RT Journal Article
T1 In-vitro metabolites characterization of 1,3-diphenylguanidine and 1,3-di-o-tolylguanidine by high-resolution mass spectrometry and urinary profiling
A1 Estévez-Danta, Andrea
A1 Riveiro Rodríguez, Iago
A1 Lage Díaz, María
A1 Quintana Álvarez, José Benito
A1 Montes Goyanes, Rosa
A1 Rodil Rodríguez, María del Rosario
K1 Rubber leachates
K1 In-vitro metabolism
K1 Human liver microsomes
K1 Suspect screening
K1 In-vivo metabolites
AB The discovery of the hazardous effects associated with the polymer additives 1,3-diphenyl guanidine (DPG) and 1,3-di-o-tolylguanidine (DTG) has prompted the need for biomonitoring studies to detect human exposure. However, limited information is available about their metabolism. To address this gap, this study investigates the Phase I and II in-vitro biotransformation of both chemicals using human liver microsomes and cytosol. The samples were analyzed using liquid chromatography coupled to high resolution-(tandem) mass spectrometry through suspect (of in-silico predicted metabolites) and non-target screening. The analysis revealed four Phase I and two Phase II metabolic products for both DPG and DTG. Hydroxylation of the benzene ring led to the tentative identification of mono- and di-hydroxylated metabolites. Subsequent Phase I deamination followed by oxidation resulted in the formation of hydroxy-phenylurea and an intramolecular cyclization resulted in the formation of hydroxy-cyclic products. Furthermore, N-glucuronidation and O-glucuronidation products were identified for the first time. After performing urinalysis, DPG and DTG could be quantified in the 0.02–0.23 μg L−1 range, and DPG-227 (mono-hydroxylated DPG) was estimated to be present at ca. 0.01–0.10 μg L−1 range, using DPG response as quantification surrogate. Finally, toxicity assessment using an in-silico tool indicated the need to consider these human metabolites in (eco)toxicological assessments, as they may have the same or even greater effects on humans and the environment.
PB Elsevier
YR 2025
FD 2025-08-23
LK https://hdl.handle.net/10347/42752
UL https://hdl.handle.net/10347/42752
LA eng
NO A. Estévez-Danta et al. In-vitro metabolites characterization of 1,3-diphenylguanidine and 1,3-di-o-tolylguanidine by high-resolution mass spectrometry and urinary profiling. Emerging Contaminants 11 (2025) 100551. https://doi.org/10.1016/j.emcon.2025.100551
NO MCIN/AEI/10.13039/501100011033 (PID2020-117686RB-C32, CNS2024-154426 and TED2021-129200B-C41 (co)funded by the EU through NextGenerationEU/PRTR funds)
NO Consellería de Cultura de Galicia, Educación e Universidades (ED481A-2020/258, ED431C-2025/21 and ED481B-2025/042)
DS Minerva
RD 20 may 2026