Metabolómica y Pesticidas: Revisión sistemática de literatura usando teoría de grafos para el análisis de referencias

Metabolomics and pesticides: systematic literature review using graph theory for analysis of references

The systematic literature review presented here is designed to illustrate the role of metabonomics and metabolomics in pesticide exposure studies. The search was conducted in Thomson Reuters Web of Science (ISI Web of Knowledge) database. The references and citations for each article were downloaded for analysis. Graph theory was used to determine relevant articles and distinct relationships between classic and current research in this field through its structural characteristics. The initial network included 4423 nodes and 4978 links, from which indegree, outdegree and betweenness indicators were extracted. After preprocessing the data, the network was reduced to 415 nodes and 974 links. From this network, 80 articles with the highest score between the three indicators were extracted for review. This methodology allowed for the identification of different perspectives of metabolomic and metabonomic pesticide studies that included the mode and mechanism of action, toxicological and biological monitoring, environmental metabolomics, metabolism, dose response and biomarkers and its role in pesticide exposure.

1. Z.-J. Wang, Y. Gao, Y.-L. Hou, C. Zhang, S.-J. Yu, Q. Bian, Z.-M. Li, and W.-G. Zhao, “Design, synthesis, and fungicidal evaluation of a series of novel 5-methyl-1H-1,2,3-trizole-4carboxyl amide and ester analogues.,” Eur. J. Med. Chem., vol. 86, pp. 87–94, Oct. 2014.
2. M. Gassel, C. Wolf, S. Noack, H. Williams, and T. Ilg, “The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity.,” Insect Biochem. Mol. Biol., vol. 45, pp. 111–24, Feb. 2014.
3. Y.-D. Li, W.-T. Mao, Z.-J. Fan, J.-J. Li, Z. Fang, X.-T. Ji, X.-W. Hua, G.-N. Zong, F.-Y. Li, C.-L. Liu, and J.-H. Yu, “Synthesis and biological evaluation of novel 1,2,4-triazole containing 1,2,3-thiadiazole derivatives,” Chinese Chem. Lett., vol. 24, no. 12, pp. 1134–1136, Dec. 2013.
4. H.-N. Guan, D.-F. Chi, J. Yu, and S.-Y. Zhang, “Novel photodegradable insecticide W/TiO(2)/Avermectin nanocomposites obtained by polyelectrolytes assembly.,” Colloids Surf. B. Biointerfaces, vol. 83, no. 1, pp. 148–54, Mar. 2011.
5. M. P. Longnecker, M. S. Wolff, B. C. Gladen, J. W. Brock, P. Grandjean, J. L. Jacobson, S. a. Korrick, W. J. Rogan, N. Weisglas-Kuperus, I. Hertz-Picciotto, P. Ayotte, P. Stewart, G. Winneke, M. J. Charles, S. W. Jacobson, É. Dewailly, E. R. Boersma, L. M. Altshul, B. Heinzow, J. J. Pagano, and A. a. Jensen, “Comparison of Polychlorinated Biphenyl Levels across Studies of Human Neurodevelopment,” Environ. Health Perspect., vol. 111, no. 1, pp. 65–70, Dec. 2003.
6. G. Ding and Y. Bao, “Revisiting pesticide exposure and children’s health: Focus on China,” Sci. Total Environ., vol. 472, pp. 289–295, 2014.
7. J. K. Nicholson, J. Lindon, and E. Holmes, “‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data,” Xenobiotica, vol. 29, no. 11, pp. 1181–1189, 1999.
8. R. N. Trethewey, A. J. Krotzky, and L. Willmitzert, “Commentary Metabolic profiling : a Rosetta Stone for genomics ?,” Curr. Opin. Plant Biol., vol. 2, pp. 83–85, 1999.
9. O. Fiehn, “Metabolomics - The link between genotypes and phenotypes,” Plant Mol. Biol., vol. 48, no. 1–2, pp. 155–171, 2002.
10. S. Robledo-giraldo, J. I. Zuluaga-giraldo, and N. D. Duque-Méndez, “Diffusion of Products Through Social Networks :,” Respuestas, vol. 18, no. 2, pp. 28–42, 2013.
11. S. Robledo-Giraldo, G. A. Osorio-Zuluaga, and C. López-Espinosa, “Networking en pequeña empresa: una revisión bibliográfica utilizando la teoría de grafos,” Rev. Vinculos, vol. 11, no. 2, pp. 6–16, 2014.
12. M. Bastian, S. Heymann, and M. Jacomy, “Gephi: An open source software for exploring and manipulating networks. BT - International AAAI Conference on Weblogs and Social,” pp.
13. –362, 2009.
14. W. D. Wallis, A Beginner’s Guide to Graph Theory. Birkhäuser Boston, 2007.
15. B. Bollobás, “The evolution of random graphs,” Trans. Am. Math. Soc., vol. 286, no. 1, pp. 257–257, 1984.
16. L. C. Freeman, “A Set of Measures of Centrality Based on Betweenness,” Sociometry, vol. 40, no. 1, pp. 35–41, 1977.
17. C. Ni, C. R. Sugimoto, and J. Jiang, “Degree , Closeness , and Betweenness : Application of group centrality measurements to explore macro-disciplinary evolution diachronically,” in 13th Meetings of International Society for Scientometrics and Informetrics (ISSI), Durban, South Africa, 2011, pp. 1–13.
18. V. D. Blondel, J. Guillaume, and E. Lefebvre, “Fast unfolding of communities in large networks,” J. Stat. Mech. Theory Exp., vol. 10, p. 1000, 2008.
19. J. Xia, D. I. Broadhurst, M. Wilson, and D. S. Wishart, “Translational biomarker discovery in clinical metabolomics: an introductory tutorial,” Metabolomics, vol. 9, no. 2, pp. 280–299, 2013.
20. J. G. Bundy, M. P. Davey, and M. R. Viant, “Environmental metabolomics: a critical review and future perspectives,” Metabolomics, vol. 5, no. 1, pp. 3–21, Dec. 2009.
21. M. J. Simpson and J. R. McKelvie, “Environmental metabolomics: new insights into earthworm ecotoxicity and contaminant bioavailability in soil.,” Anal. Bioanal. Chem., vol. 394, no. 1, pp. 137–49, May 2009.
22. J. G. Bundy, D. J. Spurgeon, C. Svendsen, P. K. Hankard, J. M. Weeks, D. Osborn, J. C. Lindon, and J. K. Nicholson, “Environmental metabonomics: applying combination biomarker analysis in earthworms at a metal contaminated site.,” Ecotoxicology, vol. 13, no. 8, pp. 797–806, Nov. 2004.
23. O. a H. Jones, D. J. Spurgeon, C. Svendsen, and J. L. Griffin, “A metabolomics based approach to assessing the toxicity of the polyaromatic hydrocarbon pyrene to the earthworm Lumbricus rubellus.,” Chemosphere, vol. 71, no. 3, pp. 601–9, Mar. 2008.
24. S. a E. Brown, A. J. Simpson, and M. J. Simpson, “Evaluation of sample preparation methods for nuclear magnetic resonance metabolic profiling studies with Eisenia fetida.,” Environ. Toxicol. Chem., vol. 27, no. 4, pp. 828–36, Apr. 2008.
25. J. R. McKelvie, J. Yuk, Y. Xu, A. J. Simpson, and M. J. Simpson, “1H NMR and GC/MS metabolomics of earthworm responses to sub-lethal DDT and endosulfan exposure,” Metabolomics, vol. 5, no. 1, pp. 84–94, Aug. 2009.
26. S. Uno, A. Shintoyo, E. Kokushi, M. Yamamoto, K. Nakayama, and J. Koyama, “Gas chromatography-mass spectrometry for metabolite profiling of Japanese medaka (Oryzias latipes) juveniles exposed to malathion.,” Environ. Sci. Pollut. Res. Int., vol. 19, no. 7, pp. 2595–605, Aug. 2012.
27. A. Lubbe, K. Ali, R. Verporte, and Y. H. Choi, “9. NMRBased Metabolomics Analysis,” in Metabolomics in practice: Successful Strategies to Generate and Analyze Metabolic Data, M. Lämmerhofer and W. Weckwerth, Eds. Weinheim, Germany:
28. Wiley-VCH Verlag GmbH & Co. KGaA, 2013, pp. 209–234.
29. M. Sugimoto, M. Kawakami, M. Robert, and T. Soga, “Bioinformatics tools for mass spectroscopy-based metabolomic data processing and analysis,” … Bioinforma., pp. 96–108, 2012.
30. M. Katajamaa and M. Oresic, “Data processing for mass spectrometry-based metabolomics.,” J. Chromatogr. A, vol. 1158, no. 1–2, pp. 318–28, Jul. 2007.
31. E. Szymańska, E. Saccenti, A. K. Smilde, and J. a Westerhuis, “Double-check: validation of diagnostic statistics for PLS-DA models in metabolomics studies.,” Metabolomics, vol. 8, no. Suppl 1, pp. 3–16, Jun. 2012.
32. J. Xia, I. V. Sinelnikov, B. Han, and D. S. Wishart, “MetaboAnalyst 3.0--making metabolomics more meaningful,” Nucleic Acids Res., pp. 1–7, 2015.
33. J. Xia and D. S. Wishart, “MSEA: a web-based tool to identify biologically meaningful patterns in quantitative metabolomic data,” Nucleic Acids Res., vol. 38, no. Web Server, pp. W71– W77, 2010.
34. T. Aittokallio and B. Schwikowski, “Graph-based methods for analysing networks in cell biology.,” Brief. Bioinform., vol. 7, no. 3, pp. 243–55, Sep. 2006.
35. Y.-J. Liang, H.-P. Wang, D.-X. Long, and Y.-J. Wu, “(1)H NMR-based metabonomic profiling of rat serum and urine to characterize the subacute effects of carbamate insecticide propoxur.,” Biomarkers, vol. 17, no. 6, pp. 566–74, Sep. 2012.
36. H.-P. Wang, Y.-J. Liang, D.-X. Long, J.-X. Chen, W.-Y. Hou, and Y.-J. Wu, “Metabolic profiles of serum from rats after subchronic exposure to chlorpyrifos and carbaryl.,” Chem. Res. Toxicol., vol. 22, no. 6, pp. 1026–33, Jun. 2009.
37. H.-D. Xu, J.-S. Wang, M.-H. Li, Y. Liu, T. Chen, and A.-Q. Jia, “1H NMR based metabolomics approach to study the toxic effects of herbicide butachlor on goldfish (Carassius auratus),” Aquat. Toxicol., vol. 159, pp. 69–80, 2015.
38. V. C. Moser, N. Stewart, D. L. Freeborn, J. Crooks, D. K. MacMillan, J. M. Hedge, C. E. Wood, R. L. McMahen, M. J. Strynar, and D. W. Herr, “Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes,” Toxicol. Appl. Pharmacol., vol. 282, no. 2, pp. 161–174, 2015.
39. P. a. Olsvik, M. H. G. Berntssen, and L. Søfteland, “Modifying Effects of Vitamin E on Chlorpyrifos Toxicity in Atlantic Salmon,” PLoS One, vol. 10, no. 3, p. e0119250, 2015.
40. S. V. Bhat, S. C. Booth, S. G. K. McGrath, and T. E. S. Dahms, “Rhizobium leguminosarum bv. viciae 3841 Adapts to 2,4-Dichlorophenoxyacetic Acid with ‘Auxin-Like’ Morphological Changes, Cell Envelope Remodeling and Upregulation of Central Metabolic Pathways,” PLoS One, vol. 10, no. 4, p. e0123813, 2015.
41. K. a. Aliferis and S. Jabaji, “Metabolomics – A robust bioanalytical approach for the discovery of the modes-of-action of pesticides: A review,” Pestic. Biochem. Physiol., vol. 100, no. 2, pp. 105–117, Jun. 2011.
42. W. Tuffnail, G. a. Mills, P. Cary, and R. Greenwood, “An environmental 1H NMR metabolomic study of the exposure of the marine mussel Mytilus edulis to atrazine, lindane, hypoxia and starvation,” Metabolomics, vol. 5, no. 1, pp. 33–43, Nov. 2008.
43. J. Yuk, M. J. Simpson, and A. J. Simpson, “1-D and 2-D NMR-based metabolomics of earthworms exposed to endosulfan and endosulfan sulfate in soil,” Environ. Pollut., vol. 175, pp. 35–44, 2013.
44. J. Yuk, M. J. Simpson, and A. J. Simpson, “1-D and 2-D NMR metabolomics of earthworm responses to sub-lethal trifluralin and endosulfan exposure,” Environ. Chem., vol. 8, no. 3, p. 281, 2011.
45. X. Zhang, K. D. Oakes, S. Wang, M. R. Servos, S. Cui, J. Pawliszyn, and C. D. Metcalfe, “In vivo sampling of environmental organic contaminants in fish by solid-phase microextraction,” TrAC Trends Anal. Chem., vol. 32, no. Table 1, pp. 31–39, Feb. 2012.
46. M. Li, J. Wang, Z. Lu, D. Wei, M. Yang, and L. Kong, “NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus).,” Aquat. Toxicol., vol. 146, pp. 82–92, Jan. 2013.
47. Q. Huang and H.-Q. Huang, “Alterations of protein profile in zebrafish liver cells exposed to methyl parathion: a membrane proteomics approach.,” Chemosphere, vol. 87, no. 1, pp. 68–76, Mar. 2012.
48. A. D. Southam, A. Lange, A. Hines, E. M. Hill, Y. Katsu, T. Iguchi, C. R. Tyler, and M. R. Viant, “Metabolomics reveals target and off-target toxicities of a model organophosphate pesticide to roach (Rutilus rutilus): implications for biomonitoring.,” Environ. Sci. Technol., vol. 45, no. 8, pp. 3759–67, Apr. 2011.
49. H.-P. Wang, Y.-J. Liang, Y.-J. Sun, J.-X. Chen, W.-Y. Hou, D.-X. Long, and Y.-J. Wu, “1H NMR-based metabonomic analysis of the serum and urine of rats following subchronic exposure to dichlorvos, deltamethrin, or a combination of these two pesticides.,” Chem. Biol. Interact., vol. 203, no. 3, pp. 588–96, May 2013.
50. S. Uno, A. Shintoyo, E. Kokushi, M. Yamamoto, K. Nakayama, and J. Koyama, “Gas chromatography-mass spectrometry for metabolite profiling of Japanese medaka (Oryzias latipes) juveniles exposed to malathion.,” Environ. Sci. Pollut. Res. Int., vol. 19, no. 7, pp. 2595–605, Aug. 2011.
51. M. Forcella, E. Berra, R. Giacchini, B. Rossaro, and P. Parenti, “Increased alanine concentration is associated with exposure to fenitrothion but not carbamates in Chironomus riparius larvae.,” Ecotoxicol. Environ. Saf., vol. 66, no. 3, pp. 326–34, Mar. 2007.
52. A. J. Mearns, D. J. Reish, P. S. Oshida, T. Ginn, and M. A. Rempel-Hester, “Effects of Pollution on Marine Organisms,” Water Environ. Res., vol. 83, no. 10, pp. 1789–1852, Jan. 2011.
53. N. Sánchez-Avila, J. M. Mata-Granados, J. Ruiz-Jiménez, and M. D. Luque de Castro, “Fast, sensitive and highly discriminant gas chromatography-mass spectrometry method for profiling analysis of fatty acids in serum.,” J. Chromatogr. A, vol. 1216, no. 40, pp. 6864–72, Oct. 2009.
54. N. Bonvallot, M. Tremblay-Franco, C. Chevrier, C. Canlet, C. Warembourg, J.-P. Cravedi, and S. Cordier, “Metabolomics tools for describing complex pesticide exposure in pregnant women in Brittany (France).,” PLoS One, vol. 8, no. 5, p. e64433, Jan. 2013.
55. Y.-J. Liang, W. HP, Y. L, L. W, and W. YJ., “Metabonomic responses in rat urine following subacute exposure to propoxur.,” Int J Toxicol, vol. 31, no. 3, pp. 287–93, 2012.
56. P. Carriquiriborde, D. J. Marino, G. Giachero, E. a Castro, and A. E. Ronco, “Global metabolic response in the bile of pejerrey (Odontesthes bonariensis, Pisces) sublethally exposed to the pyrethroid cypermethrin.,” Ecotoxicol. Environ. Saf., vol. 76, no. 2, pp. 46–54, Feb. 2012.
57. J. K. Nicholson, J. Connelly, J. C. Lindon, and E. Holmes, “Metabonomics: a platform for studying drug toxicity and gene function.,” Nat. Rev. Drug Discov., vol. 1, no. 2, pp. 153–61, Feb. 2002.
58. P. Fuentealba González, A. Llanos-Rivera, N. Carvajal Baeza, and E. Uribe Pérez, “Xenobiotic-induced changes in the arginase activity of zebrafish (Danio rerio) eleutheroembryo.,” Environ. Toxicol. Chem., vol. 30, no. 10, pp. 2285–91, Oct. 2011.
59. O. a H. Jones, S. Murfitt, C. Svendsen, A. Turk, H. Turk, D. J. Spurgeon, L. a Walker, R. F. Shore, S. M. Long, and J. L. Griffin, “Comparisons of metabolic and physiological changes in rats following short term oral dosing with pesticides commonly found in food.,” Food Chem. Toxicol., vol. 59, pp. 438–45, Sep. 2013.
60. H.-P. Wang, Y.-J. Liang, Q. Zhang, D.-X. Long, W. Li, L. Li, L. Yang, X.-Z. Yan, and Y.-J. Wu, “Changes in metabolic profiles of urine from rats following chronic exposure to anticholinesterase pesticides,” Pestic. Biochem. Physiol., vol. 101, no. 3, pp. 232–239, Nov. 2011.
61. J. Yuk, M. J. Simpson, and A. J. Simpson, “1-D and 2-D NMR metabolomics of earthworm responses to sub-lethal trifluralin and endosulfan exposure,” Environ. Chem., vol. 8, no. 3, p. 281, 2011.
62. J. Yuk, J. R. McKelvie, M. J. Simpson, M. Spraul, and A. J. Simpson, “Comparison of 1-D and 2-D NMR techniques for screening earthworm responses to sub-lethal endosulfan exposure,” Environ. Chem., vol. 7, no. 6, p. 524, 2010.
63. J. R. McKelvie, J. Yuk, Y. Xu, A. J. Simpson, and M. J. Simpson, “1H NMR and GC/MS metabolomics of earthworm responses to sub-lethal DDT and endosulfan exposure,” Metabolomics, vol. 5, no. 1, pp. 84–94, Aug. 2008.
64. S. a E. Brown, J. R. McKelvie, A. J. Simpson, and M. J. Simpson, “1H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil.,” Environ. Pollut., vol. 158, no. 6, pp. 2117–23, Jun. 2010.
65. J. G. Bundy, D. Osborn, J. M. Weeks, J. C. Lindon, and J. K. Nicholson, “An NMR-based metabonomic approach to the investigation of coelomic fluid biochemistry in earthworms under toxic stress.,” FEBS Lett., vol. 500, no. 1–2, pp. 31–5, Jun. 2001.
66. T. H. Bundy JG, Lenz EM, Bailey NJ, Gavaghan CL, Svendsen C, Spurgeon D, Hankard PK, Osborn D, Weeks JM, Trauger SA, Speir P, Sanders I, Lindon JC, Nicholson JK, “Metabonomic assessment of toxicity of 4-fluoroaniline, 3,5-difluoroaniline and 2-fluoro-4-methylaniline to the earthworm Eisenia veneta (Rosa): identification of new endogenous biomarkers.,” Env.
67. Toxicol Chem., vol. 21, no. 9, pp. 1966–72, 2002.
68. J. G. Bundy, D. J. Spurgeon, C. Svendsen, P. K. Hankard, J. M. Weeks, D. Osborn, J. C. Lindon, and J. K. Nicholson, “Environmental metabonomics: applying combination biomarker analysis in earthworms at a metal contaminated site.,” Ecotoxicology, vol. 13, no. 8, pp. 797–806, Nov. 2004.
69. J. G. Bundy, H. C. Keun, J. K. Sidhu, D. J. Spurgeon, C. Svendsen, P. Kille, and A. J. Morgan, “Metabolic Profile Biomarkers of Metal Contamination in a Sentinel Terrestrial Species Are Applicable Across Multiple Sites,” Environ. Sci. Technol., vol. 41, no. 12, pp. 4458–4464, 2007.
70. M. Mirnezhad, R. R. Romero-González, K. a Leiss, Y. H. Choi, R. Verpoorte, and P. G. L. Klinkhamer, “Metabolomic analysis of host plant resistance to thrips in wild and cultivated tomatoes.,” Phytochem. Anal., vol. 21, no. 1, pp. 110–7, 2010.
71. G. G. Siano, I. S. Pérez, M. D. G. García, M. M. Galera, and H. C. Goicoechea, “Multivariate curve resolution modeling of liquid chromatography-mass spectrometry data in a comparative study of the different endogenous metabolites behavior in two tomato cultivars treated with carbofuran pesticide.,” Talanta, vol. 85, no. 1, pp. 264–75, Jul. 2011.
72. I. J. Colquhoun, “Use of NMR for metabolic profiling in plant systems,” J. Pestic. Sci., vol. 32, no. 3, pp. 200–212, 2007.
73. M. R. Viant, C. a Pincetich, and R. S. Tjeerdema, “Metabolic effects of dinoseb, diazinon and esfenvalerate in eyed eggs and alevins of Chinook salmon (Oncorhynchus tshawytscha) determined by 1H NMR metabolomics.,” Aquat. Toxicol., vol. 77, no. 4, pp. 359–71, May 2006.
74. C. Y. Lin, M. R. Viant, and R. S. TJeerdema, “Metabolomics : Methodologies and applications in the environmental sciences,” J. Pestic. Sci., vol. 31, no. 3, pp. 245–251, 2006.
75. K. Sanford, P. Soucaille, G. Whited, and G. Chotani, “Genomics to fluxomics and physiomics — pathway engineering,” Curr. Opin. Microbiol., vol. 5, no. 3, pp. 318–322, Jun. 2002.
76. M. G. Miller, “Environmental metabolomics: a SWOT analysis (strengths, weaknesses, opportunities, and threats).,” J. Proteome Res., vol. 6, no. 2, pp. 540–5, Feb. 2007.
77. M. Merhi, C. Demur, C. Racaud-Sultan, J. Bertrand, C. Canlet, F. B. Y. Estrada, and L. Gamet-Payrastre, “Gender-linked haematopoietic and metabolic disturbances induced by a pesticide mixture administered at low dose to mice.,” Toxicology, vol. 267, no. 1–3, pp. 80–90, Jan. 2010.
78. N. J. Waters, C. J. Waterfield, R. D. Farrant, E. Holmes, and J. K. Nicholson, “Metabonomic deconvolution of embedded toxicity: application to thioacetamide hepato- and nephrotoxicity.,” Chem. Res. Toxicol., vol. 18, no. 4, pp. 639–54, Apr. 2005.
79. K.-B. Kim, S. H. Kim, S. Y. Um, M. W. Chung, J. S. Oh,
80. S.-C. Jung, T. S. Kim, H. J. Moon, S. Y. Han, H. Y. Oh, B. M. Lee, and K. H. Choi, “Metabolomics approach to risk assessment: methoxyclor exposure in rats.,” J. Toxicol. Environ. Health. A, vol. 72, no. 21–22, pp. 1352–68, Jan. 2009.
81. J. R. McKelvie, J. Yuk, Y. Xu, A. J. Simpson, and M. J. Simpson, “1H NMR and GC/MS metabolomics of earthworm responses to sub-lethal DDT and endosulfan exposure,” Metabolomics, vol. 5, no. 1, pp. 84–94, Aug. 2009.
82. M. A. Warne, E. M. Lenz, D. Osborn, and J. M. Weeks, “An NMR-based metabonomic investigation of the toxic effects of 3-trifluoromethyl-aniline on the earth worm Eisenia veneta,” Biomarkers, vol. 5, no. 1, pp. 56–72, 2000.
83. H.-P. Wang, Y.-J. Liang, Y.-J. Sun, J.-X. Chen, W.-Y. Hou, D.-X. Long, and Y.-J. Wu, “1H NMR-based metabonomic analysis of the serum and urine of rats following subchronic exposure to dichlorvos, deltamethrin, or a combination of these two pesticides.,” Chem. Biol. Interact., vol. 203, no. 3, pp. 588–96, May 2013.
84. C. Demur, B. Métais, C. Canlet, M. Tremblay-Franco, R. Gautier, F. Blas-Y-Estrada, C. Sommer, and L. Gamet-Payrastre, “Dietary exposure to a low dose of pesticides alone or as a mixture: the biological metabolic fingerprint and impact on hematopoiesis.,” Toxicology, vol. 308, pp. 74–87, Jun. 2013.
85. O. a H. Jones, S. C. Swain, C. Svendsen, J. L. Griffin, S. R. Sturzenbaum, and D. J. Spurgeon, “Potential new method of mixture effects testing using metabolomics and Caenorhabditis elegans.,” J. Proteome Res., vol. 11, no. 2, pp. 1446–53, Feb. 2012.
86. M. K. R. Mudiam, R. Ch, and P. N. Saxena, “Gas chromatography-mass spectrometry based metabolomic approach for optimization and toxicity evaluation of earthworm sub-lethal responses to carbofuran.,” PLoS One, vol. 8, no. 12, p. e81077, Jan. 2013.
87. J. F. Kenneke, D. R. Ekman, C. S. Mazur, B. J. Konwick, A. T. Fisk, J. K. Avants, and A. W. Garrison, “Integration of Metabolomics and In Vitro Metabolism Assays for Investigating the Stereoselective Transformation of Triadimefon in Rainbow Trout,” Chirality, vol. 192, no. May 2009, pp. 183–192, 2010.
88. Y. Picó and D. Barceló, “The expanding role of LC-MS in analyzing metabolites and degradation products of food contaminants,” TrAC Trends Anal. Chem., vol. 27, no. 10, pp. 821–835, Nov. 2008.
89. D. Hao, W. Xu, H. Wang, L. Du, J. Yang, X. Zhao, and C. Sun, “Ecotoxicology and Environmental Safety Metabolomic analysis of the toxic effect of chronic low-dose exposure to acephate on rats using ultra-performance liquid chromatography / mass spectrometry,” Ecotoxicol. Environ. Saf., vol. 83, pp. 25–33, 2012.
90. Z. Feng, X. Sun, J. Yang, D. Hao, L. Du, H. Wang, W. Xu, X. Zhao, and C. Sun, “Metabonomics analysis of urine and plasma from rats given long-term and low-dose dimethoate by ultra-performance liquid chromatography-mass spectrometry.,” Chem. Biol. Interact., vol. 199, no. 3, pp. 143–53, Sep. 2012.
91. D. G. Robertson, M. D. Reily, R. E. Sigler, D. F. Wells, D. a Paterson, and T. K. Braden, “Metabonomics: evaluation of nuclear magnetic resonance (NMR) and pattern recognition technology for rapid in vivo screening of liver and kidney toxicants.,” Toxicol. Sci., vol. 57, no. 2, pp. 326–37, Oct. 2000.
92. K. a. Aliferis and M. Chrysayi-Tokousbalides, “Metabolomics in pesticide research and development: review and future perspectives,” Metabolomics, vol. 7, no. 1, pp. 35–53, Aug. 2011.
93. M. R. Viant, E. S. Rosenblum, and R. S. Tjeerdema, “NMRBased Metabolomics: A Powerful Approach for Characterizing the Effects of Environmental Stressors on Organism Health,” Environ. Sci. Technol., vol. 37, no. 21, pp. 4982–89, 2003.
94. J. R. McKelvie, D. M. Wolfe, M. Celejewski, A. J. Simpson, and M. J. Simpson, “Correlations of Eisenia fetida metabolic responses to extractable phenanthrene concentrations through time.,” Environ. Pollut., vol. 158, no. 6, pp. 2150–7, Jun. 2010.
95. A. Lommen, G. van der Weg, M. C. van Engelen, G. Bor, L. a P. Hoogenboom, and M. W. F. Nielen, “An untargeted metabolomics approach to contaminant analysis: pinpointing potential unknown compounds.,” Anal. Chim. Acta, vol. 584, no. 1, pp. 43–9, Feb. 2007.
96. E. Liotta, R. Gottardo, A. Bertaso, and A. Polettini, “Screening for pharmaco-toxicologically relevant compounds in biosamples using high-resolution mass spectrometry: a ‘metabolomic’ approach to the discrimination between isomers.,” J. Mass Spectrom., vol. 45, no. 3, pp. 261–71, Mar. 2010.
97. D. Grapov, K. Wanichthanarak, and O. Fiehn, “MetaMapR : Pathway Independent Metabolomic Network Analysis In- corporating Unknowns,” Bioinforma. Adv. Access, pp. 5–8, 2015.
98. Zuluaga, M., Melchor, J. J., Tabares-Villa, F. A., Taborda, G., & Sepúlveda-Arias, J. C. (2016). Metabolite Profiling to Monitor Organochlorine Pesticide Exposure in HepG2 Cell Culture. Chromatographia, 1–8. http://doi.org/10.1007/s10337-016-3031-2
99. Ramírez LCC, Leal LCS, Rodríguez FAE. Determinación de la presencia de bacterias patógenas para el humano en aguas de riego en la cuenca alta de la sabana de Bogotá; DC Colombia. Nova. 2014;12(22).
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101. DOI: http://dx.doi.org/10.22490/24629448.1735