Testing the coherence between occupational exposure limits for inhalation and their biological limit values with a generalized PBPK-model: the case of 2-propanol and acetone.
The coherence between occupational exposure limits (OELs) and their corresponding biological limit values (BLVs) was evaluated for 2-propanol and acetone. A generic human PBPK model was used to predict internal concentrations after inhalation exposure at the level of the OEL. The fraction of workers with predicted internal concentrations lower than the BLV, i.e. the 'false negatives', was taken as a measure for incoherence. The impact of variability and uncertainty in input parameters was separated by means of nested Monte Carlo simulation. Depending on the exposure scenario considered, the median fraction of the population for which the limit values were incoherent ranged from 2% to 45%. Parameter importance analysis showed that body weight was the main factor contributing to interindividual variability in blood and urine concentrations and that the metabolic parameters Vmax and Km were the most important sources of uncertainty. This study demonstrates that the OELs and BLVs for 2-propanol and acetone are not fully coherent, i.e. enforcement of BLVs may result in OELs being violated. In order to assess the acceptability of this "incoherence", a maximum population fraction at risk of exceeding the OEL should be specified as well as a minimum level of certainty in predicting this fraction.
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.
Daan
D
Huizer
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.
Mark A J
MA
Huijbregts
Caesar Consult Nijmegen, PO Box 31070, 6503 CB Nijmegen, The Netherlands. Electronic address: joost.vanrooij@caesar-consult.nl.
Joost G M
JG
van Rooij
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.
Ad M J
AM
Ragas
D019840:2-Propanol / Q000009:adverse effects* / Q000737:chemistry*; D000096:Acetone / Q000009:adverse effects* / Q000737:chemistry*; D000280:Administration, Inhalation; D001835:Body Weight / Q000187:drug effects; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis*; D008954:Models, Biological; D009010:Monte Carlo Method; D016273:Occupational Exposure / Q000032:analysis*; D020711:Threshold Limit Values; D035501:Uncertainty
D000096:Acetone; D019840:2-Propanol
2-Propanol; Acetone; Biological limit values; Coherence; Occupational exposure limits; PBPK model; Uncertainty; Variability