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

Abstract

a b s t r a c tThe 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 V max and K m 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.

Uncertainty and variability in the exposure reconstruction of chemical incidents – the case of acrylonitrile

“…The magnitude of the reduction in the range of reconstructed air concentrations depends on the modeled chemical and the moment of data collection. In previous studies, the importance of human physiological data has also been demonstrated, especially during and shortly after exposure (Huizer et al, 2012(Huizer et al, , 2014. The shorter after the incident measurements are performed, the more relevant it is to collect individual physiological data.…”

“…The model is briefly described here (see also Fig. 1), while a more detailed model description can be found in Huizer et al (2012) and Huizer et al (2014). BioNormtox model contains 10 biological compartments.…”

“…As the exposure duration during the incident was not described, we considered two scenarios: (1) exposure to ACN in air at 3 ppm for 5 min, and (2) exposure to ACN in air at 3 ppm for 60 min. For both scenarios a light exercise level, as defined by Huizer et al (2014); was considered. Inhalation exposure was simulated without the use of respiratory protection equipment only.…”