Occupational Exposure to Cobalt: A Population Toxicokinetic Modeling Approach Validated by Field Results Challenges the Biological Exposure Index for Urinary Cobalt

Abstract

This study modeled the urinary toxicokinetics of cobalt exposure based on 507 urine samples from 16 workers, followed up for 1 week, and 108 related atmospheric cobalt measurements to determine an optimal urinary cobalt sampling strategy at work and a corresponding urinary exposure threshold (UET). These data have been used to calibrate a population toxicokinetic model, taking into account both the measurement uncertainty and intra- and interindividual variability. Using the calibrated model, urinary sampling sensitivity and specificity performance in detecting exposure above the 20 μg/m3 threshold limit value – time-weighted average (TLV-TWA) has been applied to identify an optimal urine sampling time. The UET value is obtained by minimizing misclassification rates in workplace exposures below or above the TLV. Total atmospheric cobalt concentrations are in the 5–144 μg/m3 range, and total urinary cobalt concentrations are 0.5–88 μg/g creatinine. A two-compartment toxicokinetic model best described urinary elimination. Terminal elimination half-time from the central compartment is 10.0 hr (95% confidence interval [8.3–12.3]). The optimal urinary sampling time has been identified as 3 hr before the end of shift at the end of workweek. If we assume that misclassification errors are of equal cost, the UET associated with the TLV of 20 μg/m3 is 5 μg/L, which is lower than the ACGIH-recommended biological exposure index of 15 μg/L. [Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Occupational and Environmental Hygiene for the following free supplemental resource: an appendix with discussion of the toxicokinetic model, priors, model checking, cross validation, and comparison of ROC curves for various urinary sampling strategy.]