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. 2009 Jan;27(1):75-83.
doi: 10.1016/j.etap.2008.08.014.

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

Sun Ku Lee  1 , Dwayne Hamer, Cathy L Bedwell, Manupat Lohitnavy, Raymond S H Yang
Affiliations

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

Sun Ku Lee et al. Environ Toxicol Pharmacol. 2009 Jan.

Abstract

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 maternal blood. Observed results were matched with PBPK model simulations conducted under the assumptions that (1) 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.

Keywords: MeHg; PBPK; PCBs; lactational transfer.

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Conflict of interest statement

Conflict of Interest

Authors declare there is no conflict of interest with regards to the research described in the manuscript.

Figures

Fig. 1
Fig. 1
Schematic diagrams of the PBPK model describing the lactational transfer of MeHg with or without PCB congeners. The model structure was constructed by based on a published model (Byczkowski and Lipscomb, 2001).
Fig. 2
Fig. 2
The tissue concentrations of mercury in the pup and the levels of albumin in maternal blood. Each data point represents mean±SEM. *means the statistically significant difference from the corresponding group (p < 0.05). The unit of mercury concentration is ng/g wet tissue. (A) The time-course concentration of mercury in pup’s brain. (B) The time-course concentration of mercury in pup’s carcass. (C) The time-course concentration of mercury in pup’s kidney. (D) The time-course concentration of albumin in maternal blood.
Fig. 3
Fig. 3
The tissue concentrations of PCB congeners in the pup. Each data point represents mean±SEM. *means the statistically significant difference from the corresponding group (p < 0.05). The unit of PCB concentration is ng/g wet tissue. (A) The time-course concentration of PCB 153 in pup’s brain. (B) The time-course concentration of PCB 153 in pup’s carcass. (C) The time-course concentration of PCB 153 in pup’s liver. (D) The time-course concentration of PCB 126 in pup’s liver.
Fig. 4
Fig. 4
PBPK simulation results for the lactational transfer of MeHg against albumin levels in maternal blood. At each figure we presented the simulation results for first two hypotheses respectively. (A) The simulation results for the lactational transfer of MeHg to the pups based on the assumption that free MeHg without binding to albumin can be transferred to pups. Albumin levels varied from 50% to 100% of normal levels in mice. (B) The simulation results for the lactational transfer of MeHg to the pups based on the assumption that MeHg bound with albumin can be transferred to pups. Albumin levels varied from 50% to 100% of normal levels in mice.
Fig. 5
Fig. 5
PBPK simulation of MeHg in the pup’s tissues comparing the group exposed to MeHg only with the group exposed to MeHg + PCB congeners. The only difference of the simulations between the group exposed to MeHg only and the group exposed to MeHg + PCB congeners is the levels of albumin in maternal blood.
See this image and copyright information in PMC

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