Critical evaluation of heavy metal exposure biological models: An insight from the current cadmium exposure toxicological research

The industrial development of modern society has unleashed Pandora's box of heavy-metal pollution. Shocking public pollution incidents, such as Minamata and cadmium-induced Itai-itai diseases, have drawn public attention to the importance of preventing and controlling heavy metal pollution. To clarify the circumstances, pathways and mechanisms of heavy metal effects on organisms, scientists have undertaken a series of multidimensional explorations. These investigations have significantly advanced our knowledge of the hazards associated with heavy metal exposure and the development of potential mitigation strategies. However, many scientific experiments have employed biologically unrealistic modeling methods, which can amplify certain safety risks to some extent, even affecting safety-related decision making and leading to the spread of anxiety and panic. Taking cadmium as a representative example, heavy metal exposure involves variations in their types, individual biological variability, and variations in ‘dose-response relationship’ which makes it inherently complex; thus, it is destined to be an incredibly intricate scientific issue. • Current cadmium exposure models show limitations in reflecting real-world routes and species differences. • Heavy metal pollution events underscore the need for accurate toxicological research. • Uncertainties in dose-response and individual variations complicate model applicability and risk decisions. • Ethical principles and policy frameworks guide effective prevention and intervention for vulnerable groups. • Big data, AI, and interdisciplinary methods offer potential for optimizing future models.