Bioaccumulation and Bioavailability of Lead Mixtures (PbO2 + PbS + PbCO3 + PbSO4) in Mice: Multi-Endpoint Assessment In Vitro/In Vivo and Quantitative Prediction Based on Mass Ratio Modelling

Abstract Among the most common environmental lead (Pb) species, PbO2, PbS, PbCO3, and PbSO4 are the primary lead compounds. However, the impact of mixed lead compounds on body bioaccumulation remains poorly understood. This study systematically investigated organ lead accumulation and Pb-RBA of single lead compounds and their mixtures using a steady-state mouse exposure model. Mice were exposed to diets containing 50 or 150 mg Pb·kg–1 for 15 days. The lead mixtures consisted of PbSO4, PbCO3, PbS, and PbO2, with component mass fractions of 5%, 15%, 35%, and 45%. The results show that mixtures containing 60% PbCO3 and PbO2 exhibited higher Pb-RBA. In contrast, higher proportions of PbSO4 and PbS were associated with lower Pb-RBA, indicating reduced lead bioavailability. When exposure levels were increased from 50 mg·kg–1 (Pb-RBA mean: 49.92%; range: 39.95%–56.18%) to 150 mg·kg–1 (mean: 53.05%; range: 44.61%–64.81%), an elevation in mixture Pb-RBA was observed (p > 0.05). In vitro simulations using the SBRC and UBM methods yielded gastric phase Pb-IVBA values of 54.97% ± 14% (SBRC-GP) and 49.23% ± 8% (UBM-GP). In the intestinal phase, Pb-IVBA values decreased to 4.27% ± 2% (SBRC-IP) and 7.89% ± 4% (UBM-IP). A linear regression analysis of the IVIVC indicated that UBM-GP provided better predictive performance than the other in vitro methods evaluated for the lead mixtures examined in this study. This study suggests that the Pb-RBA (or Pb-IVBA) of lead mixtures may be approximated using a mass-fraction-weighted sum of the values for individual lead compounds, providing a quantitative framework for estimating bioavailability under mixed lead exposure scenarios.