| Population Physiologically Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB-153 with Consideration of Worldwide Human Biomonitoring Results Laurel E. Redding,1* Michael D. Sohn,2 Thomas E. McKone,2,3 Jein-Wen Chen,1 Shu-Li Wang,1,4 Dennis P. H. Hsieh,1 and Raymond S.H. Yang1,5 1Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan; 2Lawrence Berkeley National Laboratory, Berkeley, California, USA; 3University of California, Berkeley, California, USA; 4Graduate Institute of Occupational and Industrial Health, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, USA Abstract
Background: One of the most serious human health concerns related to environmental contamination with polychlorinated biphenyls (PCBs) is the presence of these chemicals in breast milk. Objectives: We developed a physiologically based pharmacokinetic model of PCB-153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB-153. Data in the literature provided estimates for model development and for performance assessment. Methods: We used physiologic parameters from a cohort in Taiwan and reference values given in the literature to estimate partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data from Japan, we predicted acquired body burden of PCB-153 at an average childbearing age of 25 years and compared predictions to measurements from studies in multiple countries. We attempted one example of reverse dosimetry modeling using our PBPK model for possible exposure scenarios in Canadian Inuits, the population with the highest breast milk PCB-153 level in the world. Results: Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates. Conclusion: The model successfully describes the range of possible PCB-153 dispositions in maternal milk, suggesting a promising option for back-estimating doses for various populations. Key words: body burden, exposure reconstruction, human milk biomonitoring, lactational transfer, PCB-153, physiologically based pharmacokinetic modeling, polychlorinated biphenyls, reverse dosimetry. Environ Health Perspect 116:1629–1634 (2008) . doi:10.1289/ehp.11519 available via http://dx.doi.org/ [Online 24 July 2008]
Address correspondence to R.S.H. Yang, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Colorado State University, 137A Physiology Bldg., 1680 Campus Delivery, Fort Collins, CO 80523-1680 USA. Telephone: (970) 491-5652. Fax: (970) 491-7569. E-mail: raymond.yang@colostate.edu *Current address: School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104-6046 USA. During July 2006–June 2007, R.S.H.Y. was at the National Health Research Institutes, Taiwan, while on sabbatical leave from Colorado State University. We acknowledge the financial support from Colorado State University and the National Science Council, Taiwan, Republic of China. This study was supported by grants EO-094-PP-04, EO-096-PP-10, and EO-095-SP-01 from the Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan. M.D.S. and T.E.M. were supported in part by the U.S. Environmental Protection Agency through Interagency Agreement DW-988-38190-01-0 and carried out through U.S. Department of Energy contract DE-AC02-05CH11231. The authors declare they have no competing financial interests. Received 28 March 2008 ; accepted 23 July 2008.
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