Pharmacokinetics of Toxic Chemicals in Breast Milk: Use of PBPK Models to Predict Infant Exposure Rebecca A. Clewell1 and Jeffery M. Gearhart2 1Geo-Centers, Inc., Wright-Patterson Air Force Base, Ohio, USA; 2Mantech Environmental Technology, Inc., Dayton, Ohio, USA Abstract Factors controlling the transfer of potentially toxic chemicals in the breast milk of nursing mothers include both chemical characteristics, such as lipophilicity, and physiologic changes during lactation. Physiologically based pharmacokinetic (PBPK) models can aid in the prediction of infant exposure via breast milk. Benefits of these quantitative models include the ability to account for changing maternal physiology and transfer kinetics, as well as the chemical-specific characteristics, in order to produce more accurate estimates of neonatal risk. A recently developed PBPK model for perchlorate and iodide kinetics in the lactating and neonatal rat demonstrates the utility of PBPK modeling in predicting maternal and neonatal distribution of these two compounds. This model incorporates time-dependent changes in physiologic characteristics and includes interactions between iodide and perchlorate that alter the distribution and kinetics of iodide. Key words: breast milk, chemical exposure, lactation, PBPK modeling, pharmacokinetics. Environ Health Perspect 110:A333-A337 (2002) . [Online 13 May 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110pA333-A337clewell/ abstract.html Address correspondence to J.M. Gearhart, Mantech Environmental Technology, Inc., 2856 G Street Building 79, Wright Patterson AFB, OH 45433-7400 USA. Telephone: (937) 255-5150. Fax: (937) 255-1474. E-mail: jeff.gearhart@wpafb.af.mil This article is part of the mini-monograph "Chemical Contaminants in Breast Milk: Impact on Children's Health." We thank J. Byczkowski and J. Lipscomb for sharing their MeHg model, K. Yu and D. Mahle for experimental data, and H. Clewell and T. Sterner for editorial assistance. This work was financially supported by the United States Air Force, Contract F33615-00-C-6060. Received 20 December 2001 ; accepted 14 March 2002. The full version of this article is available for free in HTML or PDF formats. |