ARSENIC EXPOSURE: PERSPECTIVE ON RISK ASSESSMENT RABIYA SHABNAM M.S.Student ECS program NDSU12-10-2007.

ARSENIC ARSENIC EXPOSURE: EXPOSURE:

PERSPECTIVE ON PERSPECTIVE ON RISK RISK

ASSESSMENTASSESSMENTRABIYA SHABNAMRABIYA SHABNAM

M.S.Student M.S.Student ECS programECS program

NDSUNDSU12-10-200712-10-2007

OVER VIEWOVER VIEW

INTRODUCTIONINTRODUCTION GOAL OF RISK ASSESSMENTGOAL OF RISK ASSESSMENT HEALTH EXPOSURE ASSESSMENTHEALTH EXPOSURE ASSESSMENT DOSE ASSESSMENTDOSE ASSESSMENT EPIDEMIOLOGICAL STUDIESEPIDEMIOLOGICAL STUDIES METHODS OF ARSENIC METHODS OF ARSENIC

MEASUREMENTMEASUREMENT REFERENCESREFERENCES ACKNOWLEDGEMENTACKNOWLEDGEMENT

INTRODUCTIONINTRODUCTION

Arsenic in the form of Arsenic(III) & Arsenic (V) causes health hazards.Arsenic in the form of Arsenic(III) & Arsenic (V) causes health hazards.

The WHO guideline for Arsenic in drinking water is 10The WHO guideline for Arsenic in drinking water is 10μμg/L.g/L.

Arsenic in groundwater is an International Problem.Arsenic in groundwater is an International Problem.

Arsenic is also known to cause a variety of cancers including skin Arsenic is also known to cause a variety of cancers including skin cancer (non-melanoma type), kidney, bladder, lung, prostate and liver cancer (non-melanoma type), kidney, bladder, lung, prostate and liver cancer. cancer.

Acute (short-term) arsenic poisoning may cause nausea, vomiting, Acute (short-term) arsenic poisoning may cause nausea, vomiting, diarrhea, weakness, loss of appetite, shaking, cough and headache.diarrhea, weakness, loss of appetite, shaking, cough and headache.

Chronic (long-term) exposure may lead to a variety of symptoms Chronic (long-term) exposure may lead to a variety of symptoms including skin pigmentation, numbness, cardiovascular disease, including skin pigmentation, numbness, cardiovascular disease, diabetes, and vascular disease.diabetes, and vascular disease.

There is a dose-response relationship between the ratio of MMA/DMA There is a dose-response relationship between the ratio of MMA/DMA in urine and the risk for skin and bladder cancer (Chen et al, 2003).in urine and the risk for skin and bladder cancer (Chen et al, 2003).

Risk AssessmentRisk Assessment

Hazard Identification

Dose-responseAssessment

Exposure Assessment

Risk Characterization

Risk Management

Goal of risk assessmentGoal of risk assessment

Adequate Qualitative,Quantitative data Adequate Qualitative,Quantitative data concerning the exposure (Source, concerning the exposure (Source, Amounts)Amounts)

Dose (Metabolism and disposition of Dose (Metabolism and disposition of active metabolites)active metabolites)

Response – Good Arsenic risk Response – Good Arsenic risk assessment epidemiological data to assessment epidemiological data to measure risk, to understand the risk measure risk, to understand the risk factors and disease.factors and disease.

Goal of risk assessmentGoal of risk assessment

Two critical issues in arsenic risk Two critical issues in arsenic risk assessment: Methylation in the dose-assessment: Methylation in the dose-response relationship response relationship

The role of internal cancers The role of internal cancers Exposure estimate –high / low Exposure estimate –high / low Higher exposure studies has been Higher exposure studies has been

used to measure risk.used to measure risk. How arsenic can be measured using How arsenic can be measured using

analytical methodsanalytical methods

Human Health Exposure Human Health Exposure AssessmentAssessment

Exposure to iAs-Contaminated drinking Exposure to iAs-Contaminated drinking water causes development of Cancer of water causes development of Cancer of Skin and internal organs.Skin and internal organs.

Exposure sources:Water, Soil, Air, Diet.Exposure sources:Water, Soil, Air, Diet. Epidemiologic studies in highly exposed Epidemiologic studies in highly exposed

& Low levels exposure among the & Low levels exposure among the populations.populations.

Bangladesh,India,China,Taiwan, Bangladesh,India,China,Taiwan, USA(Nevada)USA(Nevada)

Dose AssessmentDose Assessment

The dose of arsenic causing a health The dose of arsenic causing a health impact.impact.

The person being exposed (children The person being exposed (children are more sensitive than adults)are more sensitive than adults)

The route of exposure.The route of exposure. The type of health impacts being The type of health impacts being

examined cancer risks.examined cancer risks. Lifetime cancer risk probability of Lifetime cancer risk probability of

1/100,000 or, 1 x 10-5.1/100,000 or, 1 x 10-5.

Arsenic metabolismArsenic metabolism The elucidation of the metabolic pathways The elucidation of the metabolic pathways

of inorganic arsenic and the toxicity profile of inorganic arsenic and the toxicity profile of the arsenic metabolites are important.of the arsenic metabolites are important.

Epidemolgical studies – geographical Epidemolgical studies – geographical distributions and diseases.distributions and diseases.

Drinking water causing different cancers Drinking water causing different cancers and mortality rates.and mortality rates.

Studies on LUNG,BLADDER,KIDNEY Studies on LUNG,BLADDER,KIDNEY cancercancer

Case studies of Taiwan, Bangladesh, IndiaCase studies of Taiwan, Bangladesh, India Chile.Chile.

R. Sams II et al. / Toxicology and Applied Pharmacology 222 (2007) 245–251

In vivo metabolism of inorganic arsenic.

ARSENIC METABOLISMARSENIC METABOLISM

Human beings do methylate Arsenic.Human beings do methylate Arsenic. Methylation – Cytosol.Methylation – Cytosol. MMAMMAv v to DMAto DMAv v –TMAO –TMA–TMAO –TMAIIII

MMAMMAIIIIII and DMA and DMAIIIIII –More toxic. –More toxic. DMA % -indicator for metabolism.DMA % -indicator for metabolism. Metabolizing iAs –differs and effects Metabolizing iAs –differs and effects

the organ system.the organ system.

Epidemiological studies-Epidemiological studies-Evidences from Taiwan Evidences from Taiwan

cancer causescancer causes Epidemiologic data in the areas of world Epidemiologic data in the areas of world

with As levels in drinking water (>150 with As levels in drinking water (>150 µg/L) shows risk.µg/L) shows risk.

Exposure to iAs through drinking well Exposure to iAs through drinking well water causes blackfoot disease (BFD) in water causes blackfoot disease (BFD) in Taiwan.Taiwan.

Arsenic exposure and arsenic methylation Arsenic exposure and arsenic methylation capacity on the development of arsenic-capacity on the development of arsenic-related skin cancers and bladder cancer.related skin cancers and bladder cancer.

Mortality rates due to Mortality rates due to increased Arsenic in increased Arsenic in drinking water(per drinking water(per 100,000/year) in Taiwan100,000/year) in TaiwanDOSE LEVEL RISK

LUNG CANCER

LUNG CANCER

BLADDERCANCER

BLADDERCANCER

KIDNEY CANCER

KIDNEY CANCER

ARSENIC μgm/L

MEN WOMEN MEN WOMEN MEN WOMEN

>300 μg/L 49.2 36.7 100.7 70.8 104.1 122.2

300-500 μg/L

22.6 25.6 61 57 92.7 111.3

≥600 μg/L 8.4 3.4 18.9 19.4 25.3 58

Source: Toxicology and Applied Pharmacology 222 (2007) 252-257Source: Toxicology and Applied Pharmacology 222 (2007) 252-257..

Epidemiological dataEpidemiological data Bangladesh and India-1950’s – Bangladesh and India-1950’s –

arsenic 50arsenic 50μμg/lg/l

Source-Source-Water Engineering & Management; Water Engineering & Management; Mar 2002; 149, 3; Mar 2002; 149, 3; ABI/INFORM Global pg35.ABI/INFORM Global pg35.

Skin Lesion-Due to Skin Lesion-Due to ArsenicArsenic

Epidemiological dataEpidemiological data IN USA the states affected by arsenic are Nevada, IN USA the states affected by arsenic are Nevada,

CaliforniaCalifornia

Source-Source-Water Engineering & Management; Water Engineering & Management; Mar 2002; 149, 3; ABI/INFORM Global Mar 2002; 149, 3; ABI/INFORM Global pg35.pg35.

Analytical methods to Analytical methods to determine arsenicdetermine arsenic

HPLCHPLC Capillary zone electrophoresisCapillary zone electrophoresis ICP-MS (As- Detection Limit ICP-MS (As- Detection Limit

(ppt)400-500)(ppt)400-500) Elevated As Concentration in Solid Elevated As Concentration in Solid

X-ray absorption technique X-ray absorption technique (e.g.XANES) (e.g.XANES)

In Humans “Total Arsenic” level in In Humans “Total Arsenic” level in the urine and Blood.the urine and Blood.

Analytical methodsAnalytical methods The coupling of GC and ICP-MS-determine The coupling of GC and ICP-MS-determine

Arsenic of gaseous / volatile species.Arsenic of gaseous / volatile species. HPLC / ICP-MS , HPLC- Arseno sugarsHPLC / ICP-MS , HPLC- Arseno sugars ICP-MS gives molecular information. ICP-MS gives molecular information. ESI-MS –binding stoichiometryESI-MS –binding stoichiometry DMADMAvv can be identified by Electron spray- can be identified by Electron spray-

MS.MS. Separation of iAs Ion-Pairing Separation of iAs Ion-Pairing

chromatography.chromatography. AsAsiiiiii, DMA, DMAvv,MMAMMAvv , AS , ASvv, MMA, MMAiiiiii and DMA and DMAiiiiii

ICP-MS ICP-MS IC-ICPMS Chromatogram of 10 ug/L Arsenic IC-ICPMS Chromatogram of 10 ug/L Arsenic

SpeciesSpecies

http://www.wcaslab.com/tech/Arsenic_Speciation.htmhttp://www.wcaslab.com/tech/Arsenic_Speciation.htm

SummarySummary

As- toxic and carcinogenic.As- toxic and carcinogenic. Sort out the risk of exposure, dose Sort out the risk of exposure, dose

response relation ship.response relation ship. Risk managementRisk management Risk of Arsenic is well known, but is Risk of Arsenic is well known, but is

used as chemotherapeutic agent –used as chemotherapeutic agent –Acute promyelocytic leukemia (APL)Acute promyelocytic leukemia (APL)

ReferencesReferences Micheal F.Hughes,Elaina M. Kenyon,Kirk T.Kitchin., 2007.Toxicology Micheal F.Hughes,Elaina M. Kenyon,Kirk T.Kitchin., 2007.Toxicology

and Applied Pharmacology 222 (2007) 399-404.and Applied Pharmacology 222 (2007) 399-404. Toxicology and Applied Pharmacology 222 (2007) 245–251.Toxicology and Applied Pharmacology 222 (2007) 245–251. Joyce S.Tuji, Lisa J.Yost, Leila M.Barraj,Carolyn G.Scrrafford, Pamela Joyce S.Tuji, Lisa J.Yost, Leila M.Barraj,Carolyn G.Scrrafford, Pamela

J.Mink,2007. Regulatory Toxicology and Pharmacology 48 (2007) 59-68.J.Mink,2007. Regulatory Toxicology and Pharmacology 48 (2007) 59-68. Jurgen Mattush, Rainer Wennrich,2005.Microchim Acta 151, 137-Jurgen Mattush, Rainer Wennrich,2005.Microchim Acta 151, 137-

139(2005).139(2005). K.P.Cantor,J.H. Lubin,Toxicology and Applied Pharmacology 222 (2007) K.P.Cantor,J.H. Lubin,Toxicology and Applied Pharmacology 222 (2007)

252-257.252-257. Jurgen Mattusch and Rainer Wennrich,Microchim Acta 151, 137-139 Jurgen Mattusch and Rainer Wennrich,Microchim Acta 151, 137-139

(2005)(2005) X.Chris Le,Xiufen Lu, Xing-Fang Li, Arsenic Speciation, Analytical X.Chris Le,Xiufen Lu, Xing-Fang Li, Arsenic Speciation, Analytical

chemistry January 1,2004,27A-33A.chemistry January 1,2004,27A-33A. John T O'Connor, Arsenic in drinking water Part 2: Human exposure John T O'Connor, Arsenic in drinking water Part 2: Human exposure

and health effects and health effects Water Engineering & Management; Water Engineering & Management; Mar 2002; 149, Mar 2002; 149, 3; ABI/INFORM Global pg35.3; ABI/INFORM Global pg35.

AcknowledgementAcknowledgement

Dr.Achintya Bezbaruah Dr.Achintya Bezbaruah All my classmates of class 479/679All my classmates of class 479/679

Question ? Question ?

THANK YOUTHANK YOU