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DOI10.1016/j.chemosphere.2015.01.056
Development of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll (R) DINCH (R)
Schuetze, Andre1; Lorber, Matthew2; Gawrych, Katarzyna1; Kolossa-Gehring, Marike3; Apel, Petra3; Bruening, Thomas1; Koch, Holger M.1
发表日期2015-06-01
ISSN0045-6535
卷号128页码:216-224
英文摘要

We developed and calibrated a multi compartment pharmacokinetic (PK) model to predict urinary concentrations after oral exposure of four specific DINCH metabolites: MINCH, OH-MINCH, cx-MINCH, and oxo-MINCH. This descriptive model has 4 compartments: a "stomach" (SC) compartment, a "holding" (HC) compartment, a "blood" (BC) compartment and a "bladder" (BLC) compartment. DINCH is assumed to first deposit into the SC, with transfer split between the HC and the BC. Unmetabolized DINCH from the HC then transfers to the BC. The DINCH metabolism is assumed to occur in the BC before excretion via the BLC. At each urination event, all the metabolite mass in the BLC is excreted. The model was calibrated using published urine metabolite data from 3 different male volunteers, each orally dosed with 50 mg DINCH. Full urine voids were taken for 48 h after dosage. The predicted values showed a good agreement with the observed urinary DINCH metabolite concentrations, with a Spearman correlation coefficient exceeding 0.7 for all oxidized metabolites. We showed the importance of a holding reservoir. Without it, a good agreement could not be found. We applied the model to a set of 24-h general population samples measured for DINCH metabolites. The model was unable to duplicate the ratio of metabolites seen in the 24-h samples. Two possibilities were offered to explain the difference: the exposure pattern in the general population did not match the oral exposure in the dosing experiments, or the long-term toxico-kinetics of DINCH was not captured in the 48-h controlled dosing experiments. (C) 2015 Elsevier Ltd. All rights reserved.


英文关键词Di(isononyl)cyclohexane-1,2-dicarboxylate;DINCH;Plasticizer;Exposure assessment;Urinary metabolites;Pharmacokinetic model
语种英语
WOS记录号WOS:000352327900030
来源期刊CHEMOSPHERE
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/58173
作者单位1.Inst Ruhr Univ Bochum IPA, German Social Accid Insurance, Inst Prevent & Occupat Med, D-44789 Bochum, Germany;
2.US EPA, Off Res & Dev, Washington, DC 20460 USA;
3.Fed Environm Agcy UBA, D-14195 Berlin, Germany
推荐引用方式
GB/T 7714
Schuetze, Andre,Lorber, Matthew,Gawrych, Katarzyna,et al. Development of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll (R) DINCH (R)[J]. 美国环保署,2015,128:216-224.
APA Schuetze, Andre.,Lorber, Matthew.,Gawrych, Katarzyna.,Kolossa-Gehring, Marike.,Apel, Petra.,...&Koch, Holger M..(2015).Development of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll (R) DINCH (R).CHEMOSPHERE,128,216-224.
MLA Schuetze, Andre,et al."Development of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll (R) DINCH (R)".CHEMOSPHERE 128(2015):216-224.
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