Particle and mass characteristics influence in vitro and in vivo lead bioavailability from multiple sources

Whilst lead (Pb) exposure poses significant risks to human health, understanding its bioavailability (BA) from multiple sources remains challenging. Current human health risk assessments (HHRA) use 250 µm as the upper limit for ingestible particles. In order to achieve a more precise definition for suitable particle sizes, we studied two common lead ores, cerussite and galena, and sieved them into two size fractions: ≤ 50 µm and 50-250 µm. We then created mixed mineral systems using varying mass ratios (0 %, 25 %, 50 %, 75 %, 100 %) of these compounds. We used a mouse model to measure the relative bioavailability (RBA) of lead in single and mixed mineral systems in five key tissues: blood, brain, liver, kidney, femur and tibia (bones), after 15 days of oral exposure. Our findings showed that the Pb-RBA across the combined endpoints was 33.1 % (95 % CI: 27.8 %-50.9 %) for the ≤ 50 µm fraction, which was 1.5 times higher than the 50-250 µm fraction (21.5 %, 95 %CI:18.4 %-34.2 %). We also assessed in vitro bioaccessibility (IVBA) using four different assays. The SBRC method proved to be the most accurate predictor of lead RBA. The study also presents a new method to estimate the RBA/IVBA of lead mixtures considering both size and mass. We hypothesized and verified that the Pb-RBA of compounds from multiple composite sources is closely related to the Pb-RBA of the single phases they contain and their fraction. The accuracy of this model predictions can reach 79.63 %, and the R² value is 0.64.