Biological Trace Element Research

, Volume 2, Issue 1, pp 1–19 | Cite as

The implications of trace metal-nitrilotriacetetic acid speciation on its environmental impact and toxicology

  • Martin Rubin
  • Arthur E. Martell
Original Articles


Substitution of nitrilotriacetic acid (NTA) for polyphosphates in detergents has brought questions concerning its potential toxicity and impact on trace metal distribution in the environment. A calculation based upon metal ligand equilibria, known environmental concentrations of NTA following extensive detergent usage, and the presence of competitive metal-binding ligands and trace elements demonstrates that NTA will be present almost completely as the calcium and magnesium chelates. An analogous estimate of the speciation of NTA in various toxicity studies demonstrates that the onset of chronic toxicity in feeding studies is coincident with the presence of significant concentrations of “free” NTA in the gastrointestinal tract. Massive doses of NTA over long periods of time cause reproducible renal tumors in rats, but dosages of 7500 ppm administered indefinitely are without measurable effect.

Index Entries

Nitrilotriacetic acid (NTA), and trace metal distribution in the environment nitrilotriacetic acid, toxicology of environmental impact of chelating agents, and NTA toxicology of chelating agents, and NTA trace metal speciation in the environment, and NTA chelating agent speciation in mammalian systems, and NTA 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    P. D. Foley, G. Becking, J. Muller, R. A. Goyer, H. L. Falk, and N. Chernoff, “Report to the Great Lakes Research Advisory Board of the International Joint Commission on the Health Implication of NTA,” Great Lakes Regional Office, Windsor, Ontario, 1977.Google Scholar
  2. 2.
    N. Chernoff and K. D. Courtney, Progress Report, National Institute of Environmental and Health Sciences, Research Triangle Park, N.C., 1 December, 1970.Google Scholar
  3. 3.
    “Assessment of the Potential of Nitrilotriacetate (NTA) to Compromise Human Health,” Assistant Secretary's Ad Hoc Group on NTA, Final Report to the Assistant Secretary for Health and Scientific Affairs, L. A. Woods, Chairman, April 19, 1972.Google Scholar
  4. 4.
    H. Tjalve,Toxicol. Appl. Pharmacol. 23, 216 (1972).PubMedCrossRefGoogle Scholar
  5. 5.
    G. A. Nolen, L. W. Klussm, D. L. Black, and E. V. Buehler,Toxicol. Appl. Pharmacol. 18, 407 (1971).CrossRefGoogle Scholar
  6. 6.
    L. G. Scharpf, Jr., F. J. Ramos, I. D. Hill,Toxicol. Appl. Pharmacol. 22, 186 (1972).PubMedCrossRefGoogle Scholar
  7. 7.
    K. R. Mahaffey and R. A. Goyer,Arch. Envir. Health 25, 271 (1972).Google Scholar
  8. 8.
    P. S. Thayer and C. J. Kensler, “Current Status of the Environmental and Human Safety Aspects of Nitriloacetic Acid (NTA),” inCritical Reviews in Environmental Control, R. B. Bond, and C. P. Straub, eds., The Chemical Rubber Co., 1973, pp. 375–404.Google Scholar
  9. 9.
    “Bioassays of Nitrilotriacetic Acid (NTA) and Nitrilotriacetic Acid Trisodium Salt Monohydrate (Na3NTA·H2O) for possible Carcinogenicity,” U.S. Dept. of Health, Education and Welfare, Public Health Service, National Institutes of Health, Technical Report, Series No. 6, January, 1977.Google Scholar
  10. 10.
    D. Hoel, L. Plumlee, M. Prival, R. Kirchstein, V. Saffiotti, and M. Schneiderman, “Subcommittee on Estimation of Risks of Irreversible, Delayed Toxicology and Related Programs,” Report of the U.S. Department of Health, Education and Welfare Committee to Coordinate Toxicology and Related Programs, June 30, 1975.Google Scholar
  11. 11.
    “Current Status of the Environment and Human Safety Aspects of Nitrilotriacetic Acid (NTA).” Arthur D. Little, Inc., Cambridge, Mass., 1972, p. 4.Google Scholar
  12. 12.
    J. M. Tiedje, B. B. Mason, C. B. Warren, and E. J. Malec,Appl. Microbiol. 25, 811 (1973).PubMedGoogle Scholar
  13. 13.
    S. S. Epstein,Internation. J. Environ. Studies 2, 291;3, 13 (1972).CrossRefGoogle Scholar
  14. 14.
    D. D. Focht and H. A. Joseph,Canada J. Microbiol. 17, 1553 (1971).CrossRefGoogle Scholar
  15. 15.
    C. B. Warren and E. J. Malec,Science 176, 277 (1972).PubMedCrossRefGoogle Scholar
  16. 16.
    J. G. Sprague,Nature 200, 1345 (1968).CrossRefGoogle Scholar
  17. 17.
    R. D. Swisher, T. A. Taulli, and E. J. Malec, “Biodegradation of NTA Metal Chelates in River Water,” inTrace Metals and Metal-Organic Interactions in Natural Waters, P. C. Singer, ed., Ann Arbor Science Publishers, 1973, pp. 237–263.Google Scholar
  18. 18.
    All metal concentrations except Zn(II) taken from Tables 6–13 of “Median Values of Water Quality in Public Water Supplies of 100 Largest Cities in the United States,” inHandbook of Environmental Control, Vol. III, Water Supply and Treatment, CRC Press, Cleveland, Ohio, 1973.Google Scholar
  19. 19.
    Zinc concentration from page 8, Table III, “Trace Metals in Waters of the United States” by J. R. Kopp and R. C. Kroner, U.S. Dept. of the Interior, FWPCA, Cincinnati, Ohio (no date). Data covered: 5 year period (Oct. 1, 1962–Sept. 30, 1967).Google Scholar
  20. 20.
    A. E. Martell and R. M. Smith,Critical Stability Constants, Vol. 1, Amino Acids, Plenum, New York, N.Y., 1974.Google Scholar
  21. 21.
    G. W. Flamm, NTA Subcommittee Report, D HEW-CCTRP, June 12, 1975.Google Scholar
  22. 22.
    W. R. Michael and J. M. Wakin,Toxicol. Appl. Pharmacol. 18, 407 (1971).PubMedCrossRefGoogle Scholar
  23. 23.
    J. A. BudnyToxicol. Appl. Pharmacol. 22, 655 (1972).PubMedCrossRefGoogle Scholar
  24. 24.
    J. A. Budny and J. D. Arnold,Toxicol. Appl. Pharmacol. 25, 48 (1973).PubMedCrossRefGoogle Scholar
  25. 25.
    J. A. Budny, R. J. Niewenhuis, E. V. Buehler, and E. K. Goldenthal,Toxicol. Appl. Pharmacol. 26, 148 (1973).PubMedCrossRefGoogle Scholar
  26. 26.
    A. Popovici, C.F. Geschickter, and M. Rubin,Georgetown Med. Ctr. Bulletin 5, 108 (1951).Google Scholar
  27. 27.
    P. D. Dollan, S. L. Schwartz, J. R. Hayes, J. C. Mullen, and N. B. Cummings,Toxicol. Appl. Pharmacol. 10, 481 (1967).CrossRefGoogle Scholar
  28. 28.
    S. L. Schwartz, C. B. Johnson, and P. D. Doolan,Molecular Pharmacology 6, 54 (1970).PubMedGoogle Scholar
  29. 29.
    S. Brahmanandam, B. Nagarajan, and V. M. Sivaramakrishnan,Indian J. Exp. Biology 3, 88 (1965).Google Scholar
  30. 30.
    G. A. Nixon, E. V. Buehler, and R. J. Niewenhuis,Toxicol. Appl. Pharmacol. 21, 244 (1972).PubMedCrossRefGoogle Scholar
  31. 31.
    M. Rubin, R. Mhatre, and E. Harmuth-Hoene, Abstract, Ninth International Congress of Clinical Chemistry, Toronto, Canada, July 13–18, 1975.Google Scholar
  32. 32.
    L. G Scharpf, Jr., Proctor and Gamble Co., October, 1976, private communication.Google Scholar
  33. 33.
    A. Albert,Selective Toxicity, Chapman and Hall, London, 5th Ed., 1973, pp. 334–391.Google Scholar
  34. 34.
    A. Popovici, C. F. Geshickter, A. Reinovsky, and M. Rubin,Proc. Soc. Exptl. Biol. Med. 74, 415 (1950).Google Scholar
  35. 35.
    A. Saffer and T. Toribora,J. Lab. Clin. Med. 58, 542 (1961).Google Scholar
  36. 36.
    R. O. Bauer, F. E. Rullo, C. Spooner, and E. Woodman,Fed. Proc. 11, 321 (1952).Google Scholar
  37. 37.
    H. Spencer, V. Vaniscot, J. Lewin and D. Laszlo,J. Clin. Invest. 31, 1023 (1952).PubMedGoogle Scholar
  38. 38.
    M. Rubin, S. Gignac, S. P. Bessman, and E. L. Belknap,117, 659 (1952).Google Scholar
  39. 39.
    H. Foreman and T. T. Trujillo,J. Lab. Clin. Med. 43, 566 (1954).PubMedGoogle Scholar
  40. 40.
    L. Mosey, cited in J. B. Sidburg, Jr., J. C. Bynum, and L. L. Fetz,Proc. Soc. Exptl. Biol. Med. 82, 226 (1953).Google Scholar
  41. 41.
    J. Boner,Strahlenterapie 142, 349 (1971).Google Scholar
  42. 42.
    H. Swenerton, and L. S. Hurley,Science 173, 62 (1971).PubMedCrossRefGoogle Scholar
  43. 43.
    G. A. Nixon,Toxicol. Appl. Pharmacol. 18, 398 (1971).PubMedCrossRefGoogle Scholar
  44. 44.
    J. V. Princiotto, E. J. Zapolski, D. H. Bagley, A. Laskey, R. Morgan, and M. Rubin,Biochem. Med. 3, 289 (970).Google Scholar
  45. 45.
    G. C. Battistone, F. A. San Filippo, M. I. Rubin, S. Silverman, D. E. Cutright, and R. E. Miller, inTrace Substances in Environmental Health, D. B. Hemphill, ed., University of Missouri, Columbia, Missouri, 1971.Google Scholar
  46. 46.
    W. D. Grover and R. I. Henkin,Trace elements in Man and Animals, Vol. 3, M. Kirchgessner, ed., Frei-sing-weihenstephen, West Germany, 1977.Google Scholar

Copyright information

© The Humana Press Inc 1980

Authors and Affiliations

  • Martin Rubin
    • 1
  • Arthur E. Martell
    • 2
  1. 1.Department of BiochemistryGeorgetown UniversityWashington D.C.
  2. 2.Department of ChemistryTexas A&M UniversityCollege Station

Personalised recommendations