Groundwater is vital for irrigated agriculture, but irrigation with arsenic (As) contaminated water can lead to significant accumulation of As in crops, adversely affecting yield and quality. This study evaluates the effects of environmentally relevant As concentrations of 200 mu gl- 1 (lower dose, LAs) and 1000 mu gl- 1 (higher dose, HAs) on metabolite profiles, nutrient levels in grains, and physiology of rice plants. Thirty-eight metabolites were identified in grains from unexposed rice plants, with substantial alterations observed due to As accumulation. Major sugar metabolites exhibited a negative correlation with As levels, with monosaccharides showing a more pronounced reduction than disaccharides. Specifically, grains from plants exposed to HAs showed reduction in D-fructose, D-ribose, D-galactose, and D-glucose levels by 78%, 42%, 40%, and 19%, respectively, compared to control. Other metabolites, including phytosterols and fatty acids (such as alpha-linolenic and tetradecanoic acids), significantly decreased under LAs and became undetectable in grains from plants exposed to HAs. Furthermore, As exposure restricted photosynthetic rates, water use efficiency, and stomatal conductance, impairing rice growth and yield. These physiological changes contributed to alterations in sugar and metabolite composition, confirmed by principal component analysis (PCA). Importantly, irrigation with groundwater containing 200 mu gl- 1 As increased cancer risk tenfold, while 1000 mu gl- 1 raised the risk twentyfold compared to the U.S. EPA threshold of 1 in 10,000 (10(-)4), highlighting a significant health risk for populations consuming As-contaminated rice grains in affected regions.