Analytical Challenges and Toxicological Implications of the Exposome: Open Issues towards a New Frontier for Medical Sciences

Jafari, Abbas; Seyfinejad, Behrouz

doi:https://doi.org/10.61882/rabms.11.4.405

Volume 11, Issue 4 (11-2025) Journal of Research in Applied and Basic Medical Sciences 2025, 11(4): 405-408 | Back to browse issues page

‎ https://doi.org/10.61882/rabms.11.4.405

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Jafari A, Seyfinejad B. Analytical Challenges and Toxicological Implications of the Exposome: Open Issues towards a New Frontier for Medical Sciences. Journal of Research in Applied and Basic Medical Sciences 2025; 11 (4) :405-408
URL: http://ijrabms.umsu.ac.ir/article-1-467-en.html

Analytical Challenges and Toxicological Implications of the Exposome: Open Issues towards a New Frontier for Medical Sciences

Abbas Jafari

, Behrouz Seyfinejad ^*

Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran , seyfinejad.b@umsu.ac.ir

Abstract: (75 Views)

Although the genome has been a cornerstone of medical research, it alone cannot describe the complex etiology of the majority of chronic diseases. The prime role of environmental exposures and lifestyle has hence introduced the concept of the exposome. The term exposome, coined by Christopher Wild, represents the totality of environmental exposures from conception onward and is considered a complement to the genome. ^{[1, 2]} Advancing exposome research offers the extraordinary opportunity for integration of exposure science, analytical chemistry, biomedicine, and toxicology within translational healthcare.
Wild's definition posited three overlapping domains: the general external environment, which includes elements such as urban/rural surroundings and climate; the specific external environment, which includes elements such as pollutants, diet, and occupation; and the internal environment, which includes metabolism, oxidative stress, and the microbiome. ^{[3, 4]} This has been further elaborated to include the behavioral factors and endogenous responses, placing environmental exposures as equivalent to genomics in determining health. ^{[5, 6]} Examples of these include air pollution and cardiovascular disease ^[7], maternal smoking and neonatal epigenetic changes ^[8], and the gut microbiome in intervening on diet and immune function. ^[9] Characterization of the exposome is both a major challenge and a tall opportunity for public health.
Characterization of the exposome necessitates a structured approach conceptualized into three phases: (1) analytical identification and measurement, (2) computational data processing, and (3) integrative understanding of exposure-effect interplay. Thousands of agents are present across biological matrices in the exposome with significant temporal variability. ^[10] Longitudinal cohort studies, such as EXPOsOMICS ^[3], HELIX ^[11], and CHEAR ^[12], are pioneering systematic approaches to capture such data.

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Type of Study: Letter to Editor | Subject: General

References

1. Rappaport SM, Smith MT. Environment and disease risks. Science. 2010;330(6003):460-1. doi: 10.1126/science.1192603 [DOI:10.1126/science.1192603] [PMID] [PMCID]

2. Wild CP. Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1847-50. doi: 10.1158/1055-9965.EPI-05-0456 [DOI:10.1158/1055-9965.EPI-05-0456] [PMID]

3. Vineis P, Chadeau-Hyam M, Gmuender H, Gulliver J, Herceg Z, Kleinjans J, et al. The exposome in practice: design of the EXPOsOMICS project. Int J Hyg Environ Health. 2017;220(2):142-51. doi: 10.1016/j.ijheh.2016.08.001 [DOI:10.1016/j.ijheh.2016.08.001] [PMID] [PMCID]

4. Dennis KK, Auerbach SS, Balshaw DM, Cui Y, Fallin MD, Smith MT, et al. The importance of the biological impact of exposure to the concept of the exposome. Environ Health Perspect. 2016;124(10):1504-10. doi: 10.1289/EHP140 [DOI:10.1289/EHP140] [PMID] [PMCID]

5. Miller GW, Jones DP. The nature of nurture: refining the definition of the exposome. Toxicol Sci. 2014;137(1):1-2. doi: 10.1093/toxsci/kft251 [DOI:10.1093/toxsci/kft251] [PMID] [PMCID]

6. Wild CP. The exposome: from concept to utility. Int J Epidemiol. 2012;41(1):24-32. doi: 10.1093/ije/dyr236 [DOI:10.1093/ije/dyr236] [PMID]

7. Brook RD, Rajagopalan S, Pope CA, Brook JR, Bhatnagar A, Diez-Roux AV, et al. Particulate matter air pollution and cardiovascular disease. Circulation. 2010;121(21):2331-78. doi: 10.1161/CIR.0b013e3181dbece1 [DOI:10.1161/CIR.0b013e3181dbece1] [PMID] [PMCID]

8. Joubert BR, Håberg SE, Nilsen RM, Wang X, Vollset SE, Murphy SK, et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect. 2012;120(10):1425-31. doi: 10.1289/ehp.1205412 [DOI:10.1289/ehp.1205412] [PMID] [PMCID]

9. Ross FC, Patangia D, Grimaud G, Lavelle A, Dempsey EM, Ross RP, et al. The interplay between diet and the gut microbiome: implications for health and disease. Nat Rev Microbiol. 2024;22(11):671-86. doi: 10.1038/s41579-024-01068-4 [DOI:10.1038/s41579-024-01068-4] [PMID]

10. Dennis KK, Marder E, Balshaw DM, Cui Y, Lynes MA, Patti GJ, et al. Biomonitoring in the era of the exposome. Environ Health Perspect. 2017;125(4):502-10. doi: 10.1289/EHP474 [DOI:10.1289/EHP474] [PMID] [PMCID]

11. Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, Van den Hazel P, et al. The human early-life exposome (HELIX): project rationale and design. Environ Health Perspect. 2014;122(6):535-44. doi: 10.1289/ehp.1307204 [DOI:10.1289/ehp.1307204] [PMID] [PMCID]

12. Kovatch P, McGuinness DL, Gennings C, Teitelbaum SL. Lessons learned from the children's health exposure analysis resource (CHEAR) data center. ISEE Conference Abstracts. 2016;28:P3-131. Doi: 10.1289/isee.2016.4355 [DOI:10.1289/isee.2016.4355]

13. Vitale CM, Price EJ, Miller GW, David A, Antignac J-P, Barouki R, et al. Analytical strategies for chemical exposomics: exploring limits and feasibility. Exposome. 2021;1(1):osab003. Doi: 10.1093/exposome/osab003 [DOI:10.1093/exposome/osab003]

14. Seyfinejad B, Jouyban A. Capillary electrophoresis-mass spectrometry in pharmaceutical and biomedical analyses. J Pharm Biomed Anal. 2022;221:115059. Doi: 10.1016/j.jpba.2022.115059 [DOI:10.1016/j.jpba.2022.115059] [PMID]

15. Seyfinejad B, Nemutlu E, Taghizadieh A, Khoubnasabjafari M, Ozkan SA, Jouyban A. Biomarkers in exhaled breath condensate as fingerprints of asthma, chronic obstructive pulmonary disease, and asthma-chronic obstructive pulmonary disease overlap: A critical review. Biomark Med. 2023;17(19):811-37. Doi: 10.2217/bmm-2023-0420 [DOI:10.2217/bmm-2023-0420] [PMID]

16. Flasch M, Koellensperger G, Warth B. Comparing the sensitivity of a low- and a high-resolution mass spectrometry approach for xenobiotic trace analysis: An exposome-type case study. Anal Chim Acta. 2023;1279:341740. Doi: 10.1016/j.aca.2023.341740 [DOI:10.1016/j.aca.2023.341740] [PMID]

17. da Silva RR, Dorrestein PC, Quinn RA. Illuminating the dark matter in metabolomics. Proc Natl Acad Sci. 2015;112(41):12549-50. Doi: 10.1073/pnas.1516878112 [DOI:10.1073/pnas.1516878112] [PMID] [PMCID]

18. Seyfinejad B, Jouyban A. Importance of method validation in the analysis of biomarker. Curr Pharm Anal. 2022;18(6):567-9. Doi: 10.2174/1573412918666211213142638 [DOI:10.2174/1573412918666211213142638]

19. Agier L, Portengen L, Chadeau-Hyam M, Basagaña X, Giorgis-Allemand L, Siroux V, et al. A systematic comparison of linear regression-based statistical methods to assess exposome-health associations. Environ Health Perspect. 2016;124(12):1848-56. Doi: 10.1289/EHP172 [DOI:10.1289/EHP172] [PMID] [PMCID]

20. Deonarine A, Batwara A, Wada R, Sharma P, Loscalzo J, Ojikutu B, et al. De Novo exposomic geospatial assembly of chronic disease regions with machine learning & network analysis. EBioMedicine. 2025;112:105575. Doi|:10.1016/j.ebiom.2025.105575 [DOI:10.1016/j.ebiom.2025.105575] [PMID] [PMCID]

21. Xue J, Lai Y, Liu C-W, Ru H. Towards mass spectrometry-based chemical exposome: Current approaches, challenges, and future directions. Toxics. 2019;7(3):41. Doi: 10.3390/toxics7030041 [DOI:10.3390/toxics7030041] [PMID] [PMCID]

22. Vermeulen R, Schymanski EL, Barabási A-L, Miller GW. The exposome and health: Where chemistry meets biology. Science. 2020;367(6476):392-6. Doi: 10.1126/science.aay3164 [DOI:10.1126/science.aay3164] [PMID] [PMCID]

23. Patel CJ, Bhattacharya J, Butte AJ. An environment-wide association study (EWAS) on type 2 diabetes mellitus. PLoS One. 2010;5(5):e10746. Doi: 10.1371/journal.pone.0010746 [DOI:10.1371/journal.pone.0010746] [PMID] [PMCID]

24. Hernández LG, van Steeg H, Luijten M, van Benthem J. Mechanisms of non-genotoxic carcinogens and importance of a weight of evidence approach. Mutat Res. 2009;682(2):94-109. Doi: 10.1016/j.mrrev.2009.07.002 [DOI:10.1016/j.mrrev.2009.07.002] [PMID]

25. Stingone JA, Buck Louis GM, Nakayama SF, Vermeulen RCH, Kwok RK, Cui Y, et al. Toward greater implementation of the exposome research paradigm within environmental epidemiology. Annu Rev Public Health. 2017;38:315-27. Doi: 10.1146/annurev-publhealth-082516-012750 [DOI:10.1146/annurev-publhealth-082516-012750] [PMID] [PMCID]

26. Stojanoska MM, Milosevic N, Milic N, Abenavoli L. The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders. Endocrine. 2017;55(3):666-81. Doi: 10.1007/s12020-016-1158-4 [DOI:10.1007/s12020-016-1158-4] [PMID]

27. Dupre TV, Schnellmann RG, Miller GW. Using the exposome to address gene-environment interactions in kidney disease. Nat Rev Nephrol. 2020;16(11):621-2. Doi: 10.1038/s41581-020-0302-9 [DOI:10.1038/s41581-020-0302-9] [PMID]

28. Abdolghaffari AH, Baghaei A, Solgi R, Gooshe M, Baeeri M, Navaei-Nigjeh M, et al. Molecular and biochemical evidences on the protective effects of triiodothyronine against phosphine-induced cardiac and mitochondrial toxicity. Life Sci. 2015;139:30-9. Doi: 10.1016/j.lfs.2015.07.026 [DOI:10.1016/j.lfs.2015.07.026] [PMID]

29. Hassani S, Sepand M, Jafari A, Jaafari J, Rezaee R, Zeinali M, et al. Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage. Hum Exp Toxicol. 2015;34(6):668-76. Doi: 10.1177/0960327114550888 [DOI:10.1177/0960327114550888] [PMID]

30. Jafari A, Bargeshadi R, Jafari F, Mohebbi I, Hajaghazadeh M. Environmental and biological measurements of isoflurane and sevoflurane in operating room personnel. Int Arch Occup Environ Health. 2018;91(3):349-59. Doi: 10.1007/s00420-017-1287-y [DOI:10.1007/s00420-017-1287-y] [PMID]

31. Merrick BA, Paules RS, Tice RR. Intersection of toxicogenomics and high throughput screening in the Tox21 program: an NIEHS perspective. Int J Biotechnol. 2015;14(1):7-27. Doi: 10.1504/IJBT.2015.074797 [DOI:10.1504/IJBT.2015.074797] [PMID] [PMCID]