II) complexes are active as antitumor drugs (Section 10.6.4) and Bi(III) complexes are used in the treatment of gastrointestinal diseases (Section 10.6.7). Insoluble salts of certain heavy metals can be applied as x-ray contrast compounds, such as BaSO4. The rare earth gadolinium is used in NMR diagnostics. Tin coordinated to protophorphyrin inhibits heme oxygenase degradation of a certain iron-heme product to bilirubin. The latter compound is the most frequent cause of neonatal jaundice.

Identification of Sperm Oxidative Stress from Clinical History

Male Infertility Causes Mnemonics

Exposure to oxins such as heavy metals through the manufacture of lead acid batteries or soldering fumes is known to create sperm oxidative stress 10, 11 and lead to sperm DNA damage, infertility and miscarriage 12, 13 . Several environmental pollutants have been linked with testicular oxidative stress. Pesticides such as lindane 14 , methoxychlor 15 and the herbicide dioxin-TCDD 16 have all been linked with testicular oxidative stress in rodent models. The commonly used preservative sulphur dioxide has also been shown to produce testicular oxidative stress in laboratory animals 17 . Air pollutants such as diesel particulate matter act as potent stimuli for leukocyte ROS generation 18, 19 . While no study has directly linked airborne pollutants with testicular oxidative stress, it is possible that this oxidative insult is responsible for the increase in sperm DNA damage seen following periods of airborne pollution 20 . Phthalates are chemicals used as a plastics softener and are...

Nonhereditary Idiopathic Cerebellar Ataxia

Differential Diagnosis and Evaluation. Xhe clinical phenotype of advanced IDCA-P MSA, consisting of ataxia, parkinsonism, and autonomic failure, is highly characteristic and rarely causes confusion with other disorders. In contrast, IDCA-C and incomplete or beginning forms of IDCA-P MSA must be carefully distinguished from symptomatic cerebellar ataxia. Degeneration of the cerebellar cortex in patients with chronic cerebellar ataxia may be due to alcoholism, various toxic causes (antiepileptics, cytostatic drugs, lithium, solvents, heavy metals), remote effects of malignancy (paraneoplastic cerebellar degeneration), malabsorption with vitamin E deficiency, increased body temperature (heat stroke, neuroleptic malignant syndrome, sepsis), and hypothyreosis.

Core Elements of Integrative Medicine

Monitoring for clinical bleeding and for low-density lipo-protein (LDL) cholesterol and glycemic response should be considered for patients taking doses higher than 3 g day, especially if they are diabetic. Unfortunately, because our waters are polluted with heavy metals, avoiding fish known to have high methyl mercury levels (especially by women who are pregnant and of childbearing age) is an important precaution when discussing fish oil use with patients (Williams, 2005). Along with fish oil consumption, other dietary modifications are also known to help lessen inflammation Table 11-7 shows guidelines for prescribing an antiinflammatory diet (Rakel, 2003 Rakel and Rindfleisch, 2006).

Origin of ROS in Semen

Cellular defence mechanisms to kill pathogens. If activated, leukocyte ROS generation can be up to 1,000-times higher than that of spermatozoa 9, 13 . In addition, ROS and oxidative stress in semen can also be caused by numerous other factors (for review see 14, 15 ). Among them are exogenous sources such as environmental pollution by heavy metals 16 or other chemical compounds 17 , and even lifestyle factors such as obesity 18 , smoking 19 , alcohol consumption 20 and certain medical conditions such as spinal cord injuries 21 or varicoceles 22 ,

Effects of Heat Stress on the Cell Kinetics of the Germ Cells

Heat Stress Fertility Decline

Nonenzymatic antioxidant molecules include a-tocopherol (vitamin E), b-carotene (vitamin A), ascorbate (vitamin C), glutathione, estrogens, creatine (related to carotene) flavonoids (aromatic oxygen heterocyclic compounds widely distributed in higher plants), resveratrol (a botanical antioxidant), metallothionein (cadmium-binding protein involved in heavy metal detoxification), taurine (an aminosulfonic acid) and its precursors, and other thiols such as nonstructural polyunsaturated lipids and melatonin. Oral administration of vitamin E reduced the level of testicular-free radicals in a rat experimental model of varicocele 119 , and the effectiveness of anti-oxidants to treat infertile men has been previously demonstrated in randomized trials 120 . Therefore, antioxidants can be effectively applied to treat heat-inducible oxidative stress in humans.

Thermistor thermometers

Thermistors are semiconductors made from the fused oxides of heavy metals such as cobalt, manganese and nickel. They demonstrate marked and non-linear variation in resistance with temperature, which is usually compensated by electronic processing. Disadvantages include inconsistent variation between individual thermistors, change in resistance over time, and hysteresis during rapid heating and cooling. However, the large temperature coefficient permits the detection of small temperature changes and the tiny 'pin-head' size results in a rapid response. They are used widely in invasive temperature monitoring, e.g. in pulmonary artery catheters.

Distribution and Incidence

Introduction of coinage during Greece's Classical Period resulted in a phenomenal increase in silver (and therefore, lead) production, which was exaggerated by Roman exploitation to the point of ore exhaustion, leading to a marked reduction of that form of mining after the decline of the Roman Empire. Reference to lead intoxication can be found in the various Greek and Roman writers of antiquity (details under History and Geography Historical Antiquity). It was then not until the late Middle Ages that lead production rose again, this time in Europe, with recognition of lead's utility now justifying its acquisition for its own sake. Although the Spanish pursuit of silver in the New World was second only to that of gold, the miners' mortality was largely due to factors other than poisoning from lead in the ore, and heavy metal toxicity during the silver extraction process was related primarily to the mercury used after 1570. It was the Industrial Revolution, with its enormous surge in...

Amyotrophic Lateral Sclerosis

Clusters of the disease have been identified, particularly in the Kii peninsula of Japan and the Mariana Islands. The only indisputable risk factor other than age and gender is genetic susceptibility, with familial cases occurring in about 10 percent of most case series. Many isolated potential etiologies have been proposed for sporadic ALS, with the only consistent associations thus far being long-term exposure to heavy metals, particularly lead, and a family history of parkinsonism and dementia.

Melanogenesis And Melanin Formation From Tyrosine

Formaci Melanina

Raper used an enzyme obtained from meal worms. He concluded that the enzyme was essential only for the first stage, i.e., the conversion of tyrosine to dopa and then dopa to dopaquinone. The latter stages occurred spontaneously without enzyme (75,76). The importance of temperature and pH control, the purity of the enzyme and hence its activity, the amount of substrate present, and the influence of certain heavy metals in the reaction rate were also recognized by Raper (77). The percentage of nitrogen (8.4 ) in the melanin formed was found to be slightly higher than in tyrosine, indicating that no deamination occurs during this enzymatic reaction (78).

Nuclear

Radiation hazards are a problem in the nuclear power industries and the health care services. Traditional protection is by shielding with materials containing heavy metals, for example, leaded aprons are used to protect against X-rays. Disposable non-woven clothing such as polyethylene spun-bonded materials are used in the nuclear power industries. They will not protect against gamma rays but stop radioactive dust and grease containing radioactive particles from coming in contact with the skin.

Clinical History

Patients should be asked whether they are receiving antiepileptic (phenytoin, carbamazepine) or cytotoxic drugs (fluorouracil, cytarabine), lithium, or alcohol, and whether they have been exposed to any toxins (heavy metals, solvents). Ataxia might be associated with primary nervous system tumors such as astrocytomas and medulloblastomas and malignant disorders (bronchial and ovarian carcinoma, Hodgkin's disease), infections (varicella, Epstein-Barr virus), or hypothyroidism.

The Nasal Route

Chemicals like lipophilic atmospheric pollutants (solvents, engine smoke, aryl hydrocarbons), or drugs of addiction like cocaine or amphetamine derivatives, may rapidly enter the brain by the nasal route (part 2 of Fig. 1), and possibly promote reversible or irreversible alterations of nervous functioning (4). Anatomical pathways may allow molecular movement in the cerebrospinal fluid (CSF) from the subepithelial olfactory space and from the olfactory bulb, to the entorhinal cortex. Another possibility involves the transport in the axons of the olfactory neurons, as demonstrated for heavy metals, which can reach easily the brain in this way (5). Nasal drug intake has appeared to be a fast and effective route of administration, suitable for drugs that must act rapidly and are taken in small amounts, like antimigraine drugs, analgesics, vitamin B-12 or apomorphine. Nasal administration also prevents gastrointestinal clearance and hepatic metabolism and seems to be a promising route for...

TABLE 638 Continued

Proximal RTA may occur as an inherited disorder (Lowe's syndrome, cystinosis, Wilson's disease, hereditary fructose intolerance and tyrosinemia) and present in infancy alternatively, it may be acquired following exposure to proximal tubular toxins (heavy metals), or in the setting of drug therapy

Trace elements

In the toxicological biological sciences, trace elements are generally considered to be those elements, including some heavy metals, which are essential to health in trace amounts, or where there is some evidence to support claims that they have some benefit to health. These are described as 'essential' or 'probably essential' and are often commercially available in multivitamin products or other food supplements. The Expert Group on Vitamins and Minerals (EVM) lists the following as trace elements boron, chromium, cobalt, copper, germanium (now withdrawn as a supplement due to toxicity), iodine, manganese, molybdenum, nickel, selenium, tin, vanadium, and zinc (EVM 2003).

Finishes

Antimicrobial agents are those that kill or inhibit the growth of microorganisms. To effectively inhibit microorganism growth, the antimicrobial agent must interrupt the growth cycle. Some important targets in the growth cycle include the cell wall, cytoplasmic membrane, protein synthesis, and nucleic acid synthesis (Brock et al. 1994). Depending on those microorganisms the chemical agents are designed to attack, antimicrobial agents can be further classified as bactericides, fungicides, disinfectants, antiseptics, chemotherapeutic agents, and antibiotics. The sensitivity of microorganisms to antimicrobial agents varies. Gram positive bacteria are usually more sensitive to antibiotics than gram negative bacteria. A broad spectrum antibiotic will act on a wider range of microorganisms than just a single group. Some agents have an extremely limited spectrum of action, being effective for only one or a few species. Likewise, different antimicrobial agents vary in their selective...

Metallic Ions

Oxidative stress is a common feature of the mechanism of injury induced by a broad range of environmental agents 34 . Metal ions also induce production of ROS directly through the Haber-Weiss reaction. Toxicologically, a wide variety of environmental contaminants ranging from aromatic hydrocarbons 35 to heavy metal ions 6 has been shown to impair mitochondrial respiration, with ensuing production of ROS. Redox-active metals, such as iron, copper, and chromium, undergo redox cycling, whereas redox-inactive metals, such as lead, cadmium, mercury, and others, deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of ROS such as hydroxyl radical (HO ), superoxide radical (O -), or hydrogen peroxide (H2O2 . Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals 36 ,

Arsenic

Chelators essentially reverse or prevent the attachment of heavy metals to various essential body chemicals. While chelation may alleviate the acute symptoms, there is no evidence indicating that it improves chronic symptoms such as peripheral neuropathy or encephalopathy. In fact, once neuropathy occurs, BAL treatment is not considered effective. Intravenous fluids for dehydration and morphine for abdominal pain should also be given. In alcoholics who develop arsenic encephalopathy, vitamins should be administered to replace nutritional deficits.

Chelation Therapy

Chelation therapy has been a proven treatment for lead and other heavy-metal poisoning for half a century. Injected into the bloodstream, chelation chemicals extract harmful overdoses of minerals, enabling their eventual excretion. Chelation is still used today as an approved treatment for heavy-metal toxicity. The danger of potentially fatal kidney damage from chelation is outweighed in these cases by the even more serious toxicity of the metal poisoning. Some practitioners, however, claim that chelation can treat illnesses and problems other than metal toxicity. Coronary artery disease is primary among these illnesses. Based on the idea that chelation chemicals may remove harmful plaque from the arteries, it is promoted as an alternative to coronary bypass surgery and angioplasty. Chelation is advertised also as a treatment for thyroid disorders, multiple sclerosis, muscular dystrophy, high cholesterol, psoriasis, hypercalcemia, hardening of the arteries, cancer, Alzheimer's...

Chelating Agents

2,3,DimercaptoI (British antilewisite 'BAL') was synthesized during World War II as an antidote for arsenic-containing lewisite gas. This compound has also been found to be effective against the toxic manifestations of arsenic, mercury, gold, antimony, and other heavy metals. With doses of 2.5 mg kg of body weight, toxic symptoms develop in less than 1 percent of individuals with twice that dose, there is a 50 to 60 percent increase in the occurrence of intoxication. Symptoms appear within 10 to 20 minutes after injection of the drug and subside within 50 to 90 minutes. The usual reaction consists of headache, burning sensations in the mouth and eyes, muscular aches, paresthesias, pain in the teeth, lacrimation, salivation, rhinorrhea, and profuse sweating. Restlessness, anxiety, and general agitation may also develop, with progression in some instances to generalized convulsions and stupor. Abdominal pain, apprehension, blepharospasm, piloerection, tachycardia, and palpitations may...

Selenium

Selenium functions as an antioxidant alone in the detoxification of heavy metals in the body and as a cofactor of the antioxidant enzyme glutathione per-oxidase. Dietary selenium deficiency increases tissue oxidative damage and it seems that selenium has a sparing effect on tissue levels of vitamin E. However in experimental studies selenium deficiency does not impair endurance capacity in rats and supplementation in humans has no effect on physical performance 82 . Selenium has also been shown to be important for the immune system. This is of special concern in the Scandinavian countries, which have selenium-poor soils, and has led to specific programs to add selenium to fertilizers in Finland in order to increase the dietary intake of selenium. In this context it is of interest that it has been shown that selenium status in Swedish athletes is subnormal and lower than in Finnish athletes

Toxic Neuropathies

Toxic neuropathies occur from repeated exposure to drugs, industrial toxins, or heavy metals (Box 42-22). Presentation depends on the exact exposure and what part of the nerve is affected. It may present as a progressive, symmetric, ascending polyneuropathy, as in many occupational exposures, or with vague sensory changes similar to those of nutritional neuropathies. Lead intoxication creates a motor neuropathy starting in the upper limbs, affecting the radial nerve and causing wristdrop. Many of these neuropathies slowly improve once the offending agent is removed however, this is not always the case. A careful medical and occupation history is important. Treatment is directed accordingly.

Fires involving wood

In addition to the hazardous products from the combustion of wood, burning of wood incorporating preservatives, such as the heavy-metal-containing preservative chromate copper arsenate, may lead to the liberation of heavy metals as oxides such as chromium trioxide and arsenic trioxide (Lundholm et al. 2007).

Assessment Protocol

Basic laboratory tests in an acute assessment include complete blood cell count, electrolytes, glucose, blood urea nitrogen, creatinine, total protein, liver function tests, calcium, magnesium, phosphorus, thyroid function tests, pregnancy test, and urinalysis. Additional tests to consider include arterial blood gases, heavy metals screening, serum B12, folate, lupus erythema-tosus preparation, antinuclear antibody, urinary porphyrins, ammonia levels, erythrocyte sedimentation rate, and HIV. Medication drug screens might include serum drug levels (lithium, anticonvulsants, tricyclic antidepressants, digoxin, and cyclosporine) and urine toxicology. Common procedures in the acute assessment include the chest X ray, lumbar puncture, computed tomography scan, magnetic resonance imaging, electroencephalogram, electrocardiogram, echocardiogram, and endoscopy.