Exposure reconstruction using a physiologically based toxicokinetic model with cumulative amount of metabolite in urine: a case study of trichloroethylene inhalation

The use of a physiologically based toxicokinetic (PBTK) model to reconstruct chemical exposure using human biomonitoring data, urinary metabolites in particular, has not been fully explored. In this paper, the trichloroethylene (TCE) exposure dataset by Fisher et al. (Toxicol Appl Pharm 152:339-359, 1998) was reanalyzed to investigate this new approach. By treating exterior chemical exposure as an unknown model parameter, a PBTK model was used to estimate exposure and model parameters by measuring the cumulative amount of trichloroethanol glucuronide (TCOG), a metabolite of TCE, in voided urine and a single blood sample of the study subjects by Markov chain Monte Carlo (MCMC) simulations. An estimated exterior exposure of 0.532 mg/l successfully reconstructed the true inhalation concentration of 0.538 mg/l with a 95% CI (0.441-0.645) mg/l. Based on the simulation results, a feasible urine sample collection period would be 12-16 h after TCE exposure, with blood sampling at the end of the exposure period. Given the known metabolic pathway and exposure duration, the proposed computational procedure provides a simple and reliable method for environmental (occupational) exposure and PBTK model parameter estimation, which is more feasible than repeated blood sampling.