The project hinges on a dual approach: a [systematic literature review][1], followed by an analysis of clinical trial results (see [Top VOCs in TMAU-negative participants][2]; Top VOCS in [TMAU positive][3]: TMAU1, TMAU2, TMAU negative individuals previously tested positive for TMAU1 or TMAU2 and top VOCs in those with TMAU-like symptoms who [never officially tested for TMAU][4]). The primary objective of [the systematic review][5] is gather comprehensive information on the subject matter. This systematic review protocol has been officially registered under the identifier [CRD397159][6] in the PROSPERO database. Research Questions: • RQ1: What range of propylene oxide concentrations has been documented in human exhaled breath across different studies? • RQ2: How do health conditions affect the levels of propylene oxide detected in exhaled breath? RQ2* How different concentrations of PO, its precursors and derivatives are associated with various health conditions • RQ3: Which biological variables are known to modulate individual susceptibility to propylene oxide and other environmental epoxides? • RQ4: What factors are proposed to influence Propylene Oxide levels in the human body, and what methods are used for quantification? • RQ5: What genetic polymorphisms could potentially affect propylene oxide metabolism? • RQ6: How does the human microbiome interact with propylene oxide metabolism, potentially influencing its concentration in exhaled breath? In addition to the literature review, the project also involves the analysis of results from a clinical study. The clinical study itself has been registered and documented with the identifier [NCT03451994][7] in clinicaltrials.gov. PROTOCOL of NCT03451994: Irene S. Gabashvili. Effects of diet, activities, environmental exposures and trimethylamine metabolism on alveolar breath compounds: protocol for a retrospective case-cohort observational study. medRxiv [2021.01.25.21250101][8] RESULTS RQ1: Filser JG, Hutzler C, Rampf F, Kessler W, Faller TH, Leibold E, Pütz C, Halbach S, Csanády GA. Concentrations of the propylene metabolite propylene oxide in blood of propylene-exposed rats and humans--a basis for risk assessment Toxicol Sci. 2008 Apr;102(2):219-31. doi: 10.1093/toxsci/kfm311. Epub 2008 Jan 4. PMID: 18178961 [Summary of Results][9] R3/R4: Lee MS, Faller TH, Kreuzer PE, Kessler W, Csanády GA, Pütz C, Ríos-Blanco MN, Pottenger LH, Segerbäck D, Osterman-Golkar S, Swenberg JA, Filser JG. Propylene oxide in blood and soluble nonprotein thiols in nasal mucosa and other tissues of male Fischer 344/N rats exposed to propylene oxide vapors--relevance of glutathione depletion for propylene oxide-induced rat nasal tumors Toxicol Sci. 2005 Jan;83(1):177-89. doi: 10.1093/toxsci/kfi006. Epub 2004 Oct 13. PMID: 15483188 [Figure 1][10]: PO concentrations in blood of rats exposed to atmospheric PO determined immediately at the end of the final exposure Relevant Databases: [Public Assessment of Propylene Oxide][11] hosted by Health Assessment Workspace Collaborative (HAWC) platform. [Queries][12] Human Breathomics Database ([HBDB][13]) Relevant Documents: Turner MC, Cogliano V, Guyton K, Madia F, Straif K, Ward EM, Schubauer-Berigan MK. Research Recommendations for Selected IARC-Classified Agents: Impact and Lessons Learned Environ Health Perspect. 2023 Oct;131(10):105001. doi: 10.1289/EHP12547. Epub 2023 Oct 30. PMID: 37902675 PMCID: PMC10615125 [Summary][14] Kolman A, Chovanec M, Osterman-Golkar S. Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990-2001). Mutat Res. 2002 Dec;512(2-3):173-94. doi: 10.1016/s1383-5742(02)00067-4. PMID: 12464351. [Table][15] Schulte Paul A, Hemminki K, Hopf Nancy B. Propylene oxide (PO). InIdentification of research needs to resolve the carcinogenicity of high-priority IARC carcinogens, views and expert opinions of an IARC/NORA expert group meeting, Lyon, France: 30 June-2 July 2009 2010 (pp. 79-86). Lyon: IARC. [PDF][16]: The publications programme of the International Agency for Research on Cancer (IARC) is an integral part of its mission to promote international collaboration in cancer research for cancer prevention. [1]: https://www.medrxiv.org/content/10.1101/2024.02.15.24302622v1 [2]: https://osf.io/6q98b [3]: https://osf.io/tybw7 [4]: https://osf.io/kjexy [5]: https://www.medrxiv.org/content/10.1101/2024.02.15.24302622v1 [6]: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=397159 [7]: https://classic.clinicaltrials.gov/ct2/show/NCT03451994 [8]: https://doi.org/10.1101/2021.01.25.21250101 [9]: https://osf.io/msyg2 [10]: https://osf.io/4v3ze [11]: https://hawcproject.iarc.who.int/lit/assessment/705/ [12]: https://osf.io/bkfn5 [13]: https://hbdb.cmdm.tw [14]: https://osf.io/bkfn5 [15]: https://osf.io/b8f4n [16]: https://publications.iarc.fr/_publications/media/download/3804/636268153bd1f9f1e20b569f1a6005d66041e95e.pdf