Arsenic and arsenic health effects

Cite as: AIP Conference Proceedings 2104, 020047 (2019); https://doi.org/10.1063/1.5100415

Published Online: 07 May 2019

Dipali P. Jasudkar, Aditi L. Tulankar, and S. R. Satone

AIP Conference Proceedings 2104, 020047 (2019); https://doi.org/10.1063/1.5100415 2104, 020047

© 2019 Author(s).
 Arsenic and Arsenic Health Effects
Dipali P. Jasudkar1,a), Aditi L. Tulankar2,b), S.R Satone3,c)
1,2
Department of Chemistry, K.D.K. College of Engineering, Nagpur, 440009, India.
3
Department of Civil, K.D.K. College of Engineering, Nagpur, 440009, India.
a)
Corresponding author: [email protected]
b)
[email protected]
c)
[email protected]

Abstract. Arsenic (As) is a common, naturally occurring drinking water contaminant, that originates from As-
containing rocks and soil and is transported to natural waters through erosion and dissolution. Chronic As poisoning
has become a worldwide public health issue. It is estimated that more than 130 million people from Asian countries
have been potentially exposed to As contamination above World Health Organization (WHO) guideline value of
As in drinking water (10 μg l−1). Epidemiologic data from regions of the world with very high levels of As in drinking
water (>150 μg/L) show a strong association between As exposure and risk of several internal cancers. Most human
As exposure occurs from consumption of drinking water containing high amounts of inorganic As. Chronic effects of
As exposure via drinking water include skin lesions, neurological effects, hypertension, peripheral vascular disease,
cardiovascular disease, respiratory disease, diabetes mellitus, and malignancies including skin cancer.

INTRODUCTION
Throughout history, people around the world have used groundwater as a source of drinking water and even
today, more than half of the world’s population depends on it for survival. The major sources of human exposure
to As may be through food, water, air and soil in that dietary intake is the major exposure route [1]. As
contamination in water, especially ground water has been recognized as a major problem of catastrophic
proportions. Exposure to inorganic As has been linked to cancer. Acute and chronic As exposure via drinking
water has been reported in many countries, especially Argentina, Bangladesh, India, Mexico, Mongolia,
Thailand, and Taiwan, where a large proportion of ground (well) water is contaminated with a high concentration
of As of 100 to over 2,000 ppb [2]. More than 38 million people are exposed to ground water with high
concentrations of As in Asian countries [3]. As contamination from several hitherto unaffected areas have also
been reported from Assam, Uttar Pradesh, Chattisgarh, Bihar, Tripura, Manipur, Arunachal Pradesh, Nagaland
and Jharkhand [4-10]. Out of the total 813 water samples analyzed from Chowki block the Koudikasa village is
severely affected and showed highest concentration of 1.8 ppm [11]. The United States and the World Health
Organization lowered the Maximum Contamination Level (MCL) for As in drinking water from 0.05 to 0.01 mg
L−1 [12]. Some countries like Bangladesh and China still have 50 ppb As in drinking water [13]. Occurrence of
As in ground water much exceeding the tolerance limit (10 ppb) is a global problem and posed an ever-increasing
degree of health hazard [14,15]. There are still great uncertainties on health effects of As at low doses. Research
is needed to investigate and assess human health effects of As at long-term low dose exposures using biologically
based mechanistic models [16]. As concentrations in hair, nails, and urine have widely served as biomarkers to
reflect recent As exposure [17,18].

Chemical Profile of As
Arsenic is a metalloid with the symbol As, atomic number 33 and relative atomic mass 74.92. It was first
documented by Albertus Magnus in 1250. The three most common allotropes are metallic grey, yellow and black
As, with grey being the most common. When heated in air, As oxidizes to As with an odour resembling garlic.
International Conference on “Multidimensional Role of Basic Science in Advanced Technology” ICMBAT 2018
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As can be present in the terrestrial, marine, and freshwater environments in various chemical forms. As occurs
naturally in the earth’s crust and is widely distributed in the environment [19]. The prevalent oxidation states of
Arsenic under environmental conditions are +V, +III, 0, -III [20,21]. In strongly reducing environments,
elemental As (0) or H3As [–III] can exist, but such conditions are rare [22]. In oxidized environment As appears
mostly as oxyanions [23].

Applications of As

• Medical use: As compounds like arsphenamine and As trioxide have been used as medicines During the
18th, 19th, and 20th centuries.
• Agricultural: The toxicity of As to insects, bacteria and fungi led to its use as a wood preservative.
Chromated copper arsenate (CCA) is a wood preservative used for timber treatment. As was also used in
various agricultural insecticides, termination and poisons. lead hydrogen arsenate was a common insecticide
on fruit trees.
• Alloys: metallic As is used for alloying with copper and especially lead. Lead components in car batteries are
strengthened by the presence of a few percent of As. Gallium arsenide is an
important semiconductor material, used in integrated circuits.
• Military: After World War I, the United States built up a stockpile of 20000
tons of lewisite (ClCH=CHAsCl2), a chemical weapon that is a vesicant (blister agent) and lung irritant.
During the Vietnam War the United States used Agent Blue, a mixture of sodium cacodylate and its acid
form, as one of the rainbow herbicides to deprive the Vietnamese of valuable crops.

As Occurences and Sources

Recently there has been increasing anxieties concerning As related problems. Occurrence
of As contamination has been reported worldwide. Average concentrations of As in the earth’s crust reportedly
range from 1.5 to 5 mg/kg. Natural concentrations of As in soil typically range from 0.1 to 40 mg/kg, with an
average concentration of 5 to 6 mg/kg [24]. More than 300 As minerals are known to occur in nature. Of these
approx. 60% are arsenates, approx. 20% are sulphides and sulphosalts, 10% are oxides and the rest are arsenites,
arsenides, native elements and metal alloys [25]. Arsenopyrite, realgar and orpiment are the most important of
these minerals, and they are commonly present in the sulfide ores of other metals including copper, lead, silver
and gold. Rate of As mineral dissolution may be enhanced by mining activity and As contamination can be
particularly severe in water associated with mine wastes and mine drainage. As-rich aquifers are characterized by
elevated concentrations of dissolved iron, bicarbonate, pH, ammonium ion and phosphate under reducing
condition [26-28] and acidity (low pH), iron and sulfate in the oxic horizon [29,30].
As is ubiquitous in the environment due to both anthropogenic and natural processes [31,32]. One is the
mobilization of As under natural conditions, such as natural weathering reactions, biological activity,
geochemical reactions, volcanic emissions and so on, and the other is anthropogenic activities, including mining
activities, combustion of fossil fuels, use of As pesticides, herbicides, crop desiccants and the use of As additives
in livestock feed [33]. As is released into the air through natural processes by volcanic eruptions, and weathering
of As-containing minerals [34]. Padma-Meghna-Brahmaputra plain in Bangladesh is considered worst affected in
world’s As scenario [35]. As contamination in the Ganges delta has been proposed to occur by two different
mechanisms oxidation of As-rich pyrite by atmospheric oxygen introduced into groundwater due to lowering of
water table [36] and the reduction of iron oxyhydroxide by organic matter [37,38]

ARSENIC TOXICITY
Arsenic and many of its compounds are especially potent poisons. As poisoning from naturally occurring As
compounds in drinking water remains a problem in many parts of the world. It is a recognized human carcinogen
[39-42]. Although some evidence suggests that trace amounts of As may be essential for good health [43]. Long-
term exposure to As results in chronic As poisoning (Arsenocosis) [44]. Arsenocosis has also been reported in
people due to occupational exposure to As [45]. Organs most affected are those involved with As in absorption,
accumulation and/or excretion are gastrointestinal tract, circulatory system, liver, kidney, skin, tissues very
sensitive to As and those tissues secondarily affected (e.g., heart) [46].

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 As disrupts ATP production through several mechanisms. These metabolic interferences lead to death from
multi-system organ failure. Toxicity of an exposure is dependent on the chemical form(s) of As. The degree of
toxicity is changed with As speciation as the following order;
MMA(III)>NDMA(III)>NAs(III)>NAs(V)>NMMA(V)>NDMA(V) [47]. To humans, arsenate is about 60 times
less toxic than arsenite, owing to the fact that arsenite reacts the sulfhydryl groups, while arsenate does not [48].
In low doses, As produces nausea, vomiting, and diarrhea. In larger doses, it causes abnormal heart beat,
damage to blood vessels, and a feeling of "pins and needles" in hands and feet. Small corns or warts may begin to
develop on the palms of the hands and the soles of the feet. Long term exposure to As and its compounds can
cause cancer. Chronic exposure to As-contaminated water, food or air causes cancer of skin, lung, bladder, liver
and kidney [49]. Skin changes, including hyperpigmentation and generalized hyperkeratosis, are the most
common signs of chronic As ingestion from drinking water [50]. In general, Preclinical, Clinical, Complications
and Malignancy are the four recognized stages of Arsenocosis, or chronic As poisoning [51,52]. Malnutrition,
poor socioeconomic conditions and illiteracy have also been implicated in As-induced toxicity [53].

• Inorganic Arsenic Toxicity

The most human health problems associated with As have been identified with inorganic As in drinking-
water, which is usually soluble inorganic As (V) [54]. In general, inorganic As is more toxic than organic As, and
trivalent arsenite is more toxic than pentavalent and zero-valent As. As (e.g., As3+) can be toxic through its
interaction with sulfhydryl groups of proteins and enzymes [55]. Ingesting inorganic As through drinking water
can also cause multi-site cancers in the human body [56]. The solubility of inorganic As compounds vary
depending on the compound and the pH of the water [57,58]. Children are most likely to be exposed to inorganic
As compounds from drinking water, or from ingesting contaminated foods or soil (predominantly via hand-to-
mouth activity) [57,59]. After absorption, inorganic As accumulates in the liver, spleen, kidneys, lungs, and
gastrointestinal tract. It is then rapidly cleared from these sites but leaves a residue in keratin-rich tissues such as
skin, hair, and nails. Arsenite undergoes biomethylation in the liver to the less toxic metabolites methylAs acid
and dimethylAs acid; biomethylation can quickly become saturated, however, and the result is the deposition of
increasing doses of inorganic As in soft tissues. As, particularly in its trivalent form, inhibits critical sulfhydryl-
containing enzymes. In the pentavalent form, the competitive substitution of As for phosphate can lead to rapid
hydrolysis of the high-energy bonds in compounds such as ATP. Increasingly it is realized that rice is a major
source of inorganic As to humans, as rice is particularly effective at accumulating As from soil and transferring
that As to the grain [60].

• Acute Arsenic Poisoning

Most cases of acute As poisoning occur from accidental ingestion of insecticides or pesticides and less
commonly from attempted suicide. Drinking water and food are the two major sources of As in human. As
concentration of human nails has been applied historically in forensic investigations to confirm acute poisonings,
since high concentrations of As can be detected at the base of the nail up to 10–14 days following death [61].
Acute exposures generally manifest with the cholera-like gastrointestinal symptoms of vomiting (often times
bloody) and severe diarrhea (which may be rice-watery in character and often bloody); these patients will
experience acute distress, dehydration (often), and hypovolemic shock. Acute As exposure causes nausea,
vomiting, colicky abdominal pain and profuse,watery diarrhea [62]. Acute As exposure produces toxicity to the
liver, kidney, intestine and brain [63]. Accidental poisonings still occur, and there is the potential for
therapeutic dosing errors with As trioxide (Trisenox), which is used to treat patients with acute
promyelocytic leukemia. The acute minimal lethal dose of As in adults is estimated to be 70 to 200 mg or
1 mg/kg/day As also still plays a role in acts of suicidal and homicidal intent. Dimercaprol (BAL) remains the
standard chelator for acute Arsenical poisoning in the United States.

• Dermatological Effects
The skin is quite sensitive to As, and skin lesions are some of the most common and earliest nonmalignant
effects related to chronic As exposure [64]. The first studies of dose dependent effects of As associated with skin
cancer were observed in Taiwan [65]. The skin is known to localize and store As because of its high keratin
content, which contains several sulfydryl groups to which As3+ may bind [66]. According to WHO, 1.0 mg of

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inorganic As per day may give rise to skin lesions within a few years [67]. Skin hyperpigmentation and
palmoplantar hyperkeratosis are characteristic dermatological lesions induced by longterm exposure to As [68].
Skin lesions, which include change of pigmentation (e.g. melanosis) and keratosis of the hands and feet are
characteristics of chronic As poisoning and usually appear after 5–15 years after exposure [69]. Major
Dermatological Signs includes Melano-keratosis, Melanosis, Spotted or rain drop pigmentation (spotted
melanosis), Spotted and Diffuse Keratosis of palms and soles Combination of pigmentation (Melanosis) and
nodular rough skin (spotted palmoplanter keratosis). Minor Dermatological Feature includes Mucus membrane
melanosis on tongue, gums, lips etc., Non-Pitting oedema, conjunctival congestion. The prevalence of skin
lesions among men and children in the small population studied was similar to that reported with corresponding
As drinking water concentrations in both Taiwan and West Bengal populations in which extensive malnutrition
has been thought to increase susceptibility [70].

• Carcinogenic Effect
As cancer risks to the health of subpopulations such as children, adolescents, and adults that occur through
dietary exposure have received increasing attention in many countries in recent years [71]. In the USEPA cancer
classifications, As belongs to Group A, and is an assured human carcinogen. As is a recognized human
carcinogen [72-75]. In the USEPA cancer classifications, As belongs to Group A, and is an assured human
carcinogen. Long-term exposure to As induces Arsenical cancers in human beings. As has been shown to induce
apoptosis in a variety of cell systems. A study on cancer risks from As in drinking water indicates that it could
cause liver, lung and kidney/bladder cancer besides skin cancer [76]. The lung is a major target of As
carcinogenesis in humans [77]. showed that the methyl derivatives of As led to production of free radicals and
damage of DNA in lung cells. Epidemiology studies show that chronic As exposure produces tumors of the skin,
urinary bladder, lung, liver, prostate, kidney, and possibly other organs [78-83,76]. The analysis of EPA, US
showed the nonlinear relationship between incidence of skin cancer and degree of As contamination in ground
water [84]. Much of the evidence has suggested that As is a cancer promoter rather than a carcinogen in animal
studies [85] has recently shown that arsenite is not a carcinogen but rather acts as an enhancing agent
(cocarcinogen) with a genotoxic partner.

• Neurological Effects
The effects of As on nervous system function have received considerably less attention than its association to
cancer, genotoxicity, and cellular disruption. Several groups reported that a symmetrical peripheral neuropathy
characterized by sensory nerves being more sensitive than motor nerves to As effects, and neurons with large
axons being more affected than neurons with short axons [86-88]. The sensory and motor signs and symptoms
usually developed within 2 h to 2 years of exposure, with vomit or diarrhea or both preceding or occurring
simultaneously with the onset of neuropathy [89]. Also some chemical toxicants have the potential to modify
brain. Physiology and can lead to mental retardation and developmental disabilities such as physical, cognitive,
psychological, sensory and speech impairments including socially undesirable outcomes [90,91]. Employing a
case-control study in an As-affected rural area in Bangladesh, it is found that significantly higher level of
depression, weakness, restlessness, insufficient sleep, drowsiness and loss of appetite among the Arsenocosis
cases as compared to controls [92]. Human fetal brain explants exposed to As in tissue culture showed
disturbance in the glutathione cycle enzymes, neuronal development, generation of reactive oxygen nitric oxide
species and apoptosis [93]. It has been reported that chronic oral exposure to inorganic As (0.05-0.1 mg/kg/day)
causes neurological and haematoladesnlogical toxicity in humans but not in monkeys, dogs, and rats exposed to
arsenite or arsenate at doses of 0.72 to 2.8 mg/kg/day [94].

• Developmental Effects
Studies show that after administration of inorganic As during gestation the metalloid can readily cross the
placenta and enter the fetal system [93,95,96,82], indicating that transplacental exposure to As is a plausible
exposure route and may carry risks typical of other types of exposure. 74As-labelled arsenate and arsenite in
pregnant mice and observed by autoradiography and gamma counting that the 74As-As passed through the
placenta [96]. An increasing concentration of As in drinking water during gestation led to increased incidence of
abortion [97]. The evidence from animal studies clearly shows thatAs is teratogenic, and the findings of limited

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human studies suggest that inorganic As may be associated with several reproductive/developmentaloutcomes
including increased rates of spontaneous abortion, low birth weight, congenital malformations, pre-eclampsia and
infant mortality [98].

RESULTS AND DISCUSSION

The incidence of As contamination of ground water used for both irrigation as well as for human
consumption or industrial activities has taken the dimension of an epidemiological problem. Chronic As
poisoning arises from consuming As contaminated drinking water for long time. As is a carcinogenic to both
humans and animals. It has been established that inorganic As is extremely toxic both acute and chronic. It is
very difficult to diagnose early symptoms of Arsenocosis because such non-specific symptoms may also be
present in many other diseases. Malnutrition, poor socioeconomic conditions and illiteracy have also been
implicated in As-induced toxicity. Epidemiological evidence indicates that As concentration exceeding 50 μg/L
in the drinking water is not public health protective. There are still great uncertainties on health effects of As at
low doses, hence the present guideline value should be lowered. As free water or decrease in As level in the
drinking water source is essential for overall development.

ACKNOWLEDGEMENT
The authors express sincere gratitude to the Department of Chemistry, K.D.K. College of Engineering,
Nagpur and National Environmental Engineering Research Institute (CSIR-NEERI), Nagpur for availing the
facility and their continuous support and guidance.

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