PMID- 36858113
OWN - NLM
STAT- MEDLINE
DCOM- 20230328
LR  - 20230330
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 465
DP  - 2023 Apr 15
TI  - Novel approach for verification of a human PBPK modeling strategy using chimeric 
      mice in the health risk assessment of epyrifenacil.
PG  - 116439
LID - S0041-008X(23)00077-7 [pii]
LID - 10.1016/j.taap.2023.116439 [doi]
AB  - In the human risk assessment by physiologically based pharmacokinetic modeling 
      (PBPK), verification of the modeling strategy and confirmation of the reliability 
      of the output data are important when the clinical data are not available. A new 
      herbicide, epyrifenacil, is metabolized to S-3100-CA in mammals and causes 
      hepatotoxicity in mice. S-3100-CA is transferred to the liver by transporters and 
      eliminated by biliary excretion and metabolism. In the previous human PBPK 
      research, we succeeded in predicting S-3100-CA pharmacokinetics by obtaining 
      human hepatic parameters from chimeric mice with humanized liver after we checked 
      the model's quantitative performance using mouse experimental data. To further 
      enhance the reliability of human PBPK data, verification of the following two 
      points was considered effective: 1) verification of model applicability to 
      pharmacokinetics prediction in multiple animal species, and 2) verification of 
      the parameter acquisition methods. In this study, we applied the same modeling 
      strategy to rats, i.e., we obtained rat hepatic parameters for PBPK from chimeric 
      mice with rat hepatocytes, not from rats. As the simulation results, rat internal 
      dosimetry was precisely reproduced, although it tended to be slightly 
      overestimated by approximately two times. From the results of the sensitivity 
      analysis, this overestimation was mainly due to hepatic parameters from chimeric 
      mice. Therefore, it is suggested that a similar slight prediction error may occur 
      also in human PBPK using chimeric mice, but considering the degree of error, it 
      can be said that our modeling strategy is robust and the predicted human internal 
      dosimetry in the previous research is reliable.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Hirasawa, Kota
AU  - Hirasawa K
AD  - Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1-98, 
      3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan. Electronic address: 
      hirasawak@sc.sumitomo-chem.co.jp.
FAU - Abe, Jun
AU  - Abe J
AD  - Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1-98, 
      3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan.
FAU - Nagahori, Hirohisa
AU  - Nagahori H
AD  - Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1-98, 
      3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan.
FAU - Kitamoto, Sachiko
AU  - Kitamoto S
AD  - Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1-98, 
      3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230227
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (epyrifenacil)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Rats
MH  - Animals
MH  - Reproducibility of Results
MH  - *Models, Biological
MH  - *Liver/metabolism
MH  - Risk Assessment
MH  - Mammals
OTO - NOTNLM
OT  - Chimeric Mice with Rat Hepatocytes
OT  - Epyrifenacil
OT  - Model Applicability
OT  - Modeling Strategy
OT  - PBPK
OT  - Reliability of Human PBPK Data
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/03/02 06:00
MHDA- 2023/03/28 17:15
CRDT- 2023/03/01 19:23
PHST- 2022/12/08 00:00 [received]
PHST- 2023/02/21 00:00 [revised]
PHST- 2023/02/23 00:00 [accepted]
PHST- 2023/03/28 17:15 [medline]
PHST- 2023/03/02 06:00 [pubmed]
PHST- 2023/03/01 19:23 [entrez]
AID - S0041-008X(23)00077-7 [pii]
AID - 10.1016/j.taap.2023.116439 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2023 Apr 15;465:116439. doi: 10.1016/j.taap.2023.116439. 
      Epub 2023 Feb 27.