title: Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools for emergency risk assessment after acute dichloromethane exposure.
abstract: BACKGROUND
  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).
  
  
  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.
authors.affiliation: 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.
authors.forename: R Z
authors.initials: RZ
authors.lastname: Boerleider
authors.affiliation: 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.
authors.forename: J D N
authors.initials: JD
authors.lastname: Olie
authors.affiliation: National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 Bilthoven, The Netherlands.
authors.forename: J C H
authors.initials: JC
authors.lastname: van Eijkeren
authors.affiliation: National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 Bilthoven, The Netherlands.
authors.forename: P M J
authors.initials: PM
authors.lastname: Bos
authors.affiliation: 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.
authors.forename: B G H
authors.initials: BG
authors.lastname: Hof
authors.affiliation: National Poisons Information Center, University Medical Center Utrecht (UMCU), P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: de Vries
authors.affiliation: National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 Bilthoven, The Netherlands.
authors.forename: J G M
authors.initials: JG
authors.lastname: Bessems
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Meulenbelt
authors.affiliation: National Poisons Information Center, University Medical Center Utrecht (UMCU), P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: C.Hunault@umcutrecht.nl.
authors.forename: C C
authors.initials: CC
authors.lastname: Hunault
mesh_terms: D015415:Biomarkers / Q000097:blood; D001711:Biotransformation; D002263:Carboxyhemoglobin / Q000378:metabolism; D003198:Computer Simulation; D004784:Environmental Monitoring; D064368:Healthy Volunteers; D006801:Humans; D019570:Inhalation Exposure; D008752:Methylene Chloride / Q000097:blood / Q000493:pharmacokinetics* / Q000506:poisoning*; D008954:Models, Biological; D018570:Risk Assessment; D012307:Risk Factors; D012997:Solvents / Q000493:pharmacokinetics* / Q000506:poisoning*; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012997:Solvents; D008752:Methylene Chloride; D002263:Carboxyhemoglobin
keywords: Acute exposure; Dichloromethane; Intoxication; PBPK model; Poisoning; Risk assessment