Pesticide residues in rice across regions and nations: Contamination profiles, dietary health risks, and mechanism-informed prioritization

Rice consumption constitutes a primary pathway for non-occupational pesticide exposure globally. However, systematic characterizations linking multi-regional residue profiles with mechanism-informed toxicity prioritization remain insufficient. Here, we applied an integrated "residue-exposure-mechanism" framework to analyze 98 pesticides across 306 rice samples, comprising 234 from China and 72 from major international producers. Forty-four pesticides were detected across rice samples, including 32 insecticides, 9 fungicides, and 3 herbicides. All samples contained detectable residues, with total concentrations ranging from 0.01 to 242.28 μg/kg dry weight. Insecticides dominated pesticide profiles, while the fungicide carbendazim was nearly ubiquitous. Pronounced spatial heterogeneity in pesticide contamination was observed across surveyed countries, as Pakistan exhibited the highest overall pesticide burden while Russia displayed the lowest. The residues within China followed a "east/south higher, west/north lower" gradient. The maximum total hazard quotient occurred in sample from Myanmar, followed by Pakistan and India, and the dietary risks were primarily driven by lambda-cyhalothrin, profenofos and chlorpyrifos. By integrating exposure metrics with ToxCast in vitro bioactivity and ADME evidence, we identified 20 priority pesticides exhibiting multi-organ bioactivity signatures. Overall, this study provides a comprehensive multi-region examination of pesticide residues in rice and offers a mechanism-informed screening strategy to guide pollutant prioritization and risk management.