Impact of Dietary Cadmium Intake from Rice on Renal Function Biomarker and Population Toxicokinetic Modelling

Cadmium (Cd) exposure in humans primarily occurs through dietary intake, with conventional one-compartment toxicokinetic (TK) models linking dietary Cd intake to urinary Cd ( U Cd ) levels, predominantly in Western populations with low background exposure. However, the applicability of this model to regions with high dietary Cd intake, particularly from rice consumption, remains uncertain. In this study, we conducted a comprehensive population-based survey involving 686 individuals from a typical Cd-polluted area and 296 from a non-polluted area in China, where rice serves as the staple food in both regions. Additionally, we selected 34 individuals from the polluted area for a 27-month intervention, during which home-grown high-Cd rice was replaced with low-Cd rice available in the market. We closely monitored temporal changes in Cd concentration and stable isotope signatures in urine samples. The adults in the polluted area had much higher dietary Cd intakes (mean 58.5 µg kg −1 body weight month −1 ) and U Cd (geometric mean 6.1 µg g −1 creatinine) than those in the non-polluted area. There was a robust dose–response relationship ( R 2 = 0.67, n = 982) between U Cd and β2-microglobulin, a biomarker of renal tubular impairment. The intervention reveals that a considerable proportion of Cd rapidly exuded after recent dietary intake, contradicting the conventional TK model. The modified TK model incorporating the direct blood-urine allocation greatly improved the association between dietary Cd intake and U Cd . These results underscore the potential for high dietary Cd intake through rice in China to cause dose-dependent kidney damage. The modified TK model offers a reliable framework to estimate Cd-related thresholds and associated health risks for populations reliant on rice-based diets.