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DOI | 10.1111/risa.12101 |
The Use of PBPK Models to Inform Human Health Risk Assessment: Case Study on Perchlorate and Radioiodide Human Lifestage Models | |
McLanahan, Eva D.1; White, Paul2; Flowers, Lynn2; Schlosser, Paul M.2 | |
发表日期 | 2014-02-01 |
ISSN | 0272-4332 |
卷号 | 34期号:2页码:356-366 |
英文摘要 | 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. |
英文关键词 | Human;PBPK model;perchlorate;radioiodide;risk assessment |
语种 | 英语 |
WOS记录号 | WOS:000331358300012 |
来源期刊 | RISK ANALYSIS
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来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/56611 |
作者单位 | 1.US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA; 2.US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA |
推荐引用方式 GB/T 7714 | McLanahan, Eva D.,White, Paul,Flowers, Lynn,et al. The Use of PBPK Models to Inform Human Health Risk Assessment: Case Study on Perchlorate and Radioiodide Human Lifestage Models[J]. 美国环保署,2014,34(2):356-366. |
APA | McLanahan, Eva D.,White, Paul,Flowers, Lynn,&Schlosser, Paul 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(2),356-366. |
MLA | McLanahan, Eva D.,et al."The Use of PBPK Models to Inform Human Health Risk Assessment: Case Study on Perchlorate and Radioiodide Human Lifestage Models".RISK ANALYSIS 34.2(2014):356-366. |
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