Identification and semi-quantification of metabolites of new plasticizers in urine collected from flemish adults and children

A suspect screening workflow combined with a semi-quantification method was applied for the investigation of metabolites of the plasticizers di-propylene glycol dibenzoate (DiPGDB) and tri-n-butyl trimellitate (TBTM) in human urine collected from adults and children during winter (W) and summer (S) seasons. Liquid chroma-tography -quadrupole time of flight mass spectrometry (LC-QTOF-MS) was applied for the analyses. Two direct and one indirect metabolites of DiPGDB were identified: 3-(3-hydroxypropoxy) propyl benzoate (DiPGDB-M194), 3,4,5-trihydroxy-6-[3-(3-hydroxypropoxy) propoxy] oxane-2-carboxylic acid (DiPGDB-M310), hippuric acid (DiPGDB-M179) and one metabolite of TBTM: bis(butoxycarbonyl) benzoyloxy]-3,4,5-trihydroxyoxane-2-carboxylic acid (TBTM-M498). The identified metabolites were reported with levels of confidence (LoC) 2 and 3 and their concentrations were assessed using a semi-quantification approach. The respective concentration ranges for W and S samples were 0.20-42 ng/mL and 0.07-29 ng/mL for DiPGDB-M194, 2.5-1420 ng/mL and 5.0-2320 ng/mL for DiPGDB-M310, 230-10840 ng/mL and 320-8420 ng/mL for DiPGDB-M179, and 0.40-30 ng/mL and 0.65-30 ng/mL for TBTM-M498. The detection frequency order in urine samples was DiPGDB-M310 = DiPGDB-M179 (100%) > TBTM-M498 (44%) > DiPGDB-M194 (28%) for W and DiPGDB-M179 (99%)> DiPGDB-M310 (98%) > TBTM-M498 (57%) > DiPGDB-M194 (30%) for S. The identified metabolites DiPGDB-M310, DiPGDB-M194 and TBTM-M498 are potential biomarkers for the evaluation of human exposure to DiPGDB and TBTM. DiPGDB-M179 cannot be used for the same purpose due to its formation from compounds with multi-source origin. The application of the semi-quantification method could be useful for further studies where analytical standards are not available.

Automated summary

In this study, a suspect screening workflow combined with a semi-quantification method was used to investigate the metabolites of DiPGDB and TBTM in human urine samples collected during winter and summer. Several metabolites were identified, and the DiPGDB-M310, DiPGDB-M194, and TBTM-M498 were suggested as potential biomarkers for assessing human exposure to DiPGDB and TBTM. The semi-quantification method is valuable for studies that lack analytical standards.