A Linked Pharmacokinetic Model and Cancer Risk Assessment for Breast-Fed Infants

Abstract

In this paper, a step-by-step process is described that allowed a physiologically-based pharmacokinetic (PK) model for tetrachloroethylene (PCE) for lactating mothers to be linked with the estimate of extra cancer risk in breast-fed infants, according to the United States Environmental Protection Agency (EPA) method. If inhaled by a lactating woman, PCE may partition to breast milk and may be transferred to the breast-fed infant. A PK model for lactational transfer of PCE in rats, including a quantitative description of milk compartment and the nursing pup, has been developed and validated experimentally. Subsequently, the model has been scaled to describe human physiology, and was validated with human literature data for PCE exposure cases. The model predictions were in good agreement with both the measured values and those reported in the literature. Further, the model has been applied to scenarios of occupationally and nonoccupationally exposed mothers, simulating PCE concentrations in breast milk and the infant exposure. Finally, the dosage predictions were linked with equations used by EPA to estimate the cancer risk from PCE. Comparison of the predictions with those from the literature confirms the usefulness of PK modeling in risk assessments.