Predicting points of departure for risk assessment based on in vitro cytotoxicity data and physiologically based kinetic (PBK) modeling: The case of kidney toxicity induced by aristolochic acid I
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- 作者：Rozaini Abdullaha ; b ; rozaini.abdullah@wur.nl" class="auth_mail" title="E-mail the corresponding author ; rozainiabdullah@upm.edu.my" class="auth_mail" title="E-mail the corresponding author ; Wasma Alhusainya ; Jasper Woutersena ; Ivonne M.C.M. Rietjensa ; Ans Punta
- 关键词：Physiologically based kinetic (PBK) model ; Aristolochic acid I (AAI) ; Kidney toxicity ; In vitro-in vivo extrapolation ; Risk assessment ; Physiologically based pharmacokinetic (PBPK) model
- 刊名：Food and Chemical Toxicology
- 出版年：2016
- 出版时间：June 2016
- 年：2016
- 卷：92
- 期：Complete
- 页码：104-116
- 全文大小：1438 K
文摘
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PBK models were developed for AAI in rat, mouse and human based on in vitro kinetic data.
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Concentration–response curves for AAI cytotoxicity were obtained with the MTT assay.
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PBK-based reverse dosimetry defined in vivo dose response curves for kidney toxicity of AAI.
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The predicted in vivo data could be used to define a POD for risk assessment of AAI.
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The approach provides a non-animal testing strategy for predicting PODs in risk assessment.