Heavy Metals

Reduces Heavy Metal Toxicity

Selenium protects against toxicity of some heavy metals such as cadmium, arsenic, lead, silver and mercury (Berry & Galle 1994, Lindh et al 1996, Navarro-Alarcon & Lopez-Martinez 2000, Yiin et al 1999a, b, 2000, 2001). A physiological role for selenium in counteracting heavy metal poisoning has been proposed (Shils et al 2006). It appears that the form of selenium is important, as inorganic selenium has been shown to enhance the toxic effects of inorganic arsenic by increasing its retention in tissues and suppressing its metabolism in vitro (Styblo & Thomas 2001).

Preface To The Series

The assessment of safe to use starts with the harvested plant material which has to comply with an official monograph. This may require absence of, or prescribed limits of, radioactive material, heavy metals, aflatoxin, pesticide residue, as well as the required level of active principle. This analytical control is costly and tends to exclude small batches of plant material. Large scale contracted mechanised cultivation with designated seed or plantlets is now preferable.

Other Aspects Of Metal Chemistry Of Biological And Toxicological Interest

Metallothionein (MT) is a low molecular mass protein of approximately 6500 Dalton with a high content of SH-groups from cysteine. Two distinct metal binding domains, the a- and P-clusters have been characterized in MT and are formed of the 61 amino acids in human MT. The genes coding for metallothioneins are present in most organisms, and their induction after exposure to metals plays an important role in the protection against metal toxicity. Both essential (zinc and copper) and nonessential (cadmium and mercury) metals can induce the synthesis of metallothioneins and also constitute part of the molecule. Thus, these proteins have a role in the metabolism of essential metals and protection against the toxicity of metals. The four major groups of metallothioneins consist of MT-1, -2, -3, and -4. Mammalian MT-1 and MT-2 are present and expressed in almost all tissues. Only MT-1 exists in many isoforms. MT-3 has seven additional amino acids for a total of 68, with differences in charge...

Excretion Rate Biological Half Time

Where T1 2 biological half time and 1n 2 natural logarithm of 2 0.693. The concept of biological half-time has been much used in evaluations of metal toxicity, and this is illustrated further in the following section of this chapter, as well as in the chapters on the various metals, where available data on the biological half-times are given.

Biomarkers Of Effects

Biomarkers of effects are molecular tools that can serve to identify changes or effects occurring in the organism as a result of exposure to any given toxicant. In the case of exposure to toxic metals, tests relying on effect biomarkers are usually only used when excessive metal levels are found in exposed populations or their environment. The combined use of biomarkers of effects and biomarkers of exposure is also important for a correct interpretation of the data, because a diagnosis of metal intoxication relying on biomarkers can be made only if the observed effects are, indeed, associated with an excessive exposure or body burden of the metal. To be applicable to the diagnosis of intoxication or to the monitoring of populations at risk, biomarkers must meet several criteria. First, they must be sensitive enough to detect effects at a stage when these are still reversible or at least not yet predictive of further organ degradation. They must also be specific of the target organ,...

Neurotoxicity Biomarkers

Neurotoxic effects of heavy metals are also well documented, especially for mercury or lead, with numerous reports of neurobehavioral changes after occupational exposure and of developmental effects in children with prenatal or early postnatal exposure. Much effort has been devoted during the past years to identify potential biomarkers of neurotoxicity. Serum prolactin and urinary homovanillic acid have been the most studied in experimental animals and in humans. These two markers that reflect the integrity of the dopaminergic system have been proposed for monitoring exposure to some metals such as lead, mercury, manganese, and aluminum. However, their sensitivity seems limited, because significant changes in these biomarkers have only been described at relatively high exposure levels such as those found in industry. At environmental exposure levels, these biomarkers show no or only weak associations with heavy metal exposure even in particularly sensitive populations such as children...

Conservation status

The soricine shrews included in the 2002 IUCN Red List often belong to very rare and endemic species with restricted distribution and low population densities. Some of the threatened species are only known from the locality of their original description. However, the major threat for the soricine shrews is environmental disturbance and pollution. Loss of forest habitats has a considerable effect on forest-dwelling species. The rate of deforestation taking place in south and Southeast Asia is an apparent reason for including several soricine species from this particular geographic region among the category of Critically Endangered. Similar threats may arise in other regions from human interference with wetlands and from freshwater pollution. Shrews are exceptionally susceptible to accumulation of heavy metals in their tissues through their diet consisting of large amounts of earthworms. Long-term persistence of DDT has also been reported in soricine shrews.

Significance to humans

Accumulation of heavy metals in insectivorous mammals through their diet containing earthworms is extremely high, and the burden in tissues of shrews may be used as a useful indicator of environmental contamination. It is unknown whether shrews have a greater resistance to heavy metals than other mammals. Strong effects of rapid environmental change on developmental stability were also recorded in free-living populations of soricine shrews and provided a tool to monitor changes in natural environments. Shrews are becoming favorable model species in research of various issues of bio-medicine and evolutionary biology.

Polymersupported Heavymetal Oxides

There are several examples of polymer-supported oxidation reagents, including heavy-metal oxides bound to ion-exchange resins. Perruthenate resin 5 , the immobilized analog of tetrapropylammonium perruthenate (TPAP), can be employed both stoichiometrically and catalytically. For the latter application additional co-oxidants are required N-methylmorpholino-N-oxide (NMO) is usually used. The use of elemental oxygen has also been described. Perruthenate resin has recently been employed in a reaction sequence leading to heterocycles (Figure 3.6.2) 6 . Published examples indicate limited reactivity with non-benzylic alcohols. In general, ion-exchange resins suffer from potential leaching of heavy metals into the product solution, because they can be exchanged for any other anions present in the solution.

Design of Gene Environment Interaction Studies

Genetic factors for metal toxicity are most often handled as effect modifiers of the exposure-disease relationship. The interpretation of genotype as an effect modifier implies that studies should be planned to have sufficient power for detecting interactions and that an interactive term should be modeled into the statistical analysis. (However, it is important to note that interaction with one genetic variant does not warrant conclusions on a causal relationship with the biochemical mechanism, because the genetic variant may be linked with the causal gene.) Another fact that stresses the importance of sufficient statistical power is that, in general, genes act in concert to exert effects. Therefore, effects on one gene may induce compensatory changes in others. Moreover, many metabolic enzymes have overlapping substrate specificities. Thus, there are several grounds for analyzing interactions between different gene loci, so-called gene-gene interactions. However, only a limited...

Basic Principles for Classifying Effect

Evaluation principles concerning adverse effects from metal toxicity have been previously developed by the ICOH Scientific Committee on the Toxicology of Metals Task Group on Metal Toxicity 1976 (Nordberg, 1976 1992 Nordberg et al, 2000) and Chapter 14 in this Handbook). Adverse effects can occur from too low or too high an intake of an EM. As mentioned (see Section 2), it may not be possible to arrive at recommendations that protect all individuals in a population from such adverse effects, because some individuals with genetically determined metabolic disorders may require intakes that are higher or lower than those that represent AROI for normal persons in a defined population (cf Section 4 and Chapter 7). AROI can, therefore, only be applicable for persons without such disorders. It is further considered that the use of sensitive indicators of adverse effects with limited functional significance as markers of critical effect will provide further safety

Biomedical Importance

Organisms adapt to environmental changes by altering gene expression. The process of alteration of gene expression has been studied in detail and often involves modulation of gene transcription. Control of transcription ultimately results from changes in the interaction of specific binding regulatory proteins with various regions of DNA in the controlled gene. This can have a positive or negative effect on transcription. Transcription control can result in tissue-specific gene expression, and gene regulation is influenced by hormones, heavy metals, and chemicals. In addition to transcription level controls, gene expression can also be modulated by gene amplification, gene rearrangement, post-transcriptional modifications, and RNA stabilization. Many of the mechanisms that control gene expression are used to respond to hormones and therapeutic agents. Thus, a molecular understanding of these processes will lead to development of agents that alter pathophysiologic mechanisms or inhibit...

WHO Classification 2001

Cluding chemotherapy arsenic intoxication exposure to heavy metals treatment of HIV or virus infections. Other factors that may mimic MDS can be the administration of cytokines, parvovirus B19 infection, and especially deficiency in vitamin E, B12, or folic acid. Even congenital dyserythropoietic anemia, hairy cell leukemia, or paroxysmal nocturnal hemoglobinuria (PNH) have been misdiagnosed as MDS. This must lead to the conclusion that the classification of MDS is still difficult, needs highly experienced cytomorphologists and cytogeneticists, and should rely on the combination of several comprehensive techniques. In equivocal cases at least two different examinations at different time points and by different observers should be performed including a close follow-up of the patient's history.

Covalent PTP Modifiers

Sulfhydryl Group Example

The PTPs employ covalent catalysis, utilizing the thiol group of the active-site Cys residue as the attacking nucle-ophile to form a thiophosphoryl enzyme intermediate (E-P) 6 . Substitutions of the Cys residue completely abrogate PTP activity. The nucleophilic cysteine is housed within the active-site architecture specifically designed to bind a negatively charged phosphoryl group. Consequently, the pKa for the sulfhydryl group of the active-site Cys is extremely low ( 5) 7 . Thus, the PTPs are very sensitive to thiol-specific alkylating agents. For example, the PTPs can be irreversibly inactivated by iodoacetate, N-ethylmaleimide, and 5,5'-dithio-2-nitrobenzoic acid 7-9 . In addition, PTPs can also be inactivated by heavy metals including Zn2+, Cu2+, and p-(hydroxymercuri)benzoate, possibly through covalent bond formation with the active-site thiol group. There were

Peptide tryptophan 23dioxygenase

Pseudomonas enzyme, optimum pH 8.0, pi 4.6 and molecular weight 300 000, is composed of subunits, molecular weights 90 000, 34 000 and 20 000 (consistent with a a2p2g2 structure), contains molybdenum, iron, acid labile sulphur and FAD. It forms kynurenic acid from quinaldate. Heavy metals are inhibitory K768 .

Copper Toxicity In Plants

The two general symptoms of copper toxicity are stunted root growth and leaf chlorosis. For ryegrass (Lolium perenne L.) seedlings in solution culture, the order of metal toxicity affecting root growth was Cu + Ni + Mn + Pb + Cd + Zn + Al + Hg + Cr + Fe (72). This order is supported by earlier experiments with Triticum spp., white mustard (Sinapis alba L.), bent grass (Agrostis spp. L.), and corn (72). Stunted roots are characterized by poor development, reduced branching, thickening, and unusual dark coloration (7,14,72,73). Small roots and apices of large roots of spinach turned black in response to 160 M Cu in nutrient solution culture (73). Root growth was decreased progressively in corn when plants were exposed to 10-5, 10-4, 10-3 M Cu2+ in solution culture (14). However, due to the complexity of cell elongation in roots and influences of hormones, cell wall biosynthesis, and cell turgor, few research studies have defined the effect of copper on root growth (74). Excess heavy...

Overview Of Biomarkers

Although biomarkers of exposure can refer to any biomarker used to estimate current or past exposure to a specific environmental agent, the traditional definition of an exposure biomarker involves measurement of a xenobiotic, its metabolite, or its interactive products found in body tissue, fluids, and excreta, such as blood, urine, feces, or milk (18). These measures provide information about the actual concentration or internal dose of a specific agent that has been absorbed and distributed in the body. Measurement of the xenobiotic itself or its metabolites has been incorporated into a number of human epidemiological studies. For example, excretion of aflatoxin M1, one of the major metabolites of aflatoxin B1, has been used as a biomarker for the evaluation of human exposure to aflatoxin, and this marker was found to be associated with the risk of liver cancer (19, 20). Specific metabolites of one of the tobacco-specific nitrosamines, (NNK), a potent chemical carcinogen, have been...

Creating Giant Mice Through Gene Regulation

If foreign genes are rarely expressed, why did the trans-genic mice with the gene for rat growth hormone grow so big Palmiter and his colleagues, aware of the need to provide sequences that control gene expression, linked the rat gene with the mouse metallothionein I promoter sequence, a DNA sequence normally found upstream of the mouse metallothionein I gene. When heavy metals such as zinc are present, they activate the metallothionein promoter sequence, thereby stimulating transcription of the metal-lothionein I gene. By connecting the rat growth-hormone gene to this promoter, Palmiter and his colleagues provided a means of turning on the transcription of the gene, simply by putting extra zinc in the food for the transgenic mice.

Ionic Surfactants Anionic Surfactants

Saturated sodium soaps are extremely soluble in water up to C8 they become less soluble up to C18 and insoluble above C20. The fatty acids can be either saturated or unsaturated (starting from Ci6 chain lengths). Unsaturated fatty acids are prone to undergo oxidation and form oxides and peroxides, which cause rancidity and yellowing. Potassium soaps and salts of alkanolamines are more fluid and also more soluble than sodium salts. The extremely low solubility of alkaline earth and heavy metals fatty acid salts makes this class of surfactants less appropriate for use in hard water.

MHydroxybenzyl alcohol 6hydroxylase

Optimum pH 7.2, requires NADPH and is inhibited by superoxide dismutase. Other substrates include 3-hydroxyanthranilate, pyrocatechuate, 3,5-dihydroxybenzoate and 3-hydroxy-5-methoxybenzoate. It is also inhibited by heavy metals, o -phenanthroline, salicylaldoxime, m-aminobenzoate, diethyldithiocarbamate and sulphydryl-binding reagents A1130, A3526 .

Phenol 2monooxygenase

Trichosporon cutaneum enzyme acts on resorcinol and m -cresol to yield hydroxyquinol and 4-methylcatechol respectively, as well as on phenol G196 . Its molecular weight is 148 000, it contains one mol mol of FAD and requires NADPH. The optimum pH is 72-1.6. Bleaching by dithionite, which inactivates the enzyme is readily reversible. It is also inactivated by heavy metals and p -chloromercuribenzoate, the latter being reversed by dithiothreitol. The specificity is broad, with substrates not being limited to monophenols catechol, for instance, yields pyrogallol. Activity towards hydroxylated benzyl alcohols, aldehydes and benzoic acids is negligible A902 .

Rejuvenation Solution

IN SITU HYBRIDIZATION Buffered formalin, pH 7.0, serves as an excellent fixative for this technology. Fixatives with picric acid (Bouin's) or heavy metals (Zenker's) may interfere with subsequent in situ hybridization. Paraffin-embedded tissue is quite suitable for many commercially available DNA probes.

Genetically Modified Nonfood Plants

Phytoremediation is the act of cleaning up polluted soils with plants. As we know, vast stretches of land, worldwide, are heavily polluted with petrochemicals or toxic heavy-metal salts such as mercury and cadmium. It so happens that soil microbes are often able to detoxify these pollutants by degrading petrochemicals and immobilizing heavy metals. However, there are potential problems with spraying contaminated soils with these microbes, for fear of creating yet another environmental problem. This is where GM plants may come to the rescue. Why not isolate the relevant bacterial genes and transfer them to plants Plants do not move, can grow fast, and, through their roots, absorb polluted water, thereby concentrating toxic chemicals inside their cells. When engineered with bacterial genes, these GM plants would be able to survive. After their detoxification job was achieved, they could be harvested and burned under controlled conditions. And yes, this has been done. There now exist...

Susceptibility to Genomic Injury Genomic Instability

Cytogenetic abnormalities in MDS result from the accumulation of genomic damage, failure to repair such damage, or both. Although the etiology of most cases of MDS is unknown, exposure to genotoxic agents such as benzene, radiation, or prior treatment with chemother-apeutic agents is known to increase the risk of developing MDS (Nisse et al. 2001). Other environmental agents that may increase the risk include smoking, heavy metals, pesticides, fertilizers, petroleum products, and organic chemicals (Garfinkel and Boffetta 1990 Rigolin et al. 1998 West et al. 1995) (see Chapter 3).

Male Reproductive Effects

The human male has a relatively low fertility potential compared with other mammals. For example, the number of sperm per human ejaculate is typically only twofold to fourfold higher than the number at which fertility is significantly reduced, whereas the number of sperm in rat, rabbit, or bull ejaculate is many times (up to 1400-fold) the number that will produce maximum fertility (Working, 1988). Human males have markedly smaller relative testis size and the lowest rate of daily sperm production per gram of testis, by a factor of more than 3, compared with mouse, rat, or monkey. The percentages of progressively motile sperm and morphologically normal sperm in human semen are also considerably lower than in experimental animals (Working, 1988). Certain rodent species and strains, commonly used in experimental studies, seem to be resistant to the male reproductive toxicity of lead (Apostoli et al., 1998) and cadmium (Gunn et al., 1965 Liu et al., 2001). The human male may be more...

Future of Transgenic Mouse Approaches Need for Inducible Expression

Many eukaryotic promoters are under natural inducible control, providing a simple means for controlling the extent and duration of expression. For example, in the absence of heavy metals, the MT promoter has low activity. Treatment with cadmium or zinc, however, increases promoter activity several fold. The effectiveness of this induction scheme was demonstrated in transgenic mice harboring a mutated sheep MT promoter linked to an ovine GH-cod-ing sequence. When maintained on water supplemented with zinc, these mice secreted excessive levels of GH and displayed a giant phenotype (Shanahan et al., 1989). Mice overexpressing GH have also been made with a transgene that utilizes the PEPCK promoter (McGrane et al., 1988). Transcription of the chimeric gene occurred after birth in the kidney, liver, and adipose tissue. This promoter is regulated by composition of the diet a diet high in carbohydrates reduces expression whereas a diet high in protein and low in carbohydrate stimulates...

Impacts of Air Pollution

Heavy metals Crop loss assessments to date have concentrated on the direct impacts of air pollution on yield, and have not taken into account effects on crop quality or the indirect impacts on yield. Reductions in income for vegetable producers and suppliers can arise from visible damage to the edible portion of the crop. In addition, there are other potential non-visible impacts of air pollution such as reductions in nutritional quality or accumulation of heavy metals, with important implications for consumers, particularly the poor.30,31

Environment as determinant of i genotype and ii disease

Second, the environment presents many exposures that directly alter the probability of occurrence of various diseases. Ionizing radiation contributes to the risks of breast cancer and leukemia. Asbestos causes asbestosis and mesothelioma. Environmental tobacco smoke increases the risks of lung cancer and coronary heart disease. Heavy metals induce various forms of organ dysfunction, for example, environmental lead exposure in early childhood impairs neurocogni-tive development. Patterns of exposure to various antigens in early childhood influence the maturation path of the young immune system, and also

Renal Toxicity Biomarkers

By measuring a panel of a few specific urinary proteins or enzymes reflecting the integrity of the glomerulus or of the proximal tubule. Table 1 lists the biomarkers that have been the most validated in humans and animals for assessing the nephrotoxicity of heavy metals such as cadmium, lead, and mercury. These biomark-ers are now routinely used in the health surveillance of industrial workers and also for screening metal-induced kidney damage in environmentally polluted areas (e.g., in Japan). To be reliable, these tests require the use of sensitive immunological methods with a detection limit lower than 1 mg L for albumin and alpha1-microglobulin and lower than 0.01 mg L for retinol-binding protein and beta2-microglobulin. Test packs based on radioimmunoassay, enzyme immu-noassay, or fluoroimmunoassay are now commercially available. When applying these tests, it is advisable to avoid first morning samples and also extreme variations in urinary flow. Samples with urinary creatinine...

Control of Gene Expression

The giant transgenic mouse on the left was produced by injecting a rat gene for growth hormone into a mouse embryo a normal-size mouse is on the right. To ensure expression, the rat gene was linked to a DNA sequence that stimulates the transcription of mouse DNA whenever heavy metals are present. Zinc was provided in the food for the transgenic mouse some transgenic mice produced 800 times the normal levels of growth hormone. (Courtesy of Dr. Ralph L. Brinster, School of Veterinary Medicine, University of Pennsylvania.)

D Staining

Thick sections are stained with toluidine or methylene blue on a hot plate. Sections are mounted on clean, glass slides, dried and stained. Electron stains like uranyl acetate and lead citrate are used routinely for thin sections. These stains contain heavy metals that enhance the electron density of the cells and make them more visible with TEM. The image is formed by scattering of electrons, which produces translucent (light) and dense (dark) areas. The cell membranes, granules and inclusions scatter electrons and appear dense, while the ground cytoplasm allows electrons to pass through and appears translucent producing a black and white image.

Platinum

After the introduction of automobile catalytic converters, platinum, palladium, and rhodium have been emitted with exhaust fumes, and increasing levels have been found in different environmental matrices such as road dusts, soils along heavily frequented roads, and sediments of urban rivers. Compared with other heavy metals, the biological availability of platinum, palladium, and rhodium in some experimental studies on road dusts ranged between that of cadmium and lead (Zimmerman and Sures, 2004). As stated by the same researchers, chronic effects on the biosphere cannot be excluded because of (1) their cumulative increase in the environment, (2) their unexpected high biological availability and bioaccumulation, and (3) their unknown toxicological and ecotoxicological potential.

Bioremediation

Both microorganisms and plants have been employed to alleviate man-made pollutants from the environment. Microorganisms are used primarily in situations where the degradation of certain pollutants (primarily petroleum hydrocarbons) is necessary. In other circumstances, plants may be preferred for phytoremedation processes where absorption of heavy metals and radionucleotides are the contaminants (Cunningham et al., 1995 Cunningham and Ow, 1996). The cost of extraction of heavy metals from soil and standing water can be extremely high, estimated to have an average cost of 1,000,000 per acre (Raskin et al, 1997). There is a need, therefore, to find more cost-effective methods to decontaminate soils. Several plant species that have the ability to grow in soils that have elevated concentrations of certain heavy metals have been identified by looking in the wild for plants that hyperaccumulate pollutants. In other laboratories, genetic transformation is being used to develop...

Liposomes

Liposomal dispersions based on unsaturated phosphatidylcholine are lacking in stability against oxidation. Like linoleic esters and linoleic glycerides, these dispersions have to be stabilized by antioxidants. Thinking naturally, a complex of Vitamin C and E (respectively, their derivatives like acetates and palmitates) can be used with success. In some cases, phosphatidylcholine and urea seem to stabilize each other 9,10 . Moreover, agents that are able to mask traces of radical-forming ions of heavy metals, like iron, can be

What Is Soap

Soap is generally defined as an alkali salt of a long-chain fatty acid. When a fat or oil is saponified, the sodium or potassium salt formed from the long-chain fatty acids is called a soap. The term ''soap'' refers to a group of neutralized long-chain carboxylic acids, which result from two primary ingredients an alkali and a triglyceride (fat or oil). The chain length of the aliphatic group is typically between 7 and 21 carbons with one carbox-ylate carbon, yielding a molecule containing 8 to 22 carbons. The cation associated with the carboxylate head group generally comprises sodium, potassium, or to a lesser extent other cations such as triethanolamine as well as heavy metals and alkali earth metals such as magnesium.

Maternal Circulation

Decidua Basalis

Exchange of gases and metabolic products occurs as the blood passes over the villi. Normally, water, carbon dioxide, metabolic waste products, and hormones are transferred from the fetal blood to the maternal blood water, oxygen, metabolites, electrolytes, vitamins, hormones, and some antibodies pass in the opposite direction. The placental barrier does not exclude many potentially dangerous agents, such as alcohol, nicotine, viruses, drugs, exogenous hormones, and heavy metals. Therefore, during pregnancy, exposure to or ingestion of such agents should be avoided to reduce the risk of injury to the embryo or fetus.

Adult Tumours

Renal cell carcinoma more than 90 of tumours in the kidney which come to surgery are renal cell carcinomas and these cause approximately 2.4 of cancer deaths. The age is usually 50 years old with a M F ratio of 2 1. A number of cellular, environmental, genetic, and hormonal factors have been studied as possible causal factors including cigarette smoking, obesity, hypertension, unopposed oestrogen therapy, and occupational exposure to petroleum products, heavy metals, solvents and asbestos. The risk of renal cell carcinoma is increased with the abuse of phenacetin-containing analgesics, acquired cystic kidney disease associated with chronic renal insufficiency, renal dialysis, tuberous sclerosis, Von Hippel-Lindau disease and renal transplantation with its associated immunosuppression. Prognostic factors include nuclear grade, tumour size, stage and metastases. Treatment usually consists of radical nephrectomy with partial nephrectomy for small ( 4 cm - pT1a) peripheral tumours. Cure...

Chromium

And Loeb (1976), trivalent chromium was shown to be more potent than hexavalent chromium in the induction of genetic miscoding (Sirover and Loeb, 1976b). A possible mechanism for chromium carcinogenesis has been proposed from these and other observations. In this model, hexavalent chromium readily traverses cell membranes and in the process it is reduced to the triva-lent form. Within the cell, trivalent chromium binds to nucleotide bases in DNA to give rise to genotoxic effects (Levis et al, 1978 Lofroth, 1978). Thus, although the cancer hazard seems to follow environmental exposure to hexavalent chromium, trivalent chromium seems to be the agent that initiates the changes within the cell. Of all the metals studied, chromium best fits the hypothesis that carcinogenesis entails mutagenic initiation of somatic cells as a result of direct interaction with DNA. The handbook has a separate chapter on mechanisms of metal toxicity and carcinogenicity and a separate chapter on chromium, and...

Vitamin E

More than other tissues, the skin is exposed to various aggressive effects of the environment. Chemical and physical agents, such as ultraviolet (UV) light, ozone, heavy metals, and many others, cause permanent stress to the outermost cell layers of the skin. In particular, regular and excessive exposure to UV light induces damage and disease in the tissue. The skin becomes wrinkled, appears older, the immune system is weakened, and, more seriously, skin cancer can develop.

Indicator Plants

Baker (328) proposed that there are three types of plant responses to increasing heavy metal contents in soil (a) accumulators, where heavy metals are concentrated in above-ground plant parts (b) indicators, where internal concentrations reflect external levels and (c) excluders, where metal concentrations in shoots are low and constant over a wide range of soil concentrations up to a critical soil level above which unrestricted transport occurs. It might be expected that aluminum accumulators would be good indicator plant species however, this relationship has not been found to be true. Truman et al. (14) reported that only a weak linear relationship was found between foliage aluminum concentration of Pinus spp. and exchangeable aluminum in soil. Even in controlled nutrient solution culture, foliar aluminum levels of red spruce varied almost fivefold at a similar solution of aluminum concentration (78).

Soil Fertility

Metal toxicity and nutrient deficiency problems in acid soils are investigated by only a handful of scientists in developed countries and this topic has thus far been largely neglected by large agrochemical companies. Sub-Saharan Africa has some of the oldest and most depleted soils in the world. Thousands of years of weathering have leached the nutrients, leaving the soil highly acidic, causing aluminium and manganese to become soluble and thereby toxic to plants. Together with high levels of iron, the aluminium oxides also hinder plant growth by chemically locking up phosphates. So far, traditional plant breeding has produced few answers for this global problem.

Welding

Exposures found no relationship with occupational exposure to heavy metals. However, only 19 PD subjects with metal exposure were studied, and welding as an occupation was not specifically identified. Other studies (51,93) have used broad occupational categories or reported exposure only to metals and did not specifically investigate welding. Several recent studies add to the controversy. A study (95) of 1423 Alabama welders referred for medical-legal evaluation found a substantially higher prevalence of parkinsonism in three standard occupational codes, using highly conservative assumptions. All patients were examined for parkinsonism with standardized videotaped assessments using the Unified Parkinson's Disease Rating Scale motor scale. Patients provided information regarding exposure to welding fumes and job titles. Job titles were matched with Department of Labor Standard Occupational Codes (SOCs). Diagnoses for parkinsonism were assigned using quantitative criteria. The...

Toxic Disorders

Acute poisoning with heavy metals (e.g., lead, mercury, cadmium, gold, arsenic, etc.) is often suggested by a history of exposure. Chronic exposure, however, may have subtle clinical findings and may present with bone marrow changes, including dysplasia, hypoplasia and aplastic anemia. The diagnosis is made by a careful occupational and exposure history, clinical examination, and a heavy metal screen of the peripheral blood.

Figure 11

Solve in fats must be used to retain membrane structures, special fixatives containing heavy metals, such as permanganate and osmium, that bind to the phospholipids must be used. The routine use of osmium tetroxide as a fixative for electron microscopy is the primary reason for the ex

Zinc In Soils

Additions of sulfur reduced the amount of ZnSO4 required to reach 60mg kg 1 to 18.8kg per tree with 4.5 kg S per tree and to 16.2kg per tree with 11.9 kg S per tree. Leaflets collected in September 1967 contained more than 60mg Zn kg 1 if ZnSO4 was applied in March 1966 at rates greater than 4.8 kg per tree. However, in 1967, at any given rate of ZnSO4 (above 1.4 kg per tree), leaflet zinc concentration was reduced by the addition of sulfur, but the concentrations of zinc in the leaflets remained above the minimum optimum level. This study indicates that leaflet zinc of pecan trees in calcareous soils can be increased by soil applications of ZnSO4, but that a larger increase will occur if S is applied with ZnSO4. On the other hand, soil applications seemed impractical considering the fact that with a planting of 86 trees per ha, an application of 120 kg of ZnSO4 ha 1 would be required. In acid soils of the southeastern United States, high rates of...

Toxic Metabolic

Exogenous Toxins Alcohol Medications Brain radiation Organic solvents Heavy metals Carbon monoxide Metabolic Abnormalities Endocrine imbalance Pulmonary insufficiency Cardiac failure Hematological disorders Renal dysfunction Hepatic failure Electrolyte derangement Nutritional deficiency

Chelation

Chelation is typically used as an intravenous therapy (sometimes oral) to remove a particular substance that is found to occur at a toxic level in the body such as lead, copper, mercury, or arsenic. The amino acid complex, ethylene-diamine-tetra-acetic acid, is the most commonly used chelating agent, though herbs and supplements may sometimes be used. Though there is a higher incidence of PD occurring in persons with chronic exposure to heavy metals such as manganese and copper and also with exposure to pesticides and herbicides, no specific toxic agent directly linked to the cause of PD has ever been identified and it is unclear what one would attempt to chelate out of the body of someone with PD. There is no scientific evidence to support the use of chelation therapy for the treatment of PD. In fact, chela-tion therapy has come under investigation and criticism for making false statements about its curative powers for a number of diseases such as multiple sclerosis, Alzheimer's...

Metallothioneins MTs

Protection against metal toxicity was probably not the intended purpose for MTs, because many of the toxic metals that they bind have only in recent times been concentrated in the biosphere through anthropogenic releases. The more likely explanation is that the ability of MTs to detoxify toxic metals is an accidental occurrence related to the ability of toxic metals to mimic physiological metals such as zinc that MTs are known to bind and perhaps regulate its homeostasis in cells (Richards and Cousins, 1975 1976). MT affects Zn absorption and excretion by the intestine, as well as the supply of Zn to cellular transport proteins like ZnT-1 and DMT1, and the supply of Zn to Zn-containing enzymes and zinc finger proteins (Gunshin et al., 1997 Palmiter and Findley, 1995 Palmiter et al., 1996a 1996b Richards and Cousins, 1975 1976). Although it seems MT can play a role in sequestering various metals, the precise physiological role is still unknown and the subject of current investigations.

Glutathione

When GSH binds to a metal, two main outcomes are possible. The metal can be stabilized in a nonre-active form, or metal compounds with different spe-ciation can be formed by redox reactions. Under the right conditions (when thiol groups dissociate to their thiolate anion), the latter can actually result in the formation of reactive oxygen species (ROS), although this event is usually quenched by other amino acid groups on GSH (Pompella et al., 2003). More often, GSH can bind to metals and prevent the toxic effects of those metals. It has been reported that 0.5 mM GSH could prevent the inhibition of ethoxyresorufin O-deethy-lase activity by Hg2+, Cu2+, and Zn2+ but not Cr(VI) or Fe2+ (Oliveira et al., 2004). The toxic effects of copper have been inversely associated with GSH concentration (Freedman et al., 1989). The addition of GSH has been shown to protect against Hg2+-mediated toxicity in in vitro preparations of renal tissue, isolated proximal tubule fragments from rabbits, and...