A Review of Thimerosal (Merthiolate) and its Ethylmercury Breakdown Product: Specific Historical Considerations Regarding Safety and Effectiveness

REFERENCES

• Aberer , W. 1991 . Topical mercury should be banned-dangerous, outmoded, but still popular . J. Am. Acad. Dermatol. , 24 : 150 – 151 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMedGoogle Scholar
• 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 .
   Google Scholar
• Anonymous . 1943 . Mercurials as ‘preservatives.’ . J. Am. Med. Assoc. , 122 : 1253
   Google Scholar
• Anonymous . 1983 . Mercury poisoning in child treated with aqueous Merthiolate . MD State Med. J. , 32 : 523
   PubMedGoogle Scholar
• 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 .
   Google Scholar
• Ardatova , A. N. , Poloz , D. and Yakusheva , O. V. 1969 . Toxic effects of Granosan . Veterinariya (Moscow) , 46 : 56 – 58 .
   PubMedGoogle Scholar
• Axton , J. H. M. 1972 . Six cases of poisoning after a parenteral organic mercurial compound (Merthiolate) . Postgrad. Med. J. , 48 : 417 – 421 .
   PubMed Web of Science ®Google Scholar
• Bakulina , A. V. 1968 . The effect of subacute Granosan poisoning on the progeny . Soviet Med. , 31 : 60 – 63 .
   PubMedGoogle Scholar
• Birbin , S. S. , Alekseeva , A. and Bulatov , A. A. 1968 . The poisoning of swine treated with Granosan . Veterinariya , 8 : 60 – 61 .
   Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• Cogswell , H. D. and Shown , A. 1948 . Reaction following the use of tincture of Merthiolate . Ariz. Med. , 5 : 42 – 43 .
   PubMedGoogle Scholar
• Cox , N. H. and Forsyth , A. 1988 . Thiomersal allergy and vaccination reactions . Contact Dermatitis , 18 : 229 – 233 .
   PubMed Web of Science ®Google Scholar
• Cummins , S. L. 1937 . Merthiolate in the treatment of tuberculosis . Lancet , 230 : 962 – 963 .
   Google Scholar
• Dahhan , S. S. and Orfaly , H. 1962 . Mercury poisoning and electorcardiographic changes . J. Fac. Med. Baghdad , 4 : 104 – 111 .
   Google Scholar
• Damlugi , S. 1962 . Mercurial poisoning with fungicide Granosan M . J. Fac. Med. Baghdad , 4 : 83 – 103 .
   Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• Derban , L. K. 1974 . Outbreak of food poisoning due to alkyl-mercury fungicide on southern Ghana state farm . Arch. Environ. Health , 28 : 49 – 52 .
   PubMed Web of Science ®Google Scholar
• 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 .
   Google Scholar
• Ellis , F. A. 1943 . Possible danger in use of Merthiolate ophthalmic ointment . Arch. Ophthalmol. , 30 : 265 – 266 .
   Google Scholar
• Ellis , F. A. 1947 . The sensitizing factor in Merthiolate . J. Allergy , 18 : 212 – 213 .
   PubMedGoogle Scholar
• Engley , F .B. 1950 . Evaluation of mercurial compounds as antiseptics . Ann. NY Acad. Sci. , 53 : 197 – 206 .
   PubMed Web of Science ®Google Scholar
• 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 .
   Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• Forstrom , L. , Hannuksela , M. , Kousa , M. and Lehymuskallio , E. 1980 . Merthiolate hypersensitivity and vaccination . Contact Dermatitis , 6 : 241 – 245 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMedGoogle Scholar
• Gibson , S. T. 1976 . “ Memorandum from Assistant to the Director, Department of Biologics, Food and Drug Administration ” . In Use of Thimerosal in Biologics Production Washington, DC
   Google Scholar
• Goncharuk , G. A. 1971 . Experimental investigations of the effect of organomercury pesticides on generative functions and on progeny . Hyg. Sanit. , 36 : 40 – 43 .
   Google Scholar
• Heinonen , O. P. , Slone , D. and Shapiro , S. 1977 . Birth defects and drugs in pregnancy , Littleton, MA : Publishing Sciences Group .
   Google Scholar
• 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 .
   Google Scholar
• Heyworth , M. F. 1982 . Clinical experience with antilymphocyte serum . Immunol. Rev. , 65 : 79 – 97 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• Hilleman , M. R. 1991 . “ Merck Memorandum ” . In Vaccine Task Force Assignment: Thimerosal (Methiolate) Preservative—Problems, Analysis, Suggestions for Resolution Whitehouse Station, NJ
   Google Scholar
• Itoi , M. , Ishii , Y. and Kaneko , N. 1972 . Teratogenicities of antiviral ophthalmics on experimental animals . Jpn. J. Clin. Ophthal. , 26 : 631 – 640 .
   Google Scholar
• Jalili , M. A. and Abbasi , A. H. 1961 . Poisoning by ethyl mercury toluene sulphonanilide . Br. J. Ind. Med. , 18 : 303 – 308 .
   PubMedGoogle Scholar
• Jamieson , W. A. and Powell , H. M. 1931 . Merthiolate as a preservative for biological products . Am. J. Hyg. , 14 : 218 – 224 .
   Google Scholar
• Kendrick , D. B. 1989 . Blood program in World War II , Washington, DC : Office of the Surgeon General, Department of the Army .
   Google Scholar
• Kharasch , M. S. Alkyl merucric sulphur Compound and process for producing it . US Patent 1,672,615 . 1928 .
   Google Scholar
• Kharasch , M. S. Stabilized bactericide and process of stabilizing it . U.S. Patent 1,862,896 . 1932 .
   Google Scholar
• Kharasch , M. S. Stabilized organo-meruri-sulphur compounds . U.S. Patent 2,012,820 . 1935 .
   Google Scholar
• Kinsella , R. A. 1941 . Chemotherapy of bacterial endocarditis . Ann. Intern. Med. , 15 : 982 – 986 .
   Google Scholar
• 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 .
   Google Scholar
• Lowe , I. and Southern , J. 1994 . The antimicrobial activity of phenoxyethanol in vaccines . Lett. Appl. Microbiol. , 18 : 115 – 116 .
   PubMed Web of Science ®Google Scholar
• Lowell , J. A. , Burgess , S. and Shenoy , S. 1996 . Mercury poisoning associated with hepatitis-B immunoglobulin . Lancet , 347 : 480
   PubMed Web of Science ®Google Scholar
• Mal'tsev , P. V. 1972 . Granosan poisoning in children . Feldsher Akush. , 37 : 14 – 16 .
   Google Scholar
• Marks , H. H. , Powell , H. M. and Jamieson , W. A. 1932 . Merthiolate as a skin disinfecting agent . J. Lab. Clin. Med. , 18 : 443 – 449 .
   Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• Mukai , N. 1972 . An experimental study of alkylmercurial encephalopathy . Acta Neuropathol. , 72 : 102 – 109 .
   Google Scholar
• 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 .
   Google Scholar
• 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 .
   PubMedGoogle Scholar
• Nelson , E. A. and Gottshall , R. Y. 1967 . Enhanced toxicity for mice of pertussis vaccines when preserved with Merthiolate . Appl. Microbiol. , 15 : 590 – 593 .
   PubMedGoogle Scholar
• Nizov , A. A. and Shestakov , H. M. 1971 . Contribution to the clinical aspects of Granosan poisoning . Sov. Med. , 11 : 150 – 152 .
   Google Scholar
• Offit , P. A. and Jew , R. K. 2003 . Addressing parents' concerns: Do vaccines contain harmful preservatives, adjuvants, additives, or residuals? . Pediatrics , 112 : 1394 – 1401 .
   PubMed Web of Science ®Google Scholar
• Oharazawa , H. 1968 . Effect of ethylmercuric phosphate in the pregnant mouse on chromosome abnormalities and fetal malformation . J. Jpn. Obstet. Gynecol. , 20 : 1479 – 1487 .
   Google Scholar
• Oliver , W. T. and Platonow , N. 1960 . Studies on the pharmacology of n-(ethylmercuri)-p-toluenesulfonanilide . Am. J. Vet. Res. , 21 : 906 – 916 .
   PubMed Web of Science ®Google Scholar
• Parry , J. M. 1977 . The use of yeast cultures for the detection of environmental mutagens using a fluctuation test . Mutat. Res. , 46 : 165 – 176 .
   PubMedGoogle Scholar
• Powell , H. M. and Jamieson , W. A. 1931 . Merthiolate as a germicide . Am. J. Hyg. , 13 : 296 – 310 .
   Google Scholar
• Ramanauskayte , M. B. and Baublis , P. P. 1973 . Clinical picture and treatment of organomercurial pesticide poisoning in children . Pediatriya Moscow , 35 : 56 – 60 .
   Google Scholar
• Rohyans , J. , Walson , P. D. , Wood , G. A. and MacDonald , W. A. 1984 . Mercury toxicity following Merthiolate ear irrigations . J. Pediatr. , 104 : 311 – 313 .
   PubMed Web of Science ®Google Scholar
• Saley , P. L. 1970 . Evaluation of slaughter products from Granosan-poisoned animals . Veterinariya , 46 : 102 – 103 .
   Google Scholar
• 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 .
   Google Scholar
• Sass , J. E. 1937 . Histological and cytological studies of ethyl mercury phosphate poisoning in corn seedlings . Phytopathologia , 27 : 95 – 99 .
   Google Scholar
• Seal , D. , Ficker , L. , Wright , P. and Andrews , V. 1991 . The case against Thiomersal . Lancet , 338 : 315 – 316 .
   PubMed Web of Science ®Google Scholar
• Shustov , V. I. A. and Syganova , S. I. 1970 . Clinical aspects of subacute intoxication with Granosan . Kazansk. Med. Zh. , 2 : 78 – 79 .
   Google Scholar
• 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 .
   Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 2003 . “ Subcommittee on Human Rights and Wellness, Government Reform Committee (Chairman Dan Burton) ” . In Mercury in medicine—Taking unnecessary risks Washington, DC
   Google Scholar
• Suzuki , T. , Takemoto , T. L. , Kashiwazaki , H. and Miyama , T. 1973 . “ Metabolic fate of ethylmercury salts in man and animals ” . In Mercury, mercurials, mercaptans , Edited by: Miller , M. W. and Clarkson , T. W. 209 – 240 . Springfield, IL : Charles C. Thomas .
   Google Scholar
• Tishkov , A. L. , Saley , P. and Vitkalov , V. P. 1968 . Poultry poisoning with Granosan . Veterinariya , 45 : 58
   PubMedGoogle Scholar
• 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 .
   PubMedGoogle Scholar
• Tryphonas , L. and Nielsen , N. O. 1973 . Pathology of chronic alkylmercurial poisoning in swine . Am. J. Vet. Res. , 34 : 379 – 392 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   Google Scholar
• Welch , H. and Hunter , A. C. 1940 . Method for determining the effect of chemical antisepsis on phagocytosis . Am. J. Public Health , 30 : 129 – 137 .
   Google Scholar
• Winship , K. A. 1986 . Organic mercury compounds and their toxicity . Adverse Drug React. Acute Poisoning Rev. , 5 : 141 – 180 .
   PubMedGoogle Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• 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 .
   PubMed Web of Science ®Google Scholar
• Zhang , J. 1984 . Clinical observations in ethyl mercury chloride poisoning . Am. J. Ind. Med. , 5 : 251 – 258 .
   PubMed Web of Science ®Google Scholar