Improved Integrated Risk Assessment of Geogenic Arsenic: Exposure and Attributable Health Risks

The linkage between arsenic contaminated water and increased cancer risk is well recognized. The potential health risk posed by separate inorganic and organic arsenic species through combined exposure to arsenic contaminated water and staple foods is not well understood though. Therefore, this research aims to improve arsenic risk assessment by investigating the primary exposure sources, pathways, metabolism and response indicators in an integrated manner. The population based water and food consumption pattern characterised by this research was used to validate the cancer risk modelling which demonstrated that using water or food intake values from the developed world may not represent cancer risks to the specific population in question. Integrating this characterisation with arsenic species provided several key insights. Arsenate was identified as the main species in the ground water aquifers of five villages whilst the predominance of arsenite and its co-existence with arsenate in one village indicated variations in aquifer redox conditions. Wheat cultivated with arsenic-rich irrigation water proved to be an alternate exposure pathway of inorganic arsenic. The species specific probabilistic cancer and non-cancer risks were found to be higher for arsenite followed by arsenate, whilst no risk was found for dimethylarsinic acid of dietary origin. The comparative impact of various reference doses on chronic health risk substantiated that children are at higher vulnerability, whilst using population based exposure characteristics of this study population and relative risk estimates from southwest Taiwan, showed females to be at higher risk of life time bladder and lung cancer due to inorganic arsenic. No risk was associated with low doses of arsenic. Total ingested arsenic from water or food under the effect of certain potential modifiers was a significant predictor of arsenic species in human biomarkers and proved toenail to be a comparatively effective biomarker. At low arsenic levels in water, food associated total arsenic was a better predictor of urinary metabolites. The total arsenic intake from water and urinary metabolites under the effect of labour jobs strongly predicted the increased risk of arsenical skin lesions. Probabilistic risk modelling indicated that persons with skin lesions were at higher risk of transformation of skin lesions into skin cancer, also evidenced with their lower methylation capability. Overall, this thesis provides evidence that species based risk assessment requires a greater understanding of exposure matrix, toxicological thresholds and metabolic reactions from ingestion to potential endpoints. This study has provided a baseline of inorganic arsenic for risk management to set public health water supply goals and to minimize the daily consumption of cooked rice for compliance with the safe arsenic limit. The findings are suitable to support future regulatory processes for species based arsenic limits in water together with staple foods