PMID- 25455448
OWN - NLM
STAT- MEDLINE
DCOM- 20170207
LR  - 20191210
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 232
IP  - 1
DP  - 2015 Jan 5
TI  - Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools 
      for emergency risk assessment after acute dichloromethane exposure.
PG  - 21-7
LID - S0378-4274(14)01382-4 [pii]
LID - 10.1016/j.toxlet.2014.10.010 [doi]
AB  - INTRODUCTION: Physiologically based pharmacokinetic (PBPK) models may be useful 
      in emergency risk assessment, after acute exposure to chemicals, such as 
      dichloromethane (DCM). We evaluated the applicability of three PBPK models for 
      human risk assessment following a single exposure to DCM: one model is 
      specifically developed for DCM (Bos) and the two others are semi-generic ones 
      (Mumtaz and Jongeneelen). MATERIALS AND METHODS: We assessed the accuracy of the 
      models' predictions by simulating exposure data from a previous healthy volunteer 
      study, in which six subjects had been exposed to DCM for 1h. The time-course of 
      both the blood DCM concentration and percentage of carboxyhemoglobin (HbCO) were 
      simulated. RESULTS: With all models, the shape of the simulated time course 
      resembled the shape of the experimental data. For the end of the exposure, the 
      predicted DCM blood concentration ranged between 1.52-4.19mg/L with the Bos 
      model, 1.42-4.04mg/L with the Mumtaz model, and 1.81-4.31mg/L with the 
      Jongeneelen model compared to 0.27-5.44mg/L in the experimental data. % HbCO 
      could be predicted only with the Bos model. The maximum predicted % HbCO ranged 
      between 3.1 and 4.2% compared to 0.4-2.3% in the experimental data. The % HbCO 
      predictions were more in line with the experimental data after adjustment of the 
      Bos model for the endogenous HbCO levels. CONCLUSIONS: The Bos Mumtaz and 
      Jongeneelen PBPK models were able to simulate experimental DCM blood 
      concentrations reasonably well. The Bos model appears to be useful for 
      calculating HbCO concentrations in emergency risk assessment.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Boerleider, R Z
AU  - Boerleider RZ
AD  - National Poisons Information Center, University Medical Center Utrecht (UMCU), 
      P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Institute for Risk Assessment 
      Sciences (IRAS), Utrecht University, P.O. Box 80178, 3508 TD Utrecht, The 
      Netherlands.
FAU - Olie, J D N
AU  - Olie JD
AD  - National Poisons Information Center, University Medical Center Utrecht (UMCU), 
      P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Radboud University Medical 
      Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
FAU - van Eijkeren, J C H
AU  - van Eijkeren JC
AD  - National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 
      Bilthoven, The Netherlands.
FAU - Bos, P M J
AU  - Bos PM
AD  - National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 
      Bilthoven, The Netherlands.
FAU - Hof, B G H
AU  - Hof BG
AD  - National Poisons Information Center, University Medical Center Utrecht (UMCU), 
      P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Department of Pharmaceutical 
      Sciences, University of Utrecht, P.O. Box 80082, 3508 TB Utrecht, The 
      Netherlands.
FAU - de Vries, I
AU  - de Vries I
AD  - National Poisons Information Center, University Medical Center Utrecht (UMCU), 
      P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
FAU - Bessems, J G M
AU  - Bessems JG
AD  - National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 
      Bilthoven, The Netherlands.
FAU - Meulenbelt, J
AU  - Meulenbelt J
AD  - National Poisons Information Center, University Medical Center Utrecht (UMCU), 
      P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Institute for Risk Assessment 
      Sciences (IRAS), Utrecht University, P.O. Box 80178, 3508 TD Utrecht, The 
      Netherlands; Department of Intensive Care Medicine, University Medical Center 
      (UMCU), P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
FAU - Hunault, C C
AU  - Hunault CC
AD  - National Poisons Information Center, University Medical Center Utrecht (UMCU), 
      P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: 
      C.Hunault@umcutrecht.nl.
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
DEP - 20141013
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Biomarkers)
RN  - 0 (Solvents)
RN  - 588X2YUY0A (Methylene Chloride)
RN  - 9061-29-4 (Carboxyhemoglobin)
SB  - IM
MH  - Biomarkers/blood
MH  - Biotransformation
MH  - Carboxyhemoglobin/metabolism
MH  - *Computer Simulation
MH  - Environmental Monitoring
MH  - Healthy Volunteers
MH  - Humans
MH  - Inhalation Exposure
MH  - Methylene Chloride/blood/*pharmacokinetics/*poisoning
MH  - *Models, Biological
MH  - Risk Assessment
MH  - Risk Factors
MH  - Solvents/*pharmacokinetics/*poisoning
MH  - Tissue Distribution
MH  - Young Adult
OTO - NOTNLM
OT  - Acute exposure
OT  - Dichloromethane
OT  - Intoxication
OT  - PBPK model
OT  - Poisoning
OT  - Risk assessment
EDAT- 2014/12/03 06:00
MHDA- 2017/02/09 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/08/25 00:00 [received]
PHST- 2014/10/02 00:00 [revised]
PHST- 2014/10/06 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2017/02/09 06:00 [medline]
AID - S0378-4274(14)01382-4 [pii]
AID - 10.1016/j.toxlet.2014.10.010 [doi]
PST - ppublish
SO  - Toxicol Lett. 2015 Jan 5;232(1):21-7. doi: 10.1016/j.toxlet.2014.10.010. Epub 
      2014 Oct 13.