ESTIMATION OF TOLUENE EXPOSURE IN AIR FROM BMA (S-BENZYLMERCAPTURIC ACID) URINARY MEASURES USING A REVERSE DOSIMETRY APPROACH BASED ON PHYSIOLOGICALLY PHARMACOKINETIC MODELING

This study aimed to use a reverse dosimetry PBPK modeling approach to estimate toluene atmospheric exposure from urinary measurements of S-benzylmercapturic acid (BMA) in a small group of individuals and to evaluate the uncertainty associated to urinary spot-sampling compared to 24-hour collected urine samples. Each exposure assessment technique was developed namely to estimate toluene air exposure from BMA measurements in 24-hour urine samples (24-h-BMA) and from distributions of daily urinary BMA spot measurements (DUBSM). Model physiological parameters were described based upon age, weight, size and sex. Monte Carlo simulations with the PBPK model allowed converting DUBSM distribution (and 24-h-BMA) into toluene air levels. For the approach relying on DUBSM distribution, the ratio between the 95% probability of predicted toluene concentration and its 50% probability in each individual varied between 1.2 and 1.4, while that based on 24-h-BMA varied between 1.0 and 1.1. This suggests more variability in estimated exposure from spot measurements. Thus, estimating toluene exposure based on DUBSM distribution generated about 20% more uncertainty. Toluene levels estimated (0.0078-0.0138 ppm) are well below Health Canada's maximum chronic air guidelines. PBPK modeling and reverse dosimetry may be combined to interpret urinary metabolites data of VOCs and assess related uncertainties.
Auteurs (Zotero)
Tohon, Honesty; Valcke, Mathieu; Aranda-Rodriguez, Rocio; Nong, Andy; Haddad, Sami
Date de publication (Zotero)
janvier, 2020