Use & Misuse of Metal Chelation Therapy

Use & Misuse Of Metal Chelation Therapy

The Role of Chelation in the Treatment of Other Metal Poisonings

Silas W. Smith, MD

REFERENCES

1. Abergel, R. J., Durbin, P. W., Kullgren, B., Ebbe, S. N., Xu, J., Chang, P. Y., Bunin, D. I., Blakely, E. A., Bjornstad, K. A., Rosen, C. J., Shuh, D. K. and Raymond, K. N. (2010). Biomimetic actinide chelators: an update on the preclinical development of the orally active hydroxypyridonate decorporation agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Health Phys. 99, 401-407.

2. Abergel, R. J., Raymond, K. N. (2011). Multidentate terephthalamidate and hydroxypyridonate ligands: towards new orally active chelators. Hemoglobin 35, 276-290.

3. Afolaranmi, G. A., Tettey, J. N., Murray, H. M., Meek, R. M. and Grant, M. H. (2010). The effect of anticoagulants on the distribution of chromium VI in blood fractions. J. Arthroplasty 25, 118-120.

4. Agency for Toxic Substances and Disease Registry, ATSDR. (2008). "Draft toxicological profile for cadmium." U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA.

5. Agency for Toxic Substances and Disease Registry, ATSDR. (2008). "Draft toxicological profile for chromium." U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA.

6. Agency for Toxic Substances and Disease Registry, ATSDR. (2004). "Toxicological profile for cobalt." U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA.

7. Alfrey, A. C., LeGendre, G. R. and Kaehny, W. D. (1976). The dialysis encephalopathy syndrome. Possible aluminum intoxication. N. Engl. J. Med. 294, 184-188.

8. Andersen, O., Nielsen, J. B. (1988). Oral cadmium chloride intoxication in mice: effects of penicillamine, dimercaptosuccinic acid and related compounds. Pharmacol. Toxicol. 63, 386-389.

9. Andersen, O., Nielsen, J. B. and Svendsen, P. (1988). Oral cadmium chloride intoxication in mice: diethyldithiocarbamate enhances rather than alleviates acute toxicity. Toxicology 52, 331-342.

10. Anderson, R. A., Bryden, N. A. and Waters, R. (1999). EDTA chelation therapy does not selectively increase chromium losses. Biol. Trace Elem. Res. 70, 265-272.

11. Andriani, M., Nordio, M. and Saporiti, E. (1996). Estimation of statistical moments for desferrioxamine and its iron and aluminum chelates: contribution to optimisation of therapy in uremic patients. Nephron 72, 218-224.

12. ApoPharma USA, I. (2011). "FERRIPROX® (deferiprone) tablets, for oral use. prescribing information." ApoPharma USA, Inc., Rockville, Maryland.

13. Bahijri, S. M., Alissa, E. M. (2011). Increased insulin resistance is associated with increased urinary excretion of chromium in non-diabetic, normotensive Saudi adults. J. Clin. Biochem. Nutr. 49, 164-168.

14. Banner, W.,Jr, Koch, M., Capin, D. M., Hopf, S. B., Chang, S. and Tong, T. G. (1986). Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds. Toxicol. Appl. Pharmacol. 83, 142-147.

15. Barata, J. D., D'Haese, P. C., Pires, C., Lamberts, L. V., Simoes, J. and De Broe, M. E. (1996). Low-dose (5 mg/kg) desferrioxamine treatment in acutely aluminium-intoxicated haemodialysis patients using two drug administration schedules. Nephrol. Dial. Transplant. 11, 125-132.

16. Barceloux, D. G. (1999). Cobalt. J. Toxicol. Clin. Toxicol. 37, 201-206.

17. Baresic, M., Gornik, I., Radonic, R., Zlopasa, O., Gubarev, N. and Gasparovic, V. (2009). Survival after severe acute chromic acid poisoning complicated with renal and liver failure. Intern. Med. 48, 711-715.

18. Basinger, M. A., Jones, M. M., Holscher, M. A. and Vaughn, W. K. (1988). Antagonists for acute oral cadmium chloride intoxication. J. Toxicol. Environ. Health 23, 77-89.

19. Bergeron, R. J., Wiegand, J. and Singh, S. (2009). Desferrithiocin analogue uranium decorporation agents. Int. J. Radiat. Biol. 85, 348-361.

20. Blanusa, M., Kostial, K., Restek-Samarzija, N., Piasek, M., Jones, M. M. and Singh, P. K. (2000). Mobilisation of cadmium by meso- and racemic-2,3-dimercaptosuccinic acid (DMSA) in rats. Pharmacol. Toxicol. 87, 179-181.

21. Blanusa, M., Varnai, V. M., Piasek, M. and Kostial, K. (2005). Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr. Med. Chem. 12, 2771-2794.

22. Canavese, C., Gurioli, L., D'Amicone, M., Cardelli, R., Caligaris, F., Bongiorno, P., Arnaud, A., Mattiello, G. and Marchiori, M. (1992). Kinetics of aluminoxamine and feroxamine chelates in dialysis patients. Nephron 60, 411-417.

23. Cannata, J. B., Fernandez-Martin, J. L., Diaz-Lopez, B., Alonso, M., Olaizola, I., Acuna, G., Caramelo, C. and Alvarez-Grande, J. (1996). Influence of iron status in the response to the deferoxamine test. J. Am. Soc. Nephrol. 7, 135-139.

24. Cantilena, L. R.,Jr, Irwin, G., Preskorn, S. and Klaassen, C. D. (1982). The effect of diethyldithiocarbamate on brain uptake of cadmium. Toxicol. Appl. Pharmacol. 63, 338-343.

25. Cantilena, L. R.,Jr, Klaassen, C. D. (1982). The effect of chelating agents on the excretion of endogenous metals. Toxicol. Appl. Pharmacol. 63, 344-350.

26. Cantilena, L. R.,Jr, Klaassen, C. D. (1982). Decreased effectiveness of chelation therapy with time after acute cadmium poisoning. Toxicol. Appl. Pharmacol. 63, 173-180.

27. Cantilena, L. R.,Jr, Klaassen, C. D. (1981). Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion, and distribution of cadmium. Toxicol. Appl. Pharmacol. 58, 452-460.

28. Cantilena, L. R.,Jr, Klaassen, C. D. (1980). The effect of ethylenediaminetetraacetic acid (EDTA) and EDTA plus salicylate on acute cadmium toxicity and distribution. Toxicol. Appl. Pharmacol. 53, 510-514.

29. Centers for Disease Control and Prevention. National Center for Environmental Health. (2011). "Fourth national report on human exposure to environmental chemicals, updated tables, february 2011." Department of Health and Human Services, Atlanta, GA.

30. Centers for Disease Control and Prevention. National Center for Environmental Health. (2009). "Fourth national report on human exposure to environmental chemicals." Department of Health and Human Services, Atlanta, GA.

31. Cobelli, N., Scharf, B., Crisi, G. M., Hardin, J. and Santambrogio, L. (2011). Mediators of the inflammatory response to joint replacement devices. Nat. Rev. Rheumatol. 7, 600-608.

32. Daniel, J., Ziaee, H., Pradhan, C., Pynsent, P. B. and McMinn, D. J. (2007). Blood and urine metal ion levels in young and active patients after Birmingham hip resurfacing arthroplasty: four-year results of a prospective longitudinal study. J. Bone Joint Surg. Br. 89, 169-173.

33. Day, J. P., Ackrill, P. (1993). The chemistry of desferrioxamine chelation for aluminum overload in renal dialysis patients. Ther. Drug Monit. 15, 598-601.

34. D'Haese, P. C., Couttenye, M. M. and De Broe, M. E. (1996). Diagnosis and treatment of aluminium bone disease. Nephrol. Dial. Transplant. 11 Suppl 3, 74-79.

35. Domingo, J. L., Llobet, J. M. (1984). Treatment of acute cobalt intoxication in rats with L-methionine. Rev. Esp. Fisiol. 40, 443-448.

36. Domingo, J. L., Llobet, J. M. and Corbella, J. (1983). The effects of EDTA in acute cobalt intoxication in rats. Toxicol. Eur. Res. 5, 251-255.

37. Domingo, J. L., Llobet, J. M. and Tomas, J. M. (1985). N-acetyl-L-cysteine in acute cobalt poisoning. Arch. Farmacol. Toxicol. 11, 55-62.

38. Douthat, W. G., Acuna Aguerre, G., Fernandez Martin, J. L., Mouzo, R. and Cannata Andia, J. B. (1994). Treatment of aluminium intoxication: a new scheme for desferrioxamine administration. Nephrol. Dial. Transplant. 9, 1431-1434.

39. Drake, T. C., Rudser, K. D., Seaquist, E. R. and Saeed, A. (2012). Chromium infusion in hospitalized patients with severe insulin resistance: a retrospective analysis. Endocr. Pract. 1-17.

40. Durakovic, A., Horan, P., Dietz, L. A. and Zimmerman, I. (2003). Estimate of the time zero lung burden of depleted uranium in Persian Gulf War veterans by the 24-hour urinary excretion and exponential decay analysis. Mil. Med. 168, 600-605.

41. Durbin, P. W. (2008). Lauriston S. Taylor Lecture: the quest for therapeutic actinide chelators. Health Phys. 95, 465-492.

42. Ellis, E. N., Brouhard, B. H., Lynch, R. E., Dawson, E. B., Tisdell, R., Nichols, M. M. and Ramirez, F. (1982). Effects of hemodialysis and dimercaprol in acute dichromate poisoning. J. Toxicol. Clin. Toxicol. 19, 249-258.

43. el-Sebae, A. K., Abou Zeid, M. M., Abdel-Rahman, F. H. and Saleh, M. A. (1994). Binding of aluminum to human serum transferrin, human serum albumin and rat serum proteins. J. Environ. Sci. Health B. 29, 303-321.

44. Eybl, V., Sykora, J., Koutensky, J., Caisova, D., Schwartz, A. and Mertl, F. (1984). Interaction of chelating agents with cadmium in mice and rats. Environ. Health Perspect. 54, 267-273.

45. Fischer, T., Rystedt, I. (1983). Cobalt allergy in hard metal workers. Contact Dermatitis 9, 115-121.

46. Food and Drug Administration, HHS. (2011). 21 CFR §201.323 Aluminum in large and small volume parenterals used in total parenteral nutrition. 89-90.

47. Friberg, L. (1956). Edathamil calcium-disodium in cadmium poisoning; a study of the excretion, distribution, and toxicity of cadmium in animals. AMA Arch. Ind. Health. 13, 18-23.

48. Friesen, M. S., Purssell, R. A. and Gair, R. D. (2006). Aluminum toxicity following IV use of oral methadone solution. Clin. Toxicol. (Phila) 44, 307-314.

49. Fukuda, S., Ikeda, M., Nakamura, M., Katoh, A., Yan, X., Xie, Y. and Kontoghiorghes, G. J. (2008). The effects of bicarbonate and its combination with chelating agents used for the removal of depleted uranium in rats. Hemoglobin 32, 191-198.

50. Gil, H. W., Kang, E. J., Lee, K. H., Yang, J. O., Lee, E. Y. and Hong, S. Y. (2011). Effect of glutathione on the cadmium chelation of EDTA in a patient with cadmium intoxication. Hum. Exp. Toxicol. 30, 79-83.

51. Goto, K. (1917). A Study of the Acidosis, Blood Urea, and Plasma Chlorides in Uranium Nephritis in the Dog, and of the Protective Action of Sodium Bicarbonate. J. Exp. Med. 25, 693-719.

52. Graves, A. B., White, E., Koepsell, T. D., Reifler, B. V., van Belle, G. and Larson, E. B. (1990). The association between aluminum-containing products and Alzheimer's disease. J. Clin. Epidemiol. 43, 35-44.

53. hameln pharmaceuticals gmbh. (2004). "Pentetate zinc trisodium injection. package insert - instruction for use." hameln pharmaceuticals gmbh, Hameln, Germany.

54. hameln pharmaceuticals gmbh. (2004). "Pentetate calcium trisodium injection. package insert - instruction for use." hameln pharmaceuticals gmbh, Hameln, Germany.

55. Hantson, P., Van Caenegem, O., Decordier, I., Haufroid, V. and Lison, D. (2005). Hexavalent chromium ingestion: biological markers of nephrotoxicity and genotoxicity. Clin. Toxicol. (Phila) 43, 111-112.

56. Henretig, F., Shannon, M. (1988). An 11-year-old boy develops vomiting, weakness, weight loss and a neck mass. Int J Med Toxicol 1, 13-15.

57. Huang, J. Y., Wu, M. S. and Wu, C. H. (2001). The effect of an iron supplement on serum aluminum level and desferrioxamine mobilization test in hemodialysis patients. Ren. Fail. 23, 789-795.

58. Ichikawa, Y., Kusaka, Y. and Goto, S. (1985). Biological monitoring of cobalt exposure, based on cobalt concentrations in blood and urine. Int. Arch. Occup. Environ. Health 55, 269-276.

59. International Agency for Research on Cancer (IARC), World Health Organization. (2011). "IARC monographs on the evaluation of carcinogenic risks to humans. A review of human carcinogens: Arsenic, metals, fibres, and dusts. volume 100C." International Agency for Research on Cancer, Lyons, France.

60. International Agency for Research on Cancer (IARC), World Health Organization. (1990). "IARC monographs on the evaluation of carcinogenic risks to humans. chromium, nickel and welding. volume 49." International Agency for Research on Cancer, Lyons, France.

61. Jacobs, J. J., Skipor, A. K., Doorn, P. F., Campbell, P., Schmalzried, T. P., Black, J. and Amstutz, H. C. (1996). Cobalt and chromium concentrations in patients with metal on metal total hip replacements. Clin. Orthop. Relat. Res. (329 Suppl), S256-63.

62. Jacobs, J. J., Skipor, A. K., Patterson, L. M., Hallab, N. J., Paprosky, W. G., Black, J. and Galante, J. O. (1998). Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study. J. Bone Joint Surg. Am. 80, 1447-1458.

63. Jones, M. M., Xu, C., Singh, P. K. and Walker, E. M.,Jr. (1996). Cadmium mobilization by nitrogen donor chelating agents. J. Toxicol. Environ. Health 48, 71-80.

64. Kan, W. C., Chien, C. C., Wu, C. C., Su, S. B., Hwang, J. C. and Wang, H. Y. (2010). Comparison of low-dose deferoxamine versus standard-dose deferoxamine for treatment of aluminium overload among haemodialysis patients. Nephrol. Dial. Transplant. 25, 1604-1608.

65. Kanabrocki, E. L., Sothern, R. B., Ryan, M. D., Kahn, S., Augustine, G., Johnson, C., Foley, S., Gathing, A., Eastman, G., Friedman, N., Nemchausky, B. A. and Kaplan, E. (2008). Circadian characteristics of serum calcium, magnesium and eight trace elements and of their metallo-moieties in urine of healthy middle-aged men. Clin. Ter. 159, 329-346.

66. Kargacin, B., Kostial, K., Arezina, R., Singh, P. K., Jones, M. M. and Cikrt, M. (1991). Influence of age and time of administration of dithiocarbamate analogues on cadmium retention in rats. J. Appl. Toxicol. 11, 273-277.

67. Kargacin, B., Kostial, K., Arezina, R., Singh, P. K., Jones, M. M. and Cikrt, M. (1991). Dithiocarbamate analog N-(4-methoxybenzyl)-N-dithiocarboxy-D-glucamine reduces the retention of ingested cadmium in rats. J. Appl. Toxicol. 11, 313-315.

68. Keberle, H. (1964). The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism. Ann. N. Y. Acad. Sci. 119, 758-768.

69. Kelly, W. F., Ackrill, P., Day, J. P., O'Hara, M., Tye, C. T., Burton, I., Orton, C. and Harris, M. (1982). Cutaneous absorption of trivalent chromium: tissue levels and treatment by exchange transfusion. Br. J. Ind. Med. 39, 397-400.

70. Kerger, B. D., Finley, B. L., Corbett, G. E., Dodge, D. G. and Paustenbach, D. J. (1997). Ingestion of chromium(VI) in drinking water by human volunteers: absorption, distribution, and excretion of single and repeated doses. J. Toxicol. Environ. Health 50, 67-95.

71. Khandelwal, S., Kachru, D. N. and Tandon, S. K. (1980). Chelation in metal intoxication. IX. Influence of amino and thiol chelators on excretion of manganese in poisoned rabbits. Toxicol. Lett. 6, 131-135.

72. Kontoghiorghes, G. J. (1995). Comparative efficacy and toxicity of desferrioxamine, deferiprone and other iron and aluminium chelating drugs. Toxicol. Lett. 80, 1-18.

73. Korallus, U., Harzdorf, C. and Lewalter, J. (1984). Experimental bases for ascorbic acid therapy of poisoning by hexavalent chromium compounds. Int. Arch. Occup. Environ. Health 53, 247-256.

74. Lantin, A. C., Mallants, A., Vermeulen, J., Speybroeck, N., Hoet, P. and Lison, D. (2011). Absence of adverse effect on thyroid function and red blood cells in a population of workers exposed to cobalt compounds. Toxicol. Lett. 201, 42-46.

75. Levitskaia, T. G., Creim, J. A., Curry, T. L., Luders, T., Morris, J. E., Woodstock, A. D., Levinson, B. and Thrall, K. D. (2010). Evaluation of Cuprimine and Syprine for decorporation of (60)Co and (210)Po. Health Phys. 98, 471-479.

76. Levitskaia, T. G., Creim, J. A., Curry, T. L., Luders, T., Peterson, J. M., Thrall, K. D. and Levinson, B. (2011). Evaluation of Cuprimine(R) and Syprine(R) for decorporation of radioisotopes of cesium, cobalt, iridium and strontium. Health Phys. 101, 118-127.

77. Levitskaia, T. G., Morris, J. E., Creim, J. A., Woodstock, A. D., Luders, T., Curry, T. L. and Thrall, K. D. (2010). Aminothiol receptors for decorporation of intravenously administered (60)Co in the rat. Health Phys. 98, 53-60.

78. Lillevang, S. T., Pedersen, F. B. (1989). Exacerbation of aluminium encephalopathy after treatment with desferrioxamine. Nephrol. Dial. Transplant. 4, 676.

79. Lin, C. C., Wu, M. L., Yang, C. C., Ger, J., Tsai, W. J. and Deng, J. F. (2009). Acute severe chromium poisoning after dermal exposure to hexavalent chromium. J. Chin. Med. Assoc. 72, 219-221.

80. Liu, K. J., Jiang, J., Swartz, H. M. and Shi, X. (1994). Low-frequency EPR detection of chromium(V) formation by chromium(VI) reduction in whole live mice. Arch. Biochem. Biophys. 313, 248-252.

81. Liu, K. J., Shi, X. (2001). In vivo reduction of chromium (VI) and its related free radical generation. Mol. Cell. Biochem. 222, 41-47.

82. Liu, L., Drouet, V., Wu, J. W., Witter, M. P., Small, S. A., Clelland, C. and Duff, K. (2012). Trans-Synaptic Spread of Tau Pathology In Vivo. PLoS ONE 7, e31302 EP -.

83. Llobet, J. M., Domingo, J. L. and Corbella, J. (1988). Comparative effects of repeated parenteral administration of several chelators on the distribution and excretion of cobalt. Res. Commun. Chem. Pathol. Pharmacol. 60, 225-233.

84. Llobet, J. M., Domingo, J. L. and Corbella, J. (1986). Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion and distribution of cobalt. Arch. Toxicol. 58, 278-281.

85. Llobet, J. M., Domingo, J. L. and Corbella, J. (1985). Comparison of antidotal efficacy of chelating agents upon acute toxicity of Co(II) in mice. Res. Commun. Chem. Pathol. Pharmacol. 50, 305-308.

86. Lyle, W. H., Green, J. N., Gore, V. and Vidler, J. (1968). Enhancement of cadmium nephrotoxicity by penicillamine in the rat. Postgrad. Med. J. Suppl:18-21.

87. Malviya, A., Ramaskandhan, J., Holland, J. P. and Lingard, E. A. (2010). Metal-on-metal total hip arthroplasty. J. Bone Joint Surg. Am. 92, 1675-1683.

88. Matey, P., Allison, K. P., Sheehan, T. M. and Gowar, J. P. (2000). Chromic acid burns: early aggressive excision is the best method to prevent systemic toxicity. J. Burn Care Rehabil. 21, 241-245.

89. Mazzaferro, S., Perruzza, I., Costantini, S., Pasquali, M., Onorato, L., Sardella, D., Giordano, R., Ciaralli, L., Ballanti, P., Bonucci, E., Cinotti, G. A. and Coen, G. (1997). Relative roles of intestinal absorption and dialysis-fluid-related exposure in the accumulation of aluminium in haemodialysis patients. Nephrol. Dial. Transplant. 12, 2679-2682.

90. McCauley, J., Sorkin, M. I. (1989). Exacerbation of aluminium encephalopathy after treatment with desferrioxamine. Nephrol. Dial. Transplant. 4, 110-114.

91. McDermott, P. H., Delaney, R. L., Egan, J. D. and Sullivan, J. F. (1966). Myocardosis and cardiac failure in men. JAMA 198, 253-256.

92. McGivern, J., Mason, J. (1979). The effect of chelation on the fate of intravenously administered cadmium in rats. J. Comp. Pathol. 89, 1-9.

93. McGrath, K. G. (2003). An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving. Eur. J. Cancer Prev. 12, 479-485.

94. Meert, K. L., Ellis, J., Aronow, R. and Perrin, E. (1994). Acute ammonium dichromate poisoning. Ann. Emerg. Med. 24, 748-750.

95. Menendez-Fraga, P., Fernandez-Martin, J. L., Blanco-Gonzalez, E. and Cannata-Andia, J. B. (1998). Low percentage of aluminoxamine and ferrioxamine in uremic serum after desferrioxamine administration. Clin. Chem. 44, 1262-1268.

96. Molina-Jijon, E., Zarco-Marquez, G., Medina-Campos, O. N., Zatarain-Barron, Z. L., Hernandez-Pando, R., Pinzon, E., Zavaleta, R. M., Tapia, E. and Pedraza-Chaverri, J. (2012). Deferoxamine pretreatment prevents Cr(VI)-induced nephrotoxicity and oxidant stress: role of Cr(VI) chelation. Toxicology 291, 93-101.

97. Nakamura, H., Rose, P. G., Blumer, J. L. and Reed, M. D. (2000). Acute encephalopathy due to aluminum toxicity successfully treated by combined intravenous deferoxamine and hemodialysis. J. Clin. Pharmacol. 40, 296-300.

98. National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration (NOAA). (1998). "Managing the nation's bycatch: Priorities, programs, and actions for the national marine fisheries service." U.S. Department of Commerce, Washington, D.C.

99. NCRP. (2008). Management of Persons Contaminated With Radionuclides: Handbook. NCRP Report No. 161 (vol. I),

100. Novartis. (2011). "Desferal®. deferoxamine mesylate for injection USP. prescribing information." Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

101. Novartis Pharmaceuticals Corporation. (2011). "EXJADE® (deferasirox) tablets for oral suspension. prescribing information." Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

102. Nowak-Wiaderek, W. (1975). Influence of various drugs on excretion and distribution of chromium-51 in acute poisoning in rats. Mater. Med. Pol. 7, 308-310.

103. Oldenburg, M., Wegner, R. and Baur, X. (2009). Severe cobalt intoxication due to prosthesis wear in repeated total hip arthroplasty. J. Arthroplasty 24, 825.e15-825.e20.

104. Pavlakis, N., Pollock, C. A., McLean, G. and Bartrop, R. (1996). Deliberate overdose of uranium: toxicity and treatment. Nephron 72, 313-317.

105. Pazzaglia, U. E., Apostoli, P., Congiu, T., Catalani, S., Marchese, M. and Zarattini, G. (2011). Cobalt, chromium and molybdenum ions kinetics in the human body: data gained from a total hip replacement with massive third body wear of the head and neuropathy by cobalt intoxication. Arch. Orthop. Trauma. Surg. 131, 1299-1308.

106. Perl, D. P., Moalem, S. (2006). Aluminum and Alzheimer's disease, a personal perspective after 25 years. J. Alzheimers Dis. 9, 291-300.

107. Phelps, K. R., Naylor, K., Brien, T. P., Wilbur, H. and Haqqie, S. S. (1999). Encephalopathy after bladder irrigation with alum: case report and literature review. Am. J. Med. Sci. 318, 181-185.

108. Porter, J. B. (1997). A risk-benefit assessment of iron-chelation therapy. Drug Saf. 17, 407-421.

109. Radiation Emergency Assistance Center/Training Site (REAC/TS). (2011). "The medical aspects of radiation incidents." REAC/TS, Oak Ridge, TN.

110. Rahman, H., Skillen, A. W., Ward, M. K., Channon, S. M. and Kerr, D. N. (1986). Affinity of the aluminium binding protein. Int. J. Artif. Organs 9, 93-96.

111. Rau, W., Planas-Bohne, F. (1989). Enhancement of the kidney Cd burden by SH-containing chelating agents. Biol. Trace Elem. Res. 21, 227-231.

112. Raval, G., Straughen, J. E., McMillin, G. A. and Bornhorst, J. A. (2011). Unexplained hemolytic anemia with multiorgan failure. Clin. Chem. 57, 1485-1488.

113. Robert A., Y. (2002). Aluminum chelation principles and recent advances. Coord. Chem. Rev. 228, 97-113.

114. Rondeau, V. (2002). A review of epidemiologic studies on aluminum and silica in relation to Alzheimer's disease and associated disorders. Rev. Environ. Health 17, 107-121.

115. Ruprecht, J. (2009). "Dimaval. scientific product monograph." 7.1st ed. HEYL Chemisch-pharmazeutische Fabrik GmbH und Co. KG, Berlin, Germany.

116. Saric, M. M., Blanusa, M., Juresa, D., Saric, M., Varnai, V. M. and Kostial, K. (2004). Combined early treatment with chelating agents DMSA and CaDTPA in acute oral cadmium exposure. Basic Clin. Pharmacol. Toxicol. 94, 119-123.

117. Sauni, R., Linna, A., Oksa, P., Nordman, H., Tuppurainen, M. and Uitti, J. (2010). Cobalt asthma--a case series from a cobalt plant. Occup. Med. (Lond) 60, 301-306.

118. Schiffl, H., Weidmann, P., Weiss, M. and Massry, S. G. (1982). Dialysis treatment of acute chromium intoxication and comparative efficacy of peritoneal versus hemodialysis in chromium removal. Miner. Electrolyte Metab. 7, 28-35.

119. Schootstra, R., van Driel, M. F., Hassankhan, R., van de Werff, R., Oremus, E. T., Uges, D. R. and Mensink, H. J. (1989). The use of an alum irrigation in the treatment of massive bladder haemorrhage. Pharm. Weekbl. Sci. 11, 175-178.

120. Sharma, B. K., Singhal, P. C. and Chugh, K. S. (1978). Intravascular haemolysis and acute renal failure following potassium dichromate poisoning. Postgrad. Med. J. 54, 414-415.

121. Sherrard, D. J., Walker, J. V. and Boykin, J. L. (1988). Precipitation of dialysis dementia by deferoxamine treatment of aluminum-related bone disease. Am. J. Kidney Dis. 12, 126-130.

122. Shoskes, D. A., Radzinski, C. A., Struthers, N. W. and Honey, R. J. (1992). Aluminum toxicity and death following intravesical alum irrigation in a patient with renal impairment. J. Urol. 147, 697-699.

123. Simonsen, L. O., Brown, A. M., Harbak, H., Kristensen, B. I. and Bennekou, P. (2011). Cobalt uptake and binding in human red blood cells. Blood Cells Mol. Dis. 46, 266-276.