Identification of in vitro metabolites of an Allium organosulfur compound and environmental toxicity prediction as part of its risk assessment

Propyl-propane-thiosulfonate (PTSO) is an organosulfur compound found inAllium spp. Due to its antioxidant and antimicrobial activities, PTSO has been proposed for applications in the agri-food sector, such as feed additive. However, its use with commercial purposes depends on its toxicity evaluation. The present work aimed to perform a pilot-study of toxicokinetic profile of PTSO combining in silico and in vitro techniques, important steps in the risk assessment process. In silico ecotoxicity studies were also performed considering the importance of the environmental impact of the compound before its commercial use. First, an analytical method has been devel-oped and validated to determine the original compound and its metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The phase I and II metabolism of PTSO was predicted using Meta-Pred Web Server. For the phase I metabolism, rat (male and female) and human liver microsomes were incubated with PTSO and NADPH regeneration system. Furthermore, in the phase II, microsomes were incubated with PTSO and glutathione or uridine 5 '- diphosphoglucuronic acid. The analysis revealed the presence of propyl-propane thiosulfinate (PTS) originated by redox reaction in phase I, and two conjugates from the phase II: S-propylmercaptoglutathione (GSSP) and S-propylmercaptocysteine (CSSP). Additionally, considering the envi-ronmental fate of PTSO and its metabolites, the ADME parameters and the potential ecotoxicity were also predicted using in silico softwares. The results of the ecotoxicity in silico study evidenced that the metabolism induced the formation of detoxified metabolites from the parent compound, except for dimercaprol and 3-mer-captopropane1,2-diol. Further in vivo assays are needed to confirm this prediction.

Automated summary

This study focused on analyzing the toxicokinetic profile of propyl-propane-thiosulfonate (PTSO) in the agricultural food sector. In silico and in vitro techniques were used to perform a pilot-study, and ecotoxicity studies were conducted to evaluate the environmental impact of the compound. The results showed the formation of detoxified metabolites and highlighted the need for further in vivo assays to confirm the findings.