Modeling Real-Time Occupational Naphthalene Exposures to Predict Urinary Biomarkers
Technical Report,01 Jan 2019,30 Sep 2019
Henry M. Jackson Foundation Wright-Patterson AFB United States
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A novel real-time naphthalene dosimeter NaDos prototype, sponsored by the U.S. Army, provides the capability for close monitoring of naphthalene concentration measurements to identify changes in occupational exposures. Quantitative real-time monitoring has the potential to be more accurate than traditional dosimeters that rely on sorbent tubes to provide a time weighted average of exposure concentrations following laboratory analysis. Continuous data every 3 minutes were collected from military fuel workers wearing the NaDos prototype monitors. Data included biometric information height, weight and sex, traditional work day naphthalene breathing zone measurements, and spot urine samples during 3 consecutive work days. Urine was analyzed for 1- and 2-naphthol and creatinine content. Additionally, hand wash wipe and exhaled breath samples were collected post-shift however, there were few results above the naphthalene limit of detection. In order to simulate real-time exposure data, a novel physiologically-based pharmacokinetic PBPK model was written to simulate the changing concentrations inhaled over time. The model structure accounted for naphthalene metabolism in the lung and liver, as well as production, distribution and urinary elimination of metabolites combined naphthols. To predict urinary concentration, the model estimated urinary flow and creatinine production based upon sex, age and body mass index. Given data limitations, the naphthalene model satisfactorily simulated urine naphthol concentrations or creatinine normalized naphthol concentrations for most individual datasets.