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

作者：Huizer Daan^*; Huijbregts Mark A J; van Rooij Joost G M; Ragas Ad M J

来源：Regulatory Toxicology and Pharmacology, 2014, 69(3): 408-415.

DOI：10.1016/j.yrtph.2014.05.004

• Coherence
• Occupational exposure limits
• Biological limit values
• PBPK model
• 2-Propanol
• Acetone
• Uncertainty
• Variability

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 DEL. 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 DEL should be specified as well as a minimum level of certainty in predicting this fraction.

• 出版日期2014-8