Original Research Article
The Use of PBPK Models to Inform Human Health Risk Assessment: Case Study on Perchlorate and Radioiodide Human Lifestage Models
Article first published online: 31 JUL 2013
© 2013 Society for Risk Analysis Published 2013. This article is a U.S. Government work and is in the public domain for the U.S.A.
Volume 34, Issue 2, pages 356–366, February 2014
How to Cite
McLanahan, E. D., White, P., Flowers, L. and Schlosser, P. M. (2014), The Use of PBPK Models to Inform Human Health Risk Assessment: Case Study on Perchlorate and Radioiodide Human Lifestage Models. Risk Analysis, 34: 356–366. doi: 10.1111/risa.12101
- Issue published online: 18 FEB 2014
- Article first published online: 31 JUL 2013
- PBPK model;
- risk assessment
Physiologically-based pharmacokinetic (PBPK) models are often submitted to or selected by agencies, such as the U.S. Environmental Protection Agency (U.S. EPA) and Agency for Toxic Substances and Disease Registry, for consideration for application in human health risk assessment (HHRA). Recently, U.S. EPA evaluated the human PBPK models for perchlorate and radioiodide for their ability to estimate the relative sensitivity of perchlorate inhibition on thyroidal radioiodide uptake for various population groups and lifestages. The most well-defined mode of action of the environmental contaminant, perchlorate, is competitive inhibition of thyroidal iodide uptake by the sodium-iodide symporter (NIS). In this analysis, a six-step framework for PBPK model evaluation was followed, and with a few modifications, the models were determined to be suitable for use in HHRA to evaluate relative sensitivity among human lifestages. Relative sensitivity to perchlorate was determined by comparing the PBPK model predicted percent inhibition of thyroidal radioactive iodide uptake (RAIU) by perchlorate for different lifestages. A limited sensitivity analysis indicated that model parameters describing urinary excretion of perchlorate and iodide were particularly important in prediction of RAIU inhibition; therefore, a range of biologically plausible values available in the peer-reviewed literature was evaluated. Using the updated PBPK models, the greatest sensitivity to RAIU inhibition was predicted to be the near-term fetus (gestation week 40) compared to the average adult and other lifestages; however, when exposure factors were taken into account, newborns were found to be populations that need further evaluation and consideration in a risk assessment for perchlorate.