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The lives of millions of people in the Indian sub-continent, including West Bengal, are detrimentally impacted by the usage, for drinking, irrigation and cooking, of groundwater containing naturally high concentrations of arsenic. Thousands of people, many from disadvantaged groups, have already died as result of such usage. Many more have had their lives blighted by social exclusion caused by disfigurement (particularly for women) and by poverty caused by arsenic-related disabling illnesses. Although remediation strategies are being implemented and developed by the Indian, regional and local governments and by international agencies, the problem is complex and expensive to fix. What is critically required is a robust, workable model of what communities or groups of people are most at risk and thus where and what remediation strategies may be the most effective. The aim of our consortium is to develop such a model. Quantifying the risks to human health from chemicals in the environment involves assessment of 3 key areas: the source of the chemicals (nature and distribution, both now and in the future, of the chemical in environment), exposure routes (e.g. drinking water, eating food, inhaling airborne particles, washing) and human responses to exposure (and these may be strongly dependent upon genetic and dietary and other cultural factors). Project objectives include: (i) development of a robust mathematical model to describe source, exposure route and response elements of the overall risk to human health from groundwater arsenic in groundwater West Bengal. The model will address the added risks of morbidity and mortality to those suffering from other (e.g. enteric) diseases and will result in objective quantitative output including disability adjusted life years (DALYs); (ii) obtaining field and laboratory data to determine the values (and distribution of values) of key model input variables (iii) application to assessing the distribution of health risks amongst various groups (e.g. women, ethnic minorities, children, those with distinctive diets for cultural reasons or because of poverty). (iv) Interactive incorporation of advice and requirements of potential end-users (v) widespread dissemination of results and information amongst the academic and end-user communities (vi) actively seek and successfully be awarded co-lateral funding for this project and complementary further projects to a value of at least 10 times the UKIERI support within 2 years of the completion of the project The project speaks to several Millenium Development Goals, notably those addressing eradication of extreme poverty, promotion of gender equality and ensuring environmental sustainability.

Proposed Research
The probabilistic risk assessment model will explicitly take into account various source, exposure route and response terms for both arsenic-related and enteric diseases and be designed to enable relative health risks to be predicted for various regions and groups of people, with particularly application to assessing the likely effectiveness of various arsenic remediation proposals by explicating taking into account the action of pathogens. The model will be validated by field studies led by IICB and also those undertaken independently by other groups. There will be a cross-sectional survey among individuals living in an area in the West Bengal state of India, where the average groundwater concentration of arsenic exceeds 50 micrograms/liter. In addition, a comparison population will be selected from a region in West Bengal that is not known to contain high arsenic content in the groundwater. In each of these areas, stratified random samples of individuals will be selected. The construction of strata of the random sampling will be based on data obtained from 2001 Indian national census. For each individual in the family, information on key variables will be obtained by using a set of structured, pre-validated questionnaires, including a food frequency questionnaire (FFQ) based on 24-hour recall of food items to ascertain nutritional status and dietary patterns. The questionnaire will contain items on demographic variables (age and gender), socioeconomic status (housing, education, and income), use of groundwater, past family history of illnesses, and total number of deaths in the family attributable to arsenic-caused illnesses. For each individual, arsenic concentration in groundwater, food (including rice), and in nails, hair and urine will be assayed by using hydride generation system in Atomic Absorption Spectrometry (AAS) at IICB and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) at University of Manchester. Lifelong exposure to arsenic in groundwater will be calculated using a time-weighted average (TWA) of the concentration of the arsenic in groundwater sources and time through which the respondent used water from the particular well. The following health outcomes will be studied: (i) Assessment of cytokinesis block micronuclei assay in lymphocytes in vitro. (ii) Assessment of skin lesions by trained field physicians (dermatologists). In order to minimize bias, the dermatologists will be blinded as to the arsenic-exposure status of the individuals they will be examining. The skin lesions will be photographed in the field and will be evaluated at the Indian Institute of Chemical Biology to ascertain outcomes. Wherever there will be difference in opinions as to the skin lesion status by the pair of field physicians, a third opinion will be obtained to confirm the diagnosis based on the picture of lesions from the field. (iii) Assessment of other health outcomes.—The following health outcomes will be considered: cancers of skin, urinary bladder, liver, and lungs, chronic bronchitis, emphysema, conjunctivitis, and peripheral neuropathy. These will be ascertained by trained physicians in their field visits as part of the cross-sectional survey (iv) DALYs (disability adjusted life years) related to health outcomes specified in items (ii) and (iii) will be calculated as the sum of the years of life lost due to premature mortality in the population (YLL) and the years lost due to disability (YLD) for incident cases of the health condition. The YLL information will be obtained from the Life Insurance Corporation of India charts (A Government of India Undertaking for calculation of actuarial statistics), and disability weights will be ascertained from data obtained from the most current wave of National Family Health Survey statistics (NFHS-II)

The proposed work will be supervised by the UK and Indian Lead and Key Researchers and be principally carried out as follows: [1] Manchester PhD (1) Mrs Mondal. Fully funded PhD student, already working on quantifying arsenic exposure routes from groundwater in Bengal. She will develop the stochastic risk assessment model over the period Jan 2008 – September 2008. The PRISM and associated AMBER models will be used to validate relevant aspects of this modelling – part of this work, carried out after training by QUINTESSA personnel, will investigate how the PRISM models (which were developed by Quintessa for the UK Food Standards Agency in a UK context) might need to be adapted in AMBER to meet the needs of West Bengal end-users. October 2008 – June 2009 will be spent in West Bengal conducting field surveys of human health impacts and arsenic exposureand of arsenic exposure routes, particularly through foodstuffs and drinking water. These data, together with data supplied from other agencies, notably UNICEF, on pathogen and arsenic hazards associated with various key remediation pilots, will be used to populate and validate the model. [2] IICB PhD (1). Fully funded PhD student already working on field studies of human health impacts of arsenic exposure in West Bengal. Will visit the UK for 9 months from Jan 2008 to collaborate with Mrs Mondal on the construction of the model, then spend the next 15 months conducting field surveys, ultimately to write up the results and make recommendations regarding key risk groups and remediation strategies. [3] Manchester PhD (2). Mr Lawson. Fully funded PhD student already working on groundwater flow and age using isotopic tracers, biogeochemical modelling of arsenic mobility and prediction of future changes in concentration. Engaged 50 % from Jan 2008 to September 2009, including a 0.5 month field placement in West Bengal in May 2008. [4] IICB PhD (2). Fully funded PhD student already working on field studies of human health impacts of arsenic exposure in West Bengal, focussing on biomarkers of arsenic exposure. Will conduct field and laboratory studies in India/IICB from January 2008 – September 2008, followed by a 9 month placement at Manchester to carry out arsenic speciation studies in urine and other media. Will subsequently complete work in the 6 months to December 2009. [5] Manchester PDRA. Fully funded already working on the molecular ecology of arsenic in shallow Bengali aquifers principally under the supervision of Professor Jon Lloyd. A 0.5 month field study in West Bengal in November 2008 will complement her largely laboratory-based microcosm, PCR-DNA and SIP work aimed at identifying the microbes responsible for controlling the release of arsenic from sediments to groundwaters in these aquifers. Will work 33.3 % of time on project. Fundamental to the success of the project will be a series of Network Conferences and Short Courses which will facilitate the exchange of complementary research expertise both amongst the Network Partners and with external scientists and stakeholders. These scientific meetings, each of which constitute a project milestone, are [1] Launch Meeting & Stakeholders Consultation (Kolkata, India) (January 2008) [2] Risk Assessment, Analytical Techniques & Geostatistics Short Course (Manchester, UK) (March 2008) [3] Field Sampling &Techniques Short Course (India) (May 2008) [4] MID-PROJECT CONFERENCE (UK) (March 2009) [5] Reporting Conference (Kolkata, India) (December 2009) Meetings of the Project Management Committee (see section B.7) will be held adjacent to all the major Network meetings to enable member to participate via keynote lectures. A project end of March 31st 2010 allows for 3 months contingency.