Effect of PCBs on the lactational transfer of methyl mercury in mice: PBPK modeling

MeHg and PCB exposure to lactating mice were analyzed and a physiologically based pharmacokinetic (PBPK) model was developed to describe the lactational transfer of MeHg in mice. The influence of albumin on the lactational transfer of MeHg was incorporated into the PBPK model. Experimental results with lactating mice and their Pups showed that co-exposure with PCB congeners increased the lactational transfer of MeHg to the pups, which was associated with the rise of albumin levels in the maternal blood. Observed results were matched with PBPK model simulations conducted under the assumptions that (I) MeHg bound to plasma albumin is transferred to maternal milk, and (2) PCB congeners may increase the lactational transfer of MeHg by escalating albumin levels in maternal blood. Further refinement of PBPK model quantitatively described the pharmacokinetic changes of MeHg by co-exposure with PCBs in pup's tissues. (C) 2008 Elsevier B.V. All rights reserved.