Arsenic Poisoning

By:Heba Numan Harara

Jamila Temraz

Submitted to:Prof.Dr. Jamal safi

2014

ObjectivesWhat is Arsenic?Arsenic CharacteristicsCircumstances Of PoisoningNatural Arsenic LevelSources of ArsenicToxic kineticsHow might I be exposed to As ?Adverse Health EffectsTreatment and managementCase studyConclusionsReferences

Elemental arsenic is a naturally-occurring silver-gray solid metalloid. The element (zero valence) form, which rarely exists in nature and has low solubility, is seldom a cause of human toxicity. (Kosnett MJ et al.2005)Inorganic As is a human carcinogen (EPA, 1984)

What is Arsenic?

Arsenic Characteristics

• It is cheap• Easily obtained• Colourless• No smell• No taste• Small quantity is required to cause death.• Can be easily administered with food or drink.• Onset of symptoms is gradual• Symptoms simulate those of Cholera.

Arsenic is the most popular Homicidal poison

Arsenic Characteristics• Most natural waters contain inorganic species

– As (III) or arsenite predominant in ground waters H3AsO3

– As (V) or arsenate in surface waters H2AsO4 & HAsO4

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Levels of As in water depend on:

Distance from pollution sources

Level of human activity

Circumstances Of PoisoningDisadvantages Of Arsenic:

• It delays putrefaction• Can be detected in completely decomposed

bodies.• Can be found in bones, hairs and nails for

several years.• Can be detected in charred bones or ashes.

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Natural Arsenic LevelsCrystalline Rock

Soil

Ground Water

Surface Water

Avg. 2 ppm

1-40 ppm

0.01 – 800 ppbAs high as 40,000 in hot springs

2.38 – 65 ppbAs high as 22,000 in river water

Sources of Arsenic

Natural

•As occurs naturally & is widely distributed in the Earth’s crust .

•Volcanic activity, rock & mineral erosion, & forest fires release As

•As is often concentrated in sulfide-bearing mineral deposits (e.g., gold and copper)

Anthropogenic Sources and uses•Smelting of metals•Pharmaceutical industry (medicines)•Pesticide manufacture (very limited)•Wood preservative – CCA [in phase out]•Cattle and sheep dips•Feed additives•Dye stuffs•Petroleum, coal, and wood burning•Semiconductor manufacture•Waste incineration•Drilling Wells•Mineral Extraction•Processing Wastes

Toxicokinetics of arsenic in the body

• Absorption– Soluble forms

• Humans – 40 % to complete absorption• Animals – 50% to complete absorption

– Insoluble forms• Limited absorption

Toxicokinetics cont.

• Distribution

– Found in all humans – Blood conc. (1-5 ppb)

• Smokers (2 – 10 ppb)

• Occupational exposure (10 ppb)

DistributionBound to red blood cells and globulin Re –distribution (24 hours): liver, lungs, spleen Binds to sulfhydryl-containing proteins Long term distribution and high concentration in bone

and keratinized tissues Hair and fingernails (Mees’ lines)

• Highest levels (ppb)– Nails (0.89)– Hair (0.18)– Bone (0.07 – 0.12)– Heart, kidney, liver, lung (0.03 – 0.05)

Excretion• Primarily via urine

– 60% - 95% in 5 days• Fecal excretion low•Arsenic is excreted mainly by the kidneys. Renal tubules can convert As5+ (Arsenate) to the more toxic As3+ (Arsenite).•Prenatal exposure to arsenic, through placental transfer, can cause marked damage to the Fetus.•Crosses placenta, may cause stillbirth

CHEMICAL COMPOSITION AND TOXICITY:ARSINE GAS (AsH3) THE MOST TOXIC

Inorganic arsenic

Trivalent (As3+) Arsenic trioxide SolubleMore toxic Pentavalent (As5+) Arsenic pentoxide e.g. Lead arsenate Lower solubility Less toxic

Organic arsenic

Less soluble Less toxic Produced by biomethylation Detoxified in humans- High source

The toxicity of arsenic depends on its chemical composition and valency, arsine gas being the most toxic form.

Inorganic Forms of As

• Inorganic arsenic compounds are used to preserve wood.

• In the environment, As combines with oxygen, chlorine, & sulfur to form inorganic compounds.

• Inorganic forms are toxic.

Organic Forms of As• As in animals and plants combines

with carbon and hydrogen to form organic arsenic compounds.

• Organic arsenic compounds are used as pesticides, primarily on cotton plants.

• Fish & shellfish can accumulate organic forms (nontoxic).

As in the Environment

• As can only change its form in the environment. It cannot be destroyed.

• As in air will settle to the ground or is washed out of the air by rain.

• Many As compounds are easily solubilized in water due to changes in pH and temperature

How might I be exposed to As ?

• Eating food, drinking water, or breathing air containing As

• Breathing sawdust or burning smoke from wood treated with As

• Living near uncontrolled hazardous waste sites containing As

• Living in areas with unusually high levels of As in rock

ARSINE GAS

The most toxic, a potent hemolytic agent Colorless Non-irritant Evolves from arsenic compounds by addition of acid Immediate death occurs at 150 ppm, or in 30 minutes from 25-50 ppm

Hemolysis from arsine inhalation may result in intra-renal deposition of hemoglobin and debris of lysederythrocytes leading to renal tubular damage and renal failure, as well as hypoxia.

Poisonous Compounds of ArsenicArsenic oxide or Arsenic Trioxide

It is the most common form of arsenic used. It is also known as White Arsenic.No taste or smell and is sparingly soluble in water. It is heavier than water by three and half times but

freely floats on water.

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Adverse Health Effects

• Non-Cancer

Acute Toxicity

lAnima

RatsMice

Guinea pigsHumans

mg/kg)(50LD

15 - 29326 - 43

91 - 4 (approx)

Acute Effects – Humans(est. LD50 1-4 mg/kg)

• Peripheral neuropathy• Anemia• Renal and liver dysfunction• Skin pigmentation• EKG abnormalities• Severe GI effects

Chronic Toxicity: Humans Vascular

• Poland

–Vintners

–6 cases of gangrene

Chronic Toxicity: Humans

• Nervous system–Peripheral neuropathy – legs and

arms• Cranial nerves

–Loss of hearing in Japanese infants

Adverse Health Effects

• Cancer

Cancers Associated with Exposure to Arsenic in Drinking Water

Cancer: Long-term Exposure (20-40 yrs)Skin cancer (Taiwan)Keratosis and Hyperpigmentation•Blackfoot Disease (Mainly Taiwan)•Lung cancer (Taiwan, Japan, & Chile)

•Bladder cancer (Taiwan, Argentina) In a study conducted in the United States no reports of bladder cancer with average 40 µg of As/L in a study.

•In a case control study in conducted in Western United States, it was found that smoking can elevate bladder cancer risk when drinking water has As levels near 200 µg/day

What Are the Symptoms of Arsenic Poisoning?

Short-term (acute) arsenic poisoning can cause:NauseaVomitingDiarrheaCoughHeadacheWeaknessLoss of appetiteShaking

Long-term (chronic) poisoning symptoms in human beings due to arsenic are:

Skin pigmentation

Numbness

Diabetes

Vascular disease

Cardiovascular disease

Protection from Arsenic ?

• An inverse correlation was found between consumption of vitamins A, C, and E, riboflavin and folic acid, and the existence of dermatological manifestations or chronic arsenic exposure.

• The population was recently surveyed and those individuals who had diets deficient in certain B vitamins and antioxidants appeared to have greater risk of arsenic dermatoses.

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Treatment and management

AirwayBreathingCirculation

Pre-Hospital care

Emergency Department

•. Hemodynamic stabilization.• Orogastric lavage – for acute arsenic poisoning• Whole bowel irrigation with polyethylene glycol may be effective to prevent GI tract absorption of arsenic

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Treatment and management

• Dimercaprol (BAL in Oil): First-line agent for treating arsenic poisoning. May be administered to patients with renal failure.

• Succimer (DSMA): used only in childhood lead poisoning.

• Dimerval (DMPS): accepted DOC for treating most heavy metal poisonings.

Chelation Agents

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Treatment and management

• Hemodialysis is especially useful in a patient with arsenic poisoning with renal failure or with impending renal failure.

Hemodialysis&exchange transfusion

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Arsenic exposure in Latin America: Biomarkers, risk assessments and related health effects, (Tyler R. McClintock a, Yu Chen,2012)

• In Latin America, several regions have a long history of widespread arsenic (As) contamination from both natural and anthropological sources. Yet, relatively little is known about the extent of As exposure from drinking water and its related health consequences in these countries.

• It has been estimated that at least 4.5 million people in Latin America are chronically exposed to high levels of As (N50 μg/L), some to as high as 2000 μg/L — 200 times higher than the World Health Organization (WHO) provisional standard for drinking water.

• .

Despite some methodological limitations, these studies suggested important links between the high levels of chronic As exposure and elevated risks of numerous adverse health outcomes in Latin America — including internal and external cancers, reproductive outcomes, and childhood cognitive function.

• An earlier study captured bladder cancer mortality in approximately 2,750,000 inhabitants living in 26 counties of Córdoba province in Argentina between 1986 and 1991.

• The study found strong association between As exposure and deaths from bladder cancer mortality.

• The finding demonstrated that mortality started to increase after 10 years of high exposure in Chile's Region II in 1958 and continue to rise even after 25 years of reducing the exposure to a low level (Marshall et al., 2007).

• In Nicaragua, high levels of As have been identified in ground water (up to 1320 μg/L) in El Zapote and Llano La Tejera (Bundschuh et al., 2008).

• A survey in 2005 found 87% of the 54 wells had higher As more than 10 μg/L (Cuevas and Bundschuh, 2010).

• Very high levels of As have been detected in the soil (50–1000 mg/kg) from the Iron Quadrangle area of the southeastern part of Brazil, where gold and other mining activities have been operating over 250 years (Matschullat et al., 2007).

• Water from the mining districts Nova Lima and Santa Barbara contain As as high as 350 μg/L (Matschullatet al., 2007).

• High levels of As in drinking water Mexico were first identified in 1958.

• Study in the region of Lagunera found 64% of the wells to have As concentrations higher than 50 μg/L, with a range of 8–624 μg/L (Del Razo et al., 1993).

• Ground water in the Zimapan and Guanajuato areas contained As between 190 and 650 μg/L (average 380 μg/L) and 280 μg/L (Armienta and Segovia, 2008).

• Latin America has, though, been the focus of important studies that have contributed significantly to current knowledge of As effects on human health — specifically with respect to the development of bladder, lung, and skin cancer. While development of and deaths from cancer may take as long 35 years after exposure.

• Deaths from cardiovascular or respiratory diseases in children seem to occur during or soon after a period of high exposure —making shorter-term consequences of exposure a vital area of research (Rosenberg, 1974; Yuan et al., 2007; Zaldivar, 1980).

• As a result, studies have observed elevated fetal mortality, neonatal mortality, post neonatal mortality, reduced birth weight, and anemia in the mother (Hopenhayn-Rich et al., 2000; Hopenhayn et al., 2006; Hopenhayn et al., 2003a)

• Smoking was also found to influence risk of bladder cancer due to As, with individuals excreting high to have a quadrupled OR if they were also smokers (Steinmaus et al., 2006).

• With respect to lung cancer, synergistic effects was observed among smokers exposed to water As more than 200 μg/L compared to nonsmokers exposed to less than 50 μg/L (Ferreccio et al., 2000).

• Such short-term effects such as low birth weight and impaired cognitive development have also been observed. As-induced DNA damage in children may explain the under lying mechanisms of cancer risk at later life and future health risk.

• With studies indicating that As can account for 7– 20% of all deaths among exposed populations (Argos et al., 2010; Smith et al., 1998)

Arsenic exposure and adverse health effects: A review of recent findings from arsenic and health studies in Matlab, Bangladesh(2011)

• The recent discovery of large-scale arsenic (As) contamination of groundwater has raised much concern in Bangladesh.

• Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality.

Arsenic exposure and adverse health effects: A review of recent findings from arsenic and health studies in Matlab, Bangladesh(2011)

[6] Rahman M, Vahter M, Wahed MA, Sohel N, Yunus M, Streatfield PK, et al. Prevalence of arsenic exposure and skin lesions. A population based survey in Matlab, Bangladesh.J Epidemiol Community Health 2006;60(3):242e8.[7] Rahman M, Vahter M, Sohel N, Yunus M, Wahed MA, Streatfield PK, et al. Arsenic exposure and age and sex specific risk for skin lesions: a population-based case-referent study inBangladesh. Environ Health Perspect 2006;114:1847e52.[16] Rahman A, Vahter M, Ekstrom EC, Rahman M, Golam Mustafa AH, Wahed MA, et al. Association of arsenic exposure during pregnancy with fetal loss and infant death: a cohortstudy in Bangladesh. Am J Epidemiol 2007;165:1389e96.[17] Hore SK, Rahman M, Yunus M, Das CS, Yeasmin S, Ahmad SK, et al. Detecting arsenic-related skin lesions: experiences from a large community-based survey in Bangladesh. Int J Environ Health Res 2007;17:141e9.[19] Sohel N, Persson LA, Rahman M, Streatfield PK, Yunus M, Ekstrom EC, et al. Arsenic in drinking water and adult mortality: a population-based cohort study in rural Bangladesh. Epidemiology 2009;20:824e30.[20] Lindberg AL, Ekstrom EC, Nermell B, Rahman M, Lonnerdal B, Persson LA, et al. Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population inBangladesh. Environ Res 2008;106:110e20.[22] Jakariya M, Vahter M, Rahman M, Wahed MA, Hore SK, Bhattacharya P, et al. Screening of arsenic in tubewell water with field test kits: evaluation of the method from publichealth perspective. Sci Total Environ 2007;379:167e75.[23] Lindberg AL, Rahman M, Persson LA, Vahter M. The risk of arsenic induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposure.Toxicol Appl Pharmacol 2008;230:9e16.

• As exposure causes significant increased risk for death in cancers, cardiovascular, and infectious diseases-relatedmortality.

• A clear dose-response relationship was observed. The results demonstrate that As exposure through drinking water has started to generate excess adult mortality after a few decades of exposure.

• Considering 25 million people are exposed, the present generation may suffer from an excess of 200,000-300,000 As-related cancer cases.

CASE STY:US WATER ARSENIC MAP

The various colours indicate different concentrations of arsenic in water, with red being the highestRef:•U.S. Geological Survey (USGS) . Map of US – arsenic in water – Available athttp://co.water.usgs.gov/trace/arsenic/ - accessed 22 September 2011.

BANGLADESH WATER ARSENIC MAP

Image: Arsenic in West Bengal & Bangladesh –Arsenic Crisis Information Center. Availableat http://bicn.com/acic –accessed 22 September 2011.

Conclusions

• Public Health Can Be Severely Impacted by presence of elevated levels of As in drinking water– ↑in mortality & morbidity– Everyone is vulnerable– Degrees of vulnerability depend on

Biological susceptibilityExposure & dose

• There Are Safe Levels Below Which No Adverse Health Effects Occur

•Reducing the arsenic MCL from 50 µg/L to 10 µg/L will help reduce Arsenic exposure to approximately 13 million Americans.

•The continued concern about the association between inorganic arsenic and cancer has raised questions regarding the implications of widespread dispersion of inorganic arsenicals in the environment.

•The use of arsenical pesticides in food crops declined greatly after introduction of the chlorinated hydrocarbon and organophosphorus chemicals.

•Symptoms of arsenic poisoning: When arsenic poisoning mouth there is a sense of astringent taste followed after swallowing latency period symptoms ranging from 15 minutes to not show them a few hours, depending on the content of the stomach of food and kind, it retards the presence of greasy food absorption of arsenic for long periods while accelerates absorption abuse arsenic in the image of a solution in a hot drink.

•And start poisoning symptoms in the form of severe vomiting and severe diarrhea (cholera-like) give rise to dry fast and collapse

References:•http://users.physics.harvard.edu/~wilson/arsenic/arsenic_project_health_effects.hml

•http://www.mnn.com/health/fitness-well-being/stories/5-facts-about-arsenics-effects-on-the-human-body

•Tyler R. McClintock a, Yu Chen b, Jochen Bundschuh c,d,e, John T. Oliver f, Julio Navoni g, Valentina Olmos g, Edda Villaamil Lepori g, Habibul Ahsan h, i, Faruque Parvez, Arsenic exposure in Latin America: Biomarkers, risk assessments andrelated health effects, ٤۲۹)۲۰۱۲ (۷٦–۹۱

•http://www.greenfacts.org•Mohammad Yunus , Nazmul Sohel , Samar Kumar Hore , Mahfuzar Rahman , 2011,Arsenic exposure and adverse health effects. 27, 371-376.•Tyler R. McClintock, Yu Chen,2012. Arsenic exposure in Latin America: Biomarkers, risk assessments and related health effects 429 (2012) 76–91•Aiva L, Marcos R, Creus A, Coggan M, Oakley AJ, Board PG. Polymorphism of glutathione transferase Omega 1 in a population exposed to a high environmental arsenic burden. Pharmacogenet Genomics 2008;18:1-10.