title: Uncertainty and variability in the exposure reconstruction of chemical incidents--the case of acrylonitrile.
abstract: The application of human physiologically based pharmacokinetic (PBPK) modeling combined with measured biomonitoring data, has a great potential to backtrack external exposure to chemicals during chemical incidents. So far, an important shortcoming of 'reversed dosimetry' is that uncertainty and variability in the model predictions are often neglected. The aim of this paper is to characterize the variation in predicted environmental air concentrations by means of reversed dosimetry as a result of uncertainty in chemical-specific input data and variability in physiological parameters. Human biomonitoring data (N-2-cyanoethylvaline in blood) from a chemical incident with acrylonitrile (ACN) combined with the BioNormtox PBPK model are used as a case to reconstruct the air concentration and uncertainty thereof at the time of the incident. The influence of uncertainty in chemical-specific properties and exposure duration, and interindividual variability in physiological parameters on the reconstructed air exposure concentrations were quantified via nested Monte Carlo simulation. The range in the reconstructed air concentrations of ACN during the incident was within a factor of 3. Uncertainty in the exact exposure duration directly after the chemical accident was found to have a dominant influence on the model outcomes. It was also shown that uncertainty can be further reduced by collecting human biomonitoring data as soon as possible after the incident. Finally, the collection of specific information about individual physiological parameters from the victims, such as body weight, may further reduce the variation by 5 to 20% in our case study. Future research should include the comparison of reversed dosimetry model outcomes with measured air and biological concentrations to further increase the confidence in the model approach and its implementation in practice.
authors: Department of Environmental Science, Institute for Water and Wetland Research, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL Nijmegen, The Netherlands; Caesar Consult Nijmegen, PO Box 31070, 6503 CB Nijmegen, The Netherlands. Electronic address: d.huizer@science.ru.nl.
authors: Daan
authors: D
authors: Huizer
authors: Department of Environmental Science, Institute for Water and Wetland Research, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL Nijmegen, The Netherlands; School of Science, Open Universiteit, PO Box 2960, 6401 DL Heerlen, The Netherlands. Electronic address: a.ragas@science.ru.nl.
authors: Ad M J
authors: AM
authors: Ragas
authors: Department of Environmental Science, Institute for Water and Wetland Research, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL Nijmegen, The Netherlands. Electronic address: r.oldenkamp@science.ru.nl.
authors: Rik
authors: R
authors: Oldenkamp
authors: Caesar Consult Nijmegen, PO Box 31070, 6503 CB Nijmegen, The Netherlands. Electronic address: joost.vanrooij@caesar-consult.nl.
authors: Joost G M
authors: JG
authors: van Rooij
authors: Department of Environmental Science, Institute for Water and Wetland Research, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL Nijmegen, The Netherlands. Electronic address: m.huijbregts@science.ru.nl.
authors: Mark A J
authors: MA
authors: Huijbregts
mesh_terms: D000181:Acrylonitrile / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D055884:Chemical Hazard Release; D003198:Computer Simulation; D004784:Environmental Monitoring / Q000379:methods*; D006801:Humans; D008297:Male; D008954:Models, Biological; D009010:Monte Carlo Method; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D035501:Uncertainty; D014633:Valine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D015415:Biomarkers; C091192:N-(2-cyanoethyl)valine; D014633:Valine; D000181:Acrylonitrile
keywords: Acrylonitrile; Chemical incident; Human biomonitoring; PBPK model; Reverse dosimetry; Uncertainty; Variability