Refining heavy metal risk in Southwest China's mining soils: Bioaccessible fractions and cellular toxicity reveal overlooked Cr hazards.

Heavy metal(loid) contamination of agricultural soils in mining areas presents a major threat to food safety and sustainable land management, especially in geochemically heterogeneous regions such as Southwest China. This study developed an integrated risk assessment framework combining physiologically based extraction tests (PBET) with human intestinal cell (Caco-2) assays to evaluate the bioaccessibility and toxicity profiles of Cu, Cd, Pb, Cr, and Ni in contaminated soils. Our results revealed that while Cd dominated ecological risks (contributing 78.7 % to the total risk index), Cr emerged as the primary carcinogenic threat with a lifetime cancer risk of 1.01 × 10⁻⁴, exceeding regulatory thresholds despite its relatively lower total concentration. The bioaccessible fractions of these metals induced significant dose-dependent cytotoxicity (5.7-26.7 % viability reduction) and oxidative stress (103-155 % ROS increase). Notably, Cr exposure caused substantial DNA damage as evidenced by γ-H2AX foci formation, confirming its underestimated genotoxic potential in conventional risk assessments. These findings demonstrate critical limitations in current models based solely on total metal concentrations, which overestimate risks from Cd and Cu while dangerously underestimating Cr's carcinogenicity. Our integrated approach provides a scientifically robust methodology that incorporates both bioaccessible fractions and cellular toxicity endpoints, offering more accurate risk stratification for contaminated sites. The study highlights the urgent need to refine existing regulatory frameworks by considering metal bioaccessibility and biological effects. These insights are particularly valuable for developing targeted remediation strategies and science-based policies in mining-affected regions with complex geochemical backgrounds, ultimately supporting sustainable agriculture and food security.