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Review

Arsenic round the world: a review


Badal Kumar Mandal, Kazuo T. Suzuki *
Graduate School of Pharmaceutical Sciences, Chiba Uni6ersity, Chiba 263 -8522, Japan Received 7 December 2001; received in revised form 8 February 2002

Abstract This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earths crust, and is a component of more than 245 minerals. These are mostly ores containing sulde, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic suldes to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, sh, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 6575%. A few recent studies report 8595% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial efuent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research studies are needed for improving arsenic risk assessment at low exposure levels urgently among all the arsenic research groups. 2002 Elsevier Science B.V. All rights reserved.
Keywords: Arsenic; Chronic arsenic toxicity; Carcinogenic effects

1. Introduction Arsenic is a ubiquitous element that ranks 20th in abundance in the earths crust, 14th in the
* Corresponding author. Tel./fax: +81-43-290-2891 E-mail address: ktsuzuki@p.chiba-u.ac.jp (K.T. Suzuki).

seawater, and 12 in the human body [1]. Since its isolation in 1250 A.D. by Albertus Magnus, this element has been a center of controversy in human history. It has been used in medicine [2]. Not only medicine, it has been used in various elds i.e. agriculture, livestock, electronics, industry and metallurgy [3]. It is now well recognized that

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consumption of arsenic, even at low levels, leads to carcinogenesis.

and less common in sphalerite [16]. The most common arsenic mineral is arsenopyrite.

2.1.2. Soil and sediment


2. Occurrence The terrestrial abundance of arsenic is around 1.5 3 mg kg 1. Source of arsenic in the environment includes natural and anthropogenic.

2.1.2.1. Soil Background 6alues of arsenic. A6erage content


Table 1 Arsenic concentrations of various terrestrial materials Materials Igneous [6] Acidic Rhyolite (extrusive) Granite (intrusive) Intermediate Latite, andesite, trachyte (extrusive) Diorite, granodiorite, syenite (intrusive) Basic Basalt (extrusive) Gabbro (intrusive) Ultrabasic Peridotite, dunite, serpentinite Metamorphic rocks [6] Quartzite Slate/phyllite Schist/gneiss Sedimentary rocks [79] Marine Shale/claystone (nearshore) Shale/claystone (offshore) Carbonates Phosphorites Sandstone Non-marine Shales Claystone Recent sediments (marine) Muds [9] Clays [9] Carbonate [10] Stream/river [11] Lake [12] Soils [13] Arsenic (mg kg1)

2.1. Natural sources


Long before mans activities had any effect on the balance of nature, arsenic was distributed ubiquitously throughout earth crusts, soil, sediments, water, air and living organisms.

3.25.4 0.1815 0.55.8 0.0913.4

2.1.1. Earth crusts Arsenic is a rare crystal element comprising about ve hundred thousandths of 1% (0.00005%) of the earths crust [4] and the average concentration of arsenic in igneous and sedimentary rocks is 2 mg kg 1. In most rocks it ranges from 0.5 to 2.5 mg kg 1 [5], though higher concentrations were found in nergrained argillaceous sediments and phosphorites. Arsenic is concentrated in some reducing marine sediment, which might contain up to 3000 mg kg 1. Arsenic might be co-precipitated with iron hydroxides and suldes in sedimentary rocks. Iron deposits, sedimentary iron ores and manganese nodules were rich in arsenic. Arsenic contents in various geochemical materials were listed in Table 1. Arsenic naturally occurs in over 200 different mineral forms, of which approximately 60% are arsenates, 20% suldes and sulfosalts and the remaining 20% includes arsenides, arsenites, oxides, silicates and elemental arsenic (As) [14]. But only certain of these are commonly encountered in signicant amounts (Table 2). Arsenic in its most recoverable form is found in various types of metalliferous deposits. The major deposits of this type are categorized into seven major groups, which are listed in Table 3. It is common in iron pyrite, galena, chalcopyrite

0.18113 0.0628 0.315.8

2.27.6 0.5143 0.018.5

4.025 3.0490 0.120.1 0.4188 0.69 3.012 3.010 3.260 4.020 B1.0 5.04000 (mineralized area) 2.0300 B0.197

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 Table 2 Major arsenic minerals occurring in nature [15] Mineral Native arsenic Proustite Rammelsbergite Saforite Seligmannite Smaltite Niccolite Realgar Orpiment Cobaltite Arsenopyrite Tennantite Enargite Arsenolite Claudetite Scorodite Annabergite Hoernesite Haematolite Conichalcite Adamite Domeykite Loellingite Pharmacosiderite Composition As Ag3AsS3 NiAs2 (Co,Fe)As2 PbCuAsS3 CoAs2 NiAs AsS As2S3 CoAsS FeAsS (Cu,Fe)12As4S13 Cu3AsS4 As2O3 As2O3 FeAsO42H2O (Ni,Co)3(AsO4)28H2O Mg3(AsO4)28H2O (Mn,Mg)4Al(AsO4) (OH)8 CaCu(AsO4)(OH) Zn2(OH)(AsO4) Cu3As FeAs2 Fe3(AsO4)2(OH)35H2O Occurrence

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Hydrothermal veins Generally one of the late Ag minerals in the sequence of primary deposition Commonly in mesothermal vein deposits Generally in mesothermal vein deposits Occurs in hydrothermal veins Vein deposits and norites Vein deposits, often associated with orpiment, clays and limestones, also deposits from hot springs Hydrothermal veins, hot springs, volcanic sublimation product High-temperature deposits, metamorphic rocks The most abundant As mineral, dominantly mineral veins Hydrothermal veins Hydrothermal veins Secondary mineral formed by oxidation of arsenopyrite, native arsenic and other As minerals Secondary mineral formed by oxidation of realgar, arsenopyrite and other As minerals Secondary mineral Secondary mineral Secondary mineral, smelter wastes Secondary mineral Secondary mineral Found in vein and replacement deposits formed at moderate temperatures Found in mesothermal vein deposits Oxidation product of arsenopyrite and other As minerals

of arsenic: The levels of arsenic in the soils of various countries are said to range from 0.1 to 40 mg kg 1 (mean 6 mg kg 1) [17], 1 to 50 mg kg 1 (mean 6 mg kg 1) [18] and mean 5 mg kg 1 [19], but varies considerably among geographic regions [20]. Arsenic is present in soils in higher concentrations than those in rocks [21]. Uncontaminated soils usually contain 1 40 mg kg 1 of arsenic, with lowest concentrations in sandy soils and those derived from granites, whereas larger concentrations are found in alluvial and organic soils [5]. The contents of arsenic in the soils of various countries are shown in Table 4. Factors inuencing arsenic content in soil: The principal factors inuencing the concentration of

elements in soils are the parent rock and human activities. Factors such as climate, the organic and inorganic components of the soils and redox potential status also affect the level of arsenic in soils. Q model factor analysis, linear discriminant analysis [35] and principal component analysis [36] indicate that the kind of parent rock is a much more important factor affecting soil metal contents than soil type. The arsenic contents of burozem soil developed on granite, calcareous rock and basic rock are 7.48, 11.9 and 8.47 mg kg 1 [37]. The arsenic content is 10.39 8.5 mg kg 1 in Japanese paddy soils, 4.692 mg kg 1 in Korean soils and 9.19 6.7 mg kg 1 in soils from Thailand [38]. When rocks weather, arsenic may

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mobilize as salts of arsenous and arsenic acids (H3AsO4) [39]. Arsenic in soil. Inorganic and organic forms: Arsenic occurs mainly as inorganic species but also can bind to organic materials in soils. Under oxidizing conditions, in aerobic environments, arsenates (iAsV) are the stable species and are strongly sorbed onto clays, iron and manganese oxides/hydroxides and organic matters. Arsenic precipitates as ferric arsenate in soil horizons rich in iron. Under reducing conditions arsenites (iAsIII) are the predominant arsenic compounds. Inorganic arsenic compounds can be methylated by microorganisms, producing under oxidizing conditions, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and trimethylarsine oxide (TMAsO) [24]. Under anaerobic conditions these can be reduced to volatile and easily oxidized methylarsines. The forms of arsenic present in soils depend on the type and amounts of sorbing components
Table 3 Arsenic deposits of the world [15] Type of deposits As mineral(s)

of the soil, the pH and the redox potential. Arsenates of Fe and Al (AlAsO4, FeAsO4) are the dominant phases in acid soils and are less soluble than calcium arsenate (Ca3AsO4), which is the main chemical form in any alkaline and calcareous soils [40]. The adsorbed arsenate fraction in soils is closely related to soil pH and redox potential (Eh). It also varied with soil type under the same pH conditions, increasing in order from sierozem to brown soil to chestnut soil [41]. Arsenic gets biomethylated (i.e. addition of CH3 to arsenic through biological activity) in the soilwater, sediment water interfaces through the activity of bacteria (such as Escherichia coli, Fla6obacteriun sp, Methanobacterium sp) and fungi (such as Aspergillus glaucus, Candida humicola). In the course of biomethylation, iAsIII is oxidized to iAsV and CH+ is reduced to CH and 3 3 stable arsenic oxy-species was formed [42]. Redox states of arsenic: Arsenic occurs frequently in the pentavalent state as arsenate and in

Average As conc. (mg kg1) 1000 (0.1%)

Location

Enargite-bearing copperzinclead deposits

Enargite

United States, Argentina, Chile, Peru, Mexico, Republic of the Philippines, Spain, Yugoslavia, USSR United States, Sweden, Federal Republic of Germany, Japan, France, USSR Canada, Norway, Germany, Democratic Republic, Czechoslovakia Unites States, Brazil, Canada, Republic of South Africa, Australia, USSR United States, Peoples Republic of China United States, Bolivia, Australia, Indonesia, Malaysia, Republic of South Africa United States, Canada, et al.

Arsenical pyritic copper deposits

Arsenopyrite, tennantite

40,000 (4%)

Native silver and nickelcobalt arsenide bearing deposits Arsenical gold deposits

Smaltite, domeykite, saforite, rammelsbergite, cobaltite, niccolite, loellingite, arsenopyrote, et al. Arsenopyrite, loellingite

25,000 (2.5%)

B5000 (0.5%)

Arsenic sulde and arsenic sulde gold deposits Arsenical tin deposits

Realgar, orpiment Arsenopyrite

2000 (0.2%) 2000 (0.2%)

Arsenical quartz, silver and leadzinc deposits

Arsenopyrite

6000 (0.6%)

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 Table 4 Arsenic contents in the soils of various countries Country West Bengal, India Bangladesh Argentina China France Germany Italy Japan Mexico South Africa Switzerland United States Types of soil/sediment Sediments Sediments All types All types All types Berlin region All types All types Paddy All types Number of samples 2235 10 20 4095 2 20 358 97 18 2 2 52 1215 Range (mg kg1) 10196 9.028 0.822 0.01626 0.15 2.54.6 1.860 0.470 1.238.2 240 3.23.7 22.4 1.020 1.672 Mean (mg kg1) References [22] [23] [24] [25] [26] [27] [28] [28] [29] [30] [31] [32] [33] [34]

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Various states Tiller

22.1 5 11.2 2 3.5 20 11 9 14 3 2.2 7.5 7.5

the trivalent state as arsenite in soil solution and both oxidation states can be subjected to chemically and microbiologically mediated oxidation, reduction and methylation reactions [43,44]. The biological availability and physiological and toxicological effects of arsenic depend on its chemical form [45]. iAsIII is much more toxic, more soluble and more mobile than iAsV. Under the inuence of oxidizing factors, the H3AsO3 in soil can be converted to H3AsO4. The theoretical oxidation reduction potential of the system is 0.557 V at 20 C. Because the redox potential of soils depends on the redox potentials of all the reducing and oxidizing systems occurring in the soils, these relationships are very complex and the redox value for soils is not directly proportional to the iAsV to iAsIII ratio [19]. Gaseous states of arsenic: Extensive use was made of sodium and ammonium salts of MMA and DMA as non-selective, post-emergent, foliarcontact herbicides with the bioaccumulation of these arsenicals, as well as their reduction by soil microorganisms to the corresponding toxic and highly volatile arsines [46,47]. Gaseous arsenic compounds are evolved by Penicillium bre6icaule, which is called arsenic fungi [48]. Certain strains of Scopulariopsis fungi evolve an arsine gas from agar solutions that contains inorganic arsenic [49]. It is found that common fungi, yeasts and bacteria can methylate arsenic to MMA, DMA and

gaseous derivatives of arsenic [47,50] and the resulting methylated arsenic is widely distributed in soils [46,51]. From literature [52], it is found that reduction to arsenic; not methylation to trimethylarsine (TMA) is the primary mechanism for gaseous loss of arsenicals from soil. Sediment. The natural level of arsenic in sediments is usually below 10 mg kg 1, dry weight [53] and varies considerably all over the world.

2.1.3. Water Arsenic is found at low concentration in natural water. The arsenic contents in groundwater of different countries are summarized in Table 5. The maximum permissible concentration of arsenic in drinking water is 50 mg l 1 and recommended value is 10 mg l 1 by EPA and WHO [15,73]. The seawater ordinarily contains 0.001 0.008 mg l 1 of arsenic. The major chemical form in which arsenic appears to be thermodynamically stable is arsenate ion. The ratio of iAsV to iAsIII based on thermodynamic calculation should be 1026:1 for oxygenated seawater at pH 8.1. In reality, it is 0.1:1 to 10:1. This unexpected high iAsIII content is caused at least in part by biological reduction in seawater [74]. The arsenic speciation was performed on well water samples from an area around Alaska containing high levels of arsenic [75] and 3 to 39% contained iAsIII and rest were iAsV. No methylated arsenic compounds

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were detected. The concentration of arsenic in unpolluted fresh waters typically ranges from 1 10 mg l 1, rising to 100 5000 mg l 1 in areas of sulde mineralization and mining [76]. At moderate or high redox potentials arsenic can be stabilized as a series of pentavalent (arsenate) oxyanions, H3AsO4, H2AsO, HAsO4 2 and 4 AsO4 3. However, under most reducing (acid and mildly alkaline) conditions and lower redox potential, the trivalent arsenite species (H3AsO3) predominate. As0 and As3 are rare in aquatic environments. Complex organic arsenic compounds such as

tetramethylarsonium salts, arsenocholine, arsenobetaine, dimethyl(ribosyl)arsine oxides and arsenic containing lipids are identied in the marine environment [39]. Only a very minor fraction of the total arsenic in the oceans remains in solution in seawater, as the majority is sorbed on to suspended particulate materials. The high levels of arsenic are in waters from areas of thermal activity in New Zealand [77] up to 8.5 mg l 1. Geothermal water in Japan [78] contains 1.86.4 mg l 1 and neighboring streams about 0.002 mg l 1. Although normally groundwater does not contain methylated form of arsenic

Table 5 Concentrations of arsenic in groundwater of the arsenic-affected countries Location Sampling period Arsenic source Concentration (mg l1)a 68 (1174) 17980 (range) 1 (median) 1160 (maximum) 48,000 (maximum) 1662 (range) 34490 (range) B1100 (range) 8624 (range) \100 470770 (range) 1003810 (range) 0.05850 (range) 0.031.41 (range) B0.7 0.0033700 (range) B5023,080 (range) B10\1000 (range) 503.5 (1.255114) 95.2 (1.251032) 0.0010.293 (range) 159 (13050) References

Hungary South-west Finland New Jersey, USA Western USA South-west USA Southern Iowa and western Missouri, USA Northeastern Ohio, USA Lagunera region, northern Mexico Cordoba, Argentina Chile Pampa, Cordoba, Argentina Kuitun-Usum, Xinjiang, PR China Shanxi, PR China Hsinchu, Taiwan West Bengal, India Calcutta, India Bangladesh Nakhon Si Thammarat Province, Thailand Fukuoka, Japan Hanoi, Vietnam

N.S. 19931994 19771979 N.S. 1970 N.S. N.S. N.S.

Deep groundwater Well waters; natural origin Well waters Geochemical environments Alluvial aquifers Natural origin Natural origin Well waters

[54] [55] [56] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [65] [66] [67] [68] [69] [70] [70] [71] [72]

N.S. 1983 1988 N.S. 19891996 19901997 19961997 1994 1994 1994 19992000

215 m, 6145%63 W; 3220%3500%S Well waters Well waters Well waters Arsenic-rich sediment Near pesticide production plant Well waters Shallow (alluvial) groundwater; mining activity Deep groundwater; mining activity Natural origin Arsenic-rich sediment

NS, not stated. a Mean and ranges of total arsenic unless stated otherwise.

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but lake and pond waters contain arsenite, arsenate as well as methylated forms, i.e. MMA and DMA.

2.1.4. Air In air, arsenic exists predominantly absorbed on particulate matters, and is usually present as a mixture of arsenite and arsenate, with the organic species being of negligible importance except in areas of arsenic pesticide application or biotic activity [79]. The human exposure of arsenic through air is generally very low and normally arsenic concentrations in air ranges from 0.4 to 30 ng m 3 [80]. According to USEPA the estimated average national exposure in the U.S. is at 6 ng As m 3. Absorption of inhaled arsenic ranges between 30 and 85%, depending on the relative portions of vapour and particulate matters. USEPA estimates that the general public will be exposed to a range of approximately 40 90 ng per day by inhalation [81]. The amount of arsenic inhaled per day is about 50 ng or less (assuming that about 20 m3 of air is inhaled per day) in unpolluted areas [82]. The daily respiratory intake of arsenic is approximately 120 ng of which 30 ng would be absorbed [83]. Typical arsenic levels for the European region are currently quoted as being between 0.2 and 1.5 ng m 3 in rural areas, 0.5 and 3 ng m 3 in urban areas and no more than 50 ng m 3 in industrial areas [84]. 2.1.5. Li6ing organisms 2.1.5.1. Plants. Arsenic is an element, which is found to be cumulative in living tissue, i.e. once ingested by any organism it is passed out of the organism only very slowly if at all. The amount of arsenic in a plant, then depends almost solely on the amount of arsenic, it is exposed to. Its concentration varies from less than 0.01 to about 5 mg g 1 (dry weight basis) [85]. There appears to be little chance that animals will be poisoned by consuming plants which absorb arsenic residues from contaminated soils, because plant injury occurs before toxic concentrations can appear [85].

2.1.5.2. Animals and human beings. As in plant tissue, arsenic is cumulative in animal tissue, allowing for a wide variation in concentration due to the variance in arsenic ingested in different areas. Among marine animals, arsenic is found to be accumulative to levels of from 0.005 to 0.3 mg kg 1 in coelenterates, some molluscs and crustaceans [86]. Some shellsh may contain over 100 mg g 1 of arsenic. The average arsenic content in freshwater sh is of 0.54 mg g 1 on the basis of total wet weight, but some values reach as high as 77.0 mg g 1 in the liver oil of freshwater bass [87]. In mammals it is found that the arsenic accumulates in certain areas of the ectodermic tissue, primarily the hair and nails. The domestic animals and human generally contain less than 0.3 mg g 1 on a wet weight basis [88]. The total human body content varies between 3 and 4 mg and tends to increase with age. With the exception of hair, nails and teeth, analyses reveal that most body tissues contain less than 0.3147 mg g 1 (dry weight) [15]. The absorption of arsenic in human body is high for anionic and soluble species and low for insoluble species. Inorganic arsenic has a special afnity for hair and other keratin-rich tissues [88]. The concentrations along the length of the hair show the exposure over a period of time [89]. The normal amount of arsenic in hair is about 0.080.25 mg g 1 with 1.0 mg g 1 being indication of the presence of excess arsenic and poisoning [90]. Nail clippings from a patient with acute polyneuritis from arsenic poisoning contain arsenic at 20130 mg g 1 [91], where the normal arsenic concentration in nail is 0.3490.25 mg g 1 [92]. The arsenic content of urine can vary normally from 5 to 40 mg per day (total). Acute and sub acute poisoning will produce an excess of 100 mg per day [90]. Great daily variation of arsenic exists and depends on the amount of arsenic in various food staffs. Higher organic arsenic compounds such as arsenobetaine and arsenocholine are found in marine organisms, and they are very resistant to chemical degradation [93]. In general, it is found that organic arsenicals are more rapidly excreted than inorganic forms and pentavalent arsenicals are cleared faster than trivalent. The detailed arsenic content of animals, human beings and plants are given in literatures [73].

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2.2. Anthropogenic sources


These exceed natural sources in the environment by 3:1 [94]. Man in his utilization of natural resources releases arsenic into the air, water and soil. These emissions can ultimately affect residue levels in plants and animals. Arsenic may accumulate in soil through use of arsenical pesticides, application of fertilizers, dust from the burning of fossil fuels, disposal of industrial and animal wastes [95,96].

2.2.1. Man made sources The main arsenic producers were China, USSR, France, Mexico, Germany, Peru, Namibia, Sweden, and USA, and these countries accounted for about 90% of the world production [97,98]. During 1970s, about 80% of the consumption of arsenic were for agriculture purpose. At present, agricultural use of arsenic is declining. Approximately, 97% of the arsenic produced enters endproduct manufacture in the form of white arsenic and remaining 3% as metal for metallurgic additives, in special lead and copper alloys [98]. 2.2.2. Insecticides Earlier arsenic was widely used for preparation of insecticides and pesticides. In 1955, the world production of white arsenic was 37,000 tons. Of this quantity, 10,800 tons were produced in the U.S., while domestic consumption exceeded 18,000 tons [99], most of it in the form of pesticides, such as lead arsenate, Ca3AsO4, copper acetoarsenite, Paris-Green (copper acetoarsenite), H3AsO4, MSMA (monosodium methanearsonate), DSMA (disodium methanearsonate) and cacodylic acid are used in cotton production as pesticides. The detailed production and uses of other arsenical pesticides are mentioned in literatures [100103]. 2.2.3. Herbicides The inorganic arsenicals, primarily, sodium arsenite, were widely used since about 1890 as weed killers, particularly as non-selective soil sterilants [103]. The literatures [103 105] document extensively on organic arsenical herbicides.

2.2.4. Desiccants and wood preser6ati6es Arsenic acid is used extensively as a cotton desiccant for many years. Two thousand and ve hundred tonnes of H3AsO4 were used as desiccants on 1,222,000 acres (about 495,000 ha) of U.S. cotton in 1964 [40]. The rst wood preservative was Fluor Chrome ArsenicPhenol (FCAP), which was used as early 1918 in USA. The production, preparation, uses of principal wood preservatives are summarized by U.S. Department of Agriculture [106]. Earlier, Chromated Copper Arsenate (CCA) and Ammonical Copper Arsenate (ACA) in combination were used in 99% of the arsenical wood preservatives [105]. Wolman salts and Osmosalts, zinc and chromium arsenate are also used as wood preservative [101]. 2.2.5. Feed additi6es Many arsenic compounds are used for feed additives, such as H3AsO4, 3-nitro-4-hydroxy phenylarsonic acid, 4-nitrophenylarsonic acid etc. All substituted phenylarsonic acids were used for feed additives under Food Additives Law of 1958 [85]. 2.3. Drugs
The medicinal virtues of arsenic are acclaimed for nearly 2500 years. In Austria, the peasants consumed a large quantity of arsenic for softness and cleanliness of the skin, to give the plumpness to the gure, beauty and freshness to the complexion and also to improve the breathing problem [107,108]. Common medicinal preparations, which contained arsenic, include Fowlers solution (potassium arsenite), Donovans solution (arsenic and mercuric iodides), Asiatic pills (arsenic trioxide and black pepper), de Valagins solution (liquor arsenii chloridi), sodium cacodylate, arsphenamine (Salvarsan), neoarsphenamine, oxophenarsine hydrochloride (Mapharsen), arsthinol (Balarsen), acetarsone, tryparsamide and carbarsone [99]. References [109111] give detailed uses of arsenic compounds as drugs and medicine.

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2.4. Poison
Arsenic compounds are infamous as very potent poisons and are preferred to homicidal and suicidal agents. Even the death of Napoleon Bonaparte was suspected to be due to arsenic poisoning [112].

3. Metabolisms and toxicity of arsenic

3.1. Metabolisms
Humans are exposed to many different forms of inorganic and organic arsenic species (arsenicals) in food, water and other environmental media. Each of the forms of arsenic has different physicochemical properties and bioavailability and therefore the study of the kinetics and metabolism of arsenicals in animals and humans is a complex matter. Large interspecies differences compared with other metals and metalloids also characterize arsenic metabolism. Routes of arsenic intake in vivo considered are respiratory for dust and fumes, and oral for arsenic in water, beverages, soil, and food. Few investigations of dermal absorption rates for arsenicals are undertaken. The available datasets indicate that absorption rates are generally low ( B 10%); however, for certain forms of arsenic higher rates may be observed [15]. Wester et al. [113] studied the percutaneous absorption of H3AsO4 from water and soil. In rhesus monkeys, arsenic uptake ranges from 6 to 2%. The same authors also reported that human cadaver skin absorbed approximately 1 2% of the administered dose over a 24-h period. Both iAsIII and iAsV are found to cross the placenta of laboratory animals [15,114,115]. This conclusion is substantiated by a more recent study conducted by Concha et al. [116] who observed that similar arsenic concentrations are found in cord blood and maternal blood ( 9 mg l 1) of maternal-infant pairs exposed to high arsenic-containing drinking water ( 200 mg l 1). Older studies demonstrated that DMA was capable of crossing the placenta of rats [117] and that the organoarsenical feed additive Roxarsone (3-nitro-

4-hydroxyphenylarsonic acid) accumulated in eggs [118]. However, more recent human or animal data are not available to substantiate these ndings. The bioavailability of ingested inorganic arsenic will vary depending on the matrix in which it is ingested (i.e. be it food, water, beverages or soil), the solubility of the arsenical compound itself and the presence of other food constituents and nutrients in the gastrointestinal tract. Tissue distributions of arsenic depend on blood perfusion, tissue volumes, diffusion coefcients, membrane characteristics, and tissue afnities. The fate of ingested arsenic in vivo depends on: (1) oxidation and reduction reactions between iAsV and iAsIII in the plasma; and (2) consecutive methylation reactions in the liver. Inorganic arsenic is methylated in vivo in human. Arsenate is rapidly reduced to arsenite, which was afterwards partly methylated. The main site of methylation appears to be the liver, where arsenic methyltransferase enzymes mediate the methylation process with S-adenosylmethionine as the methyl donor and GSH as an essential co-factor. Studies on humans suggest that methylation may begin to be limiting at dose of about 0.21 mg kg 1 (0.0030.015 mg As kg 1 per day) [119]. Raie [120] compared tissue arsenic levels in infants (aged 1 day to 5 months) and adults from Glasgow, Scotland using NAA. Mean levels of arsenic (mg kg 1 or mg g 1 dry weight) in liver, lung and spleen in infants versus adults are 0.0099 versus 0.048, 0.007 versus 0.044, and 0.0049 versus 0.015, respectively. These data suggest that arsenic accumulates in tissues with age, a nding that is wholly consistent with observations in laboratory animals [121]. In most animal studies DMA is the main metabolite, while in human the urinary excretion consists under normal conditions, i.e. without excessive ingestion of inorganic arsenic of about 20% inorganic arsenic, 20% MMA and 60% DMA. Inorganic arsenic gets methylated to MMA and DMA in vivo and during circulation in plasma MMA is partly absorbed and this absorbed MMA is further methylated to DMA, while DMA is excreted mainly in an unchanged form [122,123]. The very recent studies [124,125] informed that both MMAV and DMAV were re-

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duced to their trivalent analogues monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII), respectively and excreted through urine. Arsenobetaine is absorbed and excretes unchanged [126,127]. Similar studies are unavailable for other organoarsenicals. Studies with radioactively labeled (As74) arsenate in human show that 38% of the dose is excreted in the urine within 48 h and 58% of the total within 5 days [128]. In the subjects who ingested 500 mg As in the form of arsenite, 33% of the dose was excreted in the urine within 48 h and 45% within 4 days [123]. It is estimated that about 60 70% of the daily-ingested inorganic arsenic is excreted in the urine [129]. About 76% of the organic arsenic ingested with ounder is excreted in the urine within 8 days [130]. However, in a later study, Marafante et al. [131] reported that 3.5% of a single oral dose of DMA (0.1 mg As kg 1) was eliminated in urine as TMAO within 3 days. No metabolism studies are identied in which humans specically consumed TMA or TMAO alone rather than in seafood. Yamauchi et al. [132] calculated the biological half-lives following oral administration of organoarsenicals to hamsters from multiple studies conducted in their laboratory. They reported half-lives of 7.4 h for MMA, 5.6 h for DMA, 5.3 h for TMAO, 3.7 h for TMA and 6.1 h for arsenobetaine. No studies are identied that addressed the issue of biliary excretion or other routes of elimination for organoarsenicals in humans. Although arsenic is excreted via other routes than via urine and feces (e.g. in sweat), these routes of excretion are generally minor [15]. Since arsenic can accumulate in keratin-containing tissues [133], skin, hair and nails can also be considered as potentially minor excretory routes. Both older [15] and recent studies indicate that arsenic can be excreted in human milk, although the levels are low [134,135]. The three most commonly employed biomarkers used to identify or quantify arsenic exposure are total arsenic in hair or nails, blood arsenic, and total or speciated metabolites of arsenic in urine. Because arsenic (as the trivalent form) accumulated in keratin-rich tissues such as skin, hair and nails [133]), arsenic levels in hair and nails are used as indicators of past arsenic exposure.

Normally inorganic arsenic is very quickly cleared from human blood. For this reason blood arsenic is used only as an indicator of very recent and/or relatively high level exposure, for example, in poisoning cases [136] or in cases of chronic stable exposure (i.e. from drinking water). Studies show that in general blood arsenic does not correlate well with arsenic exposure in drinking water, particularly at low levels. In common with other biomarkers of arsenic exposure, arsenic levels in urine may result from inhalation exposure as well as ingestion from food, water and soils [137] and as such provided a measure of the total absorbed dose. However, since arsenic is rapidly metabolized and excreted into the urine, levels in urine are best suited to indicate recent arsenic exposure. Total arsenic, inorganic arsenic and the sum of arsenic metabolites (inorganic arsenic+ MMA + DMA) in urine are all used as biomarkers of recent arsenic exposure. In many older studies, total urinary arsenic is used as a biomarker of recent arsenic exposure. This approach becomes increasingly uncommon because certain organoarsenicals (for example, the practically non-toxic compound arsenobetaine) present in substantial amounts in certain foodstuffs are excreted mainly unchanged in urine [138140]. Since consumption of seafood (e.g. marine shes, crustaceans, bivalves, seaweeds) by human volunteers is associated with increased total urinary arsenic excretion [141] assessment of inorganic arsenic exposure using total urinary arsenic under these conditions will result in overestimation of inorganic arsenic exposure. To avoid the potential for over-estimation of inorganic arsenic exposure inherent in using total urinary arsenic, most studies now measure speciated metabolites in urine, and used either inorganic arsenic or the sum of arsenic metabolites (inorganic arsenic+ MMA + DMA) as an index of arsenic exposure. However, this can give misleading results unless a careful diet history is taken and/or seafood consumption is prohibited for at least 3 days prior to urine collection. There are two reasons for this. First, some seafoods contain the arsenic metabolites MMA and DMA, particularly DMA, in fairly high amounts. Secondly, arsenosugars present in seaweeds and some

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bivalves are extensively metabolized to DMA (either by the body itself or the gut microbiota), which is then excreted in urine [15,142,143]

3.2. Toxicity
The chemical forms and oxidation states of arsenic are more important as regards to toxicity. Toxicity also depends on other factors such as physical state, gas, solution, or powder particle size, the rate of absorption into cells, the rate of elimination, the nature of chemical substituents in the toxic compound, and, of course, the pre-existing state of the patient. The toxicity of arsenicals decrease in the order, arsines\iAsIII \arsenoxides (org AsIII)\iAsV \arsonium compounds\ As [87,144]. Recently Vega et al. [145] reports the toxicity order of arsenicals as iAsIII \ monomethylarsine oxide (MMAOIII) \ III V V DMA GS \DMA \MMA \iAsV. While it is generally accepted that methylation is the principal detoxication pathway, recent studies have suggested that methylated metabolites may be partly responsible for the adverse effects associated with arsenic exposure [145]. Studies in laboratory animals have demonstrated that the toxicity of arsenic is dependent on its form and its oxidation states. It is generally recognized that the soluble inorganic arsenicals are more toxic than the organic ones, and the iAsIII are more toxic than iAsV [63,146]. A few reports [147,148] documented that at low to moderate exposure levels, the long-term distribution pattern of arsenic is rather independent on exposure form, iAsIII or iAsV in rabbits and marmoset monkeys. But Maeda [146] reported that iAsV is less toxic than iAsIII to both animal and humans but can be toxic to plants. Although there are a few literatures [15,63,149 151] on chronic and acute arsenic toxicity, the species-specic epidemiological studies on chronic arsenic toxicity in arsenic endemic areas are literally nil. In the arsenic-affected areas of West Bengal, India Chatterjee et al. [152] reported that the most toxic species, iAsIII, is present in groundwater at about 50% of the total arsenic level. In the arsenic-affected areas of Bangladesh the modal proportion of iAsIII appears to be between 50 and 60% of the

total arsenic [153]. In the arsenic-affected areas of Taiwan, Chen et al. [154] reported that the average arsenic, predominately iAsIII, concentration in three wells was 6719 149 mg l 1 in the black foot disease (BFD) area. The ratio of iAsIII to iAsV was 2.6:1. But no above-mentioned studies documented any species-specic toxicity of arsenic in their publications on chronic arsenic toxicity. So, more studies on species-specic toxicity of arsenic are necessary to elucidate species-specic chronic toxicity of arsenic in the endemic arsenic-affected areas. In reality, use of new analytical methods that determine the oxidation states of arsenic in the metabolites of inorganic arsenic (iAs) in the population-based studies are likely to provide new insights into the linkage between exposure, metabolism, and toxicity [124,125,155 158]. Although studies on species-specic chronic toxicity of arsenic in the endemic arsenic-affected areas are not available several recent documents of species-specic toxicity of arsenic on animal and human cell lines suggest that trivalent arsenicals are more toxic than pentavalent arsenicals. Because ingested iAs is extensively metabolized in humans, chronic exposure to iAs results in chronic exposure to methylated and dimethylated arsenicals. MMAIII, a biotransformant of inorganic arsenic, is up to 26 times more toxic than inorganic arsenite in Chang human hepatocytes [159]. According to Lin et al. [160], MMAIII is over 100 times more potent than iAsIII as an in vitro inhibitor of thioredoxin reductase. So, formation of MMAIII appears to represent toxication of both iAsV and iAsIII. Also, in vitro studies have shown that MMAIII and DMAIII, like iAsIII, can form GSH complexes, and that these are at least as toxic as iAsIII [161,162]. Another recent in vitro study showed that MMAIII was more cytotoxic to human cells (hepatocytes, epidermal keratinocytes, and bronchial epithelial cells), compared to iAsIII and iAsV [162]. The authors concluded that high methylation capacity did not protect these cells from the acute toxicity of trivalent arsenicals. Recently Vega et al. [163] reported that trivalent arsenicals induced an increase in cell proliferation, but pentavalent arsenicals did not, in an in vitro experiment with human epidermal

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keratinicytes. Another very recent in vitro study assessed the induction of DNA damage by methylated trivalent arsenicals (MMAIII and DMAIII) in human peripheral lymphocytes using single-cell gel (SCG, comet) assay [164]. On the basis of the slopes of the concentration response curve for the tail moment in the SCG assay, MMAIII and DMAIII were 77 and 386 times more potent than iAsIII, respectively. The authors concluded that they (MMAIII and DMAIII) were considered to be direct-acting forms of arsenic that were genotoxic, though they were not, necessarily, the only genotoxic species of arsenic that could exist. The most common toxic mode of an element is the inactivation of enzyme systems, which serves as biological catalyst [69]. The iAsV does not react directly with the active sites of enzymes [165]. It rst reduces to iAsIII in vivo before exerting its

The enzymes, which generated cellular energy in the citric acid cycle, are adversely affected. The inhibitory action is based on inactivation of pyruvate dehydrogenase by complexation with iAsIII, whereby the generation of adenosine-5-triphosphate (ATP) is prevented. The enzyme system comprises of several enzymes and cofactors, one protein molecule of enzyme having one lipoic acid. In the presence of iAsIII, it replaces the two hydrogen atoms from the thiol groups and attaches with a sulfur molecule and forms a dihydrolipoylarsenite chelate complex, which prevents the reoxidation of the dihydrolipoyl group that is necessary for continued enzymatic activity, and this pivotal enzyme steps blocked. As a result, the amount of pyruvate in the blood increases, energy production is reduced, and nally the cell damages slowly [169,170]. The reactions are shown below.

toxic effect [166,167]. Aposhian postulated that the binding of trivalent arsenic to non-essential sulfhydryl groups in cells might represent an important route for arsenic detoxication [168]. Trivalent arsenic interferes with enzymes by bonding to SH and OH groups, especially when there are two adjacent HS-groups in the enzyme.

The strong bond between iAsIII and sulfur may be the reason why arsenic accumulates in the keratin tissues hair and nail. Peters proposed that trivalent arsenic form a stable ringed structure with vicinal dithilols of keratin in hair [171]. Arsenic inhibits enzymes, such as the pyruvate ox-

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idase, S-aminoacid oxidase, choline oxidase and transaminase. Although iAsIII is regarded the more toxic form of the element, iAsV as arsenate can be disruptive by competing with phosphate. For example, arsenate uncouples oxidative phosphorylation. Oxidative phosphorylation is the process by which ATP is produced, while at the same time reduced nicotinamide adenine dinucleotide (NADPH) is oxidized [172]. 3ADP + 3H3PO4 3ATP +3H2O NADPH +H+ + 1/2O2 NADP+ +H2O The arsenate disrupts this process by producing an arsenate ester of ADP, which is unstable and undergone hydrolysis non-enzymatically. This process was termed as arsenolysis [168]. Hence the energy metabolism is inhibited and glucose-6-arsenate is produced rather than glucose-6-phosphate. Arsenate may also replace the phosphorous in DNA [173] and this appears to inhibit the DNA repair mechanism. Such an action may explain the clastogenicity of arsenic, because an arsenodiester bond will most likely be weaker than the normal phosphodiester bond. However, no direct evidence is located to show that arsenate is incorporated into DNA. In environments where phosphate concentrations are high, arsenate toxicity to biota is generally reduced. Arsenic-contaminated environments are characterized by limited species abundance and diversity. If levels of arsenate are high enough, only species, which exhibited resistance, may be present [15]. Arsenic and selenium are antagonistic to each other in the body, and each counteracts the toxicity of the other. However, arsenic may also interfere with the essential role of selenium in human metabolism [174]. Arsenic inhibits the action of selenium, which causes the apparent deciency of glutathione peroxidase systema selenium dependent enzyme. The more detail information of arsenic interaction with selenium is given by Elder et al. [137,165]. Arsenic induced increases in metallothionein (MT) levels [175]. Although it is not known whether arsenic can be detoxied by MT, a low molecular weight cysteine-rich, metal binding

protein. Zinc-induced increases in MT, however, does not seem to be responsible for the protection against arsenic lethality in mice pretreated with zinc. Although the mechanism for this tolerance to arsenic toxicity is not known, zinc pretreatment is associated with increased elimination of arsenic [176]. Chronic exposure to inorganic arsenic may give rise to several health effects including effects on the gastrointestinal tract, respiratory tract, skin, liver, cardiovascular system, hematopoietic system, nervous system etc. The earliest reports date back to the latter part of the 19th century when the onset of skin effects (including pigmentation changes, hyperkerotosis and skin cancers) were linked to the consumption of arsenic in medicines and drinking water [15]. There is also no published information concerning toxicological effects in human exposed orally to organoarsenicals. The health effects of arsenic exposure to various internal and external organs are summarized as follows.

3.2.1. Respiratory effects Humans exposed to inorganic arsenic naturally and occupationally experience laryngitis, tracheae bronchitis, rhinitis, pharyngitis, shortness of breath, chest sounds (crepitations and/or rhonchi), nasal congestion and perforation of the nasal septum [119,177180]. 3.2.2. Pulmonary effects The possible role of chronic arsenic ingestion in the genesis of non-malignant pulmonary disease is suggested in a few cases due to chronically exposed to increased concentrations of arsenic in drinking water. Borgono et al. [181] reported that 38.8% of 144 subjects with abnormal skin pigmentation complained of chronic cough, compared with 3.1% of 36 subjects with normal skin in a cohort study of 180 residents of Antofagasta, Chile with arsenic contaminated drinking water (0.80 mg l 1). In a study of arsenic in drinking water in West Bengal, India, Guha Mazumder et al. [182] noted a complaint of cough in 89 (57%) of 156 patients with arsenical hyperpigmentation. Lung-function tests performed on 17 of those patients showed features of restrictive lung disease

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in nine (53%) and combined obstructive and restrictive disease in seven (41%) [182].

3.2.3. Cardio6ascular effects Both the heart and peripheral arterial tree commonly manifest effects of arsenic toxicity such as cardiovascular abnormalities, Raynauds disease, myocardial infarction, myocardial depolarization, cardiac arrhythmias, thickening of blood vessels and their occlusion and BFD. Studies from Taiwan was clearly demonstrated that exposure to arsenic via drinking water is associated with BFD, with signicant exposure response relationships relating both the duration and level of exposure to observed effects [15], which is characterized by a progressive loss of circulation in the hands and feet, which ultimately leads to severely painful gangrene formation of the extremities (particularly the toes and feet), often necessitating amputation of the limb [119,172,183]. Zaldivar [184] reported several cases of myocardial infarction and arterial thickening in children who consumed water containing 0.60 mg As l 1. The extreme form and high prevalence of BFD found in Taiwan is not observed in other regions. It is probable therefore, that other factors, such as malnutrition or concurrent exposures, are playing a role in the pathophysiology of the disease [15]. In contrast, there is only limited evidence for an association between arsenic exposure and cerebrovascular diseases. A few Taiwanese studies show an elevated risk of death from cerebrovascular disease with increasing arsenic exposure, most notably that of Chiou et al. [118]. Furthermore, studies from other countries provide only very limited support for the Taiwanese ndings [15]. Chen et al. [185] suggested that long-term arsenic exposure might induce hypertension in humans. Rahaman et al. [186] also reported induced hypertension among arsenic-affected people in Bangladesh. 3.2.4. Gastrointestinal effects The efciency of absorption of inorganic arsenicals from the gastrointestinal tract depends on their water solubility. Several gastrointestinal symptoms are common and salient features of arsenic intoxication due to ingestion of heavy

doses of arsenic. Sub-acute arsenic poisoning from lesser doses of arsenic may manifest as dry mouth and throat, heartburn, nausea, abdominal pains and cramps, and moderate diarrhea. Chronic low dose arsenic ingestion may be without symptomatic gastrointestinal irritation or may produce a mild esophagitis, gastritis, or colitis with respective upper and lower abdominal discomfort [119]. Anorexia, malabsorption and weight loss may be present [187].

3.2.5. Hematological effects The hematopoietic system is also affected by both short- and long-term arsenic exposure. Anemia (normochromic normocytic, aplastic and megaloblastic) and leukopenia (granulocytopenia, thrombocytopenia, myeloid, myelodysplasia) are common effects of poisoning and is reported as resulting from acute [188], intermediate [189] and chronic oral exposures [190,191]. These effects may be due to direct hemolytic or cytotoxic effects on the blood cells and a suppression of erythropoiesis [192]. No such effects are noticed in humans exposed chronically to 0.07 mg As kg 1 per day or less. Relatively high doses of arsenic are reported to cause bone marrow depression in human [193]. Winski and Carter [194] recently examined the effect of inorganic arsenite and arsenate on human erythrocyte morphology in an in vitro model. They estimated that human erythrocytes are at least 1000 times more sensitive to arsenate than arsenite. Recent one study documents that DMA is taken up by RBCs in the form of DMAIII, and that the uptake and efux rates are dependent on the animal species, the efux arsenic being DMAV [195]. The mechanism of hemolysis involves depletion of intracellular GSH, resulting in oxidation of sulfhydryl groups in the hemocyanin from Fe2 + to Fe3 + in mice and rats. Hemoglobin combines with arsenic, which reduces oxygen uptake by cells and therapy prevents hatching [149]. 3.2.6. Hepatic effects Since the liver tends to accumulate arsenic with repeated exposures, hepatic involvement is reported most commonly as a complication of chronic exposures over periods of months or years

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[194]. Chronic arsenic induced hepatic changes include cirrhosis, portal hypertension without cirrhosis, fatty degeneration and primary hepatic neoplasia. Patients may come to medical attention with bleeding esophageal varices, ascites, jaundice, or simply an enlarged tender liver, mitochondrial damage, impaired mitochondrial functions, and porphyrin metabolism [119,197 199], congestion, fatty inltration, cholangitis, cholecystitis and acute yellow atrophy [200], and swollen and tender liver [92,201,202]. The analysis of blood sometimes shown elevated levels of hepatic enzymes [203], hepatic fatty inltration and cirrhosis of the liver in patients who used Fowlers solution [204]. There is no evidence of hepatic dysfunction of several workers exposed to arsenic dust by inhalation [205].

thromatous ush from arsenic may phase into an actinic keratosis, a hyperkeratosis of palms and soles, papillomatosis, recurrent episodes of pruritic urticaria, or even generalized pruritis without a visible rash [220], basal cell carcinoma or squamous cell carcinoma, which are histologically indistinguishable from analogous non-arsenic tumors [119], and ngernails and toenails with transverse white indentations called Mees or Aldrich-Mees lines [221].

3.2.7. Renal effects Like the liver, the kidneys will accumulate inorganic arsenic in the presence of repeated exposures. The kidneys are the major route of arsenic excretion, as well as a major site of conversion of pentavalent arsenic [188,206]. In humans, the kidneys seem to be less sensitive to arsenic than most other organ systems. The effects of organoarsenicals on the human renal system are not reported. Sites of arsenic damage in the kidney includes capillaries, tubules and glomeruli, which leaded to hematuria and proteinuria [196], oliguria, shock and dehydration with a real risk of renal failure [207], cortical necrosis [208], and cancer [209]. 3.2.8. Dermal effects Chronic exposures to arsenic by either ingestion or inhalation will produce a variety of skin insignia of arsenic toxicity (i.e. diffused and spotted melanosis, leucomelanosis, keratosis, hyperkeratosis, dorsum, Bowens disease, and cancer). Skin disorders are documented in several epidemiological studies in which people consumed drinking water that contained arsenic at the doses of 0.01 0.1 mg As kg 1 per day or more [63,150,151,210 216], no dermal or other effects as a result of exposure to chronic doses of 0.003 0.01 mg As kg 1 per day [217,218]. Hyperpigmentation may occur, particularly in body areas where the skin tends to be a little darker [219]. The initial ery-

3.2.9. Neurological effects Several studies indicate that ingestion of inorganic arsenic can result in neural injury. Acute high exposure (1 mg As kg 1 per day or more) often causes encephalopathy with symptoms as headache, lethargy, mental confusion, hallucination, seizures and coma [222]. Intermediate and chronic exposures (0.050.5 mg As kg 1 per day) cause symmetrical peripheral neuropathy, which begins as numbness in the hands and feet but later may develop into a painful pins and needles sensation [223], wrist or ankle drop [224], asymmetric bilateral phrenic nerve [225], and peripheral neuropathy of both sensory and motor neurons causing numbness, loss of reexes, and muscle weakness [226,227]. 3.2.10. De6elopmental effects It is not well established whether ingestion of inorganic arsenic can cause developmental abnormalities in humans. No overall association between arsenic in drinking water and congenital heart defects is found in a case-control study in Boston [228], although an association with coarctation of the aorta is noted. Some researchers nd that babies born to women exposed to arsenic dusts during pregnancy has a higher than expected incidence of congenital malformations [229,230], below average birth weight [231]. The incidence of spontaneous abortion in women who lived near a copper smelter in Sweden tends to decrease as a function of distance [231], and in Eastern Massachusetts [232]. A couple of studies reported an increased number of miscarriages among women who worked in the semiconductor industry, which caused arsine [233,234].

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3.2.11. Reproducti6e effects For over 50 years, it is known that inorganic arsenic readily crosses the placental barrier and affects fetal development [235]. Organic arsenicals do not seem to cross the placenta so readily and are stored in the placenta [236]. There is an extensive documentation of experimental induction of malformations in a variety of species [235] with increased fetal, neonatal and postnatal mortalities, and elevations in low birth weights, spontaneous abortions, still-birth, pre-eclampsia and congenital malformations. A series of ecological studies involving workers and their families living in the vicinity of the Ronnskar copper smelter in Sweden, for example, reported an increase in the prevalence of low birth weight infants [231], higher rates of spontaneous abortions, elevations in congenital malformations among female employees and in women living close to the smelter relative to women living further a eld [230], and higher frequency of pregnancy complications, mortality rates at birth and low birth weights near a Bulgarian copper smelter, relative to countrywide rates [237].

3.2.13. Genotoxic effects The repair inhibition may be a basic mechanism for the comutagenecity and presumably the cocarcinogenicity of arsenic [242]. Comparisons of chromosome aberration frequencies induced by tri- and pentavalent arsenic indicate that the trivalent forms are far more potent and genotoxic than the pentavalent forms [243], whereas DMA is genotoxic in assays using mammalian and human cells [244246] and MMA is less potent than DMA, and TMAO is more potent in inducing both mitotic arrest and tetraploids [245]. It is suggested that the higher mitotic toxicity reported for organoarsenicals in some studies is a function of their greater disruptive effects on the microtubular organization of the cell [247]. 3.2.14. Mutagenetic effects Mutagenesis includes the induction of DNA damage and a wide variety of genetic alterations, which can range from simple gene mutations (DNA base-pair changed to grossly visible changes in chromosome structure or number clastogenesis). Some of these changes may cause genetic damage transmissible to subsequent generations, and/or some may cause cancer or their problems in the exposed generation [248 250]. This apparent pardon, plus occasional poor correlation between arsenic exposures doses and resultant frequency of chromosomal aberrations, is explained by the concept that arsenic promoted genetic damage in large part by inhibiting DNA repair [219,251,252]. Enzymes such as superoxide dismutase and catalase that scavenge for oxygenfree radicals seem to provide protection against arsenic-induced DNA damage, indicating a possible basis for the genotoxic effect of arsenic [253]. 3.2.15. Carcinogenic effects Over 100 years ago [254], it is observed that patients who received chronic treatment with arsenical medications have greatly increased incidence of both basal cell and squamous cell carcinomas of the skin. These arsenical skin cancers commonly occur in the presence of dermatologic manifestations of arsenicism, and some has internal neoplasms that are regarded as arsenical

3.2.12. Immunologic effects The effects on the immune system of inhalation exposure to arsenic are not well studies. No abnormalities are detected in the serum levels of immunoglobulin of workers exposed to arsenic in a coal burning power plant [238]. At low doses of arsenite (2 10 6 M) and arsenate (510 6 M), phytohemagglutinin (PHA)-induced stimulation of cultured human lymphocytes is increased 49% with arsenite and 19% with arsenate, but at high doses of arsenite (1.910 5 M) and arsenate (6 10 4 M), PHA-induced stimulation is completely inhibited [239] with an impairment of immune response. It is also supported by other study [240]. In a follow-up study, Gonsebatt et al. [241] compared lymphocyte-replicating ability in 33 individuals consuming drinking water with a mean arsenic concentration of 37 mg l 1. The peripheral blood lymphocyte count of the arsenic-exposed subjects is slightly increased relative to the controls (3.19 1.0106 versus 2.69 1.1 106).

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in origin and much of this type on the populations in the BFD-endemic parts of Taiwan [118,255,256], but there are reports of elevated cancer risks at multiple sites (notably lung, skin, bladder, kidney and liver) from other parts of the world including Japan, Bangladesh, West BengalIndia, Chile and Argentina where subsets of the population are exposed to arsenic-contaminated drinking water [15,150,257,258]. A recent analysis by Lewis et al. [259] of cancer incidence among Mormons in Utah nds no evidence of excess deaths for lung or bladder cancer among males or females. However, the study indicates a slightly elevated, but not statistically signicant mortality from kidney cancer in both males and females (SMR = 1.75 and 1.60, respectively). The most important studies of exposure through inhalation are based on data obtained from three copper smelters, in Tacoma (Washington, USA), Anaconda (Montana, USA) and Ronnskar (Sweden). In all three cohorts, a statistically signicant increase in lung cancer risk with increasing exposure is demonstrated. Now it will seem to be a cancer promoter rather than a cancer initiator, the risk of cancer that it posed will indeed seem to be dose-dependent, and that cancer risk will be expected to decline again when the arsenic exposure ceases and the substance is cleared from the body. Lee-Feldstein [260], and Nordberg and Anderson [261] suggested an alternate mechanism, which was that arsenate is incorporated in the DNA in place of phosphate. This explanation of consistent with observations that arsenate must be present during DNA synthesis in order to be effective. This also explains why arsenic is clastogenic, since the arsenate phosphate bond will be weaker than the normal phosphodiester bond [262].

when compared to residents in Taipei and the entire Taiwan population. Tsai et al. [264] reported an excess mortality from diabetes among the arsenic exposed population in four townships, relative to local and national rates. The incidence of diabetes mellitus in a cohort of inhabitants of the Taiwan BFD area is related to the cumulative exposure to arsenic in drinking water [265]. Rahman et al. [266,267] used the presence of keratosis as an indicator of arsenic exposure and showed elevated risks for diabetes in those exposed to arsenic in their drinking water (prevalence ratio= 5.9) in Bangladesh, whereas in the Utah mortality study, Lewis et al. [268] failed to nd signicant excess in the number of deaths from diabetes in males and females exposed to elevated levels of arsenic in drinking water. Two occupational studies nd an association between arsenic exposure and diabetes mellitus among glass workers in Bangladesh [269] and a case-referent study in the Ronnskar cohort [270].

3.2.16. Diabetes mellitus Diabetes mellitus has been linked with drinking water arsenic exposure. Lai et al. [263] assessed the relationship between ingested inorganic arsenic and prevalence of diabetes mellitus in 891 adults residing in southern Taiwan. Their study nds that residents in the BFDendemic areas has a twofold increase in the prevalence of diabetes mellitus (after adjustment for age and sex)

3.2.17. Biochemical effects Arsenic compounds are known to inhibit more than 200 enzymes in humans [271]. Kulanthaivel et al. [272] noted the catalytic action of vicinal thiol groups and that phenylarsine oxide (PAO) inhibited Na+ and H+ efux of human placental Na+ H exchanger [271]. Sheabar and Yanni [273] investigated the in vitro effects of arsenite on human blood enzymes. There is a 7080% inhibition of glutamylpyruvate transaminase, and glutathione peroxidase is also affected adversely by 0.8 mg As l 1. Also, blood glucose-6-phosphatase and cholinesterase are completely inhibited. Other studies show that sodium arsenite causes a marked increase in the cellular heme oxygenase activity of human Hela cells [274]. Arsenite is rapidly and extensively accumulates in the liver, where it inhibits NAD-linked oxidation of pyruvate or alpha-ketoglutarate. This is occurred by complexation of trivalent arsenic with vicinal thiols necessary for the oxidation of these substrates [235]. The theory that altered DNA repair is the cause of arsenic carcinogenesis, is particularly attractive because trivalent arsenic species, such as arsenite, can bind strongly to dithiols as well as free

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sulfhydryl groups [275,276]. Such protein binding can induce inhibited DNA repair, mutation in key genetic sites, or increased cell proliferation, which could then lead to subsequent mutation via inhibited DNA repair.

4. Arsenic episodes round the world Arsenic poisoning episodes have been reported all over the world. Exposure to arsenic may come from natural sources, from industrial sources, or from food and beverages. So, arsenic episodes all over the world are divided into three categories: 1. Natural groundwater arsenic contamination. 2. Arsenic contamination from industrial source. 3. Arsenic contamination from food and beverage.

cism is observed in a population of 40,421 in 37 villages, and 7418 cases of hyperpigmentation, 2868 of keratosis, 360 of BFD patients [281], and some cases of cancer (liver, lung, skin, prostate, bladder, kidney) [281285] are observed. The source material of the arsenic is likely to be pyretic material or black shale occurring in underlying geological strata [278]. It is thought at beginning that arsenic alone is responsible for BFD of the area [286]. The discovery in 1975 of uorescent compounds in these well waters leads to the isolation of humic substances, which in combination with arsenic is thought to be probable cause for the BFD [287]. To save the people of the Taiwan endemic areas, a water treatment plant is run to remove arsenic from groundwater before use.

4.1. Natural groundwater arsenic contamination


Background concentrations of arsenic in groundwater are in most countries less than 10 mg l 1 [277] and sometimes substantially lower. However, values quoted in the literature shows a very large range from B0.5 to 5000 mg l 1 (i.e. four orders of magnitude). This range occurs under natural conditions. High concentrations of arsenic are found in groundwater in a variety of environments. This includes both oxidizing (under conditions of high pH) and reducing aquifers and in areas affected by geothermal, mining and industrial activity. Most high-arsenic groundwater provinces are the result of natural occurrences of arsenic.

4.1.1. Taiwan incident The arsenic contamination incident in well water on the south-west coast of Taiwan (1961 1985) is well known [278 280]. The population of endemic area is about 140,000. In the villages surveyed, the arsenic content of the well water examined, ranges from 0.01 to 1.82 mg l 1. Most of the well water in the endemic area has arsenic content around 0.4 0.6 mg l 1. The predominant arsenic species in the well waters is iAsIII with an average iAsIII to iAsV ratio of 2.6. Chronic arseni-

4.1.2. Antofagasta, Chile incident About 130,000 inhabitants of the city has been drinking supplied water with high content of arsenic (0.8 mg l 1) for 12 years from 1959 to 1970 [288]. The source of the high arsenic content in water is the Tocance River, of which water comes from the Andes Mountain at an altitude of 3000 m and is brought 300 km to Antofagasta. At the beginning of 1960s, the rst dermatological manifestation was noted, especially in children [288]. Peripheral vascular manifestations in these children included Raynauds syndrome, ischemia of the tongue, hemiplegia with partial occlusion of the carotid artery, mesenteric arterial thrombosis and myocardial ischemia. One autopsy showed hyperplasia of the arterial media. In a survey of 27,088 school children, 12% are found to have the cutaneous changes of arsenicism, one-fourth to one-third of these has suggestive systematic symptoms. Eleven percent has acrocyanosis. Of the Antofagastan residents, 144 have abnormal skin pigmentation, compared with none in the 98 control subjects. Recent studies [212,289] also document arsenic-induced skin lesions, and increased bladder and lung cancer mortality in Northern Chile. To save the people, a water treatment plant is run to remove arsenic from drinking water before use. The sources of arsenic have been reported as quaternary volcanogenic sediments, minerals and

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soil [290]. Samples taken from 23 locations at Aracamenan settlements near Calama range from less than 100 to more than 800 mg As l 1. Most of the arsenic is present as arsenate, but some arsenite is also determined. Five soils irrigated with high arsenic waters range from 86 to 446 mg As kg 1 compared to 64 mg As kg 1 in one control sample.

individuals (per age group) affected with cutaneous lesion increase with age until the age of 50. The shortest is 8 years for hypopigmentation, 12 years for hyperpigmentation and palmo-planter keratosis, 25 years for papular keratosis and 38 years for ulcerative lesions [298]. The source of arsenic is assumed to be geological (volcanic sediment) [61].

4.1.3. West Bengal-India incident Around 1978 various aspects of arsenic groundwater contamination and arsenicosis among people in some villages of West Bengal rst came to the notice of Government of West Bengal [291]. Several recent studies [22,63,67,151,291 294] report that about 6 million people of 2600 villages in 74 arsenic-affected blocks of West Bengal, India are in risk and 8500 (9.8%) out of 86,000 people examined are suffering from arsenicosis, while the source is oxidation of arsenic rich pyrite or anoxic reduction of ferric iron hydroxides in the sediments to ferrous iron and thereby releasing the adsorbed arsenic to groundwater. 4.1.4. Mexico incident Chronic arsenic exposure via drinking water is reported in six areas of Region Lagunera, situated in the central part of North Mexico with a population of 200,000 during 1963 1983 [295]. The range of total arsenic concentrations is 0.008 0.624 mg l 1, and concentrations greater than 0.05 mg l 1 are found in 50% of them. Most of the arsenic is in inorganic form and pentavalent arsenic is the predominant species in 93% of the samples [61]. In 36% of the rest samples, however, variable percentages (20 50%), of trivalent arsenic are found. It is also observed that high concentrations of uoride in the range of 0.53.7 mg l 1 and concentrations greater than 1.5 mg l 1 are found in 20% of the analysed samples [296]. The symptoms observed in this area are cutaneous manifestations (skin pigmentation changes, keratosis and skin cancer), peripheral vascular disease (BFD), gastrointestinal disturbances and alteration in the coporphyrin/uroporphyrin excretion ratio [297]. It is found that the proportion of

4.1.5. Argentina incident Similar incident of arsenic contamination in groundwater is also reported in Monte Quemado of Cordoba province, north of Argentina [62]. The occurrence of endemic arsenical skin disease and cancer is rst recognized in 1955. Total population of the endemic area is about 10,000. From the observations in the Cordoba, it is concluded [62,209] that the regular intake of drinking water containing more than 0.1 mg l 1 of arsenic leads to clearly recognizable signs of intoxication and ultimately might develop into skin cancer. Biagini followed 116 patients with clear signs of chronic arsenic disease over a number of years [299]. After 15 years of follow-up, 78 had died, 24 from cancer (i.e. 30.7% of total deaths). In Monte Quemado, the problem seems to be ultimately solved by building a canal that supplies the town with arsenic free water from Salta province. Again, elevated concentrations of arsenic in surface waters, shallow wells and thermal springs are reported from the Salta and Jujay provinces in northwestern Argentina [300]. This natural contamination is related to Tertiary-Quaternary volcanic deposits, together with post-volcanic geysers and thermal springs. Waters abstracted for drinking supplies for the population of 5000 in the town of San Antonio de los Cobres ranges from 0.47 to 0.77 mg l 1. Thermal springs range from 0.05 to 9.9 mg l 1 of arsenic. A strong natural contamination of groundwater with arsenic and selenium is reported in the Pampa Province of Cordoba, southeast Argentina. The arsenic content of nearly 50% of the water samples from this area ranges from 0.1 to 0.316 mg l 1 with a maximum value of 3.81 mg l 1 [64,301]. Groundwater contamination is caused from loess, which differed in composition

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to loess from Europe, Asia and North America [64], with arsenic concentrations ranging from 5.5 to 37.3 mg kg 1, and rhyolitic volcanic glass ranging from 6.8 to 10.4 mg kg 1.

4.1.6. Millard County, Utah, USA incident West Millard County is a desert area with low population density and around 250 people drinking well water of arsenic content between 0.18 and 0.21 mg l 1 and the predominant arsenic species is arsenate (86% As5 + ) [302]. Participants are examined for specic signs of arsenic toxicity including palmer and plantar (palms and soles) keratoses, diffuse palmer and plantar hyperkeratoses and skin suggestive of arsenic toxicity is rare, with only 12 of 149 participants having any signs associated with arsenic ingestion. Participants from Deseret have the highest average arsenic in urine concern of 0.211 mg l 1 (n = 40) and that of Hinckley participants have 0.175 mg l 1 (n= 95) compared to control from Delta of 0.048 mg l 1 (n= 99). The highest average arsenic concentration in hair is 1.21 mg kg 1 (n = 80) from Hinckley residents and that of Deseret residents is 1.09 mg kg 1 (n = 37) compared to control from Delta of 0.32 mg kg 1 (n = 68). Lewis et al. [303] recently reports hypertensive heart disease, nephritis, nephrosis, and prostate cancer among the people of the arsenic-affected areas in Utah. 4.1.7. Lane County, Western Oregon, USA incident Well water in Central Lane County [304], located in Western Oregon about midway between the Colombia river and the northern boundary of California gets contaminated with arsenic during November 1962 March 1963. The concentration range of arsenic in wells is 0.05 1.7 mg l 1. Wells in Eugene, Creswell, and Grove districts in Central Lane County which were known to yield arsenic rich groundwater are in an area underlain by a particular group of sedimentary and volcanic rocks, which geologists have named the Fisher formation [305]. The largest concentrations of arsenic are found in samples from the Creswell district.

4.1.8. Lessen County, California, USA incident In the Lessen County, California, similar arsenic poisoning in well water is observed. The range of arsenic in the well water is 0.051.4 mg l 1. It is found that arsenic is present in drinking water above 0.05 (9 0.03) mg l 1 and an increased level of arsenic in their hairs reects body burden due to arsenic exposure [306]. 4.1.9. Ontario, Canada incident In 1937, Wyllie [307] reported that water from some deep wells in Rocky Mountain areas of Ontario, Canada were known to contain large amounts of arsenic. The source of arsenic in well water is ferrous arsenate where arsenic in water varies from 0.10 to 0.41 mg l 1 as As2O3. Preliminary experiments show that arsenic as arsenate is the primary source of arsenic, which contaminated the well water. One person died of arsenic dermatosis. The whole family members of the victim died are also aficted due to this arsenic poisoning. 4.1.10. No6a Scotia, Canada incident In 1976, several wells in Halifax County, Nova Scotia are contaminated with arsenic [308] with concentration greater than 3 mg l 1. More than 50 families have been affected due to arsenic poisoning [309]. Recently, Boyle et al. [310] reports also occurrences of elevated arsenic concentrations in bedrock groundwaters used for individual and municipal water supplies in the mainland coast of southern British Columbia, Canada. 4.1.11. Hungary incident In Hungary also similar arsenic contamination in the well water is observed [311,312] in the years 19411983. The amount of arsenic present in the well water is in the range of 0.064.00 mg l 1. Recently, concentrations of arsenic above 50 mg l 1 are identied in groundwaters from alluvial sediments associated with the River Danube in the southern part of the Great Hungarian Plain. Concentrations up to 150 mg l 1 (average 32 mg l 1, 85 samples) are found by Varsanyi et al. [54]. The Plain, some 110,000 km2 in area, consists of a thick sequence of subsiding Quaternary sedi-

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ments. The groundwaters have highest arsenic concentrations in the lowest parts of the basin, where the sediment is ne-grained [54]. A few thousand people are affected and several symptoms of arsenic poisoning viz, melanosis, hyperkeratosis, skin cancer, internal cancer, bronchitis, gastroenteritis, haematologic abnormalities are found among them [313].

4.1.12. New Zealand incident In 1939, Grimmet and McIntosh described arsenic contamination of groundwater and the resulting effects on the health of livestock [314]. Later on in 1961, high levels of arsenic were found in water from areas of thermal activity. Thermal waters in New Zealand contain up to 8.5 mg As l 1 [315]. Aggett and Aspell [316] studied the chemical forms of arsenic in water samples. In the geothermal bores, more than 90% of the arsenic is present in the trivalent form. 4.1.13. Poland incident A small case is observed in Poland in 1898 [317] with some skin cancer among the arsenic affected persons. It is interesting to note that there is no published data on this incident. 4.1.14. Fairbanks, Alaska incident In the well water, spring of Fairbanks, Alaska, arsenic is found above 0.05 mg l 1. The study is initiated to evaluate the arsenic content of streams and groundwaters of the Pedro-Dome Cleary Summit area approximately 30 km north of Fairbanks, Alaska in the heart of the historic Fairbanks Mining District. Arsenic is associated with gold mineralization here and is believed to reach the water of the area through weathering of arsenic containing rocks. The arsenic concentrations in 53 water samples from wells and springs range from less than 0.005 to 0.07 mg l 1. Eighty percent of the samples contain less than 0.01 mg l 1 and 95% of the samples contained less than 0.05 mg l 1 [318]. The arsenic levels in 243 well water range from less than 0.05 to greater than 0.10 mg l 1. About 28% of the samples contain arsenic less than 0.05 mg l 1, 40% of the samples contained less than 0.10 mg l 1 and about 20% of the samples con-

tain greater than 0.10 mg l 1. Well water arsenic concentrations in the Ester Dome study area range from less than 1.0 to 14 mg l 1 and for the study population range from less than 1.0 to 2.45 mg l 1 with a mean of 0.224 mg l 1. An epidemiological study was made in 1976 [319], which suggested no clinical or haematological abnormalities among these people. Urine arsenic levels above 0.02 mg l 1 are found in 130/198 (66%), hair arsenic levels above 1 mg kg 1 occur in 74/181 (41%) and nail arsenic levels above 4 mg kg 1 in 49/132 (37%) of the study population.

4.1.15. Srilanka incident In a clinical study of 13 cases of polyneuropathy connected with arsenic poisoning, in Srilanka, Senanayake et al. [320] found Mees line, i.e. transverse white bands across nger nails, to be the constant feature at least 6 weeks after the onset of initial symptoms. In seven of these cases, the source of arsenic was contaminated well water, four others had a long history of consuming illicit liquor. 4.1.16. Spain incident Manzano and Tellow summarized their experiences in treating arsenic poisoning caused by well water in certain areas of Spain [321]. 4.1.17. China incident During the 1980s, the endemic arsenicosis was found successively in many areas on mainland China such as Xinjiang Uygur A. R., Inner Mongolia, Shanxi, Liaoning, Jilin, Ningxia, Qinghai, and Henan provinces [322328]. The arsenic concentration in the groundwater in these affected areas is in the range of 2202000 mg l 1 with the highest level at 4440 mg l 1. Consequently, a large sector of the rural population has been exposed to chronic arsenic poisoning (CAP) resulting from consuming well water with naturally occurring high levels of arsenic during the past decades. At present, the population exposed to high amounts of arsenic is estimated to be over 2 million and more than 20,000 arsenicosis patients are conrmed [328]. The water of the deep-wells, however contains uoride and arsenic [323]. Fluorosis was rst found in the 1970s and arsenicism in 1980.

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One of the characteristics of the Kuitun case is the fact that there are three groups of patients among the residents who drank the same well water for a long time. Namely, one group suffers from uorosis, the second group from arsenicism and the third group from both uorosis and arsenicism combined. The cause of contamination is considered to be geological. Major clinical symptoms observed are keratosis, pigmentation, melanosis or leucoderma on the skin, often accompanied with peripheral neuritis, gastroenteritis, and hypertrophy of the liver, bronchitis or cardiac infarction. At later stages skin cancer and gangrene are also found. Feng et al. [329] recently reports DNA damage in buccal epithelial cells from individuals from this arsenic-affected area. Various measures are taken to supply clean water.

adsorbed arsenic to groundwater. To combat the situation, Bangladesh need a proper utilization of its vast surface and rainwater resources and proper watershed management.

4.1.20. Fallon, Ne6ada Incident In 1984, Viz et al. [334] were unable to detect any increase in chromosomal aberrations or sister chromatid exchange in residents of Fallon, Nevada, where drinking water contained about 0.10 mg As l 1. From literature it is found that the health status of these arsenic exposed populations is not adversely affected [335]. 4.1.21. Fukuoka Prefecture, Japan incident In March 1994, arsenic over the permissible level for drinking use (0.01 mg l 1) is detected in well waters in the southern region of Fukuoka Prefecture, Japan [71]. The highest concentration found is 0.293 mg l 1, being quite high compared to other arsenic-containing well waters reported in Japan as a geological process. The mechanisms of arsenite/arsenate elution from the soil proposed are which involved: (i) anion exchange with OH; and (ii) reductive labialization of arsenic through conversion of arsenate to arsenite. 4.1.22. New Hampshire, USA incident Arsenic concentrations are measured in 992 drinking water samples collected from New Hampshire households and in randomly selected households, concentrations ranged from B 0.0003 to 180 mg l 1, with water from domestic wells containing signicantly more arsenic than water from municipal sources. Water samples from drilled bedrock wells have the highest arsenic concentrations, while samples from surcial wells has the lowest arsenic concentrations. The authors [336] suggested that much of the groundwater arsenic in New Hampshire was derived from weathering of bedrock materials and not from anthropogenic contamination. The spatial distribution of elevated arsenic concentrations (\50 mg l 1) correlates with Late-Devonian Concordtype granite bedrock. Analysis of rock digests indicates arsenic concentrations up to 60 mg kg 1 in pegmatites, with much lower values in surrounding schists and granites.

4.1.18. Northern India incident In Ropar, Manimajra, Chandigarh, N. Garh, Patiala and Ambala around Chandigarh of Punjab and Haryana of India, the arsenic concentration in water from wells and springs were higher than the WHO limit of safety for human consumption [330] with 0.05 0.545 mg l 1 of arsenic. Cirrhosis (adult and childhood), non-cirrhotic portal brosis and extra hepatic portal vein obstruction in adults are very common in India and suggests that consumption of arsenic-contaminated water may have some role in the pathogenesis of these clinical states [331]. The patients who consumed the water containing arsenic 0.545 mg l 1 throughout life are suffering from non-cirrhotic portal brosis (N.C.P.F.), whereas their two relatives consuming same water reveal gross splenomegaly, but with normal liver function tests [332]. The source of arsenic is still unknown. 4.1.19. Bangladesh incident Several recent studies [23,216,292,333] report that about 25 million people of 2000 villages in 178 arsenic-affected blocks of Bangladesh are in risk and 3695 (20.6%) out of 17,896 people examined are suffering from arsenicosis, while the source is oxidation of arsenic rich pyrite or anoxic reduction of ferric iron hydroxides in the sediments to ferrous iron and thereby releasing the

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4.1.23. Vietnam incident This is the rst publication on arsenic contamination of the Red alluvial tract (Mekong delta region) in the city of Hanoi and in the surrounding rural districts [72]. The contamination levels vary from 1 to 3050 mg l 1 in rural groundwater samples from private small-scale tube-wells with an average arsenic concentration of 159 mg l 1. In a highly affected rural area, the groundwater used directly as drinking water has an average concentration of 430 mg l 1. Analysis of raw groundwater pumped from the lower aquifer for the Hanoi water supply show arsenic levels of 240 320 mg l 1 in three of eight treatment plants and 37 82 mg l 1 in another ve plants. Aeration and sand ltration that are applied in the treatment plants for iron removal lowers the arsenic concentrations to levels of 2591 mg l 1, but 50% remains above the Vietnamese Standard of 50 mg l 1. The arsenic in the sediments may be associated with iron oxyhydroxides and releases to the groundwater by reductive dissolution of iron. The high arsenic concentrations found in the tube-wells (48% above 50 mg l 1 and 20% above 150 mg l 1) indicate that several million people consuming untreated groundwater may be at a considerable risk of CAP. No people were found in these affected regions with symptoms of chronic arsenic toxicity. 4.2. Arsenic contamination from industrial sources 4.2.1. Ronphibun, Thailand incident In 1987, the skin manifestation of CAP was rst diagnosed among the residents of Ronphibun district, Nakorn Srithammarat Province [337]. It is seen that 85% of all reported of CAP are from Ronphibun sub-district of Ronphibun district. Most cases are of relatively mild disease, with 21.6%, however having very signicant lesions [338]. Rophibun district has eight sub-districts and 65 villages with a population of 14,085. Three out of 14 villages of Ronphibun sub-district with 19.9% of the population of the sub-district account for 60.9% of the cases. These villages use water with drains from the high-contaminated area of Suan Jun and Ronna Mountains. Their attack rate is 8.8 times, the rate in the remainder

of the sub-district. This area has 0.1% arsenopyrite. Recently, Oshikawa et al. [339] reports the long-term changes in arsenical skin lesions among this population. At many sites, the arsenic content of water exceeds by 8100 times the 0.05 mg l 1 concentration, which is the accepted safety level set down by WHO for occasional exposure [15].

4.2.2. Mindanao Island, Philippines incident Soon after the construction of a geothermal power plant on Mt. Apo started in January 1992, people living downstream along the Matingao and Marbol rivers which run through the construction site, complained of symptoms such as eruption, headache or stomach-ache. An environmental investigation carried out in August 1993, which revealed that river water downstream of the construction site contained 0.1 mg l 1 of arsenic and hair samples of some residents showed high concentrations of mercury and manganese as well as arsenic [340]. As a result, the construction of the geothermal power plant is suspected as the cause of arsenic contamination. In 1995, a medical survey of 39 residents who had rashes on their skin reveals that a few of them are suspected to be patients suffering from CAP [341]. 4.2.3. Nakajo, Japan incident Waste water from a factory producing arsenic sulde contaminated nearby well water in Nakajo, Japan in 1960 [342,343]. In this place a very small number of people drank the well water, which was contaminated with arsenic (0.0254.00 mg l 1). Melanosis, hyperkeratosis, cardiovascular disease, hepatopathy, haematologic abnormalities were observed among the residents of Nakajo. 4.2.4. Toroku and Matsuo, Japan incident Toroku is a small mountain village to the north of Miyazaki prefecture with a population of about 300 where arsenious acid was produced by roasting arsenopyrite ore from 1920 to 1962 [344]. Similarly, Matsuo is a small mountain village in the north of Miyazaki prefecture. Here, white arsenic was produced by calcinating arsenopyrite at very primitive stone-made furnaces for nearly half a century since about 1920. In this system about 10% or more of As2O3 was lost as fumes

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through the rening process. The arsenic-rich remains of calcinated ore were dumped into the river. Many mine workers and nearby residents died from acute and sub-acute arsenic poisoning. A 6-year follow-up study reveals a high prevalence of malignant neoplasms especially in respiratory tract, which was the main cause of death in the patient [345]. A total of 147 persons are examined in the study. Out of them, 125 are diagnosed as CAP. A total of 58 malignant skin tumors are noted out of 125 patients with skin lesions of CAP and out of these 58 malignant skin tumors, 51 occur on trunk and times. The appearance of multiple malignant tumors was noted in 24 cases (58.5%), including 15 cases of double cancers. The phenomenon is noted in 14 cases (42.4%) among cases of malignant skin tumor. Multiple Bowens disease is found in 12 cases (37.5%). As of 1995, there were 153 patients in Toroku and 64 in Matsuo who are recognized by the government as suffering from CAP [346].

169 years. Typical skin manifestations are found in all of them but pulmonary symptoms are present in 40% and neurological symptoms in 65% of cases. Hematomegaly (2 6 cm) is found in 80% of cases and splenomegaly (1.52.6 cm) in 35% of cases. A few died due to arsenicosis.

4.2.7. Rajnandgaon district, Madhya Pradesh, India incident Arsenic contamination of groundwater in Koudikasa village of Rajnandgaon district, Madhya Pradesh-India with a population of 1.5 million was reported rst on 1999 [350]. Most of the villagers of Koudikasa used water from a forest dug-well (0.52 mg As l 1) along with a PHED tube-well (0.88 mg As l 1). Out of the total number of adults (150 nos.) and children (58 nos.) examined at random, 42 and 9%, respectively, have arsenical skin lesions. The source of arsenic contamination is speculated to be due to percolation of gold and uranium mines tailings. 4.2.8. Australia incident In Australia, old stocks of lead arsenate, that was used as pesticides prior to 1970 remained in sheds and caused chronic poisoning among the workers [351]. 4.2.9. Czechoslo6akia incident People living near a plant burning arsenic contaminated coal containing 9001500 mg As kg 1 was responsible for the episode [352]. 4.2.10. Toronto, Ontario, Canada incident Vegetation and soil samples collected in 1974 in the vicinities of two secondary lead smelters located in a large urban area near Toronto, Ontario, Canada showed arsenic concentrations over 30 times higher than normal urban background levels of arsenic in unwashed plant foliage and 200 times higher than normal soil which were found about 200 m away from the smelters. A large number of people were found suffering from arsenic toxicity in this region [353]. 4.2.11. Greece incident Systematic sampling of soils and dusts in and around the ancient lead mining and smelting site

4.2.5. Other incidents in Japan A severe cutaneous manifestations of CAP are detected in seven out of 28 male Japanese workers, who are exposed to arsenic in the form of lead arsenate and Ca3AsO4 in the manufacture of insecticides [347]. The lesions are symmetric punctuated palmo-planter hyperkeratosis and bronze hyper-pigmentation. A retrospecic cohort study of a Japanese population in between 1954 and 1959 used well water contaminated with arsenic from a dye factory. During the follow-up period until 1987, there were 18 deaths from cancer, of which seven from lung cancer and six in the high exposure group [348]. 4.2.6. P.N. Mitra Lane, Behala, Calcutta, India incident Arsenic contamination episode in residential area of Behala, Calcutta during 1969 1989 is well known [68,92,349]. The concentration of arsenic in the tube-well water varies from 0.05 to 58 mg l 1. Chronic arsenic toxicity, resulting from household use of arsenic contaminated water occurs in 53 out of 79 members (67% of 17 families) residing near this factory area within age range

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at Lavrion, Greece, indicated extensive contamination with arsenic as well as lead and had instigated studies into possible health implications to the local community [354]. Concentrations of arsenic in garden soils and house dusts were ranged up to 14,800 and 3800 mg kg 1, respectively.

4.2.12. Ghana incident Arsenic in drinking water from streams, shallow wells and boreholes in the Obuasi gold-mining area of Ghana ranges from B0.002 to 0.175 mg l 1. The main source of pollution is due to mining activities and oxidation of naturally occurring sulde minerals, predominantly arsenopyrite (FeAsS). Some of the water samples have high arsenite content. Soils are leached kaolinite muscovite laterites overlying saprolite [355]. It is reported that in the saprolite, arsenopyrite appears to have been replaced by secondary As- and Febearing minerals, including scorodite (FeAsO42H2O), arsenolite and arsenates [356]. 4.2.13. USA incident The serious incident of air pollution by arsenic from copper smelters in the U.S. is recorded in Anaconda, Montana [357,358] with the rate of emissions of arsenic trioxide of 16,884 kg per day. Although no atmospheric concentrations are in record, edible plants contain arsenic trioxide up to 482 mg g 1, causing serious health hazard surrounding the area. Mortality from ischemic heart disease is signicantly increased among arsenic exposed workers of this smelter [359]. The initial 1938 1963 mortality analysis of workers at the copper smelter at Anaconda, Montana, demonstrated a more than threefold excess respiratory cancer ratio, with an excess risk as high as high as eightfold among heavily exposed men who had worked there 8 years or more [360]. A serious incident of air pollution by arsenic also occurs in a small Western town near a gold-smelter, USA manufacturing 36 tons of arsenic trioxide per day [361]. Some studies [362,363] involved a copper smelting plant at Tacoma in the state of Washington that produced As2O3 as a by-product. The plant had an average employment of 904 during the years 19441960 when a total of 229 deaths were

reported among active plant employees, 38 of the death were classied as exposed to arsenic. Out of these six died of cancer, including three cases of cancer of the respiratory tract. In literature [364], Perham was a town of 1900 situated on the agricultural area of western Minnesota, USA and a core sample to a depth of 20 cm revealed 3000 parts per million (mg l 1) of arsenic. The symptoms of sub-acute or chronic arsenic intoxication were conrmed to the three persons out of 13 with the highest intake.

4.2.14. British incident In 1910 and 1943, a British plant manufactured a sodium arsenite sheep dip [365,366]. The factory was in a small county town within a specic birth and death registration sub-district. Here 75 deaths are reported among factory workers 22 (29%) due to cancer. 4.2.15. Southern Rhodesia incident There was excess lung cancer mortality among southern Rhodesia miners of gold bearing ores containing large amounts of arsenic [367]. 4.2.16. Torreon, Mexico incident In the city of Torreon, Mexico, Espinosa Gonzalez [368] reported the presence of arsenic in drinking water from a deep well range from 4 to 6 mg l 1. In Silesia, Mexico the concentration of arsenic in spring water arose through leaching of arsenic wastes from mining operations (coal preparations wastes and y ash from coal-red power plants) into spring water leading to contamination [369]. 4.2.17. Northern Sweden incident At the Ronnskar smelter in northern Sweden, ores with a high arsenic content were handled. Women employed in the plant as well as those who lived nearby deliver babies having signicantly lower weight than those delivered by women who are not so exposed [231]. Among those same women, the frequency of spontaneous abortion is generally higher with closer proximity of residence to the smelter [232]. Although residential proximity to the Ronnskar smelter has no effect on the incidence of congenital malforma-

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tions, pregnancies during which the mother had worked at the smelter are signicantly more apt to babies with single or multiple malformations, particularly urogenital malformations or hip-joint dislocation [231].

4.2.18. Armadale, central Scotland incident In Armadale, a town in central Scotland [370,371] having population 7000, the standardized mortality ratio (SMR) for respiratory cancer are high and high sex-ratios of births were observed during 1969 1973 which was due to arsenic contamination from a steel foundry located in that area. The arsenic concentrations in soil samples in Armadale were higher (52 64 mg g 1) than those in the white burn soils. 4.2.19. Srednogorie, Bulgaria incident Heavy air pollution as well as high arsenic contamination of soil occur due to copper smelter located in close vicinity to the Srednogorie [372] with a population of 32,000 inhabitants and constituted the largest metallurgical center in Bulgaria. The smelter started operation in 1959 and had been processing high arsenic containing sulde ores, mainly from Tjelopet ch causing contamination of Topolnitza river water having arsenic concentration of 0.75 1.5 mg l 1 during the time period of 19871990. The aerial emission is estimated at 50100 tons per year. Exposure to the general population is mostly by inhalation and partly by ingestion of locally produced food products, like vegetables. Several health hazards are observed around the area of the exposed population with high arsenic content in hair, nails and urine. 4.3. Arsenic contamination from food and be6erage 4.3.1. Soyasauce incident in Japan Several instances of accidental arsenic poisoning through contaminated food-stuffs are reported in Japan. Soyasauce, which contained arsenic at 5.671.6 mg l 1, is implicated in a toxicity outbreak. The arsenic is in the amino acids (260275 mg l 1) used in making the sauce; hydrochloric acid may have been the source of

arsenic in the preparation of amino acid [373]. Mizuta et al. [374] examined 220 out of 417 patients, who had been poisoned by Soyasauce contaminated with inorganic arsenic at a concentration of 0.1 mg l 1. The average estimated injection of arsenic per person was 3 mg, daily for 23 weeks. The main ndings are facial oedema, anorexia, and upper respiratory symptoms followed by skin and neuritic signs at a later stage, i.e. after 1020 days. Though the livers of most patients were enlarged, relatively few abnormalities were found in the liver function tests and liver size gradually decreased after cessation of exposure. Abnormal electrocardiograms are found in 16 out of 20 cases tested [375].

4.3.2. Powdered milk incident in Japan Contaminated powdered milk was implicated in a similar outbreak in Japan. It contains arsenic at 13.521 mg kg 1 [376]. Contamination of the milk is from sodium phosphate (7.11% arsenic) used in its manufacture [377]. 4.3.3. Wine incident in Manchester, England About 500 patients of North England drinking arsenic contaminated beer of 216 pints a day (1.149.12 l per day) for many months developed cardiac, skin, neurological symptoms, either predominated or were equally mixed [378]. Repeated testimony before the Royal commission by various chemists demonstrated repeatedly the presence of toxic amount of arsenic in beer from several parts of the country [379,380]. 4.3.4. Wine Incident in Germany Exposure to arsenic-containing pesticides and contaminated wine is claimed to be the causative factor in the large number of cases of liver cirrhosis among German vintners in the 40s and 50s [381]. It is found that out of 180 vinedressers and sellarman with symptoms of CAP about 23% has evidence of vascular disorders of the extremities [382]. Of 27 moselle vintners autopsied between 1950 and 1956, 11 had lung cancers and three had hepatic angiosarcomas [383]. The number of cases diminished in the late 50s; however, less severe liver changes continued to be found regularly among the vintners [384,385]. In a 19601977

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series of 163 postmortem examinations of German wine growers diagnosed on the basis of cutaneous signs as having had CAP. Luchtrath [386] found ve cases with liver tumors, none were angiosarcomas.

4.3.5. Guizhou Pro6ince, China Incident In the Guizhou province, some coals contain high arsenic (1009600 mg kg 1) and uorine and caused arsenic poisoning among residents in one city and four prefectures. Approximately, 3000 patients were found by 1992. According to the research carried out by the Institute of Geochemistry of the Academia sinica during 1991 and 1994 in Xingren County, among 9202 people investigated, 1546 people were affected by arsenicism. The average daily intake of arsenic per person in the affected area was estimated to be 2.4 mg of which 87.92% came from food, 5.53% from air and 6.55% from drinking water. In additions to skin lesions characteristic of arsenic poisoning, many cases of them are cirrhosis, ascites, polyneutitus and skin cancer. Drastic measures are badly needed to identify alternatives to coal [387]. Zheng and Long [388] and Sun et al. [328] recently report about this incidence. 4.3.6. Yunan Incident, China The typical type of arsenic poisoning was found in 1993 in a non-ferrous smelter township with a population over 100,000 in the southern Yunan province, Dali. The air-arsenic concentration caused by smelter contaminants always exceeded the National maximum allowable (0.003 mg m 3) by several-fold contaminating the food (rice, corn) grown in the area [328]. It (food) is responsible for more than 90% of total arsenic intake, only 10% or less is directly from inhalation. By interpolation, the daily arsenic intake is in the range of 0.3 1.1 mg. In 1992 WHO suggested a daily intake of 2 mg of inorganic arsenic per kg body weight, that should not be exceeded [389].

lows Plaza, Japan for the nancial support to Dr Badal Kumar Mandal who is working in this University. This study was supported by Grantsin-Aid of Ministry of Education, Science, Sports and Culture (Nos. 12000236 and 12470509). Also, the authors thank Dr T. Roy Chowdhury, NIHS, Tokyo, Japan for his cordial help for the preparation of this manuscript. References
[1] E.A. Woolson, ACS Ser. 7 (1975) 1. [2] R.J. Sullivan, National Air Pollution Control Administration Publication No. APTD 69-26, Raleigh, NC, 1969, p. 60. [3] J.O. Nriagu, J.M. Azcue, in: J.O. Nriagu (Ed.), Arsenic in the Environment. Part 1: Cycling and Characterization, John Wiley and Sons, Inc, New York, 1990, pp. 1 15. [4] J.H. Gulledge, J.T. OConnor, J. AWWA (1973) 548. [5] A. Kabata-Pendias, H. Pendias, CRC Press, Boca Raton, FL, 1984, p. 315. [6] R.W. Boyle, I.R. Jonasson, J. Geochem. Explor. 2 (1973) 96. [7] H.A. Tourtelot, Geochem. Cosmochim. Acta 28 (1964) 1579. [8] R.A. Gulbrandsen, Geochem. Cosmochim. Acta 30 (1966) 769. [9] Y. Onishi, Arsenic, in: K.H. Wedephol (Ed.), Handbook of Geochemisty, Berlin, Germany, V-11/3, 33-A-1-33-01, 1978. [10] K.K. Turekian, K.H. Wedepohl, Geol. Soc. Am. Bull. 72 (1961) 175. [11] F.H. Wilson, D.B. Hawkins, Environ. Geol. 2 (1978) 195. [12] L.V. Benson, R.J. Spencer, U.S. Geol. Survey Open File Report, vol. 53, 1983, p. 83. [13] J.G. Boerngen, H.T. Shacklette, U.S. Geol. Survey Open File Report, vol. 143, 1981, p. 81. [14] H. Onishi, Arsenic, in: K.H. Wedepohl (Ed.), Handbook of Geochemistry, Springer-Verlag, New York, 1969, Vol. II-2, Chapter 33. [15] WHO Arsenic Compounds, Environmental Health Criteria 224, 2nd ed., World Health Organisation, Geneva, 2001. [16] V.M. Goldschmidt, Arsenic, in: A. Muir (Ed.), Geochemistry, Clarendon Press, Oxford, 1954 pp. 468 478. [17] H.J.M. Bowen, Elemental Chemistry of the Elements, Academic Press, London and New York, 1979, p. 60. [18] D.E. Backer, L. Chesnin, Adv. Agron 27 (1975) 305. [19] A.P. Vinogradov, The Geochemistry of Rare and Dispersed Chemical Elements in Soils, 2nd ed., New York, 1959, p. 65. [20] P. Collourn, B.J. Alloway, I. Thornton, Sci. Total Environ. 4 (1975) 359.

Acknowledgements The authors acknowledge the help of Japan Society for the Promotion of Science, JSPS Fel-

228

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [52] C.N. Cheng, D.D. Focht, Appl. Environ. Microbiol. 38 (1979) 494. [53] E.A. Crecelius, Thesis, University of Washington, Seattle, Washington, 1974. [54] I. Varsanyi, Arsenic in deep groundwater, in: D.L. Miles (Ed.), Proceedings of the 6th International Symposium on Water Rock Interaction (WRI-6), Malvern, Publisher AA Balkema, Rotterdam/Brookeld, 1989, pp. 715 718. [55] P. Kurttio, H. Komulainen, E. Hakala, H. Kahelin, J. Pekkanen, Arch. Environ. Contam. Toxicol. 34 (1998) 297. [56] G.W. Page, Environ. Sci. Technol. 15 (1981) 1475. [57] A.H. Welch, M.S. Lico, J.L. Hughes, Ground Water 26 (1988) 333. [58] F.N. Robertson, Environ. Geochem. Health 11 (1989) 171. [59] N.E. Korte, Q. Fernando, CRC Crit. Rev. Environ. Control 21 (1991) 1. [60] G. Matisoff, C.J. Khourey, J.F. Hall, A.W. Varnes, W.H. Strain, Ground Water 20 (1982) 446. [61] L.M. Del Razo, M.A. Arellano, M.E. Cebrian, Environ. Pollut. 64 (1990) 143. [62] E. Astol, A. Maccagno, J.C.G. Fernandez, R. Vaccaro, R. Stimola, Biol. Trace Elem. Res. 3 (1981) 133. [63] United Nations Synthesis Report on Arsenic in Drinking Water, 2001. [64] H.B. Nicolli, J.M. Suriano, M.A. Gomez Peral, et al., Environ. Geol. Water Sci. 14 (1989) 13. [65] J. Yinlong, Progress on arsenic research in China, in: M. Kabuto (Ed.), Proceedings of the First International Workshop on Arsenic Pollution of Drinking Water in South Asia and China, National Institute of Environmental Studies, R-166-2001, Tokyo, Japan, 2001, pp. 35 39. [66] S.L. Chen, S.R. Dzeng, M.H. Yang, Environ. Sci. Technol. 28 (1994) 877. [67] B.K. Mandal, T.R. Chowdhury, G. Samanta, G.K. Basu, P.P. Chowdhury, C.R. Chanda, D. Lodh, N.K. Karan, R.K. Dhar, D.K. Tamili, D. Das, K.C. Saha, D. Chakraborti, Curr. Sci. 70 (1996) 976. [68] A. Chatterjee, D. Das, D. Chakraborti, Environ. Pollut. 80 (1993) 57. [69] R.K. Dhar, B.K. Biswas, G. Samanta, B.K. Mandal, D. Chakraborti, S. Roy, A. Fafar, A. Islam, G. Ara, S. Kabir, A.W. Khan, S.A. Ahmed, S.A. Hadi, Curr. Sci. 73 (1997) 48. [70] M. Williams, F. Fordyce, A. Paijitprapapon, P. Charoenchaisri, Environ. Geol. 27 (1996) 16. [71] H. Kondo, Y. Ishiguro, K. Ohno, M. Nagase, M. Toba, M. Takagi, Water Res. 33 (1999) 1967. [72] M. Berg, H.C. Tran, T.C. Nguyen, H.V. Pham, R. Schertenleib, W. Giger, Environ. Sci. Tech. 35 (2001) 2621. [73] U.S. Environmental Protection Agency, Interim Primary Drinking Water Standards, Fed. Reg. 40 (1975) 11,990. [74] D.L. Johnson, Nature 240 (1972) 44.

[21] P.J. Peterson, L.M. Benson, R. Zeive, Metalloids, in: M.W. Lepp (Ed.), Arsenic and Effect of Heavy Metal Pollution on Plants, vol. 1, Appl. Sci. Publ, London, 1981, p. 299. [22] D. Chakraborti, G.K. Basu, B.K. Biswas, U.K. Chowdhury, M.M. Rahman, K. Paul, T. Roy Chowdhury, C.R. Chanda, D. Lodh, Characterization of arsenic bearing sediments in Gangetic delta of West Bengal-India, in: W.R. Chappell, C.O. Abernathy, R.L. Calderon (Eds.), Arsenic Exposure and Health Effects, Elsevier, Amsterdam, Lausanne, New York, Oxford, Tokyo, 2001, pp. 27 52. [23] R.T. Nickson, J.M. McArthur, P. Ravenscroft, W.G. Burgess, K.M. Ahmed, Appl. Geochem. 15 (2000) 403. [24] F. Reichert, R.A. Trelles, An. Asoc. Quim. Argent. 9 (1921) 89. [25] F.S. Wei, C.J. Zheng, J.S. Chen, Y.Y. Wu, Huanjing Kexue 12 (1991) 12. [26] E. Dulho, Bull. Soil Pharm. Bordeaux (1936). [27] G. Lockemann, Biochemistry 207 (1929) 194. [28] G. Zuccuri, Gazz. Chim. Ital. 43 (1913) 398. [29] K. Iimura, Jpn. Sci. Soc. Press, Tokyo, 1981, p. 19. [30] R.R. Whetstone, W.O. Robinson, H.G. Byers, U.S. Dep. Agric. Tech. Bull. 797 (1942) 32. [31] Copeman, Union S. Africa Dept. Agric. Sci. Bull. 252 (1945 1946) 5. [32] T.U. Fellenberg, Biochemistry Z218 (1930) 300. [33] C.S. Stater, R.S. Holmes, H.G. Byers, U.S. Dept. Agri. Tech. Bull. 552 (1937) 23. [34] J.J. Conner, H.T. Shacklette, U.S. Govern. Printing Ofce, Washington DC, 1975. [35] S. Tang, Acta Sci. Circumstantiae 7 (1987) 245. [36] S. Tang, Huanjing Kexue 6 (1985) 2. [37] Y.Y. Wu, J Environ. Sci. (China) 2 (1990) 55. [38] M. Shibuya, Sangyo Tosho City, 1979, p. 262. [39] K.J. Irgolic, H. Greschonig, A.G. Howard, Arsenic in: A. Townshend (Ed.), The Encyclopedia of Analytical Science, Academic Press, 1995, pp. 168 184. [40] F.M. Fordyce, T.M. Williams, A. Paijitpapapon, P. Charoenchaisei, British Geol. Survey, Keyworth, 1995. [41] X.G. Li, Turang Xuebao 19 (1982) 360. [42] J.E. Fergusson, The Heavy Elements: Chemistry, Environmental Impact and Health Effects, Pergamon Press, Great Britain, 1990, p. 614. [43] L.M. Walsh, D.R. Keeney, ACS Symp. Ser. 7 (1975) 35. [44] Z.M. Xie, Z.X. Zhu, K.N. Yuan, C.Y. Huaug, Huanjing Huaxue 8 (1989) 1. [45] W.R. Cullen, K.J. Reimer, Chem. Rev. 89 (1989) 713. [46] E.A. Woolson, J.H. Axley, P.C. Kearney, Environ. Sci. Technol. 7 (1973) 47. [47] B.C. McBride, R.S. Wolfe, Biochemistry 10 (1971) 4312. [48] B. Goiso, Rir Igiene Sanit Pubbl. III (8/9) (1892) 201. [49] C. Thom, K.B. Raper, Arsenic Fungi Gosio Sci. 76 (1932) 548. [50] D.P. Cox, M. Alexander, Appl. Microbiol. 25 (1973) 408. [51] E.A. Woolson, Weed Sci. 25 (1977) 412.

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [75] J.M. Harrington, J.P. Middaugh, D.L. Morse, J. Houseworth, Am. J. Epidemiol. 108 (1978) 377. [76] P.L. Smedley, W.M. Edmunds, K.B. Pelig-Ba, in: J.D. Appleton, R. Fuge, G.J.H. McCall (Eds.), Environmental Geochemistry and Health, vol. 113, Geological Society Special Publication, London, 1996, p. 153. [77] J.A. Ritchie, N.Z. J. Sci. 4 (1961) 218. [78] H. Nakahara, M. Yanokura, Y. Murakami, Anal. Chem. 45 (1978) 25. [79] C.I. Davidson, W.D. Goold, T.P. Mathison, G.B. Wiersma, K.W. Brown, M.T. Reilly, Environ. Sci. Technol. 19 (1985) 27. [80] Guidelines for Drinking Water Quality, Recommendations, 2nd ed., vol. 2, World Health Organisation, Geneva, 1996. [81] F.W. Pontius, K.G. Broun, C.J. Chen, J. AWWA 86 (1994) 52. [82] Arsenic, Environmental Health Criteria 18, World Health Organisation, Geneva, 1981. [83] J.D. Zuane, Handbook of Drinking Water Quality, Standards and Controls, 1990. [84] DG Environment, Ambient air pollution by As, Cd and Ni compounds, Position Paper, Working Group on Arsenic, Cadmium and Nickel Compounds, DG Environment European Commission, 2000. [85] Feed Additive Compendium, vol. 13, Munneapolis, The Miller Publishing Company, 1975, p. 330. [86] H.J.M. Bowen, Trace Elements in Biochemistry, Academic Press, London and New York, 1966, p. 16, 19, 31, 39, 75, 174, 175. [87] R.W. Whitacre, C.S. Pearse, Arsenic and the Environment, Mineral Industries Bulletin, Colorado, School of Mines, 1972, p. 1. [88] H. Smith, Forensic Sci. Soc. 4 (1964) 192. [89] E.F. Pearson, C.A. Pounds, J. Forensic Sci. Soc. 11 (1971) 229. [90] H.L. Arnold, R.B. Odam, W.D. James, Disease of the skin Clinical Dermatology, 8th ed., Saunders W.B. Company, Philadelphia 1990, p. 121. [91] L. Van Itallie, Pharm. Weekblad 69 (1932) 1134. [92] D.N. Guha Mujumder, A.K. Chakraborty, A. Ghosh, J.D. Gupta, D.P. Chakraborty, S.B. Dey, N. Chattopadhyay, Bull. World Health Organ. 66 (1988) 499. [93] R.R. Lauwerys, J.P. Buchet, H. Roels, Arch. Toxicol. 41 (1979) 239. [94] E.A. Woolson, in: W.H. Lederer, R.J. Fensterheim (Eds.), Industrial, Biomedical and Environmental Perspective, Van Nostrand Reinhold Company, New York, 1983, p. 393. [95] W.T. Piver, Top. Environ. Health 6 (1983) 1. [96] E.A. Woolson, Top. Environ. Health 6 (1983) 51. [97] K.W. Nelson, Environ. Health Perspect. 19 (1977) 31. [98] U.S. Department of the Interior Bureau of Mines, in: Minerals Yearbook, vol. 1, 1973, p. 1360. [99] B.L. Vallee, D.D. Ulmer, W.E.C. Wacker, Arch. Ind. Health 21 (1960) 132. [100] W.T. Thompson, Agricultural Chemicals Book 1, Insec-

229

[101]

[102] [103]

[104] [105] [106] [107] [108] [109]

[110] [111] [112] [113] [114] [115] [116] [117]

[118] [119]

[120] [121] [122] [123] [124] [125] [126] [127]

ticides, Indianpolis, Thompson Publication, Washington, 1973, p. 300. A.M. Lansche, Bureau of Mines, Bulletin 630, U.S. Department of the Interior, Washington DC, 1965, p. 75. U.S. Department of Agriculture, The Pesticides Review, 1970, p. 46. Environmental Protection Agency, Ambient Water Quality Criteria for Arsenic, U.S. Environ. Prot. Agency Rep., 440/5-80-021, 1980, p. 1. R.S. Baker, H.F. Arle, J.H. Miller, J.T. Halstun, Weed Sci. 17 (1969) 37. C.L. Perker, USEPA Contract No. 68-01-5965, The Mitre Corporation, 1981, p. 1. U.S. Department of Agriculture, Wood Preservatives, in: The Pesticide Review, Washington DC, 1974, p. 21. Arsenic-eaters, Boston Med. Surg. J. 51 (1854) 189. T. Sollman, A Manual of Pharmacology, WB Saunders Company, Philadelphia, 1957. G.O. Doak, L.D. Freedman, in: A. Burger (Ed.), Medicinal Chemistry, Wiley Inter Science, New York, 1970, pp. 610 625. R.J. Sullivan, Administration Publication No. APTD 69-26, Releigh, NC, 1969, p. 60. M.N. Bates, A.M. Smith, C.H. Rick, Am. J. Epidemiol. 135 (1992) 462. H. Marcelet, Bull. Sci. Pharmacol. 20 (1913) 271. R.C. Wester, H.I. Maibach, L. Sedik, J. Melendres, M. Wade, Fundam. Appl. Toxicol. 20 (1993) 336. G. Lugo, G. Cassady, P. Palmisano, Ann. J. Dis. Child 117 (1969) 328. C.T. Bollinger, P. Van Zijl, J.A. Louw, Respiration 59 (1992) 57. G. Concha, B. Nermell, M. Vahter, Toxicol. Sci. 44 (1998) 185. J.T. Stevens, L.L. Hall, J.D. Farmer, L.C. DiPasquale, N. Chernoff, W.F. Durham, Environ. Health Perspect. 19 (1977) 151. P.W.S. Chiou, K.L. Chen, B. Yu, J. Sci. Food Agric. 74 (1997) 229. S.M. Nagvi, C. Vaishnavi, H. Singh, Toxicity and metabolism of arsenic in vertebrates, in: J.O. Nriagu (Ed.), Arsenic in the Environment. Part II: Human Health and Ecosystem Effects, John Wiley and Sons, Inc, New York, 1994, pp. 55 91. R.M. Raie, Ecotoxicol. Environ. Safety 35 (1996) 248. E. Marafante, F. Bertolero, J. Edel, R. Pietra, E. Sabbioni, Sci. Total Environ. 24 (1982) 27. M. Vahter, E. Marafante, L. Dencker, Arch. Environ. Contam. Toxicol. 13 (1984) 259. J.P. Buchet, R. Lauwerys, H. Roels, Int. Arch. Occup. Environ. Health 48 (1981) 71. B.K. Mandal, Y. Ogra, K.T. Suzuki, Chem. Res. Toxicol. 14 (2001) 371. X.C. Le, X. Lu, M. Ma, W.R. Cullen, H.V. Aposhian, B. Zheng, Anal. Chem. 72 (2000) 5172. M. Vahter, J. Envall, Environ. Res. 32 (1983) 14. R.M. Brown, D. Newton, C.J Pickford, J.C. Sherlock, Hum. Exp. Toxicol. 9 (1990) 41.

230

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [153] BGS and DPHE, 2001. [154] S.L. Chen, S.R. Dzeng, M.H. Yang, K.H. Chiu, G.M. Shieh, C.M. Wai, Environ. Sci. Technol. 28 (1994) 877. [155] X.C. Le, M. Ma, W.R. Cullen, H.V. Aposhian, X. Lu, B. Zheng, Environ. Health Perspect. 108 (2000) 1015. [156] H.V. Aposhian, B. Zheng, M.M. Aposhian, X.C. Le, M.E. Cebrian, W.R. Cullen, R.A. Zakharyan, M. Ma, R.C. Dart, Z. Cheng, P. Andrewes, L. Yip, G.F. OMalley, R.M. Maiorino, W.V. Voorhies, S.M. Healy, A. Titcomb, Toxicol. Appl. Pharmacol. 165 (2000) 74. [157] H.V. Aposhian, E.S. Gurzau, X.C. Le, A. Gurzau, S.M. Healy, X. Lu, M. Ma, L. Yip, R.A. Zakharyan, R.M. Maiorino, R.C. Dart, M.G. Tircus, D. GonzalezRamirez, D.L. Morgam, D. Avram, M.M. Aposhian, Chem. Res. Toxicol. 13 (2000) 693. [158] L.M. Del Razo, M. Styblo, W.R. Cullen, D.J. Thomas, Toxicol. Appl. Pharmacol. 174 (2001) 283. [159] J.S. Petrick, F. Ayala-Fierro, W.R. Cullen, D.E. Carter, H.V. Aposhian, Toxicol. Appl. Pharmacol. 163 (2000) 203. [160] S. Lin, W.R. Cullen, D.J. Thomas, Chem. Res. Toxicol. 12 (1999) 924. [161] M. Styblo, S.V. Serves, W.R. Cullen, D.J. Thomas, Chem. Res. Toxicol. 10 (1997) 27. [162] M. Styblo, L.M. Del Razo, L. Vega, D.R. Germolec, E.L. LeCluyse, G.A. Hamilton, W. Reed, C. Wang, W.R. Cullen, D.J. Thomas, Arch. Toxicol. 74 (2000) 289. [163] L. Vega, M. Styblo, R. Patterson, W.R Cullen, C. Wang, D. Germolec, Toxicol. Appl. Pharmacol. 172 (2001) 225. [164] M.J. Mass, A. Tennant, B.C. Roop, W.R. Cullen, M. Styblo, D.J. Thomas, A.D. Kligerman, Chem. Res. Toxicol. 14 (2001) 355. [165] R.M. Johnstone, Sulfhydryl agents: arsenicals, in: R.M. Hochster, J.H. Quastel (Eds.), Metabolic Inhibitors: A Comprehensive Treatise, vol. 2, Academic Press, New York, 1963, pp. 99 118. [166] G.W.F. Pauwels Borst, J.K. Peter, S. Jager, C.C.B. Wijffels, Biochim. Biophys. Acta 94 (1965) 312. [167] J.M. Ginsburg, W.D. Lotspeich, Am. J. Physiol. 205 (1963) 707. [168] H.V. Aposhian, Rev. Biochem. Toxicol. 10 (1989) 265. [169] J.C. Belton, N.C. Benson, M.L. Hanna, R.T. Taylor, J. Environ. Sci. Health 20A (1985) 37. [170] H. Wolochow, E.M. Putman, M. Domdoroff, W.Z. Hassid, H.A. Barker, J. Biol. Chem. 180 (1949) 1237. [171] R.A. Peters, Sym. Soc. Exp. Biol. 3 (1949) 36. [172] H.B.F. Dixon, Adv. Inorg. Chem. 44 (1997) 191. [173] J. Elder, T.T. Davies, Draft drinking water criteria, Document on Arsenic, U.S. EPA, Under EPA Contract No. 68-C8-0033, Washington DC, 20460, VIII-4, 1993, p. 1. [174] E.M. Kenyon, M.F. Hughes, O.A. Levander, J. Toxicol. Environ. Health 51 (1997) 279. [175] H. Kreppel, J. Liu, Y. Liu, F.X. Reichl, C.D. Klaassen, Fundam. Appl. Toxicol. 23 (1994) 32.

[128] G.K.H. Tam, S.M. Charbonneau, F. Bryce, C. Pomroy, E. Sandi, Toxicol. Appl. Pharmacol. 50 (1979) 319. [129] J.P. Buchet, R. Lauwerys, H. Roels, Arch. Occup. Environ. Health 48 (1981) 111. [130] G.K.H. Tam, S.M. Charbonneau, F. Brice, E. Sandi, Bull. Environ. Contam. Toxicol. 28 (1982) 69. [131] E. Marafante, M. Vahter, H. Norin, J. Envall, M. Sandstrom, A. Christakopoulos, R. Ryhage, J. Appl. Toxicol. 7 (1987) 111. [132] H. Yamauchi, T. Kaise, K. Takahashi, Y. Yamamura, Fundam. Appl. Toxicol. 14 (1990) 399. [133] V. Benko, A. Dobisova, M. Macaj, Atmos. Environ. 5 (1971) 275. [134] P. Grandjean, P. Weihe, L.L. Needham, V.W. Burse, D.G. Patterson, E.J. Sampson, P.J. Jorgensen, M. Vahter, Environ. Res. 71 (1995) 29. [135] G. Concha, G. Vogler, B. Nermell, M. Vahter, Int. Arch. Occup. Environ. Health 71 (1998) 42. [136] M.J. Ellenhorn, Arsenic, in: Ellenhorns Medical Toxicology: Diagnosis and Treatment of Human Poisoning, 2nd ed., Williams and Wilkins, Baltimore, 1997, p. 1538. [137] ATSDR toxicological prole for arsenic, Agency for Toxic Substances and Disease Registry, Atlanta, Georgia, U.S. Department of Health and Human Services, TP-92/02, 1993. [138] W.R. Cullen, K.J. Reimer, Chem. Rev. 89 (1989) 713. [139] T. Kaise, S. Fukui, Appl. Organomet. Chem. 6 (1992) 155. [140] X.C. Le, W.R. Cullen, K.J. Reimer, Environ. Sci. Technol. 28 (1994) 1598. [141] J.P. Buchet, D. Lison, M. Ruggeri, V. Foa, G. Elia, Arch. Toxicol. 70 (1996) 773. [142] X.C. Le, W.R. Cullen, K.J. Reimer, Clin. Chem. 40 (1994) 617. [143] M. Ma, S.C. Le, Clin. Chem. 44 (1998) 539. [144] J.T. Hindmarsh, R.F. McCurdy, Crit. Rev. Clin. Lab. Sci. 23 (1986) 315. [145] L. Vega, M. Styblo, R. Patterson, W. Cullen, C. Wang, D. Germolec, Toxicol. Appl. Pharmacol. 172 (2001) 225. [146] S. Maeda, Biotransformation of arsenic in the freshwater environment, in: J.O. Nriagu (Ed.), Arsenic in the Environment Part I, Cycling and Characterization, Wiley, New York, 1994, pp. 155 187. [147] E. Marafante, M. Vahter, J. Envall, Chem. Biol. Interact. 56 (1985) 225. [148] M. Vahter, E. Marafante, Arch. Toxicol. 57 (1985) 119. [149] K.C. Saha, J.C. Saha, A.K. Dikshit, M. Bandyapadhyay, Environ. Sci. Technol. 29 (1999) 281. [150] NRC (National Research Council), Arsenic in Drinking Water, National Academy Press, Washington DC, 1999. [151] K.C. Saha, Seventeen years experiences in arsenicosis in West Bengal, India, in: W.R. Chappell, C.O. Abernathy, R.L Calderon (Eds.), Arsenic Exposure and Health Effects, Elsevier Science, Amsterdam, Lausanne, New York, Oxford, Tokyo, 2001, pp. 387 396. [152] A. Chatterjee, D. Das, B.K. Mandal, T. Toy Chowdhury, G. Samanta, D. Chakraborti, Analyst 120 (1995) 643.

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [176] O. Ramos, L. Carrizales, L. Yanez, J. Mejia, L. Batres, D. Ortiz, F. Diaz-Barriga, Environ. Health Perspect. 103 (1) (1995) 85. [177] L. Gerhardsson, E. Dahlgren, A. Eriksson, B.E.A. Lagerkvist, J. Lundstrom, G.P. Nordberg, Scan. J. Work Environ. Health 14 (1988) 130. [178] W.E. Morton, D.A. Dunnette, in: J.O. Nriagu (Ed.), Arsenic in the Environment. Part 11: Human Health and Ecosystem Effects, John Wiley and Sons, Inc, New York, 1994, pp. 17 34. [179] D.N. Guha Mazumder, R. Haque, N. Ghosh, B.K. De, A. Santra, D. Chakraborti, A.H. Smith, Int. J. Epidemiol. 29 (2000) 1047. [180] A.H. Milton, Z. Hasan, A. Rahman, M. Rahman, J. Occup. Health 43 (2001) 136. [181] J.M. Borgono, P. Vincent, H. Venturino, Environ. Health Perspect. 19 (1977) 103. [182] D.N. Guha Mazumder, J. Das Gupta, A. Santra, A. Pal, A. Ghose, S. Sarkar, N. Chattapadhaya, D. Chakraborti, Non-cancer effects of chronic arsenicosis with special reference to liver damage, in: C.O. Abernathy, R.L. Calderon, W.R. Chappell (Eds.), ArsenicExposure and Health Effects, Chapman and Hall, London, 1997, p. 112. [183] B.E.A. Lagerkvist, H. Linderholm, G.F. Nordberg, Int. Arch. Occup. Environ. Health 60 (1988) 361. [184] R. Zaldivar, Beitr. Pathol. 151 (1974) 384. [185] C.J. Chen, Y.M. Hsueh, M.S. Lai, M.P. Shyu, S.Y. Chen, M.M. Wu, T.L. Kuo, T.Y. Tai, Hypertension 25 (1995) 53. [186] M. Rahman, M. Tondel, et al., Hypertension 33 (1999) 74. [187] H.H. Goebel, P.F. Schmidt, J. Bohl, B. Tettenborn, G. Kramer, L. Guttman, J. Neuropathol. Exp. Neurol. 49 (1990) 137. [188] C.W. Armstrong, R.B. Stroube, T. Rubio, W.S. Beckett, Arch. Environ. Health 39 (1984) 274. [189] A. Franzblau, R. Lilis, Arch. Environ. Health 44 (1989) 385. [190] F.S. Glazener, J.G. Ellis, P.K. Johnson, Calif. Med. 109 (1968) 158. [191] C.W. Armstrong, R.B. Stroube, T. Rubio, W.S. Backett, Arch. Environ. Health 39 (1884) 276. [192] B.B. Lerman, N. Ali, D. Green, Anal. Clin. Lab. Sci. 10 (1980) 515. [193] Environmental Protection Agency (EPA), Health Assessment Document for Inorganic Arsenic, Final Report, EPA 600/8-83-021F, USEPA, Environmental Criteria and Assessment Ofce, Research Triangle Park, NC, 1984. [194] S.L. Winski, D.E. Carter, J. Toxicol. Environ. Health 53 (1998) 345. [195] Y. Shiobara, Y. Ogra, K.T. Suzuki, Chem. Res. Toxicol. 14 (2001) 1446. [196] T.W. Clarkson, Inorganic and organometal pesticides, in: W.J. Hayes Jr. (Ed.), Handbook of Pesticide Toxicology, Academic Press, San Diego, 1991, pp. 545 552.

231

[197] D.N. Guha Mazumder, J. Indian Med. Assoc. 99 (2001) 311. [198] A. Santra, A. Maity, S. Das, et al., Clin. Toxicol. 38 (2000) 395. [199] A. Santra, J. Das Gupta, B.K. De, et al., Ind. Soc. Gastroenterol. 18 (1999) 152. [200] K.A. Winship, Adv. Drug React. 3 (1984) 129. [201] A.K. Chakraborty, K.C. Saha, Indian J. Med. Res. 85 (1987) 326. [202] G. Ding, et al., J. China Med. Univ. 16 (1987) 368. [203] A. Franzblau, R. Lilis, Arch. Environ. Health 44 (1989) 385. [204] M. Franklin, W. Bean, R.C. Harden, Am. J. Med. Sci. 219 (1950) 589. [205] C.W. Ide, G.R. Bullough, J. Soc. Occup. Med. 38 (1988) 85. [206] W.L. Schoolmeester, D.R. White, South Med. J. 73 (1980) 198. [207] A. Giberson, N.D. Vaziri, K. Mirahamadi, S.M. Rosen, Arch. Intern. Med. 136 (1976) 1303. [208] R.E. Gerhardt, J.B. Hudson, R.N. Rao, R.E. Sobel, Arch. Intern. Med. 138 (1978) 1267. [209] C. Hopenhayn-Rich, M.L. Biggs, A.H. Smith, Int. J. Epidemiol. 27 (1998) 561. [210] D.N. Guha Mazumder, J. Assoc. Phys. India 49 (2001) 650. [211] D.N. Guha Mazumder, B.K. De, A. Santra, J. Dasgupta, N. Ghosh, B.K. Roy, U.C. Ghoshal, J. Saha, A. Chatterjee, S. Dutta, R. Haque, A.H. Smith, D. Chakraborti, C.R. Angle, J.A. Centeno, Chronic arsenic toxicity epidemiology, natural history and treatment, in: W.R. Chappell, C.O. Abernathy, R.L. Calderon (Eds.), Arsenic Exposure and Health Effect, Elsevier, Amsterdam, Lausanne, New York, Oxford, Tokyo, 1999, pp. 335 347. [212] A.H. Smith, A.P. Arroyo, D.N. Guha Mazumder, M.J. Kosnett, Environ. Health Perspect. 108 (2000) 617. [213] P.C. Paul, A. Chattopadhyay, S.K. Dutta, et al., Ind. J. Pathol. Microbiol. 43 (2000) 257. [214] H. Ahsan, M. Perrin, A. Rahman, A. Rahman, F. Parvez, M. Stute, Y. Zheng, A.H. Milton, P. BrandtRauf, A. van Geen, J. Graziano, J. Occup. Environ. Med. 42 (2000) 1195. [215] A.H. Milton, M. Rahman, J. Occup. Health 41 (1999) 207. [216] M. Tondel, M. Rahman, A. Magnuson, I.A. Chowdhury, M.H. Faruquee, S.A. Ahmad, Environ. Health Perspect. 107 (1999) 727. [217] J.W. Southwick, A.E. Western, M.M. Beck, Community health associated with arsenic in drinking water in Millard Country, Utah, EPA-600/1-81-064, NTIS No. PB82-108374, USEPA, Health Effects Laboratory, Cincinnati, OH, 1981. [218] J.L. Valentine, L.S. Reisbord, H.K. Kang, M.D. Schluchter, Arsenic effects of population health histories, in: C.F. Mills, I.M. Bremner, K.J. Chesters (Eds.), Trace Elements in Man and Animals, Commonwealth Agricultural Bureau, Slough, UK, 1985, pp. 289 294.

232

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [248] G.R. Hoffman, Genetic toxicology, in: M.O. Amdur, J. Doull, C.D. Klaassen (Eds.), Toxicology, Pergamon Press, New York, 1991, pp. 201 225. [249] R.A. Goyer, Toxic effect of metals, in: M.O. Amdur, J. Doull, C.D. Klaassen (Eds.), Toxicology, Pergamon Press, New York, 1991, pp. 629 633. [250] A.L. Cantellano, G. Viniegra, G.R. Eslava, A.J. Alvarez, Salud. Publ. Mex. 6 (1964) 375. [251] V. Bencko, V. Wagner, M. Wagnerova, J. Botora, J. Hyg. Epidemiol. Microbial. Immunol. 32 (1988) 137. [252] E. Astol, A. Maccagno, J.C.G. Fernandez, R. Vaccaro, R. Stimola, Biol. Trace Elem. Res. 3 (1981) 133. [253] I. Nordenson, L. Beckman, Hum. Hered. 41 (1991) 71. [254] J. Hutchinson, Br. Med. J. 2 (1887) 1280. [255] C.J. Chen, M.M. Wu, S.S. Lee, J.D. Wang, S.H. Cheng, H.Y. Wu, Arteriosclerosis 8 (1988) 452. [256] K.H. Morales, L. Ryan, T.L. Kuo, M.M. Wu, C.J. Chen, Environ. Health Perspect. 108 (2000) 655. [257] IARC arsenic and arsenic compounds, in: IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans: Some Metals and Metallic Compounds, vol. 23, International Agency for Research on Cancer, Lyon, 1980, p. 39. [258] C. Hopenhayn-Rich, M.L. Biggs, A. Fuchs, R. Bergoglio, E.E. Tello, H. Nicolli, A. Smith, Epidemiology 7 (1996) 117. [259] D.R. Lewis, J.W. Southwick, L.P. Scanlan, J. Rench, R.L. Calderon, J. Environ. Health 60 (1998) 14. [260] A. Lee-Feldstein, J. Occup. Med. 28 (1986) 296. [261] G.F. Nordberg, O. Anderson, Environ. Health Perspect. 40 (1981) 65. [262] D. Jacobson-Kram, D. Montalbano, Environ. Mutagen. 7 (1985) 787. [263] M.S. Lai, Y.M. Hsueh, C.J. Chen, M.P. Shyu, S.Y. Chen, T.L. Kuo, M.M. Wu, T.Y. Tai, Am. J. Epidemiol. 139 (1994) 484. [264] S.M. Tsai, T.N. Wang, Y.C. Ko, Arch. Environ. Health 54 (1999) 186. [265] C.H. Tseng, C.K. Chong, L.T. Heng, C.P. Tseng, T.Y. Tai, Diabetes Res. Clin. Pract. 50 (Suppl. 2) (2000) 61. [266] M. Rahman, M. Tondel, S.A. Ahmad, O. Axelson, Am. J. Epidemiol. 148 (1998) 198. [267] M. Rahman, M. Tondel, Occup. Environ. Med. 56 (1999) 277. [268] D.R. Lewis, R. Calderon, J.W. Southwick, R. OuelletHelstrom, J. Rench, Environ. Health Perspect. 107 (1999) 359. [269] M. Rahman, G. Wingren, O. Axelson, Scand. J. Work Environ. Health 22 (1996) 146. [270] O. Axelson, E. Dahlgren, C.D. Jansson, S.O. Rehnlund, Br. J. Ind. Med. 35 (1978) 8. [271] C.O. Abernathy, Y.P. Lui, D. Longfellow, H.V. Aposhian, B. Beck, B. Fowler, R. Goyer, R. Menzer, T. Rossman, C. Thompson, M. Waalkes, Environ. Health Perspect. 107 (1999) 593. [272] P. Kulanthaivel, B.J. Simon, F.H. Leibach, Biochim. Biophys. Acta 1024 (1990) 385.

[219] R.L. Shannon, D.S. Strayer, Hum. Toxicol. 8 (1989) 198. [220] A.B. Cannon, N.Y. State J. Med. 36 (1936) 219. [221] R.M. Adams, Occupational Skin Disease, 2nd ed., Saunders, Philadelphia, 1990, p. 147. [222] D.A. Grantham, J.F. Jones, J. Am. Water Works Assoc. 69 (1977) 653. [223] S.L. Wagner, J.S. Malinder, W.E. Morton, R.S. Braman, Arch. Dermatol. 115 (1979) 1205. [224] P.N. Chhuttani, L.S. Chawla, T.D. Sharma, Arsenical Neuropathy Neurol. 17 (1967) 269. [225] S.K. Bansal, N. Haldar, U.K. Dhand, et al., Int. J. Dermatol. 30 (1991) 304. [226] W.E. Morton, G.A. Coron, Am. J. Ind. Med. 15 (1989) 1. [227] D. Base, J. Das Gupta, A. Mukherjee, D.N. Guha Mazumder, J. ANEI (1996) 45. [228] S. Zierler, M. Theodore, A. Cohen, Int. J. Epidemiol. 17 (1988) 589. [229] S. Nordstrom, L. Beckman, I. Nordenson, Hereditas 88 (1978) 43. [230] S. Nordstrom, L. Beckman, I. Nordenson, Hereditas 90 (1979) 297. [231] S. Nordstrom, L. Beckman, I. Nordenson, Hereditas 90 (1979) 291. [232] A. Aschengran, S. Zierler, A. Cohen, Arch. Environ. Health 44 (1989) 283. [233] E.J. Calabrese, P.T. Kostecki, C.E. Gilbert, Comments Toxicol. 1 (1987) 229. [234] J. La Dou, Scan. J. Environ. Health 9 (1983) 42. [235] K.S. Squibb, B.A. Fowler, The toxicity of arsenic and its compounds, in: B.A. Fowler (Ed.), Biological and Environmental Effects of Arsenic, Elsevier, New York, 1983, pp. 233 269. [236] A. Leonard, R.R. Lauwerys, Mutat. Res. 75 (1980) 49. [237] S. Tabacova, D.D. Baird, L. Balabaeva, D. Lolova, I. Petrov, Placenta 15 (1994) 873. [238] V. Benko, V. Wagner, M. Wagnerova, J. Batora, J. Hyg. Epidemiol. Microbiol. Immunol. 32 (1988) 137. [239] M. McCabe, D. Maguire, M. Nowak, Environ. Res. 31 (1983) 323. [240] R. Stockman, Br. Med. J. 18 (1902) 1227. [241] M.E. Gonsebatt, L. Vega, R. Montero, G. Garcia-Vargas, L.M. Del Razo, A. Albores, M.E. Cebrian, Mutat. Res. 313 (1994) 293. [242] T. Okui, Y. Fujiwara, Mutat. Res. 172 (1986) 69. [243] J.C. Barrett, P.W. Lamb, T.C. Wang, T.C. Lee, Biol. Trace Elem. Res. 21 (1989) 421. [244] G. Endo, K. Kuroda, A. Okamoto, S. Horiguchi, Bull. Environ. Contam. Toxicol. 48 (1992) 131. [245] N. Eguchi, K. Kuroda, A. Okamoto, S. Horiguchi, Arch. Environ. Contam. Toxicol. 32 (1997) 141. [246] M.M. Moore, K. Harrington-Brock, C.L. Doerr, Mutat. Res. 386 (1997) 279. [247] L. Bernstam, J. Nriagu, J. Toxicol. Environ. Health B Crit. Rev. 3 (2000) 293.

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [273] F.Z. Sheabar, S. Yanni, Vet. Hum. Toxicol. 31 (1989) 528. [274] S. Taketani, H. Kohno, T. Yoshinaga, R. Tokunaga, Aust. N.Z. J. Med. 19 (1989) 730. [275] F.W. Sunderman, Fed. Proc. 37 (1978) 40. [276] H.B.F. Dixon, Adv. Inorg. Chem. 44 (1997) 191. [277] M. Chen, L.Q. Ma, C.G. Hoogeweg, W.G. Harris, Environ. Forensics 2 (2001) 117. [278] I. Thornton, M. Farago, The geochemistry of arsenic, in: C.O. Abernathy, R.L. Calderon, W.R. Chappell (Eds.), Arsenic: Exposure and Health Effects, Chapman and Hall, Kluwer Academic Publishers, London, 1997, pp. 1 16. [279] S. Yeh, The Conference on Botany of Cutaneous Cancer, Philadelphia, Penns, April 6 11, 1962. [280] W.P. Tseng, H.M. Chu, S.W. How, J.M. Fong, C.S. Lin, S. Yeh, J. Natl. Cancer Inst. 40 (1968) 453. [281] C.J. Chen, T.L. Kuo, M.M. Wu, Lancet 1 (1988) 414. [282] S.M. Tsai, T.N. Wang, Y.C. Ko, J. Toxicol. Environ. Health A 55 (1998) 389. [283] H.R. Guo, H.S. Chiang, H. Hu, S.R. Lipsitz, R.R. Monson, Epidemiology 8 (1997) 545. [284] M.N. Bates, A.H. Smith, C. Hopenhayn-Rich, Am. J. Epidemiol. 135 (1992) 462. [285] F.J. Lu, C.K. Yang, K.H. Lin, J. Formosan. Med. Assoc. 79 (1975) 596. [286] M.M. Wu, T.L. Kuo, Y.H. Hwang, C.J. Chen, Am. J. Epidemiol. 130 (1989) 1123. [287] F.J. Lu, Lancet 336 (1990) 115. [288] J.M. Borgono, R. Greiber, Env. Health, D.D. Hemphill (Ed.), University of Missouri, 1972, p. 13. [289] A.H. Smith, M. Goycolea, R. Haque, M.L. Biggs, Am. J. Epidemiol. 147 (1998) 660. [290] L. Caceres, E. Gruttner, R. Cantreras, Ambio. 21 (1992) 138. [291] Arsenic Pollution in Groundwater in West Bengal June, Steering Committee, Arsenic Investigation Project, PHED, Government of West Bengal, 1991. [292] U.K. Chowdhury, M.M. Rahman, B.K. Mandal, K. Paul, D. Lodh, B.K. Biswas, G.K. Basu, C.R. Chanda, K.C. Saha, S.C. Mukherjee, S. Roy, R. Das, I. Kaies, A.K. Barua, S.K. Palit, Q. Quamruzzaman, D. Chakraborti, Environ. Sci. 8 (2001) 393. [293] D. Das, G. Samanta, B.K. Mandal, T. Roy Chowdhury, C.R. Chanda, P.P. Chowdhury, G.K. Basu, D. Chakraborti, Environ. Geochem. Health 18 (1996) 5. [294] P. Bhattacharaya, D. Chatterjee, G. Jacks, Water Res. Dev. 13 (1997) 79. [295] M.E. Cebrian, A. Albores, M. Aguilar, E. Blakely, Hum. Toxicol. 23 (1983) 121. [296] L.M. Del Razo, J.C. Corona, V.G. Garcia, A. Albores, M.E. Cebrian, Environ. Pollut. 80 (1993) 91. [297] A. Albores, M.E. Cebrian, I. Tellez, B. Valdez, Bol. Sanit. Panam. 86 (1979) 196. [298] M.E. Cebrian, A. Albores, M. Aguilar, E. Blakely, Hum. Toxicol. 2 (1983) 121. [299] R. Biagni, La Semana Medica 141 (1972) 812.

233

[300] R.B.R. De Sastre, A. Varillas, P. Kirschbaum, Proceeding of International Seminar on Arsenic in the Environment and its Incidence on Health, Universidad de Chile, Santiago, Chile, 1992. [301] G. Concha, B. Nermell, M. Vahter, Environ. Health Perspect. 106 (1998) 355. [302] J.W. Southwick, A.E. Western, M.M. Beck, T. Whitley, R. Isaacs, J. Petajan, C.D. Hansen, in: W.H. Leaderer, J. Robert (Eds.), Arsenic: Industrial, Biomedical, Environmental Perspectives, Van Nostrand Reinhold Company, Fensterheim, 1983, pp. 210 225. [303] D.R. Lewis, J.W. Southwick, R. Ouellet-Hellstrom, J. Rench, R.L. Calderon, Environ. Health Perspect. 107 (1999) 359. [304] E.L. Goldblatt, A.S. Van Denburg, R.A. Marsland, Oregon Department of Health, 1963, p. 24. [305] Geology of the Anlauf and Drain Quadrangles, Douglas and Lane Counties, Oregon Linn. Hoover, U.S. Geol. Survey Byll, 1122-D, 1963, p. 62. [306] J.R. Goldsmith, M. Deane, J. Thom, G. Gentry, Water Res. 6 (1972) 1133. [307] J. Wyllie, Can. Public Health J. 28 (1937) 128. [308] D.A. Grantham, J.F. Jones, J. Am. Water Works Assoc. 69 (1977) 653. [309] K.S. Subramanian, J.C. Meranger, R.F. McGurdy, Atom. Spectrom. 5 (1984) 192. [310] D.R. Boyle, R.J.W. Turner, et al., Environ. Geochem. Health 20 (1998) 199. [311] K. Egyedi, E. Pataky, Derm. Berufu. Umwelt. 26 (1978) 54. [312] G. Nagy, L. Korom, Z. Hautkr. 58 (1983) 961. [313] J. Pataky, G. Lusztig, Z. Inner. Med. 17 (1958) 668. [314] R.E.R. Grimmet, I.G. McIntosh, N.Z. J. Sci. Tech. 21 (1939) 138. [315] J.A. Ritchie, N.Z. J. Sci. 4 (1961) 218. [316] J. Aggett, A.C. Aspell, Release of arsenic from geothermal sources, New Zealand Energy Research and Development Committee, Report No. 35. [317] Arch. F. Dermat. 43 (1898) 221. [318] F.H. Wilson, D.M. Hawkins, Environ. Geol. 2 (1978) 195. [319] J.M. Harrington, J.P. Middaugh, D.L. Morse, J. Housworth, Am. J. Epidemiol. 108 (1978) 377. [320] N. Senanayake, W.A.S. De Silva, M.S.L. Salgado, Ceylon Med. J. 17 (1972) 195. [321] I. Manzano, E.E. Tello, Revista de la Faeultad de Ciences Medicas de la Universitad Nacional de Corboda 13 (1955) 133. [322] W. Lianfang, H. Jianghong, in: J.O. Nriagu (Ed.), Arsenic in the Environment, Part II: Human Health and Ecosystem Effects, John Wiley and Sons, Inc, New York, 1994, pp. 159 172. [323] N. Hotta, Asia Arsenic Network, October 1995. [324] G. Xiaojuan, Asia Arsenic Network, October 1995. [325] X.H. Zhao, Z. Chen, Chin. J. Epidemiol. 15 (1996) 18. [326] S.R. Cao, Chin. J. Epidemiol. 15 (1996) 1. [327] Proceedings of Pan-Asia Pacic Conference on Fluoride and Arsenic Research, Shenyang, China, 1999, p. 70.

234

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [354] P. Stavrakis, A. Demetriades, K. Vergou-Vichou et al., in: S.P. Varnavas (Ed.), Proceeding of 6th International Conference on Environmental Contamination, Delphi, Greece, CEP Consultants, Edinburgh, 1994. [355] R.J. Bowell, Chem. Geol. 106 (1993) 345. [356] R.J. Bowell, Mineralogical Mag. 56 (1992) 545. [357] W.D. Hawkins, R.E. Swain, J. Am. Chem. Soc. 29 (1907) 970. [358] J.K. Haywood, J. Am. Chem. Soc. 29 (1907) 998. [359] K. Welch, I. Higgins, M. Oh, C. Burchel, Arch. Environ. Health 37 (1982) 325. [360] A.M. Lee, J.F. Fraumeni Jr., J. Natl. Cancer Inst. (US) 42 (1969) 1045. [361] D.J. Birmingham, M.M. Key, D.A. Itoladays, V.B. Perone, Arch. Derm. 91 (1965) 457. [362] S.S. Pinto, C.M. McGill, Ind. Med. Surg. 22 (1953) 281. [363] S. Milhan Jr., T. Strong, Environ. Res. 7 (1974) 176. [364] E.J. Feinglass, N. Engl. J. Med. 288 (1973) 828. [365] A.B. Hill, E.L. Farming, Br. J. Ind. Med. 5 (1948) 1. [366] K. Perry, R.G. Bowler, H.M. Buckell, H.A. Druett, R.S.F. Shilling, Br. J. Ind. Med. 5 (1948) 6. [367] H.S. Osburn, Central African J. Med. 3 (1957) 215. [368] E.E. Gonzalez, Mexico Biol. Epidemiol. 27 (1963) 213. [369] P.L. Williams, E.M. Wewerka, N.E. Vanderborhg, P. Wagner, P.L. Wanek, J.D. Olsen, Proceedings of the Symposium on Mine Drainage, Control, at NCA/BRC Coal Conference, Louisville, Los Alamos, New Mexico, Los Alamos Scientic Laboratary, 1977. [370] O.L. Lloyd, Lancet 1 (1978) 318. [371] G.H. Smith, O.L. Lloyd, Arch. Environ. Health 41 (1986) 120. [372] R. Nilsson, A.N. Jha, Z. Zaprianov, A.T. Natarajan, Fresenius Environ. Bull. 2 (1993) 59. [373] Y. Nose, Public Health (Koshu Eisei) 21 (1957) 29. [374] N. Mizuta, M. Mizuta, F. Ito, T. Ito, H. Vchida, Y. Watanable, H. Akama, T. Murakami, F. Hayashi, K. Nakamura, T. Yamagachi, W. Mizua, S. Oishi, H. Matsumura, Bull. Yamaguchi Med. Sch. 4 (1956) 131. [375] O.A. Levander (Ed.), Arsenic: National Academy of Sciences, Washington DC, 1977. [376] N. Kitamura, T. Kasuyama, Okayamaken Eisei Kenkyujo Nenpo 6 (1955) 42 (English Translation from Japanese, TR-115-74, EPA). [377] J. Kodama, N. Kimura, K. Inoue, Okayamaken Eisei Kenkyujo Nenpo 6 (1955) 44 (English translation from Japanese, TR-115-74, EPA). [378] Epidemic of arsenical poisoning in bur drinkers in the North of England during the year 1900, Lancet I (1901) 98. [379] Arsenic in Beer, The Lancet I (1901) 496. [380] Royal Commission on Arsenical Poisoning, The Lancet I (1901) 672 673, 753, 904 905. [381] F.Z. Roth, Krebsforsch 61 (1957) 468. [382] K.H. Butzengeiger, Klin. Wochenschr. 19 (1940) 523. [383] P. Roth, Germ. Med. Monthly 82 (1957) 172. [384] H. Luchtrath, Dtsch Med. Wochenschr. 97 (1972) 21. [385] R. Wolf, Berufs. Dermatosen 22 (1974) 34.

[328] G.-F. Sun, S. Liu, B. Li, X. Li, X. Sun, X.-Y. Guo, C. Qian, J.-B. Pi, Environ. Sci. 8 (2001) 425. [329] Z. Feng, Y. Xia, D. Tian, K. Wu, M. Schmitt, R.K. Kwok, J.L. Mumford, Anticancer Res. 21 (2001) 51. [330] S. Nordstrom, L. Beckman, I. Nordenson, Hereditas 90 (1979) 291. [331] D.V. Datta, Lancet 1 (1976) 433. [332] D.V. Datta, M.K. Kaul, J. Asso. Phys. Ind. 24 (1976) 599. [333] K. Ushijima, T. Inaoka, T. Kadono, N. Murayama, M. Nagano, S. Nakamura, C. Watanabe, M. Ohtsuka, A.T.M.M.H. Bokul, Environ. Sci. 8 (2001) 449. [334] B.K. Viz, M.L. Figueroa, M.N. Conforth, S.H. Jenkins, Am. J. Ind. Med. 6 (1984) 325. [335] J.L. Valentine, S.Y. He, L.S. Reisbord, P.A. Lachendruch, J. Clin. Epidemiol. 45 (1992) 487. [336] S.C. Peters, J.D. Blum, B. Klaue, M.R. Karagas, Environ. Sci. Technol. 33 (1999) 1328. [337] C.P. Choprapawon, Asia Arsenic Network, October 1995. [338] A. Rodklai, S. Shindell, FETP, Ranphibun, Thailand, 1988. [339] S. Oshikawa, A. Geater, V. Chongsuvivatwong, T. Piampongsan, D. Chakraborti, G. Samanta, B.K. Mandal, N. Hotta, Y. Kojo, H. Hironaka, Environ. Sci. 8 (2001) 435. [340] H. Hironaka, Asia Arsenic Network, October 1995. [341] H. Hironaka, Director of Asia Arsenic Network/ Chemist and Environ., Inspector of Hakata Health Ofce, Fukuoka, 1995. [342] H. Terado, K. Katsuta, T. Sasagawa, H. Saito, H. Shirata, K. Fukuchi, T. Sekiya, Y. Yokoyama, S. Hirokawanm, Y. Watanabe, K. Hasegawa, T. Oshina, T. Sekigucg, Nihon Rinsho 118 (1960) 2394. [343] T. Yoshikawa, J. Utsumi, T. Okada, M. Moriuchi, K. Ozawa, Y. Kaneko, Chiryo 42 (1960) 1739. [344] N. Hotta, Jpn. J. Constitutional Med., Kumamoto, Japan 53 (1989) 49. [345] T. Tsuda, T. Nagira, M. Yamamoto, Y. Kume, Ind. Health 28 (1990) 53. [346] H. Yokoi, Director of Asia Arsenic Network/Exe Dir. of Oita Kyowa Hospital, Oita, Japan, 1995. [347] T. Hamada, S. Horiguchi, Jpn. J. Ind. Health 18 (1976) 103. [348] M.N. Bates, A.H. Smith, C.H. Rich, Am. J. Epidemiol. 135 (1992) 462. [349] A. Chattergee, A. Mukherjee, Sci. Total Environ. 225 (1999) 249. [350] D. Chakraborti, B.K. Biswas, T.R. Chowdhury, B.K. Basu, B.K. Mandal, U.K. Chowdhury, S.C. Mukherjee, J.P. Gupta, S.R. Chowdhury, K.C. Rathore, Curr. Sci. 77 (1999) 502. [351] G.A. Tallis, Aust. M.Z.J. 19 (1989) 730. [352] V. Bencko, K. Symon, Environ. Res. 13 (1977) 378. [353] P.J. Temple, S.N. Linzon, B.L. Chai, Environ. Pollut. 12 (1977) 311.

B.K. Mandal, K.T. Suzuki / Talanta 58 (2002) 201235 [386] H. Luchtrath, J. Cancer Res. Clin. Oncol. 105 (1983) 173. [387] N. Hotta, Representative Dir, ANN and Psychriatrist at Amakusa Hospital, Kumamoto, China, 1995. [388] B.S. Zheng, J.P. Long, Inner Mongolia J. Preven. Treat.

235

Endemic Dis. 19 (Suppl.) (1994) 41. [389] WHO, Guidelines for Drinking Water Qualilty, vol. 2, Health Criteria and Other Supporting Information, Chapter 2, Chemical Aspects, WHO, Draft, Geneva, Switzerland, 1992, p. 151.