Dissertationen zum Thema „Drinking water Arsenic content Bangladesh“

Safe water options for five arsenic-affected villages (Sarupie, Manikganj; Daniapara, Shirajdekhan; Babutepara, Muradnagar; Iruaien, Laksham; Rahulllabad, Nabinagar) in central Bangladesh were studied in order to assist the local people and to obtain an indication of general solutions to the arsenic problem that is currently affecting ~100 million people on the Indian subcontinent. Arsenic concentrations were measured in all drinking waters believed to be safe and in a random sample of "red" (unsafe) tubewell waters. Depending on geography, history of safe water sources and availability of pond/river, the options of dugwells, deep tubewells and sand filters were recommended for core village areas, combined with sustainable output testing and a distribution system to maximise the benefits of sustainable water output. Very shallow tubewells were recommended for testing in villages where dugwells were successful. Rainwater harvesting was not recommended, due to expense, small storage capacity and summer dry periods. Two dugwells of optimised design were constructed in Iruaien and Daniapara, each serving 50-100 families. The knowledge gained in the villages was incorporated into the first draft of a "Safe Water Book" for dissemination of honest and accurate information about solutions to the arsenic problem. An air/iron treatment system was developed for removal of arsenic from tubewell water in locations where water treatment is the only option available. The system is based on the Bangladeshi "three kalshi" method, but optimised for efficient contact of water with air and iron. It can be constructed like a sand filter, and requires no chemical input, except for clean scrap iron. Spent scrap iron containing arsenic can be incorporated into concrete for safe disposal. A model air/iron system was constructed and run for two years to demonstrate the long-term viability of the device. A colorimetric method, using silver diethyldithiocarbamate, was developed for determination of arsenic in the villages of Bangladesh. The equipment was adapted for rugged field use, and performed successfully without electricity or running water in improvised laboratory space in villages, providing linear calibrations 0-500 ??g/L and a 2σ limit of detection of 5 ??g/L. The appropriate technologies that should be developed or optimised for the arsenic affected region are described and preliminary suggestions are given about means by which self-propagating solutions might be developed in villages to solve the arsenic problem.

The poor in most developing countries are persistently marginalised in their living conditions, including their access to safe drinking water. The research objectives have been (1) to better understand why this state of affairs has endured despite decades of efforts and interventions, and (2) to propose more adequate alternatives. The central case study was concerned with drinking water in rural Bangladesh ?? a matter of grave urgency since the discovery of arsenic in the groundwater more than a decade ago. Millions of users are exposed to dangerous levels of contamination, and the implementation of solutions has been slow and inadequate. Little has been done so far to integrate the research on this complex humanitarian crisis. Many have argued that conventional views on development are ill-equipped to address the ??growing gap?? between rich and poor; the models often fail to interpret inequity beyond mere financial indicators. This thesis therefore puts forward a different analytical framework (based on the theoretical concepts of core-periphery and capital stock). This was designed to increase our understanding of marginalisation by taking into account unequal ownership of, entitlement to, and control over, ecological, technological, organisational and human assets. Through an action research methodology, this analytical framework was informed by a participatory programme that established safe drinking water supplies in several poor and arsenic-affected villages. The learning experience was then fed back into the programme. This pragmatic approach was also systemic, i.e., it emphasised the community level, which was framed within the context of external influences, various other programmes and national policies. This resulted in a clarification of the problem in terms of (1) lack of ownership of community land, resources, drinking water institutions and technical knowledge; (2) restricted access to (non-) governmental services and benefits from public or collective assets; and (3) exclusion from decision-making in new water sector developments. It was concluded that alternative strategies need to focus on vesting ownership, entitlement and control in marginalised communities. The steps to achieve this will have far-reaching ramifications for how organisations, policymakers and funding agencies perceive and plan development projects. The analytical and methodological approach of this thesis is relevant to other cases of marginalisation in different socio-economic contexts.

Naturally occurring arsenic (As) in Holocene aquifers in Bangladesh have undermined a long success of supplying the population with safe drinking water. Arsenic is mobilised in reducing environments through reductive dissolution of Fe(III)-oxyhydroxides. Several studies have shown that many of the tested mitigation options have not been well accepted by the people. Instead, local drillers target presumed safe groundwater on the basis of the colour of the sediments. The overall objective of the study has thus been focussed on assessing the potential for local drillers to target As safe groundwater. The specific objectives have been to validate the correlation between aquifer sediment colours and groundwater chemical composition, characterize aqueous and solid phase geochemistry and dynamics of As mobility and to assess the risk for cross-contamination of As between aquifers in Daudkandi and Matlab Upazilas in SE-Bangladesh. In Matlab, drillings to a depth of 60 m revealed two distinct hydrostratigraphic units, a strongly reducing aquifer unit with black to grey sediments overlies a patchy sequence of weathered and oxidised white, yellowish-grey to reddish-brown sediment. The aquifers are separated by an impervious clay unit. The reducing aquifer is characterized by high concentrations of dissolved As, DOC, Fe and PO43--tot. On the other hand, the off-white and red sediments contain relatively higher concentrations of Mn and SO42- and low As. Groundwater chemistry correlates well with the colours of the aquifer sediments. Geochemical investigations indicate that secondary mineral phases control dissolved concentrations of Mn, Fe and PO43--tot. Dissolved As is influenced by the amount of Hfo, pH and PO43--tot as a competing ion. Laboratory studies suggest that oxidised sediments have a higher capacity to absorb As. Monitored hydraulic heads and groundwater modelling illustrate a complex aquifer system with three aquifers to a depth of 250 m. Groundwater modelling illustrate two groundwater flowsystems: i) a deeper regional predominantly horizontal flow system, and ii) a number of shallow local flow systems. It was confirmed that groundwater irrigation, locally, affects the hydraulic heads at deeper depths. The aquifer system is however fully recharged during the monsoon. Groundwater abstraction for drinking water purposes in rural areas poses little threat for cross-contamination. Installing irrigation- or high capacity drinking water supply wells at deeper depths is however strongly discouraged and assessing sustainability of targeted low-As aquifers remain a main concern. The knowledge gained here can be used for developing guidelines for installing safe wells at similar environments in other areas of Bangladesh.
QC 20111227

A number of low-cost synthetic filtration media have been proposed for the removal of arsenic (As) from drinking water in areas such as Bangladesh, where exposure to environmental arsenic is a major human health issue. This PhD research project examines the application of recycled glass and waste stainless steel fragments as a practical medium for arsenic removal at a household scale. To assess the performance of recycled glass media as a practical filter bed, glass granules were differentiated by colour, size and mode of glass size reduction (imploded and ground). The selected glass granules were used as media for batch adsorption and column filtration experiments using a prepared As (III) test solution and using natural As-contaminated water in Bangladesh, where recycled glass in column filtration mode was used to treat arsenic contaminated natural water in the presence of other metalloids. Filter media made from recycled glass and waste stainless steel fragments were characterized via SEM and PXRF. SEM study also gave information about the mechanism of arsenic removal by glass granules. Sequential extraction experiments were also performed on used filtration media to assess arsenic removal and adsorption processes. Results indicate that glass granules associated with stainless steel fragments (sstl) can remove arsenic from drinking water at an efficiency suitable for household application. Arsenic removal effectiveness depends largely on the presence of stainless steel fragments with glass (introduced with the glass media during the recycling and preparation process). The glass particle size and mode of size reduction was also found to influence the removal of arsenic: ground glass performed better than imploded glass and smaller ground glass particles (s < 0.5 mm) performed better than imploded glass of the same size. Batch experiment results concluded that glass colour may have minor influences on arsenic removal although the differences were not significant. Further results also revealed that < 0.05 kg sstl can remove arsenic to below acceptable limits from a 0.50 ppm arsenic solution with an effectiveness > 0.168 mg/g sstl. It was found that 57 kg of small clear DSGF (dry sieved ground fresh) glass (s < 0.5 mm) can treat 132.5 l of water with 100% removal of arsenic from starting concentrations of 0.50 ppm, using a recycled glass filter column. There is a scope for improvement of the glass filter media by adding stainless steel fragments but the study did not determine the potential and further work is required to optimize the ratio of DSGF glass and stainless steel fragments. Considering the price and operational drawbacks of other existing filters in Bangladesh, recycled glass has potential to be used in more sustainable arsenic filter filtration units. The results, coupled with the low cost of waste glass, indicate that waste glass should be investigated further for use in domestic water filtration for arsenic removal.

Arsenic-contaminated drinking water exposes ~230 million people worldwide to increased risks of several diseases and is considered one of the greatest threats to public health. In Bangladesh, arsenic-contaminated water has been declared the largest poisoning of a population in history, where 39 million people are exposed to arsenic levels above the WHO guidelines (>10 μg/L). Drinking water is mainly provided by tube-wells installed by local drillers and the majority are located in aquifers with high arsenic levels. The major challenges of identifying arsenic-safe aquifers consist of a lack of a common tool for quality assurance of hydrogeological data, post-processing of the data, and a possibility to forward analyzed data to national and local stakeholders. Therefore, the purpose of this study was to investigate the potential of applying a digital solution for collecting and managing hydrogeological data in a quality assured platform. This study was a pilot-project in the sub-district Daudkandi, Bangladesh in collaboration with the KTH-International Groundwater Research Group. To fulfill the purpose, a method was developed for systematic and automated data capturing of hydrogeological information in GeoGIS, an advanced software that proved to be an efficient tool for visualizing hydrogeological data. The results show that collecting a few field data in a systematic and automated way is helpful for interpreting aquifer sequences and will enable better prerequisites for targeting safe aquifers and installing safe tube-wells. Conclusions are that the integration of a digital platform as a decision tool may significantly improve arsenic mitigation strategies. Furthermore, providing information to public and private sectors in Bangladesh would increase the transparency of hydrogeological conditions and may help improve safe water access to high arsenic areas of Bangladesh.
Över 230 miljoner människor världen över exponeras dagligen för arsenik-förorenat dricksvatten vilket kan ge upphov till hjärt- och kärlsjukdomar, diabetes samt olika cancersjukdomar. Arsenik (As) är en extremt giftig halvmetall som är naturligt förekommande i grundvatten och klassas som ett utav de största hoten mot allmän folkhälsa, vilket gör reducerande åtgärder till en samhällsutmaning av global karaktär. Ett land som är hårt drabbat av höga arsenikhalter är Bangladesh, där miljontals människor utsätts för arsenik-nivåer som överstiger WHO:s rekommenderade riktlinjer (>10 μg/L). Dricksvattenförsörjningen tillhandahålls framförallt genom vattenbrunnar installerade av lokala borrare och där majoriteten är placerade i akviferer med skadligt höga arsenikhalter.  Utmaningarna med att identifiera arseniksäkra akviferer är flera, bland annat saknas ett gemensamt verktyg för att hantera, kvalitetssäkra och analysera hydrogeologisk data, samt för att delge denna till olika parter på lokal, regional och nationell nivå. Syftet med den här studien var således att undersöka potentialen i att tillämpa ett digitalt verktyg för insamling och hantering av fältdata från olika databaser till en kvalitetssäkrad plattform. Studien genomfördes som ett pilotprojekt i distriktet Daudkandi, Bangladesh i samarbete med forskningsgruppen KTH-International Groundwater Research Group. För att uppfylla syftet utvecklades en metod för systematisk och automatiserad datainsamling av hydrogeologisk information i GeoGIS, en avancerad mjukvara som visade sig vara ett effektivt verktyg för visualiseringar av hydrogeologiska data. Resultaten visar att insamling av en liten mängd fältdata är till stor hjälp för att tolka akvifersekvenser samt för att urskilja arseniksäkra akviferer, vilket skapar bättre förutsättningar för installation av säkra vattenbrunnar. En slutsats som dras är att integreringen av en digital plattform för datainsamling avsevärt kan förbättra beslutsfattandet för arsenikreducerande strategier samt underlättar ett transparent informationsflöde. Genom att tillhandahålla transparent hydrogeologisk information till privat och offentlig sektor i Bangladesh kan även tillgången på säkert dricksvatten förbättras.

Arsenic (As) contamination in groundwater is a severe and adverse water quality issue for drinking purposes, particularly in Southeast Asia, where groundwater is the main drinking water source. Bangladesh is one of the countries where arsenic poisoning in groundwater is massive and it is essential to find out a reliable alternative safe drinking water source. In this process, it is very much needed to identify As-rich wells to avoid drinking water from them and to assess the extent of contamination as well. This study attempts to evaluate the potentiality of tube-well (TW) platform color as low-cost quick screening tool for As and Mn as well in drinking water wells (n=272). The result shows strong association of red color platform with As-rich water in the corresponding wells compared to WHO guideline value of 10 μg/L (98.7% certainty) and regional (Bangladesh/India) standard of 50 μg/L (98.3% certainty). The sensitivity and efficiency of red color platforms to screen high As water in TW for 10 μg/L are 98% and 97%. Similarly, for 50 μg/L, it is 98% for both sensitivity and efficiency. However, because of a very low number (n=4) of TW platform stained with black color, it is not possible to make any conclusion on the potentiality of black color as a screening tool for Mn. This study suggests that red colored platform can be potentially used for primary identification of TWs with elevated As concentration and to prioritise sustainable As mitigation management. However, this study does not discard the concept of black colored platform as a screening tool for Mn-rich water. Further study is recommended to evaluate the efficiency of black color as a screening tool for Mn.

In rural Bangladesh, the drinking water supply is mostly dependent upon manually operated hand pumped tubewells, installed by the local community. The presence of natural arsenic (As) in groundwater and its wide scale occurrence has drastically reduced the safe water access across the country and put tens of millions of people under health risk. Despite significant progress in understanding the source and distribution of As and its mobilization through sediment-water interactions, there has been limited success in mitigation since the problem was discovered in the country’s water supply in 1993. This study evaluated the viability of other kinds of alternative safe drinking water options and found tubewells are the most suitable due to simplicity and technical suitability, a wide acceptance by society and above all low cost for installation, operation and maintenance. During planning and decision making in the process of tubewell installation, depth of the tubewell is a key parameter as it is related to groundwater quality and cost of installation. The shallow wells (usually < 80m) are mostly at risk of As contamination. One mitigation option are deep wells drilled countrywide to depths of around 250 m. Compared to safe water demand, the number of deep wells is still very low, as the installation cost is beyond affordability of the local community, especially for the poor and disadvantaged section of the society. Using depth-specific piezometers (n=82) installed in 15 locations spread over the 410 km2 area of Matlab (an As-hot spot) in southeastern Bangladesh, groundwater monitoring was done over a 3 year period (pre- and post-monsoon for 2009-2011 period). Measurements were performed for hydrogeological characterization of shallow, intermediate deep and deep aquifer systems to determine the possibility of targeting safe aquifers at different depths as the source of a sustainable drinking water supply. In all monitoring piezometers, As was found consistently within a narrow band of oscillation probably due to seasonal effects. Hydrogeochemically, high-As shallow groundwaters derived from black sands are associated with elevated DOC, HCO3, Fe, NH4-N and PO4-P and with a relatively low concentration of Mn and SO4. Opposite to this, shallow aquifers composed of red and off-white sediments providing As-safe groundwater are associated with low DOC, HCO3, Fe, NH4-N and PO4-P and relatively higher Mn and SO4. Groundwaters sampled from intermediate deep and deep piezometers which were found to be low in As, are characterized by much lower DOC, HCO3, NH4-N and PO4-P compared to the shallow aquifers. Shallow groundwaters are mostly Ca-Mg-HCO3 type and intermediate deep and deep aquifers’ groundwaters are mostly Na-Ca-Mg-Cl-HCO3 to Na-Cl-HCO3 type. A sediment color tool was also developed on the basis of local driller’s color perception of sediments (Black, White, Off-white and Red), As concentration of tubewell waters and respective color of aquifer sediments. A total of 2240 sediment samples were collected at intervals of 1.5 m up to a depth of 100 m from all 15 nest locations. All samples were assigned with a Munsell color and code, which eventually led to identify 60 color varieties. The process continued in order to narrow the color choices to four as perceived and used by the local drillers for identification of the targeted As-safe aquifers. Munsell color codes assigned to these sediments render them distinctive from each other which reduces the risk for misinterpretation of the sediment colors. During the process of color grouping, a participatory approach was considered taking the opinions of local drillers, technicians, and geologists into account. In addition to the monitoring wells installed in the piezometer nests, results from 87 other existing drinking water supply tubewells were also considered for this study. A total of 39 wells installed in red sands at shallow depths producing As-safe water providing strong evidence that red sediments are associated with As-safe water. Average and median values were found to be less than the WHO guideline value of 10 μg/L. Observations for off-white sediments were also quite similar. Targeting off-white sands could be limited due to uncertainty of proper identification of color, specifically when day-light is a factor. Elevated Mn in red and off-white sands is a concern in the safe water issue and emphasizes the necessity of a better understanding of the health impact of Mn. White sediments in shallow aquifers are relatively uncommon and seemed to be less important for well installations. Arsenic concentrations in more than 90% of the shallow wells installed in black sands are high with an average of 239 μg/L from 66 wells installed in black sediments. It is thereby recommended that black sands in shallow aquifers must be avoided. This sediment color tool shows the potential for enhancing the ability of local tubewell drillers for the installation of As-safe shallow drinking water tubewells. Considering the long-term goal of the drinking water safety plan to provide As-safe and low-Mn drinking water supply, this study also pioneered hydrogeological exploration of the intermediate deep aquifer (IDA) through drilling up to a depth of 120 m. Clusters of tubewells installed through site optimization around the monitoring piezometer showed a similar hydrochemical buffer and proved IDA as a potential source for As-safe and low-Mn groundwater. Bangladesh drinking water standard for As (50 µg/L) was exceeded in only 3 wells (1%) and 240 wells (99%) were found to be safe. More than 91% (n=222) of the wells were found to comply with the WHO guideline value of 10 µg/L. For Mn, 89% (n=217) of the wells show the concentration within or below the previous WHO guideline value of 0.4 mg/L, with a mean and median value of 0.18 and 0.07 mg/L respectively. The aquifer explored in the Matlab area shows a clear pattern of low As and low Mn. The availability of similar sand aquifers elsewhere at this depth range could be a new horizon for tapping safe drinking water at about half the cost of deep tubewell installation. All findings made this study a comprehensive approach and strategy for replication towards As mitigation and scaling-up safe water access in other areas of Bangladesh and elsewhere having a similar hydrogeological environment.

QC 20151211

Sida-SASMIT project (Sida Contribution 75000854).

Exposure to arsenic in drinking water can cause several types of cancer and numerous cardiovascular and respiratory diseases. A country that suffers from widespread contamination of arsenic in drinking water is Bangladesh, where the contamination has been classified as the largest mass poisoning of a population in history. Around 90 percent of the existing tubewells used for drinking water in Bangladesh were installed by the private sector and local drillers, which makes their knowledge on drinking water contamination crucial in order to make them contributory for scaling up access to safe drinking water. The aim of the thesis was to develop an interactive map model to enhance the access to information for the local governments, communities, and private sector in three upazilas (sub- districts) of Bangladesh: Assasuni, Daudkandi, and Gowainghat, regarding how they can access safe drinking water in their local areas. The interactive map model for this thesis was developed in ArcGIS with supporting information from local drillers’ survey and Arsenic Safe Union project implementation data. The resulting maps contain information such as wells located in the upazilas, drillers’ working areas, years of working experience, contact information, certification and driller hubs (hardware shops). The map model is expected to be operationalised by creating a digital water platform through a mobile application, in a stand-alone website, or to be integrated in a government information centre to enable access for the community, local technocrats, the private sector and other concerned stakeholders. Moreover, the map can easily be scaled-up in the future to include additional areas with similar hydrogeology and arsenic or trace elements contamination problems, in other regions of South Asia, Africa and Latin America.
Exponering för arsenik i dricksvatten kan orsaka flera olika typer av cancer samt ett flertal hjärt- och luftvägssjukdomar. Ett land som är utsatt för utbredd arsenikförorening i dricksvatten är Bangladesh, där föroreningen har klassificerats som den största massförgiftningen av en befolkning i historien. Ungefär 90 procent av alla existerande dricksvattensrörbrunnar i Bangladesh installerades av den privata sektorn och av lokala brunnsborrare, vilket gör deras kunskap om dricksvattenföroreningar avgörande för att de ska kunna bidra till att öka tillgången till säkert dricksvatten. Syftet med denna uppsats var att utveckla en interaktiv kartmodell för att öka tillgången till information för lokala myndigheter och samhällen, samt för den privata sektorn i tre upazilor (kommuner) i Bangladesh: Assasuni, Daudkandi och Gowainghat, angående hur de kan få tillgång till säkert dricksvatten i deras område. Den interaktiva kartmodellen utvecklades i ArcGIS och innehåller information från en enkät ifylld av lokala brunnsborrare samt data från projektet Arsenic Safe Union. De resulterande kartorna innehåller information om brunnar belägna i upazilorna, information om lokala brunnsborrares arbetsområden samt deras arbetserfarenhet, kontaktinformation, certifiering och brunnsborrarnav (järnhandlare). Kartmodellen förväntas göras tillgänglig för samhället, lokala myndigheter, den privata sektorn och andra berörda aktörer, genom en digital vattenplattform i en mobilapplikation, på en fristående webbplats eller genom att integreras i ett statligt informationscenter. I framtiden kan kartan enkelt skalas upp för att inkludera ytterligare områden med liknande hydrogeologi och föroreningsproblem, till följd av arsenik eller andra spårelement, för regioner i Sydasien, Afrika och Latinamerika.

Background: Chronic arsenic (As) exposure in a global public health concern. Arsenic exposure through drinking water affects over 140 million people in at least 70 countries, including 40 million people in Bangladesh. In the United States (US), 2.4 million people rely on private wells or public water systems with As levels above the US maximum contaminant level. Ingested inorganic arsenic (InAs) is methylated to monomethyl (MMAs)- and dimethyl (DMAs)-arsenical species using the methyl donor S-adenosylmethionine (SAM). Full methylation of InAs to DMAs decreases As toxicity and facilitates urinary As excretion. Arsenic methylation capacity is influenced by nutrients involved in one-carbon metabolism (OCM), the biochemical pathway that synthesizes SAM. Folate recruits one-carbon units for the remethylation of homocysteine and the synthesis of SAM. The availability of one-carbon units is also impacted by nutrients including the alternative methyl donor betaine, its precursor choline, and possibly the cofactor vitamin B12. In addition, As methylation capacity may also be influenced by creatine; an estimated 50% of SAM is consumed by the final step of endogenous creatine synthesis. The adverse health outcomes associated with chronic As exposure include impaired intellectual function, cardiovascular disease, diabetes, inflammation, and cancers of the bladder, lung, kidney, liver, and skin. In utero As exposure is associated with adverse birth outcomes include decreased birth weight and gestational age. Elevated health risks persist after exposure has been reduced or ended, leading to the hypothesis that epigenetic dysregulation, including changes in DNA methylation, may be a biological mechanism linking As exposure to health outcomes. Objectives: This research has three main objectives: (1) to investigate the influence of OCM nutritional factors on As methylation by evaluating effects of folic acid (FA) and creatine supplementation on As methylation capacity, and effect modification by baseline status of OCM-related nutrients; (2) to examine associations between As exposure and loci-specific DNA methylation in an epigenome-wide association study (EWAS); and (3) to assess mediation of the association between in utero As exposure and birth outcomes (i.e., gestational age and birth weight) by DNA methylation of target genes identified in an EWAS, as well as the candidate gene DNA methyltransferase 3 alpha (DNMT3A), a protein-coding gene involved in de novo DNA methylation. Methods: This research used data from three studies of As-exposed individuals. To address the first objective, we used data from the Folic Acid and Creatine Trial (FACT), a 24-week randomized clinical trial of FA (400 or 800 μg/day) and/or creatine supplementation (3 g/day or 3 g creatine and 400 μg FA/day) among As-exposed adults in Bangladesh recruited independent of folate status (N = 622). We investigated overall FA and creatine treatment effects on mean within-person changes in As metabolite proportions in urine compared to the placebo group (weeks 0 to 12). Rebound of As methylation capacity following the cessation of FA supplementation was assessed from weeks 12 to 24. We also assessed effect modification by baseline choline, betaine, vitamin B12, and plasma folate of treatment effects on changes in homocysteine, guanidinoacetate (GAA) (biomarkers of OCM and endogenous creatine synthesis, respectively), total blood As, and urinary As metabolite proportions and indices. To address the second objective, we used data from the Strong Heart Study (SHS), a population-based prospective cohort of American Indians with low-moderate levels of As exposure. DNA methylation was measured in 2,325 participants using the Illumina MethylationEPIC array, which interrogates > 850,000 loci. We tested for differentially methylated positions (DMPs) and regions (DMRs), and conducted gene ontology (GO) enrichment analysis to understand functions of genes containing differential methylation. To address the third objective, we used data from a prospective birth cohort in Bangladesh. In a discovery phase, an EWAS was conducted to identify CpGs with methylation measured in cord blood that are associated with maternal water As levels and birth outcomes (N = 44). In a validation phase, DNA methylation in cord blood was measured using bisulfite pyrosequencing at three target CpGs annotated to miR124-3, MCC, and GNAL (N = 569). We applied structural equation models (SEMs) to assess mediation of the association between in utero As exposure and gestational age by DNA methylation. In addition, mediation of the association between in utero As exposure and birth outcomes by DNA methylation of the candidate gene DNA methyltransferase alpha (DNMT3A) was assessed. Results: In FACT, the mean within-person decreases %InAs and %MMAs and increase in %DMAs were greater among all groups receiving FA supplementation at weeks 6 and 12 compared to placebo (P < 0.05) (Chapter 3). Stratified by median choline and betaine concentrations at baseline, we observed a trend towards greater FA treatment effects among participants with levels below the median of both nutrients compared to participants above the median (Chapter 4). Among participants who discontinued FA supplementation, at week 24, %InAs and %DMAs were not significantly different than baseline levels, suggesting a rebound in As methylation capacity with cessation of FA supplementation. We observed a significantly greater mean within-person decreases in %MMAs with creatine supplementation compared to placebo at weeks 1, 6, and 12; mean within-person changes in %InAs and %DMAs did not differ significantly between the creatine and placebo groups (Chapter 3). The mean within-person decrease in urinary %MMAs at week 12 with creatine treatment was significantly greater than placebo among participants with baseline choline concentrations below the median, but did not differ from placebo among participants with choline concentrations above the median (Chapter 4). In an EWAS conducted in SHS, we identified 20 DMPs associated with urinary As levels at FDR < 0.05; five DMPs were significant at PBonferroni < 0.05 (Chapter 5). The top significant CpG, cg06690548, was located in solute carrier family 7 member 11 (SLC7A11 ), part of the amino-acid transporter cystine:glutamate antiporter system xc-, which is involved in biosynthesis of the endogenous antioxidant glutathione (GSH). Additional Bonferroni-significant CpGs were located in ANKS3, LINGO3, CSNK1D, and ADAMTSL4. We identified one FDR-significant DMR (chr11:2,322,050-2,323,247) including the open reading frame C11orf21 and tetraspanin 32 (TSPAN32 ). Mediation of the association between in utero As exposure and birth outcomes by cord blood DNA methylation was assessed in a Bangladeshi birth cohort. In the discovery phase (N = 44), the association between maternal water As levels and gestational age was fully mediated by DNA methylation of the top 10 CpGs associated with both variables. In a discovery phase (N = 569), there were significant indirect effects of maternal water As levels on gestational age through DNA methylation of miR124-3 and MCC ; the indirect effect through DNA methylation of GNAL was not significant (Chapter 6). In an adjusted SEM including miR124-3 and MCC, mediation of the association between in utero As exposure and gestational age by DNA methylation of miR124-3 was borderline significant (P = 0.06); DNA methylation of MCC did not act as a mediator. We also assessed mediation by DNA methylation of DNMT3A (Chapter 7). In an adjusted SEM including birth weight and gestational age, there was a significant indirect effect of maternal toenail As levels on gestational age through DNMT3A methylation, the indirect effect on birth weight was borderline significant (P = 0.082). However, the indirect effects of maternal toenail As levels on birth weight through all pathways including gestational age were statistically significant. A doubling in maternal toenail As concentrations had a total effect of a decrease in gestational age of 2.1 days and a decrease in birth weight of 28.9 g. Conclusions: Results from FACT (Chapters 3 and 4) provide evidence of the associations between OCM-related nutrients and As methylation capacity. Specifically, FA and creatine supplementation may increase As methylation capacity by increasing the availability of SAM, and treatment effects may be greater among individuals with low betaine and choline status, respectively. In addition, results reported in Chapters 5-7 support the hypotheses that chronic As exposure is associated with epigenetic dysregulation, and that changes in the epigenome may mediate the association between As exposure and adverse health effects. Findings from the research presented here may help inform public health interventions to reduce the adverse health effects of chronic As exposure. However, further research is needed to fully understand the biological mechanism that influence As methylation and that underlie the associations between chronic As exposure and adverse health outcomes.

Millions of villagers in Bangladesh drink water which exceeds the Bangladesh arsenic (As) standard of 50 micrograms per liter. Exposure to elevated levels of inorganic As (As) is associated with cancers of the skin, bladder, and lung, developmental effects, cardiovascular disease, skin lesions, and decreased children's intellectual functioning. Arsenic mitigation typically involves an outsider coming into a village to test the well water for As. After the results of the As test are provided this person typically leaves the village without providing the resources to address health concerns or give advice on mitigation options. In this dissertation, in an effort to provide ongoing resources on the health implications of As and to reduce As exposure, we sought to evaluate community level intervention strategies that could be used for successful As mitigation in Bangladesh. In Singair, Bangladesh, we conducted a household drinking water survey of 6649 households. The results of our survey indicated that 80% of wells were untested for As. Furthermore, we demonstrated that testing all of these untested wells would increase the number of households that lived with fifty meters of an As safe drinking water source by nearly 2.5 fold. In a cluster based randomized control trial (RCT) of 1000 households, we evaluated the effectiveness of having community members, compared to outside representatives, disseminate As education and conduct water As (WAs) testing. In 10 villages, a community member disseminated As education and provided WAs testing. In a second set of 10 villages an outside representative performed these tasks. Overall, fifty three percent of respondents with unsafe wells at baseline switched after receiving the As education and WAs testing intervention. There was no significant association observed between the type of As tester and well switching (Odds ratio (OR) =0.77; 95% confidence interval (CI) (0.37-1.61)). At follow-up, the average UAs concentrations for those with unsafe wells at baseline who switched to safe wells significantly decreased. In both intervention groups a significant increase in knowledge of As was observed at follow-up compared to baseline. The unavailability of As-safe drinking water sources in some villages was the most substantial barrier to well switching identified. The Hach EZ As field test kit measurements conducted by the As testers were highly correlated with laboratory results. This finding indicates that the As testers were able to accurately measure the WAs concentration of wells. Furthermore in our pilot study, the performance of the Econo-Quick (EC) kit, a new field WAs testing kit, was comparable to that of the commonly used EZ kit and the Wagtech Arsenator kit. The EC kit has the advantage of a substantially shorter reaction time of only 12 minutes in comparison to the 40 minutes required by these other kits. Through this dissertation, we have demonstrated that As education and WAs testing programs can be used as an effective method to reduce As exposure and increase As awareness in many As affected areas of Bangladesh. Furthermore, our findings indicated that many households are using tubewells that are untested for As therefore demonstrating the urgent need for access to water As testing services.

The worldwide natural occurrence of high levels of arsenic (As) in groundwater and its deleterious effects on human health have inspired a great amount of related research in public health and geosciences internationally. With >100 million people in South and Southeast Asia exposed to >10 µg/L As in shallow groundwater that they use for drinking, the installation of deeper, low-As wells has emerged as a major strategy for lowering the exposure. As the magnitude of deep pumping continues to increase, this work focuses on the geochemical and hydrologic questions surrounding the vulnerability and sustainability of low-As aquifers in Bangladesh, the country most affected by As crisis. In an effort to better understand the residence time of groundwater in low-As aquifers at depth, radiocarbon (14C) and 13C in dissolved inorganic carbon, tritium (3H), stable isotopes of hydrogen (2H) and oxygen (18O), and noble gas concentrations were measured across a ~25 km2 area of Araihazar, ~30 km east of Dhaka. Groundwater from >120 m depth is shown to be ~10,000 years old and its isotopic signatures indicate that recharge occurred at the time of changing climate from the late Pleistocene to early Holocene, with little recharge occurring since. In contrast, the intermediate depth low-As aquifers (<120 m) have a heterogeneous distribution of groundwater chemistry and ages, and contain groundwater recharged <60 years ago in certain locations. In one such area surrounding a small village, the effects that subsurface clay layer distribution has on recharge patterns and redox status of the intermediate aquifer was investigated. The relevant hydrogeologic and geochemical processes that led to documented failures of a community well at the site were assessed using a combination of solid and water phase geochemistry with tritium-helium (3H/3He) dating, hydraulic head monitoring, and pumping tests. Organic matter seeping from a compressible clay layer, which is subject to a pumping-induced, downward hydraulic gradient, reduces iron oxides and helps release As in the grey, upper part of the intermediate aquifer. No recent recharge was detected by 3H measurements in the upper, grey sand layer, however a layer of orange sand beneath it contains groundwater that was recharged 10-60 years ago. This groundwater laterally bypasses the confining clay layer to recharge the middle of the aquifer and contains dissolved As levels of <10 µg/L. In this particular case, the pore water that leaches from clay layers contributes to As contamination, whereas the lateral recharge with shallow groundwater coincides with the low-As depth. Thus, clay layers may not always protect the low-As aquifers from As contamination, even if they can block direct vertical recharge with shallow groundwater enriched in As and organics. Finally, the adsorption of As to aquifer sediments, as a natural mechanism of the low-As aquifer defense against contamination, was assessed in the field via a column study. The column experiments were conducted by pumping shallow, high-As groundwater through freshly collected sediment cores to quantify the retardation of As transport through the aquifer. This study demonstrated an elegant method of assessing contaminant transport under nearly in situ conditions that resulted in sorption estimates similar to those made by field studies using more challenging methods or located at hard-to-find sites with convenient flow patterns. My work, therefore, contributed to a better understanding of low-As aquifers in Bangladesh from the perspectives of both the groundwater flow and water-sediment interactions on various scales, and it integrated methods that can be employed elsewhere to characterize aquifers and study contaminant transport.

Inorganic arsenic exposure is a well-known toxicant of which we are still discovering harmful effects. People are exposed to inorganic arsenic in the environment through either drinking arsenic-contaminated groundwater or consuming arsenic-contaminated food. Regarding global public health, drinking water is still the most important source of inorganic arsenic exposure and is the main focus of this work. The overall goal of this dissertation is to answer some pointing epidemiological questions about exposure to inorganic arsenic: How much do we know about inorganic arsenic and non-malignant lung disease in the general population? To what extent are adolescents with lifetime arsenic exposure susceptible to the respiratory consequences seen in adults? And what actions can be taken to effectively reduce exposure from arsenic-contaminated drinking water? First, we conducted a systematic review of 29 peer-reviewed articles from various populations around the world. The review focused on the different ways in which arsenic is associated with respiratory health to help inform policy makers and public health researchers on the existing evidence. In short, associations between arsenic and respiratory health were noted throughout the lifespan: in infancy, there was growing evidence that in utero arsenic exposure was associated with increased frequency and severity of respiratory tract infections; in childhood, evidence of respiratory symptoms also began to appear; and in adulthood, there was consistent evidence that arsenic exposure was associated with deficits in lung function and increased reports of coughing and breathing problems. The review also uncovered some research gaps, including few studies with strong exposure history from early life and few studies examining respiratory effects during adolescence. Next, we used a life course epidemiological approach to create a more precise understanding of arsenic exposure and respiratory health during the teenage years. This study examined the relationship between lifetime arsenic exposure and lung function in 14-17 year olds, thus studying the period of maximal lung function before natural decline. Overall, higher arsenic exposure was associated with lower lung function levels; however, these associations were only observed in males. This study used a sensitive marker of lung function to investigate early signs of small airway disease. Incorporating this common marker of small airway disease and airflow limitation in future studies on arsenic and respiratory health may help clarify how inorganic arsenic contributes to the development of chronic respiratory disease. Lastly, we evaluated the effectiveness of arsenic removal filters at the household-level in rural Bangladesh. Identifying sustainable ways of reducing exposure to arsenic from naturally contaminated groundwater has been a major environmental health challenge. Although lab-approved arsenic removal water filters exist, there was limited evidence of their prolonged efficacy in the field. To our knowledge, this was the largest and longest deployment of filters accompanied by monitoring of urinary arsenic. Our results demonstrated that filters can temporarily reduce arsenic exposure for weeks to a few months, but should not be considered as a long-term arsenic mitigation option. This failed attempt to reduce exposure confirmed that alternative mitigation strategies need to be employed in Bangladesh, particularly among more vulnerable populations, including pregnant women and young children. This dissertation has important policy implications for future arsenic research and mitigation efforts and should be effectively communicated to policy makers, public health officials, and the general population. Given the pervasive nature of arsenic exposure and the growing evidence of health consequences at different stages throughout the life course, the continued integration of information on inorganic arsenic and research collaborations across disciplines is critical for the prevention and mitigation of arsenic-induced health consequences.

In rural Bangladesh people drink water from an estimated 10-11 million tube wells, many with arsenic concentrations well above the national standard of 50µg/L. Characteristic skin lesions and more serious health effects are probable. The research reported here was designed to determine the relation between arsenic concentration and skin lesions on hands and feet controlling for education, use of tube well water, protein consumption and body mass index (BMI). The investigation included a well survey, a prevalence survey and a nested case-referent analysis. Studies were conducted in two villages (population 11670) in northern Bangladesh. In the well survey 1509 wells in use were identified and measurements of arsenic concentration made in 1422 (94%). Three estimates were made for each well, which yielded correlation among repeats = 0.93. The overall median was 47mg/L and the highest recorded 1760 mg/L. Paramedics examined soles and palms of 11087 individuals for skin lesions and identified 168 cases (1.5%). In the third phase, cases (over 16 years) were matched by age, gender and village to referents (target of 3) without skin lesions. Cases and referents were interviewed about protein in diet, use of well water, education and residential history. Conditional logistic regression was used to assess the effects of arsenic concentration, controlling for confounders. Subjects with lesions had a higher median concentration (250µg/L) than those without (47µg/L). Prevalence increased with both age and arsenic concentration, reaching 26.7% in those over 50 years of age and >500 µg/L. Of the 160 cases (≥16 years) 137 were interviewed, 127 with arsenic concentration measured in well water, together with their 504 referents. Cases were somewhat more likely to have lived in the villages throughout their lives and less likely to report using tube well water for cooking. The final model confirmed the high risk of lesions associated with arsenic concentrations. Using ≤50µg/L for comparison, an odds ratio of 15.2 (95%CI 7.2-32.2) was observed for those using tube wells with concentrations >500 µg/L, adjusting for use of tube well water in cooking and lifetime residence in the villages. The results from this research provide continuing support for the use of 50µg/L as a useful national standard. While the enforcement of this standard has immediate value, it cannot be considered final without comparable information on more serious health risks.

Reducing population exposure to inorganic arsenic (iAs), a known carcinogen and highly toxic metalloid of great public health concern, remains an ongoing challenge worldwide and in the United States (US). In the US, the Environmental Protection Agency (EPA) regulates the maximum contaminant level (MCL) for total arsenic in public drinking water supplies through the Safe Drinking Water Act. In 2001, the US EPA implemented the Final Arsenic Rule, which lowered the MCL for arsenic in public drinking water supplies from 50 to 10 µg/L. Reductions in iAs exposure and subsequent related disease associated with this important regulatory change have not been quantified. Currently, no national-level exposure estimates of iAs drinking water exposure are available for US residents reliant on public drinking water. There is a critical need to identify susceptible subgroups of the US population who remain at risk for elevated iAs drinking water exposure. This dissertation aimed to quantify the reduction in drinking water iAs exposure resulting from the US EPA MCL regulatory change, to estimate drinking water iAs exposure for US residents reliant on public drinking water, to identify susceptible subgroups across the US whose water iAs remains high, and to determine if iAs exposure was associated with heart disease mortality in the general US population. Chapter 1 provides background information necessary to contextualize the work contained in this dissertation. In Chapter 2, we conducted a cross-sectional analysis of dietary sources of iAs exposure in the Strong Heart Family Study, a cohort of American Indian adults followed primarily for cardiovascular disease, using a self-reported food frequency questionnaire and urinary iAs measurements. Self-reported intake of rice, organ meat, processed meat, and non-alcoholic drinks was associated with increased urinary iAs concentrations. Diet alone explained only 3% of total variability in urinary iAs concentrations, indicating that the majority of iAs exposure for SHFS participants occurs from drinking water. Second, (in Chapter 3), we explored trends in water iAs exposure in the general US population associated with the EPA’s MCL change using the National Health and Nutrition Examination Survey (NHANES) from 2003-2014, separately for participants reliant on public drinking water vs. private well water (which is not subject to US EPA regulation). We estimated that implementation of the new US EPA MCL was associated with a 17% reduction in drinking water iAs exposure for all participants reliant on public drinking water; the corresponding reduction was 32% for Mexican-American participants. No reduction was observed for participants reliant on private wells. Third (in Chapter 4), we estimated drinking water iAs exposure at the community water system and county-level across the entire US from 2006-2011 using the US EPA’s Six Year Review of Contaminant Occurrence database. We estimated that nationwide public drinking water iAs concentrations decreased by 8.5% and 21.6% at the 80th and 99th percentiles of the water iAs distribution in accordance with the MCL implementation, with significant differences across US subgroups. Greater decreases in iAs concentrations were reported for systems reliant on groundwater, systems serving smaller populations, and systems in the Northeast, Central Midwest, and Southwestern regions of the US. Susceptible subgroups whose public drinking water iAs exposure remains high include populations served by small community water systems reliant on groundwater, communities in the Southwestern US, Semi-Urban, Hispanic communities, and Rural, American Indian communities. Fourth (in Chapter 5), we assessed six-year average arsenic concentrations in community water systems exclusively serving correctional facilities in the US (e.g. prisons, jails, detention centers) compared to other community water systems. Average arsenic concentrations were twice as high in correctional facility community water systems located in the Southwest (6.41 µg/L, 95% CI 3.48, 9.34) compared to all other community water systems in the Southwest (3.11 µg/L, 95% CI 2.97, 3.24). Over a quarter of correctional facility systems in the Southwest reported a six-year average arsenic concentration exceeding the 10 µg/L MCL. Persons incarcerated in the Southwestern US were at disproportionate risk of drinking water arsenic exposure and related disease from 2006-2011. Fifth (in Chapter 6), we multiply imputed urinary arsenic concentrations below the limit of detection (LOD) in NHANES 2003-2016 using a Bayesian Tobit regression model. Epidemiological analyses of urinary arsenic data in NHANES are limited by the relatively high analytical LODs and large proportion of participants with undetectable values. Distributions of urinary arsenic originally reported in NHANES, which replace values below the LOD with the LOD divided by the square root of two, likely overestimate iAs exposure at the lowest exposure levels and may introduce significant bias. Bayesian-multiply imputed datasets may improve the assessment of iAs exposure in cohorts with high analytical LODs for arsenic species. Finally (in Chapter 7), we evaluated the association between urinary iAs concentrations (internal dose) and heart disease mortality as recorded in the National Death Index in NHANES 2003-2014 participants. We found a positive but non-significant prospective association between increasing iAs exposure and heart disease mortality for all participants (hazard ratio 1.15, 95% CI 0.77, 1.70), and a significant positive association for non-Hispanic white participants using flexible spline models. Geometric mean ratios of iAs exposure were higher among cases compared to non-cases, especially for Mexican-American participants (1.30, 95% CI 0.90, 1.88). These findings further support the potential association between low- to moderate- iAs exposure and cardiovascular disease in the US population, and indicate that further high-quality prospective studies of Hispanic and Latino Americans are needed to investigate the potential increased susceptibility of Mexican-Americans to iAs-related cardiovascular disease. Taken together, these studies suggest that while the implementation of the US EPA’s 10 µg/L MCL has reduced drinking water arsenic exposure for many Americans reliant on public drinking water systems, these reductions were not uniform across all US populations. Populations who remain at risk of elevated drinking water arsenic exposure include those reliant on domestic wells, those located in the Southwest, persons incarcerated in the Southwest, tribal communities, and Hispanic communities. Further high-quality epidemiologic research is needed to evaluate the association between low- to moderate iAs exposure and cardiovascular disease in these populations. Stronger federal regulations, targeted compliance enforcement and technical assistance, and other public health interventions are needed to reduce drinking water arsenic exposure in these communities.

Background: Environmental exposure to inorganic arsenic (InAs) is a considerable worldwide problem, and over 57 million people in Bangladesh have been chronically exposed to arsenic-contaminated drinking water. Ingested inorganic arsenic (InAs) undergoes hepatic methylation generating monomethyl- (MMAs) and dimethyl- (DMAs) arsenic species in a process that facilitates urinary As (uAs) elimination. Of these three metabolites (InAs, MMA and DMA), MMA the most toxic, InAs is the second most toxic, and DMA is the least toxic. Consequently, increased MMAs is associated with increased risk of As-related adverse health outcomes. One-carbon metabolism (OCM), the biochemical pathway that provides methyl groups for As methylation, is influenced by folate and B12. A growing body of research, including cell-culture, animal-model, and epidemiological studies, have demonstrated the role of OCM-related micronutrients in As methylation. While folate supplementation is known to increase As methylation and lowers blood As (bAs) in adults, little data is available for adolescents. OCM also supports nucleotide and amino acid synthesis, particularly during periods of rapid growth, such as adolescence. In Bangladesh, deficiencies in folate and vitamin B12 are widespread. These micronutrients are essential for OCM and As methylation, and they are also critical for neural development, since they are necessary for the synthesis of neurotransmitters and myelin, and critical for generation of S-adenosyl-methionine (SAM) via OCM. Deficiencies in folate and B12 have been shown to negatively influence cognitive function in adults and children, but this has not been adequately characterized in adolescents. Individuals living in Bangladesh, facing As exposure and nutritional deficiency, also experience environmental exposure to elevated levels of cadmium (Cd), manganese (Mn), and lead (Pb). These metals have been linked to adverse neurocognitive outcomes in adults and children, though their effects on adolescents are not yet fully characterized. Additionally, previous studies have linked selenium (Se) levels to protective effects against toxicity of these other metals, as Se is an essential nutrient. Metal mixtures are also understudied in adolescents, and more research is needed. Objectives: Firstly, the research presented in this dissertation will examine the previously published evidence that nutritional status and nutritional interventions can influence the metabolism and toxicity of As, with a primary focus on folate. Secondly, the associations between OCM-related micronutrients and As methylation in Bangladeshi adolescents chronically exposed to As-contaminated drinking water will be studied. Thirdly, this dissertation will investigate the associations between folate and B12 nutritional status, homocysteine, and cognitive function as measured by two different test instruments in Bangladeshi adolescents. Finally, the associations between mixed metals exposure and cognitive function in Bangladeshi adolescents will be examined. Methods: The Metals, Arsenic, & Nutrition in Adolescents study (MANAs) is a cross-sectional study of 738 Bangladeshi adolescents aged 14-16 years, whose parents were enrolled in our group’s previous Health Effects of Arsenic Longitudinal Study (HEALS). Venous blood samples were collected from adolescent participants for measurement of plasma folate, red blood cell (RBC) folate, plasma B12, plasma homocysteine (Hcys), blood As (bAs), blood cadmium (bCd), blood manganese (bMn), blood lead (bPb), and blood selenium (bSe). Urine samples were collected for measurement of urinary arsenic and urinary arsenic metabolites (InAs, MMA, and DMA) expressed as a percentage of total urinary As: %InAs, %MMAs, %DMAs. Additionally, participants completed a modified version of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and an abbreviated version of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Associations between predictors and outcomes were assessed using linear regression analyses. Associations for the mixture of metals were also examined via Bayesian Kernel Machine Regression (BKMR), which assessed the effects of the metals mixture in addition to examining the effects each individual metal component. Results: In the linear regression analyses examining associations between nutritional status and arsenic methylation profiles controlling for water As and BMI, in girls we observed that RBC folate was inversely associated with bAs, plasma B12 was inversely associated with uAs, and, somewhat unexpectedly, plasma Hcys was inversely associated with %MMA. Among boys, we saw that plasma folate was inversely associated with %InAs and positively associated with %DMA, RBC folate was inversely associated with %InAs and positively associated with %MMA, while Hcys was positively associated with %InAs. In linear regression analyses examining the associations between nutritional status and cognitive function controlling for covariates, we found no significant associations between nutritional status and cognitive function as measured by WISC. For cognitive function as measured by CANTAB, we observed positive associations between plasma folate and spatial recognition memory, and between plasma B12 and spatial working memory. In our investigation of the associations between metal exposures and cognitive outcomes, linear regression analysis revealed negative associations between exposure to As and Mn and spatial working memory. Negative associations were also seen between bCd and Spatial Recognition Memory, and between bPb and Delayed Match to Sample. Finally, a positive association was seen between bSe and Spatial Span Length. Our BKMR results showed no overall effect of the mixture but further characterized the associations for individual metals within the mixture. BKMR analyses indicate that bPb has a negative association to Delayed Match to Sample, and that there are positive associations between bSe and Planning, Reaction Time, and Spatial Span. BKMR also showed higher concentrations of bCd to be negatively associated with Spatial Recognition Memory. Posterior inclusion probability consistently rated Se, which has a protective effect, as the most influential component of the mixture. Conclusions: These findings suggest that associations between OCM nutritional status, blood arsenic, and distribution of urinary As metabolites in adolescents are similar to previously reported observations in adults and in children. The inverse association between Hcys and %MMA in girls is unexpected since Hcys is known to be an indicator of impaired OCM and low folate/B12 in adults. These findings also suggest that associations between nutritional status and cognitive function in adolescents are consistent with previously reported associations in adults and children. The observation of positive associations between folate and spatial recognition memory and between B12 and spatial working memory are consistent with findings in animal models, children, and adults, all of which link deficiencies in these two micronutrients to memory deficits. The findings of the metals investigation are also consistent with previously reported observations in adults and children, and these results also suggest agreement between linear regression and BKMR analysis of the mixed metal exposure, with the BKMR further demonstrating associations seen in the linear regression analysis. Generally, Se had a protective effect for cognitive outcomes, whereas Mn and As were linked to poorer working memory, and Cd and Pb were linked to poorer visual recognition and memory. BKMR reinforced and further characterized results of the linear regression analyses. Overall, these results indicate that the associations between OCM-related micronutrients, arsenic methylation, metal exposure, and cognitive function in adolescents are generally similar to prior findings in adults and children. However, additional studies are needed to evaluate the impact of OCM and As methylation on As-related adverse health outcomes (such as cancer and cardiovascular disease) in people exposed to As during adolescence. These results also suggest that further investigation into the associations between nutritional status and measures of cognitive function in adolescents is merited, and that further exploration of homocysteine’s role in adolescent physiology is needed. Most importantly, these findings suggest that both nutritional interventions involving B12 and folate supplementation and metal exposure mitigation efforts may have a positive impact on overall health and well-being for individuals facing these environmental exposures. In the long term, interventions to reduce exposure to metals and nutritional deficiency, and interventions to attenuate the effects of these exposures have the potential to influence lifelong cognitive function, possibly influencing professional achievement and economic outcomes in regions having a high prevalence of nutritional deficiencies, arsenic exposure, and environmental exposure to metals mixtures.

Background: In the country of Bangladesh, arsenic (As) exposure and high plasma homocysteine (hyperhomocysteinemia; HHcys) are widely prevalent. An estimated 35-77 million people in Bangladesh are exposed to As above the World Health Organization standard of 10 μg/L, while a cross-sectional study by our group estimated that 63% of men and 26% of women had HHcys. Both As exposure and HHcys are associated with adverse health outcomes. Arsenic exposure is an established cause of skin, lung, and bladder cancer, and cardiovascular disease, while HHcys is a strongly associated with increased risk for cardiovascular disease. Chronic kidney disease is emerging as an As-linked disease outcome. Potential mechanisms for adverse health effects induced by As (e.g. nephrotoxicity) include oxidative stress and inflammation. Inorganic As is metabolized through a series of methylation and reduction reactions which facilitate As excretion in urine; arsenite (AsIII), the primary form of As in Bangladesh drinking water, is converted to monomethylarsonic acid (MMAV), monomethylarsonous acid (MMAIII), and dimethylarsinic acid (DMAV). The methyl donor for these methylation reactions is S-adenosylmethionine (SAM). Because the availability of SAM is modulated by various nutritional parameters, nutritional interventions have the potential to enhance As methylation. Supplementation with folic acid (FA), which increases liver SAM, has been shown by our group to enhance As methylation and lower blood As in folate-deficient Bangladeshi adults. The endogenous synthesis of creatine from guanidinoacetate (GAA) consumes a large proportion of SAM, and creatine supplementation in the diet can downregulate endogenous creatine synthesis by inhibiting GAA production. In this way, creatine supplementation has the potential to spare SAM, enhance As methylation, and also lower homocysteine (Hcys), a by-product of SAM-dependent methylation. The potential for dietary creatine to enhance As methylation may explain the frequently observed associations of urinary creatinine with a decreased proportion of inorganic As in urine out of total urinary As (u%InAs), and an increased proportion of DMA in urine out of total urinary As (u%DMA) in epidemiological studies. Alternatively, it is possible that these associations are due to confounding by renal function, which could influence both As and creatinine excretion. Objectives: Our objectives were to determine (1) whether folic acid and creatine lower blood As in a mixed folate-deficient and replete population, (2) whether creatine lowers plasma total homocysteine (tHcys), (3) whether As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR), and whether these effects are greater in those with a more oxidized plasma glutathione redox potential (EhGSH), and (4) whether As metabolite proportions in urine and blood are associated with eGFR, and whether these associations may explain the relationship between As metabolite proportions and urinary creatinine. Methods: We addressed these objectives in five epidemiologic investigations of As-exposed Bangladeshi adults, employing data from a randomized placebo-controlled trial (the Folic Acid and Creatine Trial (FACT)) and two cross-sectional studies (the Nutritional Influences on Arsenic Toxicity (NIAT) study, and the Folate and Oxidative Stress (FOX) study). In the 24-week FACT study, participants were randomized to receive either placebo, 400 μg/day FA (FA400), 800 μg/day FA (FA800), 3 g/day creatine (Cr), or 3 g/day creatine + 400 μg/day FA (Cr+FA400). At week 12, half of the participants in the FA400 and FA800 groups were switched to placebo, while the other half continued their assigned supplements. Additionally, at week 12 participants in the Cr and Cr+FA400 groups were switched to placebo. In Chapter 4 (FACT), we examined whether FA400, FA800, Cr, or Cr+FA00 lowered blood As to a greater extent than placebo over the first 12 weeks of the trial, and whether a rebound in blood As occurred from week 12 to 24 related to cessation of FA supplementation. In Chapter 5 (FACT), we examined whether Cr or Cr+FA400 lowered plasma tHcys to a greater extent than placebo or FA400 alone, respectively, over the first 12 weeks of the trial. In Chapter 6 (NIAT), we examined the associations of water and urinary As with eGFR, and whether eGFR confounded the associations between urinary creatinine and the urinary %As metabolites; we also explored the associations of eGFR with the urinary %As metabolites. In Chapter 7 (FOX), we examined the associations of eGFR with the urinary and blood %As metabolites; we also examined whether the relationship between blood and urinary %As metabolites was decreased among those with reduced renal function. In Chapter 8 (FOX), we examined the associations of water, blood, and urinary As with markers of inflammation (C-reactive protein (CRP) and α-1 acid glycoprotein (AGP)), and eGFR, and investigated whether these associations were modified by the plasma EhGSH. Results: FA800 lowered blood As to a significantly greater extent than placebo over the 24 weeks of the FACT study, with no rebound in blood As related to cessation of FA supplementation. FA400, Cr, and Cr+FA400 did not lower blood As to a greater extent than placebo (Chapter 4). Cr and Cr+FA400 did not lower plasma tHcys to a greater extent than placebo or FA400 alone, respectively. However, in the Cr+FA400 group we observed a significant correlation between a decrease in plasma GAA over time and a decrease in plasma tHcys over time (Chapter 5). Total urinary As was marginally associated with a decrease in eGFR in the NIAT study, though water As was not. Additionally in the NIAT study, while eGFR did not confound the relationship between urinary creatinine and urinary %As metabolites, we observed a positive association between eGFR and u%InAs, and a negative association between eGFR and u%DMA (Chapter 6). Likewise in the FOX study, eGFR was positively associated with u%InAs and negatively associated with u%DMA; the associations of eGFR with the blood %As metabolites were in the same direction, although not statistically significant. We additionally observed that for a given increase in blood %InAs, the increase in urinary %InAs tended to be smaller in those with reduced renal function, compared to those with normal renal function (Chaper 7). In the FOX study we also observed the total blood As and urinary As were marginally associated with decreased eGFR, while water As was not. Water As, urinary As, and blood As were significantly positively associated with plasma CRP in those with low plasma GSH or a more oxidized plasma EhGSH (Chapter 8). Conclusions: Strategies to reduce risk for As-induced diseases are sorely needed, particularly due to barriers to As exposure removal and/or persistent elevated risk from past As exposure. Several susceptibility factors which can potentially be intervened upon have been discussed in this dissertation, namely folate nutritional status, redox status, and renal capacity to excrete As. Our finding that folic acid supplementation (800 μg/day) lowered blood As to a greater extent than placebo in a randomized trial indicates that improving the folate status of the general Bangladeshi population may reduce the body burden of As. Folate fortification of food in Bangladesh, in addition to potentially reducing risk for As-induced diseases, would have the additional benefit of substantially lowering the prevalence of HHcys. Our finding in a cross-sectional study that individuals with a more oxidized plasma glutathione redox potential were susceptible to As-induced inflammation may indicate that improving redox status can protect against As-induced inflammation. Randomized trials are needed to confirm a protective effect of antioxidants; upon confirmation, antioxidant dietary recommendations for As-exposed populations could potentially be implemented. Finally, our cross-sectional finding of a positive association between eGFR and urinary %InAs, and that eGFR modified the relationship between blood and urinary %InAs, suggests that InAs excretion may be impaired among individuals with reduced renal function. A decreased renal capacity to excrete InAs may lead to accumulation of InAs in tissues, and related health effects. Potential interventions related to renal function include treatment of risk factors for chronic kidney disease (e.g. blood pressure, blood glucose) in order to prevent onset of renal function deterioration, or to screen for chronic kidney disease in order to identify susceptible individuals and conduct directed interventions. Of these three susceptibility factors, the strongest evidence exists for the potential of folic acid to lower blood As. In Bangladesh, where As exposure and HHcys are widely prevalent, folate fortification should be considered a viable option for reducing risk for As- and Hcys-related diseases.

This dissertation examines topics related to development, environment and health in developing countries using empirical methods. In the first chapter, I study how developing countries can increase enforcement to reduce subsidy leakage in public programs, by investing in the state capacity to target program beneficiaries. This chapter further attempts to understand how the formal sector and black market respond to a policy that reduces diversion of a subsidized commodity. I explore these questions using the case of a Unique ID-based direct fuel subsidy transfer policy in India. Second chapter focuses on the health and wealth trade off near mineral mining operations in developing countries. Using extensive data on mining, health outcomes and assets from 44 developing countries, this study quantifies the wealth gain and adverse health impact of mineral mining. With a number of empirical strategies, this study shows that, despite high wealth gains, how heavy metal mining significantly increases the level of anemia in women and stunting in children living near mines. In the third chapter, I estimate demand for a water quality diagnostic product -- arsenic testing, when it is offered at a price. I further look into various aspects related to selection, learning and households behavioral response to the information. This study is based on a field experiment in Bihar, India.

PhD (Environmental Sciences)
Department of Ecology and Resource Management
The presence of arsenic in groundwater has drawn worldwide attention from researchers and public health officials due to its effects on human health such as, cancer, skin thickening, neurological disorders, muscular weakness, loss of appetite and nausea. World Health Organisation (WHO) has set the limit of 10 μg/L for arsenic in drinking water in trying to reduce the effects of arsenic. This was further adopted by South African National Standard (SANS). The present study aims at evaluating arsenic concentration in selected groundwater sources around Greater Giyani Municipality in Limpopo Province and further synthesize clay based adsorbents for arsenic removal using Fe3+ and Mn2+ oxides and hexadecylammonium bromide (HDTMA-Br) cationic surfactant as modifying agents. The first section of the work presented the hydrogeochemical characteristics of groundwater in the Greater Giyani Municipality. The results showed that the pH of the samples ranges from neutral to weakly alkaline. The dominance of major anionic and cationic species was found to be in the order: HCO3 ->Cl->SO4 2->NO3 - and Na+>Mg2+>Ca2+>K+>Si4+, respectively. Hydrogeochemical facies identified in the study area include CaHCO3 (90%) and mixed CaNaHCO3 (10%) which shows the dominance of water-rock interaction. About 60% of the tested samples contains arsenic concentration above 10 μg/L as recommended by SANS and WHO. Concentration of arsenic was found to be ranging between 0.1 to 172.53 μg/L with the average of 32.21 μg/L. In the second part of this work, arsenic removal efficiency of locally available smectite rich and kaolin clay was evaluated. Results showed that the percentage As(V) removal by kaolin clay was optimum at pH 2 while the percentage As(III) removal was greater than 60% at pH 2 to 12. For smectite rich clay soils, the percentage of As(III) and As(V) removal was found to be optimum at pH between 6 and 8. The adsorption isotherm data for As(III) and As(V) removal by both clays fitted better to Freundlich isotherm. Adsorption of both species of arsenic onto the clay mineral occurred via electrostatic attraction and ion exchange mechanisms. Both clay soils could be regenerated twice using Na2CO3 as a regenerant. Kaolin clay showed a better performance and was selected for further modification. In the third section of this work, Fe-Mn bimetal oxide modified kaolin clay was successfully synthesized by precipitating Fe3+ and Mn2+ metal oxides to the interlayer surface of kaolin clay. Modification of kaolin clay increased the surface area from 19.2 m2/g to 29.8 m2/g and further v decreased the pore diameter from 9.54 to 8.5 nm. The adsorption data fitted to the pseudo second order of reaction kinetics indicating that adsorption of As(III) and As(V) occurred via chemisorption. The adsorption isotherm data was described by Langmuir isotherm models showing a maximum As(III) and As(V) adsorption capacities of 2.16 and 1.56 mg/g, respectively at a temperature of 289 K. Synthesized adsorbent was successfully reused for 6 adsorptiondesorption cycles using K2SO4 as a regenerant. Column experiments showed that maximum breakthrough volume of ≈2 L could be treated after 6 hours using 5 g adsorbent dosage. Furthermore, the concentration of Fe and Mn were within the WHO permissible limit. In the fourth part of the work kaolin clay was functionalized with hexadecyltrimethylamonium bromide (HDTMA-Br) cationic surfactant and its application in arsenic removal from groundwater was investigated. The results revealed that adsorption of As(III) and As(V) is optimum at pH range 4-8. The maximum As(III) and As(V) adsorption capacities were found 2.33 and 2.88 mg/g, respectively after 60 min contact time. Pseudo first order model of reaction kinetics described the adsorption data for As(V) better while pseudo second order model described As(III) adsorption data. The adsorption isotherm data for As(III) and As(V) fitted well to Langmuir model indicating that adsorption of both species occurred on a mono-layered surface. Adsorption thermodynamics model revealed that adsorption of As(III) and As(V) was spontaneous and exothermic. The As(III)/As(V) adsorption mechanism was ascribed to electrostatic attraction and ion exchange. The regeneration study showed that synthesized adsorbent can be used for up to 5 times. In the firth part of the work inorgano-organo modified kaolin clay was successfully synthesized through intercalation of Fe3+ and Mn2+ metal oxides and HDTMA-Br surfactant onto the interlayers of the clay mineral. The batch experiments showed that As(III) removal was optimum at pH range of 4-6, while the As(V) removal was optimum at pH range 4-8. The adsorption data for both species of arsenic showed a better fit to pseudo second order of reaction kinetics which suggest that the dominant mechanism of adsorption was chemisorption. The isotherm studies showed better fit to Langmuir isotherm model as compared to Freundlich model. The maximum adsorption capacity As(III) and As(V) at room temperature as determined by Langmuir model were found to be 7.99 mg/g and 7.32 mg/g, respectively. The thermodynamic studies for sorption of As(III) and As(V) showed negative value of ΔGᴼ and ΔHᴼ indicating that adsorption process occurred spontaneously and is exothermic in nature. The regeneration study showed that the vi inorgano-organo modified kaolin clay can be reused for up 7 adsorption-regeneration cycles using 0.01 M HCl as a regenerant. Thomas kinetic model and Yoon-Nelson model showed that the rate of adsorption increases with increasing flow rate and initial concentration and decreases with increasing of the bed mass. In conclusions, adsorbents synthesized from this work showed a better performance as compared to other adsorbents available in the literature. Among the synthesized adsorbents, inorgano-organo modified clay showed highest adsorption capacity as compared to surfactant functionalized and Fe-Mn bimetal oxides modified kaolin clay. However, all adsorbents were recommended for use in arsenic remediation from groundwater. The following recommendations were made following the findings from this study: 1) routine monitoring of arsenic in groundwater of Greater Giyani Municipality, 2) evaluating the possible link between arsenic exposure and arsenic related diseases within Giyani in order to find the extent of the problem in order to establish the population at risk, 3) The toxicity assessment for HDTMA-Br modified kaolin clay should be carried out, 4) Materials developed in the present study should be modeled and tested at the point of use for arsenic removal, and lastly, 5) this study further encourage the development of other arsenic removal materials that can be used at household level.
NRF

This dissertation discusses three questions of development and environmental economics. First, it assesses the impact of mineral mining on the health and wealth of households in local communities across 44 developing countries, using micro data. Secondly, it presents evidence from a randomized controlled trial on the cost-shared provision of well-water tests for arsenic. Finally, it analyzes measurement error in a satellite night light data product widely used in development research, and investigates the scope for using the data in very high spatial resolution.