Heavy metals toxicity pdf

Need an account? Click here to sign up. Download Free PDF. Heavy Metals' Toxicity. A short summary of this paper. Parents may bring lead dust. Lead laced Marijuana producing sociopaths? It is therefore particularly toxic to multiple enzyme systems. Protoporphyrin accumulates in RBCs and chelate zinc. EP reflects chronic lead exposure. Their width is related to the duration of exposure.

Skip to main content. By using our site, you agree to our collection of information through the use of cookies. To learn more, view our Privacy Policy. Log In Sign Up. Download Free PDF. Detrimental impacts of heavy metals on animal reproduction: A review Journal of entomology and zoology studies, Ranjeet Verma. Download PDF. A short summary of this paper. Detrimental impacts of heavy metals on animal reproduction: A review.

The indiscriminate human activities like rapid industrialization, overgrowing Kennady Vijayalakshmy urbanization and environmental manipulation have drastically altered the biogeochemical cycles. Department of Veterinary Aggregation with polluted water tends to pollute the agricultural soil and the crops that grow in this soil Physiology, Lala Lajpat Rai will be having a more heavy metal accumulation. These crops that have been used by animal for grazing University of Veterinary and or feed purpose will be accumulated with heavy metals that can reach the animal body, in other ways Animal Sciences, Hisar, heavy metals can directly reach the animal body by means of drinking contaminated water.

Prolonged Haryana, India exposure to heavy metals such as lead, mercury, cadmium and arsenic causes deleterious health effects in animals. Heavy metal primarily affects the liver, kidney, brain and other body systems.

Lead, mercury, Vikas Chaudhiry arsenic and cadmium are the most common heavy metals that are found in industrial and domestic Senior Research Fellow, Central wastages. With exposure to heavy metals, reproductive system shows the chronic type of toxicity and Institute for Research on produces cellular impairments at both structural and functional level. It could cause impairment in Buffaloes, Hisar, Haryana, India steroidogenesis, hormonal regulation, gametogenic process, affect leydig cells and spermatogenesis in males and granulosa cells, theca cells in females; placental growth, pregnancy rate and development of fetus in females.

Animals that are reared near the area that are having extreme level of heavy metals contamination are highly prone to infertility problems. Keywords: Heavy metals, toxicity, steroidogenesis, infertility, reproduction Introduction The heavy metals are a heterogeneous group of elements that are having more than 5g cm3 specific weight and atomic weight greater than sodium They act as a cumulative poison for living creatures.

They enter into an animal body either through inhalation; ingestion or absorption direct contacts and they develop the carcinogenicity, mutagenicity, embryotoxicity, hepatotoxicity and renal toxicity.

The heavy metals are mostly present in soil and aquatic ecosystem rather than atmosphere. In natural way, they originates during the origin of earth and it is distributed all over the earth may or may not be evenly. In other hand, anthropogenic activities such as rapid industrialization, overgrowing urbanization and environment manipulation split heavy metals into the environment. The accumulation of heavy metals through emissions from the rapidly expanding industrial areas, mine tailings and disposal of high metal wastes etc.

At room temperature it is found in liquid state. Its fertilizers, animal manures, sewage sludge, pesticides, waste Atomic Number: 80, Atomic Weight: Heavy metal enters into the animal body by K It indirect means like eating or grazing of contaminated fodder, enters into the animal body as like Lead.

Its toxicity depends drinking contaminated water and sometimes respiration with on its chemical form, methyl mercury is found to be more polluted air. Heavy metals may enter into plant tissue by hazardous than metallic form of mercury.

It alters the activity means of crop production in polluted soils or irrigation with of enzymes that are having —SH group [5].

Selenium and contaminated water. Vitamin E help in protecting against mercuric toxicity by their antagonistic mechanism. Chronic exposures to mercury cause Lead Pb neuro-degeneration, behavioral changes and ultimately end up In periodic table Lead is situated at group 14 IVthA and in death.

Large-scale mercury poisoning has occurred in period 6th. It is a bluish or silvery grey soft metal with atomic Minamata and Niigata in Japan and Iraq by industrial or number 82; atomic weight It is a In animals, reproductive toxicity may be developed after ubiquitous environmental contaminant.

It enters into the chronic exposure but sometimes it is even acute. Young animal body by indirect sources. It gets accumulated in the ruminants are more susceptible to mercury poisoning rather liver, kidney, brain and bone. Similar to copper, several other essential elements are required for biologic functioning, however, an excess amount of such metals produces cellular and tissue damage leading to a variety of adverse effects and human diseases. For some including chromium and copper, there is a very narrow range of concentrations between beneficial and toxic effects [ 19 , 20 ].

Other metals such as aluminium Al , antinomy Sb , arsenic As , barium Ba , beryllium Be , bismuth Bi , cadmium Cd , gallium Ga , germanium Ge , gold Au , indium In , lead Pb , lithium Li , mercury Hg , nickel Ni , platinum Pt , silver Ag , strontium Sr , tellurium Te , thallium Tl , tin Sn , titanium Ti , vanadium V and uranium U have no established biological functions and are considered as non-essential metals [ 20 ].

In biological systems, heavy metals have been reported to affect cellular organelles and components such as cell membrane, mitochondrial, lysosome, endoplasmic reticulum, nuclei, and some enzymes involved in metabolism, detoxification, and damage repair [ 21 ]. Metal ions have been found to interact with cell components such as DNA and nuclear proteins, causing DNA damage and conformational changes that may lead to cell cycle modulation, carcinogenesis or apoptosis [ 20 — 22 ].

Several studies from our laboratory have demonstrated that reactive oxygen species ROS production and oxidative stress play a key role in the toxicity and carcinogenicity of metals such as arsenic [ 23 , 24 , 25 ], cadmium [ 26 ], chromium [ 27 , 28 ], lead [ 29 , 30 ], and mercury [ 31 , 32 ]. Because of their high degree of toxicity, these five elements rank among the priority metals that are of great public health significance.

They are all systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. Heavy metal-induced toxicity and carcinogenicity involves many mechanistic aspects, some of which are not clearly elucidated or understood. However, each metal is known to have unique features and physic-chemical properties that confer to its specific toxicological mechanisms of action.

This review provides an analysis of the environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity of arsenic, cadmium, chromium, lead, and mercury. Arsenic is a ubiquitous element that is detected at low concentrations in virtually all environmental matrices [ 33 ]. The major inorganic forms of arsenic include the trivalent arsenite and the pentavalent arsenate. The organic forms are the methylated metabolites — monomethylarsonic acid MMA , dimethylarsinic acid DMA and trimethylarsine oxide.

Environmental pollution by arsenic occurs as a result of natural phenomena such as volcanic eruptions and soil erosion, and anthropogenic activities [ 33 ]. Several arsenic-containing compounds are produced industrially, and have been used to manufacture products with agricultural applications such as insecticides, herbicides, fungicides, algicides, sheep dips, wood preservatives, and dye-stuffs.

They have also been used in veterinary medicine for the eradication of tapeworms in sheep and cattle [ 34 ]. Arsenic compounds have also been used in the medical field for at least a century in the treatment of syphilis, yaws, amoebic dysentery, and trypanosomaiasis [ 34 , 35 ].

Arsenic-based drugs are still used in treating certain tropical diseases such as African sleeping sickness and amoebic dysentery, and in veterinary medicine to treat parasitic diseases, including filariasis in dogs and black head in turkeys and chickens [ 35 ].

Recently, arsenic trioxide has been approved by the Food and Drug Administration as an anticancer agent in the treatment of acute promeylocytic leukemia [ 36 ]. Its therapeutic action has been attributed to the induction of programmed cell death apoptosis in leukemia cells [ 24 ]. It is estimated that several million people are exposed to arsenic chronically throughout the world, especially in countries like Bangladesh, India, Chile, Uruguay, Mexico, Taiwan, where the ground water is contaminated with high concentrations of arsenic.

Exposure to arsenic occurs via the oral route ingestion , inhalation, dermal contact, and the parenteral route to some extent [ 33 , 34 , 37 ]. Intake from air, water and soil are usually much smaller, but exposure from these media may become significant in areas of arsenic contamination.

Workers who produce or use arsenic compounds in such occupations as vineyards, ceramics, glass-making, smelting, refining of metallic ores, pesticide manufacturing and application, wood preservation, semiconductor manufacturing can be exposed to substantially higher levels of arsenic [ 39 ].

Arsenic has also been identified at sites of the 1, hazardous waste sites that have been proposed by the U. EPA for inclusion on the national priority list [ 33 , 39 ]. Human exposure at these sites may occur by a variety of pathways, including inhalation of dusts in air, ingestion of contaminated water or soil, or through the food chain [ 40 ].

Contamination with high levels of arsenic is of concern because arsenic can cause a number of human health effects. Several epidemiological studies have reported a strong association between arsenic exposure and increased risks of both carcinogenic and systemic health effects [ 41 ]. Interest in the toxicity of arsenic has been heightened by recent reports of large populations in West Bengal, Bangladesh, Thailand, Inner Mongolia, Taiwan, China, Mexico, Argentina, Chile, Finland and Hungary that have been exposed to high concentrations of arsenic in their drinking water and are displaying various clinico-pathological conditions including cardiovascular and peripheral vascular disease, developmental anomalies, neurologic and neurobehavioural disorders, diabetes, hearing loss, portal fibrosis, hematologic disorders anemia, leukopenia and eosinophilia and carcinoma [ 25 , 33 , 35 , 39 ].

Arsenic exposure affects virtually all organ systems including the cardiovascular, dermatologic, nervous, hepatobilliary, renal, gastro-intestinal, and respiratory systems [ 41 ]. Research has also pointed to significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, and liver in many areas of arsenic pollution. The severity of adverse health effects is related to the chemical form of arsenic, and is also time- and dose-dependent [ 42 , 43 ].

Although the evidence of carcinogenicity of arsenic in humans seems strong, the mechanism by which it produces tumors in humans is not completely understood [ 44 ]. Analyzing the toxic effects of arsenic is complicated because the toxicity is highly influenced by its oxidation state and solubility, as well as many other intrinsic and extrinsic factors [ 45 ].

Several studies have indicated that the toxicity of arsenic depends on the exposure dose, frequency and duration, the biological species, age, and gender, as well as on individual susceptibilities, genetic and nutritional factors [ 46 ]. Most cases of human toxicity from arsenic have been associated with exposure to inorganic arsenic. By binding to thiol or sulfhydryl groups on proteins, As III can inactivate over enzymes. As V can replace phosphate, which is involved in many biochemical pathways [ 5 , 47 ].

One of the mechanisms by which arsenic exerts its toxic effect is through impairment of cellular respiration by the inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorous in a variety of biochemical reactions [ 48 ].

Arsenic in vitro reacts with protein sulfhydryl groups to inactivate enzymes, such as dihydrolipoyl dehydrogenase and thiolase, thereby producing inhibited oxidation of pyruvate and betaoxidation of fatty acids [ 49 ]. The major metabolic pathway for inorganic arsenic in humans is methylation. Arsenic trioxide is methylated to two major metabolites via a non-enzymatic process to monomethylarsonic acid MMA , which is further methylated enzymatically to dimethyl arsenic acid DMA before excretion in the urine [ 40 , 47 ].

It was previously thought that this methylation process is a pathway of arsenic detoxification, however, recent studies have pointed out that some methylated metabolites may be more toxic than arsenite if they contain trivalent forms of arsenic [ 41 ]. Tests for genotoxicity have indicated that arsenic compounds inhibit DNA repair, and induce chromosomal aberrations, sister-chromatid exchanges, and micronuclei formation in both human and rodent cells in culture [ 50 — 52 ] and in cells of exposed humans [ 53 ].

Reversion assays with Salmonella typhimurium fail to detect mutations that are induced by arsenic compounds. Although arsenic compounds are generally perceived as weak mutagens in bacterial and animal cells, they exhibit clastogenic properties in many cell types in vivo and in vitro [ 54 ].

In the absence of animal models, in vitro cell transformation studies become a useful means of obtaining information on the carcinogenic mechanisms of arsenic toxicity. Based on the comet assay, it has been reported that arsenic trioxide induces DNA damage in human lymphophytes [ 57 ] and also in mice leukocytes [ 58 ]. Arsenic compounds have also been shown to induce gene amplification, arrest cells in mitosis, inhibit DNA repair, and induce expression of the c-fos gene and the oxidative stress protein heme oxygenase in mammalian cells [ 58 , 59 ].

They have been implicated as promoters and comutagens for a variety of toxic agents [ 60 ]. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic and able to transcriptionally induce a significant number of stress genes and related proteins in human liver carcinoma cells [ 61 ].

Epidemiological investigations have indicated that long-term arsenic exposure results in promotion of carcinogenesis. Several hypotheses have been proposed to describe the mechanism of arsenic-induced carcinogenesis. Zhao et al. Additionally, it was found that arsenic is a potent stimulator of extracellular signal-regulated protein kinase Erk1 and AP-1 transactivational activity, and an efficient inducer of c-fos and c-jun gene expression [ 63 ].

Induction of c-jun and c-fos by arsenic is associated with activation of JNK [ 64 ]. However, the role of JNK activation by arsenite in cell transformation or tumor promotion is unclear.

In another study, Trouba et al. Collectively, several recent studies have demonstrated that arsenic can interfere with cell signaling pathways e. However, the specific alterations in signal transduction pathways or the actual targets that contribute to the development of arsenic-induced tumors in humans following chronic consumption of arsenic remains uncertain. Recent clinical trials have found that arsenic trioxide has therapeutic value in the treatment of acute promyelocytic leukemia, and there is interest in exploring its effectiveness in the treatment of a variety of other cancers [ 69 , 70 ].

In acute promyelocytic leukemia, the specific molecular event critical to the formation of malignant cells is known. A study by Puccetti et al. They also concluded that arsenic trioxide is a tumor specific agent capable of inducing apoptosis selectively in acute promyelocytic leukemia cells. Several recent studies have shown that arsenic can induce apoptosis through alterations in other cell signaling pathways [ 72 , 73 ].

In addition to acute peomyelocytic leukemia, arsenic is thought to have therapeutic potential for myeloma [ 74 ]. In summary, numerous cancer chemotherapy studies in cell cultures and in patients with acute promyelocytic leukemia demonstrate that arsenic trioxide administration can lead to cell-cycle arrest and apoptosis in malignant cells.

Previous studies have also examined p53 gene expression and mutation in tumors obtained from subjects with a history of arsenic ingestion. Additional support for the hypothesis that arsenic can modulate gene expression has been provided by several different studies [ 75 , 76 ]. Collectively, these studies provide further evidence that various forms of arsenic can alter gene expression and that such changes could contribute substantially to the toxic and carcinogenic actions of arsenic treatment in human populations [ 77 ].

We have further demonstrated that the toxicity of arsenic depends on its chemical form, the inorganic form being more toxic than the organic one [ 42 ]. Various hypotheses have been proposed to explain the carcinogenicity of inorganic arsenic.

Nevertheless, the molecular mechanisms by which this arsenical induces cancer are still poorly understood. Results of previous studies have indicated that inorganic arsenic does not act through classic genotoxic and mutagenic mechanisms, but rather may be a tumor promoter that modifies signal transduction pathways involved in cell growth and proliferation [ 68 ].

Presently, three modes chromosomal abnormality, oxidative stress, and altered growth factors of arsenic carcinogenesis have shown a degree of positive evidence, both in experimental systems animal and human cells and in human tissues. The remaining possible modes of carcinogenic action progression of carcinogenesis, altered DNA repair, p53 suppression, altered DNA methylation patterns and gene amplification do not have as much evidence, particularly from in vivo studies with laboratory animals, in vitro studies with cultured human cells, or human data from case or population studies.

Thus, the mode-of-action studies suggest that arsenic might be acting as a cocarcinogen, a promoter, or a progressor of carcinogenesis. Cadmium is a heavy metal of considerable environmental and occupational concern.

It is widely distributed in the earth's crust at an average concentration of about 0. Cadmium is frequently used in various industrial activities. The major industrial applications of cadmium include the production of alloys, pigments, and batteries [ 89 ]. Although the use of cadmium in batteries has shown considerable growth in recent years, its commercial use has declined in developed countries in response to environmental concerns.

In the United States for example, the daily cadmium intake is about 0. This decline has been linked to the introduction of stringent effluent limits from plating works and, more recently, to the introduction of general restrictions on cadmium consumption in certain countries. The main routes of exposure to cadmium are via inhalation or cigarette smoke, and ingestion of food. Skin absorption is rare.

Human exposure to cadmium is possible through a number of several sources including employment in primary metal industries, eating contaminated food, smoking cigarettes, and working in cadmium-contaminated work places, with smoking being a major contributor [ 91 , 92 ]. Other sources of cadmium include emissions from industrial activities, including mining, smelting, and manufacturing of batteries, pigments, stabilizers, and alloys [ 93 ]. Cadmium is also present in trace amounts in certain foods such as leafy vegetables, potatoes, grains and seeds, liver and kidney, and crustaceans and mollusks [ 94 ].

In addition, foodstuffs that are rich in cadmium can greatly increase the cadmium concentration in human bodies. Examples are liver, mushrooms, shellfish, mussels, cocoa powder and dried seaweed.

An important distribution route is the circulatory system whereas blood vessels are considered to be main stream organs of cadmium toxicity. Chronic inhalation exposure to cadmium particulates is generally associated with changes in pulmonary function and chest radiographs that are consistent with emphysema [ 95 ].

Workplace exposure to airborne cadmium particulates has been associated with decreases in olfactory function [ 96 ]. Several epidemiologic studies have documented an association of chronic low-level cadmium exposure with decreases in bone mineral density and osteoporosis [ 97 — 99 ]. Exposure to cadmium is commonly determined by measuring cadmium levels in blood or urine. Blood cadmium reflects recent cadmium exposure from smoking, for example. It is estimated that about 2. Blood and urine cadmium levels are typically higher in cigarette smokers, intermediate in former smokers and lower in nonsmokers [ , ].

Because of continuing use of cadmium in industrial applications, the environmental contamination and human exposure to cadmium have dramatically increased during the past century [ ]. Cadmium is a severe pulmonary and gastrointestinal irritant, which can be fatal if inhaled or ingested. After acute ingestion, symptoms such as abdominal pain, burning sensation, nausea, vomiting, salivation, muscle cramps, vertigo, shock, loss of consciousness and convulsions usually appear within 15 to 30 min [ ].

Acute cadmium ingestion can also cause gastrointestinal tract erosion, pulmonary, hepatic or renal injury and coma, depending on the route of poisoning [ , ]. Chronic exposure to cadmium has a depressive effect on levels of norepinephrine, serotonin, and acetylcholine [ ]. Rodent studies have shown that chronic inhalation of cadmium causes pulmonary adenocarcinomas [ , ]. It can also cause prostatic proliferative lesions including adenocarcinomas, after systemic or direct exposure [ ]. Although the mechanisms of cadmium toxicity are poorly understood, it has been speculated that cadmium causes damage to cells primarily through the generation of ROS [ ], which causes single-strand DNA damage and disrupts the synthesis of nucleic acids and proteins [ ].

Studies using two-dimensional gel electrophoresis have shown that several stress response systems are expressed in response to cadmium exposure, including those for heat shock, oxidative stress, stringent response, cold shock, and SOS [ — ]. In vitro studies indicate that cadmium induces cytotoxic effects at the concentrations 0. However, cadmium is a weak mutagen when compared with other carcinogenic metals [ ]. Previous reports have indicated that cadmium affects signal transduction pathways; inducing inositol polyphosphate formation, increasing cytosolic free calcium levels in various cell types [ ], and blocking calcium channels [ , ].

Cadmium compounds are classified as human carcinogens by several regulatory agencies. National Toxicology Program have concluded that there is adequate evidence that cadmium is a human carcinogen. This designation as a human carcinogen is based primarily on repeated findings of an association between occupational cadmium exposure and lung cancer, as well as on very strong rodent data showing the pulmonary system as a target site [ 91 ].

Thus, the lung is the most definitively established site of human carcinogenesis from cadmium exposure. Other target tissues of cadmium carcinogenesis in animals include injection sites, adrenals, testes, and the hemopoietic system [ 91 , , ]. In some studies, occupational or environmental cadmium exposure has also been associated with development of cancers of the prostate, kidney, liver, hematopoietic system and stomach [ , ].

Carcinogenic metals including arsenic, cadmium, chromium, and nickel have all been associated with DNA damage through base pair mutation, deletion, or oxygen radical attack on DNA [ ]. Animal studies have demonstrated reproductive and teratogenic effects. Small epidemiologic studies have noted an inverse relationship between cadmium in cord blood, maternal blood or maternal urine and birth weight and length at birth [ , ].

Chromium compounds are stable in the trivalent [Cr III ] form and occur in nature in this state in ores, such as ferrochromite. The hexavalent [Cr VI ] form is the second-most stable state [ 28 ].

Elemental chromium [Cr 0 ] does not occur naturally. Chromium enters into various environmental matrices air, water, and soil from a wide variety of natural and anthropogenic sources with the largest release coming from industrial establishments. Industries with the largest contribution to chromium release include metal processing, tannery facilities, chromate production, stainless steel welding, and ferrochrome and chrome pigment production.

The increase in the environmental concentrations of chromium has been linked to air and wastewater release of chromium, mainly from metallurgical, refractory, and chemical industries. Chromium released into the environment from anthropogenic activity occurs mainly in the hexavalent form [Cr VI ] [ ].

Hexavalent chromium [Cr VI ] is a toxic industrial pollutant that is classified as human carcinogen by several regulatory and non-regulatory agencies [ — ]. The health hazard associated with exposure to chromium depends on its oxidation state, ranging from the low toxicity of the metal form to the high toxicity of the hexavalent form.

All Cr VI -containing compounds were once thought to be man-made, with only Cr III naturally ubiquitous in air, water, soil and biological materials. Chromium is widely used in numerous industrial processes and as a result, is a contaminant of many environmental systems [ ]. Commercially chromium compounds are used in industrial welding, chrome plating, dyes and pigments, leather tanning and wood preservation.

Chromium is also used as anticorrosive in cooking systems and boilers [ , ]. It is estimated that more than , workers are exposed annually to chromium and chromium-containing compounds in the workplace.

In humans and animals, [Cr III ] is an essential nutrient that plays a role in glucose, fat and protein metabolism by potentiating the action of insulin [ 5 ]. However, occupational exposure has been a major concern because of the high risk of Cr-induced diseases in industrial workers occupationally exposed to Cr VI [ ].

Also, the general human population and some wildlife may also be at risk. It is estimated that 33 tons of total Cr are released annually into the environment [ ]. The U. Non-occupational exposure occurs via ingestion of chromium containing food and water whereas occupational exposure occurs via inhalation [ ].

Chromium content in foods varies greatly and depends on the processing and preparation. Present day workers in chromium-related industries can be exposed to chromium concentrations two orders of magnitude higher than the general population [ ]. Even though the principal route of human exposure to chromium is through inhalation, and the lung is the primary target organ, significant human exposure to chromium has also been reported to take place through the skin [ , ].

For example, the widespread incidence of dermatitis noticed among construction workers is attributed to their exposure to chromium present in cement [ ]. Occupational and environmental exposure to Cr VI -containing compounds is known to cause multiorgan toxicity such as renal damage, allergy and asthma, and cancer of the respiratory tract in humans [ 5 , ]. Breathing high levels of chromium VI can cause irritation to the lining of the nose, and nose ulcers.

The main health problems seen in animals following ingestion of chromium VI compounds are irritation and ulcers in the stomach and small intestine, anemia, sperm damage and male reproductive system damage. Chromium III compounds are much less toxic and do not appear to cause these problems.

Some individuals are extremely sensitive to chromium VI or chromium III , allergic reactions consisting of severe redness and swelling of the skin have been noted.

An increase in stomach tumors was observed in humans and animals exposed to chromium VI in drinking water. Accidental or intentional ingestion of extremely high doses of chromium VI compounds by humans has resulted in severe respiratory, cardiovascular, gastrointestinal, hematological, hepatic, renal, and neurological effects as part of the sequelae leading to death or in patients who survived because of medical treatment [ ].

Although the evidence of carcinogenicity of chromium in humans and terrestrial mammals seems strong, the mechanism by which it causes cancer is not completely understood [ ]. Major factors governing the toxicity of chromium compounds are oxidation state and solubility. Cr VI compounds, which are powerful oxidizing agents and thus tend to be irritating and corrosive, appear to be much more toxic systemically than Cr III compounds, given similar amount and solubility [ , ].

Although the mechanisms of biological interaction are uncertain, the variation in toxicity may be related to the ease with which Cr VI can pass through cell membranes and its subsequent intracellular reduction to reactive intermediates. It can be absorbed by the lung and gastrointestinal tract, and even to a certain extent by intact skin. The reduction of Cr VI is considered as being a detoxification process when it occurs at a distance from the target site for toxic or genotoxic effect while reduction of Cr VI may serve to activate chromium toxicity if it takes place in or near the cell nucleus of target organs [ ].

If Cr VI is reduced to Cr III extracellularly, this form of the metal is not readily transported into cells and so toxicity is not observed. The balance that exists between extracellular Cr VI and intracellular Cr III is what ultimately dictates the amount and rate at which Cr VI can enter cells and impart its toxic effects [ ].

Any of these species could attack DNA, proteins, and membrane lipids, thereby disrupting cellular integrity and functions [ , ]. Studies with animal models have also reported many harmful effects of Cr VI on mammals.

Subcutaneous administration of Cr VI to rats caused severe progressive proteinuria, urea nitrogen and creatinine, as well as elevation in serum alanine aminotransferase activity and hepatic lipid peroxide formation [ ]. Similar studies reported by Gumbleton and Nicholls [ ] found that Cr VI induced renal damage in rats when administered by single sub-cutaneous injections. Bagchi et al. Adverse health effects induced by Cr VI have also been reported in humans.

Epidemiological investigations have reported respiratory cancers in workers occupationally exposed to Cr VI -containing compounds [ , ]. DNA strand breaks in peripheral lymphocytes and lipid peroxidation products in urine observed in chromium-exposed workers also support the evidence of Cr VI -induced toxicity to humans [ , ].

Oxidative damage is considered to be the underlying cause of these genotoxic effects including chromosomal abnormalities [ , ], and DNA strand breaks [ ]. Nevertheless, recent studies indicate a biological relevance of non-oxidative mechanisms in Cr VI carcinogenesis [ ]. The toxicology of Cr VI does not reside with the elemental form. It varies greatly among a wide variety of very different Cr VI compounds [ ]. Epidemiological evidence strongly points to Cr VI as the agent in carcinogenesis.

Solubility and other characteristics of chromium, such as size, crystal modification, surface charge, and the ability to be phagocytized might be important in determining cancer risk [ ]. Studies in our laboratory have indicated that chromium VI is cytotoxic and able to induce DNA damaging effects such as chromosomal abnormalities [ ], DNA strand breaks, DNA fragmentation and oxidative stress in Sprague-Dawley rats and human liver carcinoma cells [ 27 , 28 ].

Recently, our laboratory has also demonstrated that chromium VI induces biochemical, genotoxic and histopathologic effects in liver and kidney of goldfish, carassius auratus [ ]. Various hypotheses have been proposed to explain the carcinogenicity of chromium and its salts, however some inherent difficulties exist when discussing metal carcinogenesis. A metal cannot be classified as carcinogenic per se since its different compounds may have different potencies.

Because of the multiple chemical exposure in industrial establishments, it is difficult from an epidemiological standpoint to relate the carcinogenic effect to a single compound. Today, all the reaches to plains in Garhwal Himalayas. This work also aims water bodies from river systems to canal systems, are under to classify the water quality into different quality categories threat with quality problems due to discharge of untreated by using pollution index.

This has directed the atten- tion of researchers, environmentalist, government agencies Samples Collection and Analysis and health practitioners.

The presence of these toxic metals in the water ecosystem has extensive consequences on the Total 48 samples of water were collected from 12 different living organism and man; their harmful property on man are locations from Rishikesh and Haridwar viz. Rishikesh-Byasi, linked to lung, nasal sinus and dermal cancers. Natural influences and anthropogenic Roorkee Table 1 , seasonally, viz. The sample was collected from the depth of 1 ft ing, industrial, agricultural or other purposes Matta et al.

About 10 L of water samples was While traveling the km long stretch River Ganga Samples were collected in triplicate from each site, and hold the life to millions of peoples in 29 cities, 7 towns, and the mean value for each parameter was reported.

Many of the paper of Whatman No. Individual heavy metal trialized and urbanized areas polluted with a concentration was observed with the help of a flame atomic absorption of variable and unsuitable physic-chemical characteristics spectrophotometer FAAS , using model: ECIL AAS and heavy metals Matta and Gjyli ; Matta and Uniyal PC-based.

Alaknanda and its tributaries may further influence hourly variation in flow. The river bed consisting of large and small pebble with some boulders and sand Thare et al. In at different parameters. Third—summing up of these sub-indices Qi in the over- Heavy metal pollution index Heavy metal pollution all index. The overall water quality and its appro- proportionality. Wi is the unit weight for an ith parameter; n is the number of parameters The critical pollution index value is Prasad 10 and Bose The maximum Zn con- 8 centration was found The maximum Pb concentration was found The maximum concentration of 6 Mn was found The maximum It may be attributed to the soil—water inter- The 4 low concentration of Cu shows there is no significant source of pollution.

The maximum Cu value was found 6.