A review of Thimerosal (Merthiolate) and its ethylmercury breakdown product: Specific historical considerations regarding safety and effectiveness

Journal of Toxicology and Environmental Health - Part B: Critical Reviews

Volumn 10, Issue 8, 2007, Pages 575-596

  Geier, David A ^a,d   Sykes, Lisa K ^b   Geier, Mark R ^c  

^a Institute of Chronic Illnesses Inc   (United States)

^b Department of Research   (United States)

^c Genetic Centers of America   (United States)

^d NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; CHLORAMPHENICOL; ETHYLMERCURIC CHLORIDE; ETHYLMERCURY DERIVATIVE; RHESUS D ANTIBODY; SPERMICIDAL AGENT; THIOMERSAL;

AEROSOL; AUTOPSY; BACTERIAL ENDOCARDITIS; BLOOD STORAGE; CYTOTOXICITY; DIAPER DERMATITIS; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG SYNTHESIS; FOOD AND DRUG ADMINISTRATION; HOT FLUSH; HUMAN; IMMUNIZATION; INJECTION SITE NECROSIS; INJURY; IRRITABILITY; MERCURIALISM; NERVE CONDUCTION DISORDER; NONHUMAN; OCCUPATIONAL EXPOSURE; PHOTOPHOBIA; PRURITUS; REVIEW; SIDE EFFECT; SKIN TOXICITY; STREPTOCOCCUS; TREMOR; UNITED STATES; VAGINA;

ANIMALS; ETHYLMERCURY COMPOUNDS; HUMANS; LEGISLATION, DRUG; PRESERVATIVES, PHARMACEUTICAL; THIMEROSAL; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION; VACCINES;

EID: 36749095785     PISSN: 10937404     EISSN: 15216950     Source Type: Journal    
DOI: 10.1080/10937400701389875     Document Type: Review

References (84)

1. Aberer, W. 1991. Topical mercury should be banned-dangerous, outmoded, but still popular. J. Am. Acad. Dermatol., 24:150-151.
2. Advisory Committee on Immunization Practices. 2006. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). Mortal. Morbid. Weekly Rev. 55:1-42.
3. Al-Kassab, S., and Saigh, N. 1962. Mercury and calcium excretion in chronic poisoning with organic mercury compounds. J. Fac. Med. Baghdad 4:118-123.
4. Anonymous. 1943. Mercurials as 'preservatives.' J. Am. Med. Assoc. 122:1253.
5. Anonymous. 1983. Mercury poisoning in child treated with aqueous Merthiolate. MD State Med. J. 32:523.
6. Anundi, I., Hogberg, J., and Stead A. H. 1979. Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and cellular damage. Acta Pharmacol. Toxicol. 49:45-51.
7. Ardatova, A. N., Poloz, D., and Yakusheva, O. V. 1969. Toxic effects of Granosan. Veterinariya (Moscow) 46:56-58.
8. Axton, J. H. M. 1972. Six cases of poisoning after a parenteral organic mercurial compound (Merthiolate). Postgrad. Med. J. 48:417-421.
9. Bakulina, A. V. (1968). The effect of subacute Granosan poisoning on the progeny. Soviet Med. 31:60-63.
10. Birbin, S. S., Alekseeva, A., and Bulatov, A. A. 1968. The poisoning of swine treated with Granosan. Veterinariya 8:60-61.
11. Blair, A. M. J. N., Clark, B., Clark, A. J., and Wood, P. 1975. Tissue concentrations of mercury after chronic dosing of squirrel monkeys with Thiomersal. Toxicology 3:171-176.
12. Brunner, M., Albertini, S., and Wurgler, F. E. 1991. Effects of 10 known or suspected spindle poisons in the in vitro porcine brain tubulin assembly assay. Mutagenesis 6:65-70.
13. Cinca, I., Dumitrescu, I., Onaca, P., Serbanescu, A., and Nestorescu, B. 1980. Accidental ethyl mercury poisoning with nervous system, skeletal muscle, and myocardium injury. J. Neurol. Neurosurg. Psychiat. 43:143-149.
14. Cogswell, H. D., and Shown, A. 1948. Reaction following the use of tincture of Merthiolate. Ariz. Med. 5:42-43.
15. Cox, N. H., and Forsyth, A. 1988. Thiomersal allergy and vaccination reactions. Contact Dermatitis 18:229-233.
16. Cummins, S. L. (1937). Merthiolate in the treatment of tuberculosis. Lancet 230:962-963.
17. Dahhan, S. S., and Orfaly, H. 1962. Mercury poisoning and electorcardiographic changes. J. Fac. Med. Baghdad 4:104-111.
18. Damlugi, S. 1962. Mercurial poisoning with fungicide Granosan M. J. Fac. Med. Baghdad 4:83-103.
19. Davisson, E.O., Powell, H. M., MacFarlane, J. O., Hodgson, R., Stone, R. L., and Culbertson C. G. 1956. The preservation of poliomyelitis vaccine with stabilized Merthiolate. J. Lab. Clin. Med. 47:8-19.
20. Derban, L. K. 1974. Outbreak of food poisoning due to alkyl-mercury fungicide on southern Ghana state farm. Arch. Environ. Health 28:49-52.
21. Digar, A., Sensharma, G. C., and Samal, S. N. 1987. Lethality and teratogenecity of organic mercury (Thimerosal) on the chick embryo. J. Anat. Soc. India 36:153-159.
22. Ellis, F. A. 1943. Possible danger in use of Merthiolate ophthalmic ointment. Arch. Ophthalmol. 30:265-266.
23. Ellis, F. A. 1947. The sensitizing factor in Merthiolate. J. Allergy 18:212-213.
24. Engley, F .B. 1950. Evaluation of mercurial compounds as antiseptics. Ann. NY Acad. Sci. 53:197-206.
25. Engley, F. B. 1956. Mercurials as disinfectants: Evaluation of mercurial antimicrobic action and comparative toxicity for skin tissue cells. Chicago: 42nd Mid-Year Meeting of the Chemical Specialties Manufacturer's Association.
26. Fagan, D. G., Pritchard, J. S., Clarkson, T. W., and Greenwood, M. R. 1977. Organ mercury levels in infants with omphaloceles treated with organic mercurial antiseptic. Arch. Dis. Child. 52:962-964.
27. Forstrom, L., Hannuksela, M., Kousa, M., and Lehymuskallio, E. 1980. Merthiolate hypersensitivity and vaccination. Contact Dermatitis 6:241-245.
28. Francois, G., Duclos, P., Margolis, H., Lavanchy, D., Siegrist, C. A., Meheus, A., Lambert, P. H., Emiroglu, N., Badur, S., and Van Damme, P. 2005. Vaccine safety controversies and the future of vaccination programs. Pediatr. Infect. Dis. J. 24:953-961.
29. Gasset, A. R., Itoi, M., Ishii, Y., and Ramer, R. M. 1975. Teratogenicities of ophthalmic drugs. 2. Teratogenicities and tissue accumulation of Thimerosal. Arch. Ophthalmol. 93:52-55.
30. Gibson, S. T. 1976. Memorandum from Assistant to the Director, Department of Biologics, Food and Drug Administration, "Use of Thimerosal in Biologics Production." Washington, DC.
31. Goncharuk, G. A. 1971. Experimental investigations of the effect of organomercury pesticides on generative functions and on progeny. Hyg. Sanit. 36:40-43.
32. Heinonen, O. P., Slone, D., and Shapiro, S. 1977. Birth defects and drugs in pregnancy. Littleton, MA: Publishing Sciences Group.
33. Hekkens, F. E. A., Polak-Vogelzang, A. A., and Kreeftenberg, J. G. 1983. The antimicrobial effectiveness of some preservatives in inactivated human vaccines. J. Biol. Stand. 9:277-285.
34. Heyworth, M. F. 1982. Clinical experience with antilymphocyte serum. Immunol. Rev. 65:79-97.
35. Heyworth, M. F., and Truelove, S. C. 1979. Problems associated with the use of Merthiolate as a preservative in anti-lymphocytic globulin. Toxicology 12:325-333.
36. Hilleman, M. R. 1991. Merck Memorandum, "Vaccine Task Force Assignment: Thimerosal (Methiolate) Preservative - Problems, Analysis, Suggestions for Resolution." Whitehouse Station, NJ.
37. Itoi, M., Ishii, Y., and Kaneko, N. 1972. Teratogenicities of antiviral ophthalmics on experimental animals. Jpn. J. Clin. Ophthal. 26:631-640.
38. Jalili, M. A., and Abbasi, A. H. 1961. Poisoning by ethyl mercury toluene sulphonanilide. Br. J. Ind. Med. 18:303-308.
39. Jamieson, W. A., and Powell, H. M. 1931. Merthiolate as a preservative for biological products. Am. J. Hyg. 14:218-224.
40. Kendrick, D. B. 1989. Blood program in World War II. Washington, DC: Office of the Surgeon General, Department of the Army.
41. Kharasch, M. S. 1928. Alkyl merucric sulphur Compound and process for producing it. US Patent 1,672,615.
42. Kharasch, M. S. 1932. Stabilized bactericide and process of stabilizing it. U.S. Patent 1,862,896.
43. Kharasch, M. S. 1935. Stabilized organo-meruri-sulphur compounds. U.S. Patent 2,012,820.
44. Kinsella, R. A. 1941. Chemotherapy of bacterial endocarditis. Ann. Intern. Med. 15:982-986.
45. Kravchenko, A. T., Dzagurov, S. G., and Chervonskaia, G. P. 1983. Evaluation of the toxic action of prophylactic and therapeutic preparations on cell cultures. III. The detection of toxic properties in medical biological preparations by the degree of cell damage in the L132 continuous cell line. Zh. Mikrobiol. Epidemiol. Immunobiol. 3:87-92.
46. Lowe, I., and Southern, J. 1994. The antimicrobial activity of phenoxyethanol in vaccines. Lett. Appl. Microbiol. 18:115-116.
47. Lowell, J. A., Burgess, S., and Shenoy, S. 1996. Mercury poisoning associated with hepatitis-B immunoglobulin. Lancet 347:480.
48. Mal'tsev, P. V. 1972. Granosan poisoning in children. Feldsher Akush. 37:14-16.
49. Marks, H. H., Powell, H. M., and Jamieson, W. A. 1932. Merthiolate as a skin disinfecting agent. J. Lab. Clin. Med. 18:443-449.
50. Matheson, D. S., Clarkson, T. W., and Gelfand, E. W. 1980. Mercury toxicity (acrodynia) induced by long term injection of gammaglobulin. J. Pediatr. 97:153-155.
51. Morton, H. E., North, L L., and Engley, F. B. 1948. The bacteriostatic and bactericidal actions of some mercurial compounds on Hemolytic streptococci: In vivo and in vitro studies. J. Am. Med. Assoc. 136:37-41.
52. Mukai, N. 1972. An experimental study of alkylmercurial encephalopathy. Acta Neuropathol. 72:102-109.
53. Mukhtarova, N. D. 1977. Late sequelae of nervous system pathology caused by the action of low concentrations of ethyl mercury chloride. Gig. Tr. Prof. Zabol. 3:4-7.
54. Nascimento, L. O., Lorenzi Filho, G., and Rocha Ados, S. 1990. Lethal mercury poisoning due to ingestion of Merthiolate. Rev. Hosp. Clin. Fac. Med. Sao Paulo 45:216-218.
55. Nelson, E. A., and Gottshall, R. Y. 1967. Enhanced toxicity for mice of pertussis vaccines when preserved with Merthiolate. Appl. Microbiol. 15:590-593.
56. Nizov, A. A., and H. M. Shestakov, H. M. 1971. Contribution to the clinical aspects of Granosan poisoning. Sov. Med. 11:150-152.
57. Offit, P. A., and Jew, R. K. 2003. Addressing parents' concerns: Do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics 112:1394-1401.
58. Oharazawa, H. 1968. Effect of ethylmercuric phosphate in the pregnant mouse on chromosome abnormalities and fetal malformation. J. Jpn. Obstet. Gynecol. 20:1479-1487.
59. Oliver, W. T., and Platonow, N. 1960. Studies on the pharmacology of n-(ethylmercuri)-p-toluenesulfonanilide. Am. J. Vet. Res. 21:906-916.
60. Parry, J. M. 1977. The use of yeast cultures for the detection of environmental mutagens using a fluctuation test. Mutat. Res. 46:165-176.
61. Powell, H. M., and Jamieson, W. A. 1931. Merthiolate as a germicide. Am. J. Hyg. 13:296-310.
62. Ramanauskayte, M. B., and Baublis, P. P. 1973. Clinical picture and treatment of organomercurial pesticide poisoning in children. Pediatriya Moscow 35:56-60.
63. Rohyans, J., Walson, P. D., Wood, G. A., and MacDonald, W. A. 1984. Mercury toxicity following Merthiolate ear irrigations. J. Pediatr. 104:311-313.
64. Saley, P. L. 1970. Evaluation of slaughter products from Granosan-poisoned animals. Veterinariya 46:102-103.
65. Salle, A. J., and Lazarus, A. S. 1935. A comparison of the resistance of bacteria and embryonic tissue to germicidal substances. Proc. Soc. Exp. Biol. Med. 32:665-667.
66. Sass, J. E. 1937. Histological and cytological studies of ethyl mercury phosphate poisoning in corn seedlings. Phytopathologia 27:95-99.
67. Seal, D., Ficker, L., Wright, P., and Andrews, V. 1991. The case against Thiomersal. Lancet 338:315-316.
68. Shustov, V. I. A., and Syganova, S. I. 1970. Clinical aspects of subacute intoxication with Granosan. Kazansk. Med. Zh. 2:78-79.
69. Smithburn, K. C., Kempf, G. F., Zerfas, L. G., and Gilman, L. H. 1930. Meningococcic meningitis: a clinical study of one-hundred and forty-four epidemic cases. J. Am. Med. Assoc. 95:776-780.
70. Spann, J. W., Heath, R. G., Kreitzer, J. F., and Locke, L. N. 1972. Ethyl-mercury-p-toluene-sulfonanilide: Lethal and reproductive effects on pheasants Science 175:328-330.
71. Stetler, H. C., Garbe, P. L., Dwyer, D. M., Facklam, R. R., Ornstein, W. A., West, G. R., Dudley, J., and Bloch, A. B. 1985. Outbreaks of group a streptococcal abscesses following diphtheria-tetanus-toxoid pertussis vaccination. Pediatrics 75:299-303.
72. Subcommittee on Human Rights and Wellness, Government Reform Committee (Chairman Dan Burton). 2003. Mercury in medicine - Taking unnecessary risks. Washington, DC.
73. Suzuki, T., Takemoto, T. L., Kashiwazaki, H., and Miyama, T. 1973. Metabolic fate of ethylmercury salts in man and animals. In Mercury, mercurials, mercaptans, eds. M. W. Miller and T. W. Clarkson, pp. 209-240. Springfield, IL: Charles C. Thomas,
74. Tishkov, A. L., Saley, P., and Vitkalov, V. P. 1968. Poultry poisoning with Granosan. Veterinariya 45:58.
75. Trakhtenberg, I. M. 1950. The toxicity of vapors of organic mercury compounds (ethlmercuric phosphate and ethylmercuric chloride) in acute and chronic intoxication (experimental data). Gig. Sanit. 6:13-17.
76. Tryphonas, L., and Nielsen, N. O. 1973. Pathology of chronic alkylmercurial poisoning in swine. Am. J. Vet. Res. 34:379-392.
77. Van Horn, D. L., Edlehauser, H. F., Prodanovich, G., Eiferman, R., and Pederson, H. J. 1977. Effect of ophthalmic preservative Thimerosal on rabbit and human corneal endothelium. Invest. Ophthalmol. Visual Sci. 16:273-280.
78. Welch, H. 1939. Mechanism of the toxic action of germicides on whole blood measured by the loss of phagocytic activity of leucocytes. J. Immunol. 37:525-533.
79. Welch, H., and Hunter, A. C. 1940. Method for determining the effect of chemical antisepsis on phagocytosis. Am. J. Public Health 30:129-137.
80. Winship, K. A. 1986. Organic mercury compounds and their toxicity. Adverse Drug React. Acute Poisoning Rev. 5:141-180.
81. Withrow, T. J., Brown, N. T., Hitchins, V. M., and Strickland, A. G. 1989. Cytotoxicity and mutagenicity of ophthalmic solution preservatives and UVA radiation in L5178Y cells. Photochem. Photobiol. 50:385-389.
82. Wright, F. C., Palmer, J. S., and Riner, J. C. 1973. Retention of mercury in tissues of cattle and sheep given oral doses of a mercurial fungicide, Ceresan M. J. Agric. Food Chem. 21:614-615.
83. Yonaha, M., Ishikura, S., and Uchiyama, M. 1975. Toxicity of organic mercury compounds. III. Uptake and retention of mercury in several organs of mice by long term exposure of alkoxyethlmercury compounds. Chem. Pharm. Bull. 23:1718-1725.
84. Zhang, J. 1984. Clinical observations in ethyl mercury chloride poisoning. Am. J. Ind. Med. 5:251-258.