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ARSENIC ESTABLISHED CARCINOGEN

CONTENT

  • 1. What is Arsenic?
  • 2. Why is Arsenic Bad for Health?
  • 3. WILL ARSENIC IN MY WATER CAUSE HEALTH PROBLEMS?
  • 4. HEALTH EFFECTS - RESEARCHES
  • 4. 1. TOXICOLOGICAL STUDIES
  • 5. Arsenic Contamination - Bengal Delta
  • 6. India, West Bengal
  • 7. Arsenicosis In Bangladesh : Samta, an Isolated Village
  • 7.1. Exposure to arsenic has ‘alarmingly’ increased the infant death rate
  • 8. Is your food tainted with arsenic?
  • 1. What is Arsenic?

    arsenic -SEM, The round blobs are framboidal pyrite, which is suspected to be a candidate arsenic

    Arsenic – a metalloid element – is a natural part of the earth's crust in some parts of the world and may be found in water that has flowed through arsenic-rich rocks. Arsenic is also emitted into the atmosphere by high-temperature processes such as coal-fired power generation plants, burning vegetation and volcanic action. High concentrations of arsenic in drinking-water are found in various parts of the world including Argentina, Bangladesh, Chile, China, Hungary, India (West Bengal), Mexico, Nepal, Pakistan, Thailand, USA, and Viet Nam. A variety of instrumental techniques available for the determination of arsenic in water and air. (WHO Environmental Health Criteria, No. 224: Arsenic)
    .

    arsenic in pyriteDomestic demand for arsenic in the wood preservative industry was relatively unchanged . World production of arsenic trioxide in tons as follows (1996): Belgium 2, 000, Chilie 6, 500, China 13, 000, France 4, 000, Kazakstan 1, 500, Mexico 4, 500, Nambia 2, 300, Philippines 2, 000, Russia 1, 500, Others Countries 3, 000. World resources of copper and lead contain about 11 million tons of arsenic. Substantial resources of arsenic occur in copper ores in northern Peru and the Philippines and in copper-gold ores in Chile. Inaddition, world gold resources, particularly in Canada, contain substantial resources of arsenic. (USGS, 1997).

    Arsenic in Drinking Water


    Arsenic is a semi-metal element in the periodic table. It is odorless and tasteless. It enters drinking water supplies from natural deposits in the earth or from agricultural and industrial practices. Non-cancer effects can include thickening and discoloration of the skin, stomach pain, nausea, vomiting; diarrhea; numbness in hands and feet; partial paralysis; and blindness. Arsenic has been linked to cancer of the bladder, lungs, skin, kidney, nasal passages, liver, and prostate. EPA has set the arsenic standard for drinking water at .010 parts per million (10 parts per billion) to protect consumers served by public water systems from the effects of long-term, chronic exposure to arsenic. Water systems must comply with this standard by January 23, 2006, providing additional protection to an estimated 13 million Americans. This web site is designed to provide you with information about arsenic in drinking water and provide guidance materials to help the states and water systems comply with the standard

    In most drinking water sources, the inorganic form of arsenic tends to be more predominant than organic forms. Inorganic arsenic in drinking water can exert toxic effects after acute (short-term) or chronic (long-term) exposure. Although acute exposures to high doses of inorganic arsenic can cause adverse effects, such exposures do not occur from public water systems in the U.S. that are in compliance with the existing MCL of 50 µg/L. Today's final rule addresses the long-term, chronic effects of exposure to low concentrations of inorganic arsenic in drinking water. Studies link inorganic arsenic ingestion to a number of health effects. These health effects include:

  • Cancerous Effects: skin, bladder, lung, kidney, nasal passages, liver and prostate cancer; and
  • Non-cancerous effects: cardiovascular, pulmonary, immunological, neurological and endocrine (e.g., diabetes) effects

  • Arsenic in drinking water WHO

    EPA's Office of Research and Development (ORD) is spearheading an arsenic research program to provide information to fill in research gaps that exist for a number of technologies or compliance approaches and provide this information to utilities, engineering firms, regulatory officials, and others. ORD is conducting treatment technology demonstration projects; short-term performance verification studies of commercially-ready arsenic treatment technologies; research to emphasize management of residuals from arsenic treatment, improved analytical methods, treatment process optimization and distribution system studies; and, assisting states and utility operators by developing training materials, software and design manuals, and by providing direct training and technical assistance on how to meet the new standard.

    Consider testing your well for pesticides, organic chemicals, and heavy metals before you use it for the first time. Test private water supplies annually for nitrate and coliform bacteria to detect contamination problems early. Test them more frequently if you suspect a problem. Be aware of activities in your watershed that may affect the water quality of your well, especially if you live in an unsewered area.

    What concerns should I have after a flood if I have a private well?

    Stay away from the well pump while flooded to avoid electric shock, AND . . .

  • Do not drink or wash from the flooded well to avoid becoming sick.
  • Get assistance from a well or pump contractor to clean and turn on the pump.
  • After the pump is turned back on, pump the well until the water runs clear to rid the well of flood water.
  • If the water does not run clear, get advice from the county or state health department or extension service.
  • CHEMICAL AND PHYSICAL PROPERTIES

    Arsenic is an element with atomic number of 33. The most common form of the element is a silver-grey brittle crystalline solid. Given below are some of its properties:

    Atomic weight: 74.9
    Specific gravity: 5.73 :
    Melting point 817°C at 28atm
    Boiling point: 613°C (sublimes)
    Vapour pressure: 1mm Hg at 372°C

    When arsenic is heated in air, it will burn and form a white smoke consisting of arsenic trioxide (As203).

    Carcinogen category notice: Category 1. Established human carcinogen known to be carcinogenic to humans. There is sufficient evidence to establish a causal association between human exposure to these substances and the development of cancer.
    Carcinogen Category 1 (Confirmed Human Carcinogen)

    Arsenic poisoning does cause a variety of systemic problems when and if an individual does get the toxic of arsenic poisoning. The typical symptoms are; diaphoresis, muscle spasms, nausea, vomiting, abdominal pain, garlic odour to the breath, diarrhoea, anuria, dehydration, hypertension, cardiovascular collapse, aplastic anaemia and death. The degree to which symptoms a person has will be determined by the severity of the exposure.

    Possible methods of exposure to toxic substances is common to all products. The possible methods of exposure are contact, ingestion and inhalation.
    The first method is by contact and when the substances is arsenic the initial complication is a corrosive effect to the dermal layers. Over a prolonged contact exposure the resulting symptoms can be very dangerous and can cause focal hyperaemia, which means it decreases to blood flow to your arteries and veins and vesicular eruptions

    vesicular eruptions      contaminated person    amputee  feet amputed leg

    The second possible method of poisoning with an arsenic compound is by ingestion. The ingestion of arsenic will typically lead to the development of symptoms within thirty minutes. The initial symptoms may include a metallic taste in the mouth, hypersalivation, and dysphagia. The progression of symptoms would then include; vomiting, cramps, diaphoresis, breath odour (garlic like), and diarrhoea. If the exposure was of a large concentration then the progression of the arsenic poisoning event would lead to seizures, electrolyte disturbances and systemic shock. An exposure of an individual to arsenic that has resulted from a large quantity or concentration usually will result in death. If death does not occur with in a few hours then death will occur during the next few days due to renal failure.
    The third methodof exposure is by inhalation. The inhalation of arsenic compounds can lead to inflammation of the mucous membranes of the nasal and oral pharyngeal passage ways. The process may be delayed by this type of exposure because the concentration may be lower, but the end result will be the same symptoms as arsenic poisoning by contact, and by ingestion . Regardless of the method of the exposure toxic event can end in the same result, death!

    Arsenic is a metal compound that can easily find its way into the environment and the human population. The substance is found in our water, soil, food products and eventually , us3. Even though we have governmental guidelines for controlling such toxic "substances" or "compounds" on a daily basis, we drink contaminated water and eat contaminated food products. This will lead to some degree of arsenic poisoning in each of us, according to Joe Harrison the technical director of Water Quality Association. Daily consumption of water with greater than 50 micrograms per liter of arsenic, less than 1 % of the fatal dose, can lead to problems with skin, circulatory and nervous systems3. Greater problems can occur if the arsenic poisoning is of a chronic nature and resulting in neural disorders, vital organ damage and eventually death.

    Arsenic is a compound that should be more closely monitored by parents, teachers and children because of its fatal results. The three main methods of exposure are contact, ingestion and inhalation. Regardless of the method of exposure all can produce basically the same symptoms.

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    2. Why is Arsenic Bad for Health?

    Arsenic dissolved in water is acutely toxic and can lead to a number of health problems. Long-term exposure to arsenic in drinking-water causes increased risks of cancer in the skin, lungs, bladder and kidney. It also leads to other skin-related problems such hyperkeratosis and changes in pigmentation. Consumption of arsenic also leads to disturbance of the cardiovascular and nervous system functions and eventually leads to death. These health effects – sometimes collectively referred to as arsenicosis – have been demonstrated in many studies. Increased risks of lung and bladder cancer and of arsenic-associated skin lesions have been reported for consuming drinking-water with arsenic concentrations equal to or greater than 50 parts per billion (or microgram per liter). (WHO Environmental Health Criteria, No. 224: Arsenic).

    Arsenicosis is recognizable from skin colour changes, blotches all over the face and body, hyper pigmentation on the chest and upper arms, hard patches on palms and soles of the feet, inability to walk, debilitating pain, watery eyes

    Arsenicosis, or arsenic toxicity, develops after two to five years of exposure to arsenic contaminated drinking water, depending on the amount of water consumption and arsenic concentration in water. Initially, the skin begins to darken (called diffuse melanosis). This happens first in the palms. Diffuse melanosis leads to spotted melanosis, when darkened spots begin to appear on the chest, back and limbs, although the latter is what is usual among people, and so is taken to be an early symptom. At a later stage, leucomelanosis sets in: the body begins to show black and white spots.

    Keratosis is the middle stage of arsenicosis. The skin, in portions, becomes hard and fibrous; it is as if the body has broken out into hard boils, or ulcers. Diffuse or nodular keratosis on the palm of the hand or sole of the foot is a sign of moderately severe toxicity. Rough dry skin, often with palpable nodules on hands, feet and legs means severe toxicity. This can lead to the formation of gangrene, and cancer.

    Arsenic poisoning brings with it other complications: liver and spleen enlargement and cirrhosis of the liver; myocardial degeneration and cardiac failure; peripheral neuropathy affecting primary sensory functions; diabetes mellitus and goitre; and skin cancers.

    Three types of skin cancers are observed: Bowen’s disease (form of squamous cell carcinoma); basal cell carcinoma and squamous cell carcinoma. These cancers develop primarily from keratosis.

    "Another unfortunate and complicating fact about arsenic poisoning," Hiroki Hashizume adds, "is that it generally takes from seven to 10 years sometimes longer, for the disease to be recognized. When it finally is, it may be too late to treat." Professor Robert Goyer, who headed a nine-member commission of the US National Academies of Science, says its findings bolster a 1999 study by the Academy that found that men and women who drink every day water with 10 ppb of arsenic have an increased risk of more than 3 in 1000 of developing bladder or lung cancer during their lifetime. That risk rises to 7 in 1000 at 20 ppb.

    WHO reports(Sept. 8, 2000):

    Bangladesh is facing the largest mass poisoning of a population in history because of arsenic contamination of its drinking water supplies. The research by Allan H. Smith, professor of epidemiology at the University of California at Berkeley, said that between 33 and 77 millions of Bangladesh's 125 million population was at risk. Smith predicted a big increase over the coming years in the number of cases of disease caused by arsenic. These ranged from skin lesions to cancers of the bladder, kidney, lung and skin to cardiovascular problems. Bangladesh is grappling with the largest mass poisoning of a population in history because groundwater used for drinking has been contaminated with naturally occurring inorganic arsenic. The scale of this environmental disaster is greater than any seen before. It is beyond the accidents at Bhopal, India, in 1984 and Chernobyl, Ukraine, in 1986 (Smith).

    The Bangladesh Observer adds (editorial, 17. 02. 03):

    Though the mere mention of cancer brings the image of death, the fact is that in the case of children, around 70 per cent cases of cancer can be cured if treatment is provided at the right time. Ashic (A Shelter for Helpless Children) disclosed at a press conference that every year 2,50,000 children are affected by cancer and added that in 80 per cent of the cases, children are deprived of treatment as proper diagnosis is not done. We are also greatly alarmed to find that in the Bangladesh context between 5000 and 6000 children below the age of 15 become afflicted. A more searching look informs us that one child in 600 develops cancer before reaching the age of nine.

    Mass majority of the rural population does not have any alternative. While those problems remain unsolved, thousands of villagers in Bangladesh will never be able to recover from a condition that has ruined their lives. "For the last ten years I've had spots on my body," says one villager, Aleya Begum, "but it's only recently that it has become a lot worse. Now, it feels that my body is burning and a continuous itching which I'm told won't go away for the rest of my life."

    A neighbour, Iqbal Hossain, has a similar story. "In this village of ours, nearly three thousand people are living and about twenty-five people have been subjected to arsenic poisoning. Among them my condition is the most severe. Although the government had committed to supply arsenic free water two years ago, that commitment has not been fulfilled yet. The villagers didn't take notice of this problem at the beginning and now, although they are trying to stay free from arsenic poisoning, there is no way to resist it."

    While the number of arsenic victims is increasing, so too is the level of acrimony as to who is responsible for this humanitarian disaster. The British Geological Survey is currently being sued by a Bangladeshi non-governmental organization. It allegedly conducted a survey in 1992 which revealed large quantities of arsenic, yet failed to provide thousands of villagers with adequate warning (Sakil Faizullah, 26 September 2002).

    The regulatory regime in Bangladesh entangles in a number of governance issues... The rules as followed by the bureaucrats are, in most cases, outdated, complicated, ineffective and provide no scope for monitoring, transparency and above all accountability. (Patel, P. H., 2001).

    You can’t go into a village and just screen. Say, as it has happened in many cases, that you have 100% of the tube wells contaminated. So one day people are very happily drinking from what they think to be safe sources and the next day an organization like BRAC or any other NGO, goes over and paints all the tube wells red because they’re contaminated far higher than the WHO or the Bangladesh standards. And they, the people, are left scratching their heads, "Where do we drink water from?" (B. Kabir, The world Bank, 2001)

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    3. WILL ARSENIC IN MY WATER CAUSE HEALTH PROBLEMS?

    If you are exposed to arsenic, several factors that work in combination with each other will determine whether harmful health effects may occur. These factors are:

    • DOSE How much arsenic am I exposed to?
    • DURATION How long and how often have I been exposed?
    • TYPE of ARSENIC Have I been exposed to inorganic or organic arsenic?

    GENERAL HEALTH, NUTRITIONAL STATUS, AGE, and LIFESTYLE

    Some people may be affected by lower levels of arsenic than others. Young children, the elderly, people with long-term illnesses, and unborn babies are at greatest risk of being affected. They can be more sensitive to chemical exposures. Babies are not exposed to arsenic through breast milk at levels of concern even when their mothers have been exposed.

    WHAT ARE THE HEALTH EFFECTS ASSOCIATED WITH ARSENIC EXPOSURE?

    foot amputee     feet infection    infected hands

    Based on studies in other countries, long-term exposure to high arsenic levels in drinking water has caused the following health effects:

    • THICKENING and DISCOLORATION of the SKIN. Sometimes these changes can lead to skin cancers. These cancers can be easily cured if discovered early.
    • STOMACH PAIN, NAUSEA, VOMITING and DIARRHEA.
    • NUMBNESS in the HANDS and FEET.

    Many of the health effects of arsenic exposure are often seen with other common illnesses, which makes it difficult for a doctor to recognise. If you or your family members are concerned about health problems you believe are related to arsenic in your well water, you should discuss them with your doctor. You should also consider having your well water tested.

    TOXICOKINETICS

    The half-life of inorganic arsenic in blood is about 2 hours; the half-life of the methylated metabolites range from 5 to 20 hours.

    Absorption

    Pentavalent arsenic is well absorbed through the gut, but the trivalent form is more lipid soluble. Toxicity results from the arsenite form (As+3), especially by dermal absorption. Inhalation can result in symptomatic chronic exposure, particularly with arsine gas, which causes severe symptom by inhalation. Arsenic compounds are well absorbed parenterally within 24 hours.

    Distribution

    Arsenic initially localizes in the blood bound to globulin. Redistribution occurs within 24 hours to the liver, lungs, intestinal wall, and spleen, where arsenic binds to the sulfhydryl groups of tissue proteins. Only small amounts of arsenic penetrate the blood-brain barrier. Arsenic replaces phosphorus in the bone where it may remain for years. Within 30 hours postingestion, arsenic deposits in the hair. Arsenic levels in hair sections may provide an indication of the time of exposure based on length from growth site. The hair of an individual who died 6 to 8 hours after ingestion of an arsenic overdose generally does not contain arsenic.

    Organic Arsenic Sources

    The two most commonly found organic, nontoxic variants of arsenic found in food regularly consumed by humans are arsenobetaine and arsenocholine. Considerable concentrations of organic acid are found in shellfish, cod, and haddock. After arsenobetaine and arsenocholine are ingested, they are rapidly cleared in the urine where they are completely excreted within 1 to 2 days (Fig. 1). No residual toxic metabolites are present. The half?life of organic arsenic is 4 to 6 hours.


    Figure 1.

    Pregnancy

    Inorganic arsenic crosses the placenta. A 22 year old female at 20 weeks of gestation ingested 340 mg of sodium arsenate. The initial 24 hour urinary arsenic level was 3030 mg/L. Dimercaprol was administered. Fetal heart tones were normal. A healthy infant was delivered at 36 weeks. At birth 24 hour urinary arsenic levels were <50 mg/L in the infant and <100 mg/L in the mother. Another case of maternal arsenic ingestion at 30 week gestation resulted in infant death shortly after birth. Dimercaprol appears to be the agent of choice. D penicillamine has been associated with teratogenicity.

    Gastrointestinal Tract

    Dilation of splanchnic vessels causes submucosal vesicle formation. Rupture of these vesicles leads to rice?water stools and bleeding. Subsequently, a protein?losing enteropathy may develop.

    Despite aggressive management of arsenic intoxication and a rapid decrease in blood and urine arsenic levels, neurologic defects may persist. It appears that distribution into neural tissue is rapid and may be irreversible even with chelation.

    Muscle

    Fatal rhabdomyolysis dysfunction has been reported after an acute arsenic overdose.

    Metabolic/Hepatic

    Negative nitrogen balance, hepatic fatty degeneration, central necrosis and cirrhosis, antagonism of thyroid hormone.

    Skin Appendages

    Alopecia (late), brittle fingernails, Mees's lines (horizontal white lines that appear after exposed nail bed area grows to exterior).


    Blackfoot Disease

    Blackfoot disease is a unique peripheral artery disease in an endemic area of chronic arsenicism on the southwest coast of Taiwan. Humic acid in well water may be the main cause of the disease. Platelet activation and hypercoagulability may play a role in causing this disease.

    LABORATORY Analytic Methods

    The current standard for arsenic analysis is atomic absorption spectroscopy, which measures total arsenic, does not distinguish between pentavalent, trivalent, or organic arsine.

    Blood Levels

    The short half?life of arsenic in the blood means that blood arsenic levels are less useful than urine levels unless exposure occurred on the same day. Serum (or blood) arsenic levels are detectable only during the first 2 to 4 hours after ingestion, after which arsenic in any form is not readily detected in blood or serum.

    Inorganic AS+3 and AS+5

    AS+3 is more toxic than AS+5. AS+3 and AS+5 are detected in the body shortly after ingestion. Monomethylarsine and dimethylarsine predominate more than 24 hours after ingestion. Urinary AS+3 and AS+5 levels present about 10 hours and return to normal in 20 hours. Urinary monomethylarsine and dimethylarsine levels peak at 40 to 60 hours and return to baseline in 6 to 20 days after ingestion. The half?life of inorganic arsenic in blood is 2 hours and that of the methylated metabolites 5 to 20 hours. Serum (or blood) arsenic levels are only detectable during the first 2 to 4 hours after ingestion.

    Organic As (Fig. 1)

    Arsenobetaine and arsenocholine have a half-life of about 4 hours and are completely excreted in I to 2 days.

    Urine: No exposure-less than 25 mg/daily.

    Toxic levels 50 to 50,000 mg daily.

    After seafood-50 to 2,000 mg daily.

    Hair Levels

    Hair analysis for arsenic is a semireliable method for confirming chronic toxicity. It does not discriminate between externally deposited arsenic and arsenic found within the hair shaft.

    Fingernails

    Fingernail arsenic may provide an estimate of the air arsenic exposure for a worker.

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    4. HEALTH EFFECTS - RESEARCHES

    Researches at the University California, PROGRAM IN ARSENIC HEALTH EFFECTS RESEARCH School of Public Health and Centre for Occupational and Environmental Health University of California, Berkeley (1998) provided the following accomplishment on arsenic studies:

    • Provided definitive evidence (from studies conducted in Argentina and Chile) that arsenic is a potent cause of human bladder cancer.
    • Provided definitive evidence (from studies conducted in Argentina and Chile) that arsenic is a potent cause of human lung cancer.
    • Demonstrated results which indicate that epidemiological and experimental human data do not support the methylation hypothesis.
    • Showed that with exposure to water containing around 600 µµg/L, 1 in 10 adult cancer deaths may be due to arsenic-caused cancers, the highest environmental cancer risk ever reported.
    • Identified a dose-response relationship between arsenic exposure and bladder cell micronuclei, a genotoxic marker of effect.
    • Identified a preliminary dose-response relationship between arsenic concentration in well water in India and the occurrence of keratoses and hyperpigmentation.
    • Studies currently underway in India, Chile and the US, will allow projection of cancer risks with individual exposure data.
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    4. 1. TOXICOLOGICAL STUDIES

    NONMALIGNANT HEALTH EFFECTS OF ARSENIC EXPOSURE

    This thesis comprises a series of studies concerning occupational and environmental exposure to arsenic and some novel chronic health effects of this element, namely diabetes mellitus and hypertension. Substantial prevalence of the well-known skin manifestations of arsenic ingestion was also found to occur as a result of environmental exposure through drinking water.

    Two case-control studies on diabetes mellitus and occupational exposure to arsenic included individuals employed at a copper smelting industry (Paper I) and in art glassworks (Paper II) in Sweden. Although the number of smelter workers involved was small (12 cases and 31 controls), a significant exposure-response trend was obtained (p = 0.03). The assessment of arsenic exposure among 888 glass workers was less detailed, nonetheless it revealed an approximately doubled risk (MH-OR = 2.1; 95% confidence interval 1.2-3.7) for the workers with occupational titles that suggested exposure. Overall, the results of these studies provide evidence that occupational arsenic exposure may play a role in the development of diabetes mellitus.

    Four cross-sectional studies were carried out in Bangladesh, where a fairly large part of the population is exposed to inorganic arsenic in drinking water. In the first study (Paper III), the prevalence of diabetes mellitus among subjects with keratosis (n = 163) was compared with unexposed subjects (n = 854); keratosis was considered to be a definite sign of exposure.

    A dose-response relationship was found between categories of time-weighted arsenic exposure (mg/L in drinking water) and the prevalence of diabetes mellitus (p < 0.001), and the crude overall prevalence ratio amounted to 4.4. Despite the lack of detailed individual exposure data and information on potential confounders other than age, sex, and body mass index (BMI), the association seems strong enough to support a causal relationship, because the adjusted overall prevalence ratio was 5.9 (95% confidence interval 2.9-11.6).

    One of the other studies performed in Bangladesh (Paper V; 1481 exposed individuals, 430 exhibiting keratosis) showed a somewhat higher prevalence rate of skin lesions in males (31%) than females (26%) due to chronic arsenic toxicity.

    The crude overall prevalence was 29% in the studied villages, and there was a distinct dose-response relationship between arsenic concentrations in drinking water and skin lesions (p < 0.01).

    A clear dose-response relationship was also observed (Paper VI) between arsenic exposure and glucosuria for subjects both with and without skin lesions (p < 0.01). The possibility of using the skin lesions for initial screening for glucosuria was considered. However, the appearance of dermatological signs of chronic arsenic toxicity proved to be a poor marker in this respect, because glucosuria also occurred in the absence of skin lesions.

    A third Bangladeshi study (Paper IV) indicated a significantly increased risk of hypertension in connection with exposure to inorganic arsenic in drinking water (1481 exposed and 114 unexposed subjects). The overall crude prevalence ratio of hypertension amounted to 1.7, and the adjusted (for age, sex, and BMI) ratio was 1.9 (95% confidence interval 1.0-3.6). A significant trend in risk (p << 0.001) was observed between an approximate time-weighted mean exposure to arsenic, considered in milligrams per liter or milligram-years per liter, which strengthens the possibility of a causal association.

    (Mahfuzar Rahman , Akademisk Avhandling,Environ Health Perspect 1999 Sep;107(9):727-729 Department of Health and Environment, Faculty of Health Scien
    ces, Linköping University)

    Chronic Effects of Arsenic (professor Wilson, Havard University, 1999::

    • <i>Melanosis</i>
      After a few years of continued low level of arsenic exposure, many skin ailments appears i.e. Hypopigmentation (white spot), Hyperpigmentation (dark spots), collectively called Melanosis and keratosis (breakup of the skins and on hands and feet).
    • After a letency of 10 years, skin cancers appear.
    • After a latency of 29-30 years, internal cancers - particularly bladder and lung. These all have been seen in Taiwan and in Chilie
    • The number of cancers expected in bangladesh from the exposure already undergone can be very roughly estimated by using "defalut" (lower exposure of 0. 05 ppm (Bangladesh standard) - the risk 1 %) there are 20,000, 000 to 70, 000, 000 exposed persons at levels between 0. 05 ppm and 0.5 ppm.

    Arsenic poses stroke risk

    Contaminated water has affected people in Bangladesh Arsenic poisoning through contaminated drinking water can lead to diseased arteries, which in turn can cause heart attacks and strokes, research shows.

    Scientists say they have identified a link between long-term exposure to arsenic and the accelerated development of atherosclerosis or progressive narrowing and hardening of the arteries leading to the brain.

    The findings, published in the Journal of the American Heart Association, strongly point to arsenic and possibly other pollutants, as risk factors for blood vessel disease throughout the body.

    Arsenic in Drinking Water May Accelerate Artery Disease

    Determining a new federal standard for acceptable levels of arsenic in drinking water was no easy task. Now new research adds to the list of ills caused by exposure to the element. According to a study published in Circulation: Journal of the American Heart Association, long-term exposure to arsenic in drinking water is directly related to the development of atherosclerosis in the arteries leading to the brain.

    Chih-Hao Wang of the National Taiwan University and colleagues studied 463 people living in an area of Taiwan with high rates of arseniasis, or chronic arsenic poisoning. Scientists have tracked the amount of arsenic in well water in the region for more than four decades. Combining these records with detailed residential and medical histories allowed the team to determine the amount of arsenic exposure for each participant. The researchers then used ultrasound to measure the amount of atherosclerotic plaque in subjects' carotid arteries, which carry blood to the brain.

    The team found that three indices of long-term exposure to arsenic correlated directly with the amount of atherosclerosis present in the carotid arteries. People with the highest arsenic exposure, they report, had three times the risk of atherosclerosis as seen in those who were not exposed to the element. "Our results indicate that long-term arsenic exposure may lead to the progression or acceleration of carotid artery disease and most likely generalized artery disease in humans," Wang notes. Because this study occurred in a region characterized by extremely high levels of arsenic in drinking water, the lowest level of contamination examined was 50 micrograms per liter. The authors note that further research is required to assess the arterial risks associated with arsenic levels between five and 50 micrograms per liter (Sarah Graham,March 26, 2002 )

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    5. Arsenic Contamination - Bengal Delta

    Twenty-six years after arsenic contamination of water supplies was first detected in West Bengal, symptoms of the problem are being observed in more and more Indian states. Here Kimberlye Kowalczyk reports from Delhi on a pollution problem that is now affecting millions in the sub-continent. The crippled hands of Ravindra Nath Mishra of Ballia district, Uttar Pradesh, India. Source: WFS The crippled hands of Ravindra Nath Mishra of Ballia district, Uttar Pradesh, India. Recently, the ground water in Uttar Pradesh's Ballia district was found to be contaminated with arsenic. It is just the latest evidence of a problem that now affects the drinking water of 35 million people in Bangladesh and India, according to the latest UN estimates.

    Now around these paddy fields a disguised evil has crushed the nation, a catastrophe that is more severe than flood or tidal storm, Chernobyl, Bhopal or any kind of disaster that human being has ever faced to a such large extent. Slowly, but severely, painful deaths are occurring and most of the rural population of Bangladesh do not know why! A poison that you cannot see or even smell in the drinking water is hardly thinkable for such a simple-minded nation. The decision to change (so called "improvement") their life-style comes from the luxurious offices of the richest capitals of the world. A modern agrochemical /technological based agricultural system was imposed on them about three decades ago but they were never consulted nor asked for their advice.

    Priya Harish Patel, Harvard University, USA,( 2001) writed, "Where are we going to land?" I thought, inwardly panicking as acres and acres of water drew ever nearer with each passing second. At that moment, I recalled that Bangladesh was in fact the most densely populated country in the world and that 35 million people in this watery wonderland were suffering from lack of safe drinking water. I ignored these distracting thoughts as my plane safely landed on a magically appearing island of hard ground. A week later, I was rudely awakened to the reality of Bangladeshi life when I visited a rural village. There, within the wetlands and rivers that are Bangladesh, millions of people had erected little huts held up by hardy strips of bamboo. And there, I saw my first arsenicosis patient - his hands and chest were discolored and three fingers had been cut off due to gangrene, a symptom of advanced, chronic arsenic-poisoning. Here, within this green haven, millions of people were and are still living in a kind of hell - a hell they cannot see, taste, or feel but which invades their bodies through the water they drink and will eventually kill them."

    Before the beginning of the century there were 15 countries in the world that had arsenic contamination in water.Four countries,Bangladesh,West Bengal —India, China,and Taiwan, had populations that were suffering seriously.
    In fact, in the time span of only two years (2000 –2002) six more nations have found significant ground- water arsenic contamination.These are Cambodia, Lao People Democratic Republic, Pakistan, Myanmar, Vietnam, and Nepal.The International Arsenic Conference at San Diego (July, 2002 ) brought out a new aspect of this debacle. For the first time the serious situation of Bihar (another state of India in Middle Ganga Plain), was confirmed. This new discovery reveals that a good portion of the Ganges Plain,with an area of about 530,831 sq.km.,may be contaminated with arsenic.This area has a population of about 450 million (including Bangladesh) (Chakroborti, 2003)

    The largest mass poisoning of a population in history is now underway in Bangladesh. It is a terrible public catastrophe, asserts Allan H. Smith, Professor of Epidemiology at the University of California, Berkeley, and a WHO consultant who has investigated arsenicosis in Bangladesh on several trips. The number of people affected by this arsenic disaster is among the greatest of any disease facing the world today. "By virtue of its sheer size it is pushing the limits of our knowledge and capacity to respond to it," asserts Professor Hans van Ginkel, Rector of the United Nations University in Tokyo (WHO,Friday 22 March 2002)

    Smedley, P. L. and Kinniburgh (British Geological Survey, 2002) describes:

    The scale of the problem in terms of population exposed to high arsenic concentrations is greatest in Bengal Basin with more than 40 million people drinking water containing 'excessive' arsenic.

    "There is a serious concern," says Han Heijnen, a spokesman for the World Bank, "if we don´t take action now, in five to 10 years we will see a very strong increase of the number of people affected either by skin lesions due to arsenicosis or by cancers and other serious conditions. That will be a very serious problem for the socio-economic system of Bangladesh as well as for the health system."

    Among 64 districts of Bangladesh, 44 districts have arsenic contamination in groundwater (Mitul, 1998). There are reports of deaths and serious infection relating to arsenic poisoning. It is reasonable to believe that widespread areas of Bangladesh have been contaminated. Arsenic poisoning leading eventually to death,. as world-wide poisoning outbreaks are shown as follows (Pearce, 1995, Chakroborti, 1997):

    It is difficult to predict how many Bangladeshis will eventually die from causes related to the arsenic. Most researchers, including Dr. Smith, are shy with estimates. Richard Wilson, a Harvard physicist who is an expert in risk analysis, puts the number at one million. Dr. Sk. Ahktar Ahmad, a public health specialist with the government, predicts a total of three million to five million (New York Times (14. 07. 02).

    Deep tubewells

    The World Health Organisation (WHO) has proclaimed that clean drinking water in place of contaminated water will eventually bring a patient back to good health by flushing the arsenic out of the system. Assuming, of course, that they are not at different developed stages of cancer, which is the case for many who have been drinking arsenic contaminated water for 10-20 years.

    According to Paul Deverill, project officer of child environment for UNICEF, this organisation has confirmed the existence of arsenic contamination (at toxic levels) in India in West Bengal, Bihar, Uttar Pradesh, Assam, Jharkhand and Chhattisgarh. West Bengal is the most heavily affected state. Most of the people who are at risk in these states are very poor and cannot afford access to alternative drinking water, nor can they afford expensive treatment for the effects of arsenic poisoning.

    In both Bangladesh and India, arsenic contamination has been linked to the digging of deep tubewells - proposed by the UN and the World Bank from the 1970s onwards - for a regular supply of "safe" drinking water. During this period, water from deep tubewells was considered a viable and healthy alternative because in many areas, the surface water bodies - lakes, ponds and tanks - had become heavily polluted by industrial effluents and sewage.

    Consequently, tubewells that would bring up deep groundwater through handpumps appeared to be an efficient solution for hundreds of villages. However, millions of dollars in aid later, this solution has created severe problems. Jan Willem Rosenboom, arsenic project officer in Dhaka (Bangladesh) for UNICEF, said, "The scale is overwhelming. The UN has been identified right from the start as having something to do with it. We put the message across to sink these wells. We advised the government and now we are blamed. Yes, we do have a responsibility."

    Bangladesh's arsenic woes are here to stay

    Hopes that the arsenic that contaminates well water in Bangladesh might naturally fall to safer levels were dashed this week with the discovery that the deep aquifers from which it is extracted receive an arsenic top-up every rainy season.

    Groundwater from deep "tube wells" has been widely used for drinking water in Bangladesh since the 1970s, but it has emerged more recently that naturally occurring arsenic taints the water in many of the country's 10 million wells. A programme of testing wells and closing down those found to be tainted continues, but some 57 million Bangladeshis still drink water with unsafe arsenic levels, which can cause skin lesions and cancer.

    It had been thought that the arsenic came from rock sediments deep underground, and that knowing where they were could lead to a long-term solution. But when Scott Fendorf and colleagues at Stanford University in California analysed core samples they found that the arsenic is in sediments close to the surface (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0509539103).

    Fendorf speculates that arsenic gets into the aquifers when seasonal flood waters trigger its release, transporting it down into the aquifers. "We cannot assume that arsenic will be naturally removed from the aquifer with time or that we only have to deal with a finite quantity," he says. ( From issue 2530 of New Scientist magazine, 17 December 2005)

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    6.India, West Bengal

    Arsenic in groundwater above the WHO maximum permissible limit of 0.05 mg l -1 has been found in six districts of West Bengal covering an area of 34 000 km2 with a population of 30 million. At present, 37 administrative blocks by the side of the River Ganga and adjoining areas are affected. Areas affected by arsenic contamination in ground-water are all located in the upper delta plain, and are mostly in the abandoned meander belt. More than 800 000 people from 312 villages/wards are drinking arsenic contaminated water and amongst them at least 175 000 people show arsenical skin lesions. Thousands of tube-well water in these six districts have been analysed for arsenic species. Hair, nails, scales, urine, liver tissue analyses show elevated concentrations of arsenic in people drinking arsenic-contaminated water for a longer period. The source of the arsenic is geological. Bore-hole sediment analyses show high arsenic concentrations in only few soil layers which is found to be associated with iron-pyrites. arsenic .- West bengal, India

    Various social problems arise due to arsenical skin lesions in these districts. Malnutrition, poor socio-economic conditions, illiteracy, food habits and intake of arsenic-contaminated water for many years have aggravated the arsenic toxicity. In all these districts, major water demands are met from groundwater and the geochemical reaction, caused by high withdrawal of water may be the cause of arsenic leaching from the source. If alternative water resources are not utilised, a good percentage of the 30 million people of these six districts may suffer from arsenic toxicity in the near future (Source, D. Das et al. 1997)




    Country  Number affected
    Taiwan       20 000
    Inner Mongolia   50 000
    Obuasi Ghana    Unknown
    Cordoba Argentina   10 000
    Antofagasta Chile 20 000
    Lagunera Mexico     20 000
    Cornwall Britain          Effect unknown
    W. Bengal, India      38, 000 000
    Bangladesh 50, 000 000

    Statistics of Arsenic Calamity

    Total Number of districts in Bangladesh 64
    Total Area of Bangladesh 148,393 sq.km
    Total Population of Bangladesh      120 Million
    GDP per capita (1998) US$260
    WHO arsenic drinking water standard     0,01ppm
    Maximum permissible limit of arsenic in drinking water of Bangladesh   0,005pm
    Number of districts surveyed for arsenic contamination 64
    Number of districts having arsenic above maximum permissible limit 59
    Area of affected 59 districts 126,134 sq.km
    Population at risk of the affected districts  75 Million
    Potentially exposed population 24 Million
    Number of patients suffering from arsenicosis  7000
    Total number of tubewells in Bangladesh 4 Million

    Source: BBS, Dhaka Community Hospital, NIPSOM, DPHE.

    Affected tube-wells, 1999 Assuming 0.250 mg/litre as the mean content of arsenic in groundwater, a person who consumes 1500 ml of this water each day for 10 years will consume about 6 gm of arsenic only from water. It is reported in the literature that 3 to 25 grams of arsenic when consumed over 1 to 22 years produces hepatic damage in the form of cirrhosis and non-cirrhotic hypertension (Morris, et al., 1974). Considering the poor health situation of the majority of the population in Bangladesh and double the amount of water consumption it is very likely dose-response effects will be more severe and devastating.

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    7. Arsenicosis In Bangladesh : Samta, An Isolated Village

    THE CURSE

    This is the story of Samta, a sleepy village in south-western Bangladesh- calm and quiet, and full of traditional natural beauty. A small river called Betna is flowing beside the village which is not extraordinary in nature, but has some certain reasons to be different from others

    Now, nobody wants to marry any girl of Samta, nobody wants to choose bridegroom from the village. The reason is that arsenic was found in the groundwater of the village at alarming level. Water of 97% tube-wells of the village is unsuitable for drinking due to arsenic contamination

    THE FINDINGS

    Symptoms of diseases caused by arsenic have been found in the bodies of 97% people. 16 people already died from arsenic-related diseases and some others are making their journey towards inevitable death. The people of Samta do not know to what extent they are responsible for the disaster or for which reasons they have become isolated from others and are deprived of the sympathies of their neighbours who preferred to keep themselves away from them.

    The village Samta is in Sharsha thana of Jessore district. Some 4,841 people live in Samta, in an area of 3.2 square kilometer. Dhaka Community Hospital carried out a survey and tested the water of 265 tube-wells out of the total 279 of the village. It was found that only 2% or 5 tube-wells are safe from arsenic contamination. Arsenic upto the maximum permissible limit was found in the water of 7% or 18 tube-wells while the water of the rest 91% or 242 tube-wells were found totally unsuitable for drinking

    Besides, Miazaki University of Japan, the Japan-based Asia Arsenic Network, and Bangladesh Institute of Preventive and Social Medicine also carried out survey at Samta. According to their statistics, there are 284 tube-wells in the village and only 10 of them are safe. Arsenic upto the maximum permissible level was found in the water of 13 tube-wells while the rest 92% or 261 tube-wells were found contaminated alarmingly.

    Ten years back, nobody in the village could understand the reasons behind the strange diseases which affected their skins, eyes, lungs, stomach, and intestines. When they found that their skin was pigmented and ulcerated, they thought that it might be leprosy. Some of them thought that these were symptoms of cancer. But the real reason of the diseases was detected in January,1997 when a team of experts led by Dr. Dipankar Chakraborty, carried out a study at the village. They found at least 330 people infected with skin diseases and identified arsenic pollution as the main reason behind it. They apprehended that the number of affected people is higher than the number detected

    While conducting preliminary survey, they collected the samples of hair, nails and urine of 334 people and found 99 people affected with arsenic-related skin diseases. The skins of 120 people were not found affected by arsenic. Some 88 children were found affected with skin diseases caused by arsenic while 27 were found safe

    But a disastrous picture revealed when the samples were tested in the laboratory. The presence of arsenic at dangerous level was found in the urine of 324 people (97%), in the hair of 284 people (85%) and in the nails of 321 people(96%), out of the total 334.

    Later Dhaka Community Hospital collected urine samples from 301 more people including children. 118 of them were suffering from skin problems caused by arsenic. The results of the laboratory tests of these samples were more disastrous. Arsenic was found at safe level in the urine of only 8 people (3%) while the presence of arsenic at dangerous level was found in the urine of the rest 293 people(97%). After completion of the study, the report apprehended that most people of the village were affected with arsenic. As a matter of fact, a good number of people of this village have died of arsenic pollution. Dhaka Community Hospital has records of their names, age and other particulars (Dhaka Community Hospital, June 2001).

    There are hundreds or thousands of such villages in Bangladesh that are not yet known but confronting the worst scenerio like Samta village.

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    7.1 Exposure to arsenic has ‘alarmingly’ increased the infant death rate

    Exposure to arsenic has ‘alarmingly’ increased the infant death rate, cardiovascular and cancer deaths and skin lesions in the regions with high arsenic concentration, said experts at a seminar in Dhaka on Tuesday. More than a half of the population has been drinking arsenic-contaminated water for many years, which has caused serious health problems, they said.

    People in 61 districts, out of the 64, are exposed to high concentration of arsenic and most of the people, adversely affected, live below poverty line, they said. BRAC in collaboration with the International Centre for Diarrhoeal Diseases Research, Bangladesh organised the seminar on ‘arsenic exposure and health effects’ in its Sasakawa Auditorium.

    The centre’s executive director David A Sack chaired the opening session. The Directorate of Health Services director general, Abdur Rahman Khan, spoke as chief guest. BRAC executive director Abdul Muyeed Chowdhury also spoke; Mahfuzur Rahman presented a study on the prevalence of arsenic-induced effects.

    A project, launched by BRAC and the ICDDR,B initiated the study in 2001 at Matlab in Chandpur. Five keynote papers were read out in the seminar. Mahfuzur Rahman presented the paper on the assessment of exposure urine analysis, MA Wahed on the assessment of exposure by water analysis, Md Yunus on the effect of arsenic exposure on reproduction, Jena Hamadani on the effect of arsenic exposure on child development and Md Jakariya on arsenic mitigation experience at Matlab.

    About 220,000 people were identified based on early arsenic-induced effects in the form of skin lesions, and water of 13,286 tube wells was tested. The study found that more than 60 per cent of the tube wells had arsenic concentration exceeding the stipulated limit of 50 micrograms a litre. Of the tube wells tested, 9 per cent had arsenic levels over 500 micrograms a litre.

    Eighteen per cent of infant deaths could be attributed to arsenic exposure and arsenic was found to increase the number of deaths among infants less than a month and also among infants aged between 1 and 11 months, the study observed. The infant death rate also increased because of the infection, caused by arsenic contamination, it said. Speaking about the national arsenic control policy, Abdur Rahman Khan said three ministries including the LGRD and cooperatives, health and agriculture in compliance with the instruction of the prime minister have prepared a comprehensive plan to save people from arsenic contamination (New Age, August 17, 2005).

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    8. Is your food tainted with arsenic?

    Today most of us are aware of arsenic contamination in groundwater and its ill effects on rural population of Bangladesh. In addition to Bangladesh where the situation is most serious, similar contamination has been reported in at least 19 other countries including India (West Bengal), Taiwan, Chile, Argentina, USA, inner Mongolia, New Zealand, Hungary, Nepal, Thailand, Cambodia and Vietnam. Arsenic is classified as human carcinogen by the Agency for Toxic Substances and Disease Registry (ATSDR), USA, the United States Environmental Protection Agency (USEPA) and the International Agency for Research on Cancer (IARC). Chronic exposure to high levels of arsenic has resulted into severe health effects including skin cancer, internal organ cancer, cardiovascular and neurological disorders.

    Ingestion and inhalation of arsenic compounds are common routes of exposure in work environments in certain industries, during wood preservation, agricultural use such as arsenic containing herbicides. But common population is exposed to arsenic mostly through drinking water and food. The maximum permissible level of arsenic in drinking water in Bangladesh is 50 microgram per liter. An individual drinking 2 liters of water in a day is ingesting 100 microgram of arsenic from water. Now consider the fact that the arsenic concentration (natural) in a typical lobster or shrimp is 20 microgram per gram. Someone consuming a 250 gram of lobster or shrimp is ingesting 5000 microgram of arsenic, which is 50 times the daily intake from water.

    Arsenic is abundant in most fish and sea food sometimes at a level as high as few hundred microgram per gram.

    Does that mean your favorite fish or seafood is contaminated with arsenic and unsafe for consumption? The answer lies in the understanding of a chemical term “speciation of elements” and relative toxicity. Speciation means specific chemical forms in which the element exists in a material. Neither all chemical forms of an element is toxic to the same extent, nor all forms of an element are metabolized by mammals after ingestion. Toxicity depends on the specific chemical form of an element. Methyl mercury is more toxic than inorganic mercury. Chromium (VI) and butyl tin are very toxic while chromium (III) and inorganic tin are not. The toxicity of a substance is indicated by median lethal dose (LD50) which indicate the dose that is lethal to 50% of experimental animals. Arsenic can exist in the environment and biological system as arsenous acid (As(III)) , arsenic acid (As(V)), monomethyl arsenic acid (MMA), dimethyl arsenic acid (DMA), arsenocholine, arsenobetaine and about a dozen type of arsenosugars. Arsenosugars are predominant form of arsenic in marine macroalgae. Arsenous acid produces arsenite ion As(III) and arsenic acid produces arsenate ion As(V) are inorganic arsenic and the rest of the arsenic species mentioned above are organoarsenic.

    The LD50 for As(III) is about 14 milligram per kilogram of material, while it is over 10,000 milligram per kilogram for arsenobetaine. The lower the number more toxic it is. The toxicity of arsenic species varies in the order arsenous acid > arsenic acid > MMA > DMA > arsenocholine > arsenobetaine. Only a few milligram of arsenous acid can be lethal to someone, while ingestion of a tablespoon of arsenobetaine does not create any adverse health effect. Marine organisms, fish and seafood contain arsenic mostly in the form of arsenobetaine and after ingestion it is readily excreted through urine without being metabolized by human. So enjoy your lobster or shrimp dinner without worrying about arsenic.

    It is apparent from the above discussion that the total amount of arsenic in a food or any material is misleading and often doesn’t tell you the whole story. Estimation of environmental impact, human health risk based solely on the determination of total concentration of arsenic in a material is not reliable. Rather assessment of the level of toxic exposure to an individual warrants complete speciation of arsenic in food or consumables. Unfortunately, the groundwater in Bangladesh contain mostly (`95-98%) arsenite As(III) and arsenate, the most toxic form of arsenic. Organic arsenic (MMA, DMA) are present at trace level. Since arsenic laced groundwater has been abundantly used in irrigation in a number of regions in Bangladesh, arsenic has found its way into the crops and food. Again, assessment of health risk associated with consumption of rice, vegetables, other food items must take into consideration of speciation of arsenic in it.

    Our own work on speciation of a few samples of rice from Bangladesh indicate the predominant presence of arsenite, followed by the presence of arsenate, MMA and DMA. In a recent report from Jadavpur University (Kolkata) indicated the presence of arsenobetaine in rice from Bangladesh. What happens after ingestion of inorganic arsenic? What is the fate of ingested arsenic?

    How much of it is retained and where is it retained, how is it metabolized and how can it be washed out of the body?

    Researchers are still trying to get the answers to these questions. The understanding of toxicokinetics, fate of ingested arsenic in human body and detoxification of arsenic are crucial in developing strategies for patient care, treatment and saving lives. Ingested inorganic arsenic are bound to thiol containing proteins. Inorganic arsenic undergo biotransformation inside the body. This biotransformation occurs in a number of steps and the process is specifically known as biomethylation. In a series of biochemical reactions catalyzed by very specific enzymes inorganic arsenic is transformed into a number of organic arsenic species. The metabolism of arsenic involves conversion of arsenate to arsenite, which then adds a methyl group from a donor, converts to MMA, which in turn adds another methyl group from the same donor to convert to DMA. The end products for primary and secondary methylation processes are MMA and DMA respectively and these are easily excreted through urine. Hence methylation of arsenic is considered an effective detoxification pathway for arsenic. The compound s-adenosylmethionine (SAM) acts as the methyl donor in the body and the enzyme that facilitates the addition of methyl group is methyl transferase.

    Many a times we hear, drinking from the same tube well, different members of the same household show varied clinical manifestations. Human body has a complement of SAM and it participates in 40 different methylation reaction in the body. Different members of the same household have different amount of SAM and methyl transferase and it is no wonder they have different capacities to methylate and detoxify arsenic. Someone with poor methylation capacity will detoxify less, retain more arsenic and show more symptoms of arsenicosis. Within the last four years researchers have identified a host of other methylated arsenic in urine from arsenic patients, namely, MMA(III), MMA(V), DMA(III), DMA(V), where III and V are two chemical states of arsenic in these compounds. Of these, MMA(III) is believed to be the most toxic. However, this species is very unstable and believed to convert to MMA(V). The methylation somewhat stops up to the formation of DMA for human being. It is interesting to note that there are considerable variation in the methylation capacities among animals. Rats, mice, dogs, rabbits, hamsters show very efficient methylation. On the other hand Guniea pigs and Chimpanzee are unable to methylate arsenic. Lack of appropriate enzymes have been attributed to the inability to methylate arsenic. There are considerable variations among tissues in methylation capacities in human. Liver plays a vital role in methylation. However, most methylation activities have been observed in kidney, liver and lung.

    What happens to SAM after giving its methyl group? It is converted to s-adenosylhomocysteine (SAH). In order to continue the methylation process and excrete arsenic, SAM must be regenerated. It is obvious that in the event the SAH does not convert back to SAM, the effective removal of arsenic from the body cannot continue for long. The SAH converts to homocysteine which in turns adds a methyl group supplied by 5-methylene tetrahydrofolate (MTHF) in presence of Vitamin B12. By gaining the methyl group homocysteine converts to methionine. Finally methionine converts back to SAM in presence of specific enzyme (SAM synthase). The regenerated SAM can continue detoxifying arsenic or any toxin in the body. Two important points must be mentioned here. First, the MTHF, folates, Vitamin B12 are supplied through food (fresh green leafy vegetables, fruits) or supplements. Methionine is furnished through consumption of protein rich food (chicken meat, egg). Is it any surprising that we constantly hear good nutrition can combat arsenic poisoning. How much of it can be afforded by rural people and most arsenic patients is another issue. Second, the homocysteine formed from the SAM is a vasoconstrictor, causes hypertension.

    So if homocysteine is not converted to methionine, a build up of homocysteine can lead to cardiovascular disease.

    So, improved nutrition, vitamin supplements can help a patient fight arsenic poisoning. Of course the patient must stop drinking arsenic contaminated water in the first place.

    The thiol containing protein bound arsenic in hair, nail indicate long term accumulation of arsenic in the body.

    The urinary arsenic tells recent exposure of arsenic. However, measurement of total arsenic in urine cannot tell the whole story. Urinary arsenic is a mixture of inorganic arsenic (arsenite, arsenate) and organic arsenic (MMA, DMA), and some arsenobetaine from fish consumption. The analytical technique for quantification of these key metabolites is complex and often challenging. It involves separation of components by high performance liquid chromatography followed by sensitive detection by atomic absorption or atomic fluorescence emission or mass spectrometry technique. Using the advanced technique of high performance liquid chromatography and atomic fluorescence spectrometry, the author has carried out (at Exonics Technology Center, Uttara, Dhaka) extensive speciation to identify As(III), As(V), MMA, DMA in over two thousand patient urine samples from twenty Upazilas in Bangladesh. The characterization and quantification of arsenic metabolite study was carried out by the author with funding from the UNICEF, Dhaka. The desirable condition is to observe a high percentage of metabolite in the form of methylated arsenic. More DMA in urine indicates a better methylating capacity, better metabolic activity and better detoxification ability. In general it has been observed that younger patients (age less than 20 years) are better methylator than their older counterparts.

    In our cohort in some subgroups, we also observed that men are better methylator than women. Traditionally in rural families men have better nutritional status than women. It is possible that the differences in detoxification ability we are observing are tied to their nutrition intake. A number of studies in the past reported that people with better nutrition (with higher level of arsenic in their drinking water) developed less arsenicosis symptoms than those with poor nutrition and less arsenic in their water. More studies on metabolites are on the way in the author’s laboratory involving patients from arsenic affected areas.

    Important message is, the speciation of metabolites in patient urine will tell us the detoxification ability of an individual. The detoxification capacity can be enhanced by improving nutritional status, intake of methionine rich food, or administering vitamin, folate supplements. Better nutrition is the key to fighting arsenic poisoning. The biomethylation cycle for arsenic clearly indicates that subjects with poor nutrition are more vulnerable to arsenic poisoning than someone with access to better nutrition. If the following intervention steps are taken for victims in the early stage of melanosis, we strongly believe that they will be prevented from progressing towards developing keratosis or more advanced stage of arsenic poisoning :

  • a. as a first condition, the patient must be provided with arsenic safe drinking water,
  • b. this must be followed by improved nutrition,
  • c. in addition, vitamin, folate supplements should be provided to lactating and child bearing mothers. In conclusion, speciation of key arsenic metabolites in patient samples identify important biomarkers for arsenic removal capacity of an individual. This information should be taken into consideration in providing supplements and improving patient’s detoxification ability. Speciation of both inorganic and organic arsenic in food or consumable products permits better assessment of toxic level and health risk posed by arsenic in this materials (Dr. M. Alauddin, New Age Second Anniversary Special | Health).

  • Last Modified:January 23, 2008


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