Innovative accumulative risk assessment of co-exposure to Cd, As, and Pb in contaminated rice based on their in vivo bioavailability and in vitro bioaccessibility

The consumption of cadmium (Cd), arsenic (As), and lead (Pb) co-contaminated rice exposes humans to multiple heavy metals simultaneously, with relative bioavailability (RBA) and bioaccessibility (BAc) being important determinants of potential health risks. This study evaluated the relationship between in vivo RBA and in vitro BAc of Cd, As, and Pb in rice and their cumulative risk to humans. A total of 110 rice samples were collected in Zhejiang Province, China, and 10 subsamples with varying concentration gradients were randomly selected to measure RBA using a mouse model (liver, kidney, femur, blood, and urine as endpoints) and BAc using four in vitro assays (PBET, UBM, SBRC, and IVG). Our results indicated that Cd-RBA varied from 21.2 % to 67.5 %, As-RBA varied from 23.2 % to 69.3 %, and Pb-RBA varied from 22.2 % to 68.9 % based on mouse liver plus kidneys. The BAc values for Cd, As, and Pb in rice varied according to the assay. Compared to Cd and As, Pb exhibited a lower BAc in the gastric (GP) and intestinal (IP) phases. According to the relationship between the BAc and RBA values, IVG-GP (R2 = 0.92), SBRC-IP (R2 = 0.73), and UBM-GP (R2 = 0.80) could be used as predictors of Cd-, As-, and Pb-RBA in rice, respectively. The health risks associated with co-exposure to Cd, As, and Pb in contaminated rice for both adults and children exceeded the acceptable threshold, with Cd and As being the primary risk factors. The noncarcinogenic and carcinogenic risks were markedly reduced when the RBA and BAc values were incorporated into the risk assessment. Due to the risk overestimation inherent in estimating the risk level based on total metal concentration, our study provides a realistic assessment of the cumulative health risks associated with co-exposure to Cd, As, and Pb in contaminated rice using in vivo RBA and in vitro BAc bioassays.