1H NMR metabonomic study of rat response to tri-phenyl phosphate and tri-butyl phosphate exposure
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The industrial application of organophosphates provides the opportunity for environmental exposure. While the toxicity of organophosphate compounds has been the target of significant work, studies directed towards the identification of metabolite markers to assess phosphate exposure are more limited. In this study the urine metabolite profiles for rats following single dose exposure to either tributyl phosphate (TBP, 15 mg/kg body weight) or triphenyl phosphate (TPP, 2 and 20 mg/kg body weight) were characterized using proton nuclear magnetic resonance (1H NMR) and orthogonal-partial least squares discriminate analysis (O-PLSDA). Using the developed O-PLSDA models it was possible to clearly identify TBP or TPP exposed animals. The performance of these models was validated using cross validation and permutation testing. Utilizing the variable importance in projection (VIP) coefficients from the O-PLSDA the metabolites that were most responsible for the classification of TBP or TPP exposure were determined. This initial study demonstrates the potential for NMR metabonomic studies for the identification and separation of environmental exposure to organophosphates.
- Alam, M. K., Alam, T. M., Volk, D. E., Neerathilingam, M., Sarkar, S., Shakeel Ansari, G. A., & Luxon, B. A. (2008). Chemical and biological defense physical science and technology conference, New Orleans, LA.
- Arnold, LL, Christenson, WR, Cano, M, St. John, MK, Wahle, BS, Cohen, SM (1997) Tributyl phosphate effects on urine and bladder epithelium in male Sprague-Dawley rats. Fundamental and Applied Toxicology 40: pp. 247-255 CrossRef
- Auletta, CS (1998) A dietary oncogenicity study of tributyl phosphate in the CD-1 mouse. Toxicology 128: pp. 135-141 CrossRef
- Auletta, CS, Weiner, ML, Richter, WR (1998) A dietary toxicity/oncogenicity study of tributyl phosphate in the rat. Toxicology 128: pp. 125-143 CrossRef
- Budavari, S. (Ed.). (1989). The merck index (9th ed., p. 1514). Rahway, New Jersey: Merck and Company, Inc.
- Burka, LT, Sanders, JM, Herr, DW, Matthews, HB (1991) Metabolism of tris(2-choloethyl) phosphate in rats and mice. Drug Metabolism and Disposition 19: pp. 443-447
- Cavaghan, CL, Wilson, ID, Nicholson, JK (2002) Physiological variation in metabolic phenotyping and functional genomic studies: Use of orthogonal signal correction and PLS-DA. FEBS Letters 530: pp. 191-196 CrossRef
- Chong, I-G, Jun, C-H (2005) Performance of some variable selection methods when multicollinearity is present. Chemometrics and Intelligent Laboratory Systems 78: pp. 103-112 CrossRef
- Clarke, CJ, Haselden, JN (2008) Metabolic profiling as a tool for understanding mechanisms of toxicity. Toxicologic Pathology 36: pp. 140-147 CrossRef
- Cloarec, O, Dumas, ME, Trygg, J, Craig, A, Barton, RH, Lindon, JC, Nicholson, JK, Homes, E (2005) Evaluation of the orthognal projection on latent structure model limitations caused by chemical shift variability and improved visualization of the biomarker changes in 1H NMR spectrscopic metabonomic studies. Analytical Chemistry 77: pp. 517-526 CrossRef
- Coen, M, Holmes, E, Lindon, JC, Nicholson, JK (2008) NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology. Chemical Research in Toxicology 21: pp. 9-27 CrossRef
- Craig, A, Cloarec, O, Holmes, E, Nicholson, JK, Lindon, JC (2006) Scaling and normalization effects in NMR spectroscopic metabonomic data sets. Analytical Chemistry 78: pp. 2262-2267 CrossRef
- Dave, G, Lidman, U (1978) Biological and toxicological effects of solvent extraction chemicals. Range finding acute toxicity in the rainbow trout (Salmo gaidnerii Rich.) and in the Rat (Rattus norwegicus L.). Hydrometallurgy 3: pp. 201-216 CrossRef
- Dieterle, F, Ross, A, Schlotterbeck, G, Senn, H (2006) Probalistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. Analytical Chemistry 78: pp. 4281-4290 CrossRef
- Hinton, D. M., Jessop, J. J., Arnold, A., Albert, R. H., Hines, F. A. (1987). Evaluation of immunotoxicity in a subchronic feeding study of triphenyl phosphate. Toxicology and Industrial Health, 3, 71–89.
- Hinton, DM, Jessop, JJ, Arnold, A, Albert, RH, Hines, FA (1996) Evaluation of immunotoxicity in a subchronic feeding study of triphenyl phosphate. International Journal of Occupational Medicine, Immunology and Toxicology 5: pp. 43-60
- Laham, S, Long, G, Broxup, B (1984) Subacute oral toxicity of tri-n-butyl phosphate in the Sprague-Dawley rat. Journal of Applied Toxicology 4: pp. 150-154 CrossRef
- Laham, S, Long, G, Broxup, B (1985) Induction of urinary bladder hyperplasia in Sprague-Dawley rats orally administered tri-n-butyl phosphate. Archives Environmental Health 40: pp. 301-306
- Laham, S, Szabo, J, Long, G (1983) Effects of tri-n-butyl phosphae on the peripheral nervous system of the Sprague-Dawley rat. Drug and Chemical Toxicology 6: pp. 363-377 CrossRef
- Lindon, J. C., Nicholson, J. K., Holmes, E. (Eds.). (2007). The handbook of metabonomics and metabolomics. Amsterdam: Elsevier.
- Lindon, JC, Nicholson, JK (2008) Analytical technologies for metabonomics and metabolomics, and multi-omic information recovery. Trends Analytical Chemistry 27: pp. 194-204 CrossRef
- Lindon, JC, Nicholson, JK (2008) Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. Annual Review Analytical Chemistry 1: pp. 45-69 CrossRef
- Noda, T, Yamano, T, Shimizu, M, Morita, S (1994) Effects of tri-n-butyl phosphate on pregnancy in rats. Food and Chemical Toxicology 32: pp. 1031-1036 CrossRef
- Oishi, H, Oishi, S, Hiraga, K (1980) Toxicity of tri-n-butyl phosphate, with special reference to organ weights, serum components and chilinesterase activity in male rats. Toxicology Letters 6: pp. 81-85 CrossRef
- Oishi, H, Oishi, S, Hiraga, K (1982) Toxicity of several phosphoric acid esters in rats. Toxicology Letters 13: pp. 29-34 CrossRef
- Paiva, AP, Malik, P (2004) Recent advances on the chemistry of solvent extraction applied to the reprocessing of spent fuels and radioactive wastes. Journal of Radioanalytical and Nuclear Chemistry 261: pp. 485-496 CrossRef
- Sood, DD, Patil, SK (1996) Chemistry of nuclear processing: current status. Journal of Radioanalytical and Nuclear Chemistry 203: pp. 547-573 CrossRef
- Suzuki, Y, Kikuchi, H, Kato, C, Horiuchi, Y, Tomita, K, Hashimoto, Y (1977) Effect of alkyl phosphates on B-glucuronidase in rats: Release of b-glucuonidase from liver microsomes into serum. Biochemical Pharmacology 26: pp. 881-885 CrossRef
- Suzuki, T, Sasaki, K, Takeda, M, Uchiyama, M (1984) Metabolism of tributyl phosphate in male rats. Journal of Agriculture and Food Chemistry 32: pp. 603-610 CrossRef
- Suzuki, T, Sasaki, K, Takeda, M, Uchiyama, M (1984) Some S-containing metabolites of tributyl phosphate in the Rat. Journal of Agriculture and Food Chemistry 32: pp. 1278-1283 CrossRef
- Trygg, J, Holmes, E, Lundstedt, T (2007) Chemometrics in metabonomics. Journal of Proteome Research 6: pp. 469-479 CrossRef
- Trygg, J, Wold, S (2002) Orthogonal projections to latent structures (O-PLS). J of Chemometrics 16: pp. 119-128 CrossRef
- Vitols, C., Mercier, P. (2006). CHENOMX (Edmonton, Canada). http://www.chenomx.com/publications/applicationNotes/HTML/ar04.html.
- Welsh, JJ, Collins, TFX, Whitby, KE, Black, TN, Arnold, A (1987) Teratogenic potential of triphenyl phosphate in Sprague–Dawly (Spartan) rats. Toxicology and Industrial Health 3: pp. 357-369
- Westerhuis, JA, Hoefsloot, HCJ, Smit, S, Vis, DJ, Smilde, AK, Velzen, EJJ, Duijnhoven, JPM, Dorsten, FA (2008) Assessment of PLSDA cross validation. Metabolomics 4: pp. 81-89 CrossRef
- Wishart, DS (2008) Quantitative metabolomics using NMR. Trends Analytical Chemistry 27: pp. 228-237 CrossRef
- Wold, S., Johansson, E., Cocchi, M. (1993). In: 3D QSAR in drug design: Theory methods and applications (pp. 523–550). Dordrecht, The Netherlands: Kluwer Academic Publishers.
- 1H NMR metabonomic study of rat response to tri-phenyl phosphate and tri-butyl phosphate exposure
Volume 6, Issue 3 , pp 386-394
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Nuclear magnetic resonance (NMR)
- Organophosphate toxicology
- Discriminate analysis
- Urine metabolites
- Industry Sectors
- Author Affiliations
- 1. Department of Electronic and Nanostructured Materials, Sandia National Laboratories, Albuquerque, NM, 87185, USA
- 2. Energetics Characterization Department, Sandia National Laboratories, Albuquerque, NM, 87185, USA
- 3. Department of Chemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, 77555, USA