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Arsenic is a well-known natural environmental contaminant distributed in food, water, air, and soil. The developmental toxicity of arsenic exposure is a significant concern in large parts of the world. Unlike acute toxic exposure, the classical dose–response relationship is not adequate for estimating the possible impact of chronic low-level arsenic exposure. The real-life risk and impact assessments require the consideration of the co-exposure to multiple toxins, individual genetic and nutritional predisposition, and the particularly vulnerable stages of the neurodevelopment. This context shifts the assessment model away from the 'one-exposure-for-one-health-effect.' We underscore the need for a comprehensive risk assessment that takes into account all relevant determinants. We aim to elaborate a model that can serve as a basis for an understanding of complex interacting factors in a long-lasting and ongoing low-level arsenic exposure, to identify, protect, and support the children at risk. [ABSTRACT FROM AUTHOR]