Skip to main content
Log in

Thiomersal in Vaccines

Balancing the Risk of Adverse Effects with the Risk of Vaccine-Preventable Disease

  • Current Opinion
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

A number of affluent countries are moving to eliminate thiomersal (thimerosal), an ethylmercury preservative, from vaccines as a precautionary measure because of concerns about the potential adverse effects of mercury in infants. The WHO advocates continued use of thiomersal-containing vaccines in developing countries because of their effectiveness, safety, low cost, wide availability and logistical suitability in this setting.

The guidelines for long-term mercury exposure should not be used for evaluating risk from intermittent single day exposures, such as immunisation using thiomersal-containing vaccines. Similar or higher mercury exposures likely occur from breast feeding and the health benefit of eliminating thiomersal from a vaccine, if any, is likely to be very small. On the other hand, the benefits accrued from the use of thiomersal-containing vaccines are considerably greater but vary substantially between affluent and developing regions of the world. Because of the contribution to overall mercury exposure from breast milk and diet in later life, the removal of thiomersal from vaccines would produce no more than a 50% reduction of mercury exposure in infancy and <1% reduction over a lifetime.

Different public policy decisions are appropriate in different settings to achieve the lowest net risk, viewed from the perspectives of the individual vaccinee or on a population basis. In developing regions of the world, at least over the next decade, far more benefit will accrue from protecting children against widely prevalent vaccine-preventable diseases by focusing efforts aimed at improving infant immunisation uptake by using current, inexpensive, domestically-manufactured, thiomersal-containing vaccines, than by investing in thiomersal-free alternatives.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Figure 1
Table IV

Similar content being viewed by others

References

  1. Clements CJ, Ball LK, Ball R, et al. Thiomersal in vaccines: is removal warranted? Drug Saf 2001; 24(8): 567–74

    Article  PubMed  CAS  Google Scholar 

  2. Schuster PF, Krabbenhoft DP, Naftz DL, et al. Atmospheric mercury deposition during the last 270 years: a glacial ice core record of natural and anthropogenic sources. Environ Sci Technol 2002; 36(11): 2303–10

    Article  PubMed  CAS  Google Scholar 

  3. Clarkson TW. Mercury: major issues in environmental health. Environ Health Perspect 1993 Apr; 100: 31–8

    Article  PubMed  CAS  Google Scholar 

  4. Campbell L, Dixon DG, Hecky RE. A review of mercury in Lake Victoria, East Africa: implications for human and ecosystem health. J Toxicol Environ Health B Crit Rev 2003; 6(4): 325–56

    Article  PubMed  CAS  Google Scholar 

  5. Tchounwou PB, Ayensu WK, Ninashvili N, et al. Environmental exposure to mercury and its toxicopathologic implications for public health. Environ Toxicol 2003; 18(3): 149–75

    Article  PubMed  CAS  Google Scholar 

  6. Aschner M, Walker SJ. The neuropathogenesis of mercury toxicity. Mol Psychiatry 2002; 7: S40–1

    Article  PubMed  CAS  Google Scholar 

  7. Goyer RA. Toxic effects of metals. In: Klaassen CD, editor. Casseret & Doull’s toxicology: the basic science of poisons. 5th ed. New York: McGraw-Hill, 1995: 691–736

    Google Scholar 

  8. Clarkson TW. The three modern faces of mercury. Environ Health Prospect 2002; 110Suppl. 1: 11–23

    Article  CAS  Google Scholar 

  9. Harada M. Minamata disease: methylmercury poisoning in Japan caused by environmental pollution. Crit Rev Toxicol 1995; 25(1): 1–24

    Article  PubMed  CAS  Google Scholar 

  10. Bakir F, Damluji SF, Amin-Zaki L, et al. Methylmercury poisoning in Iraq. Science 1973; 181(96): 230–41

    Article  PubMed  CAS  Google Scholar 

  11. Pichichero ME, Cernichiari E, Loprelato J, et al. Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: a descriptive study. Lancet 2002; 360: 1737–41

    Article  PubMed  CAS  Google Scholar 

  12. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury: current exposures and clinical manifestations. N Engl J Med 2003; 349(18): 1731–7

    Article  PubMed  CAS  Google Scholar 

  13. Egeland GM, Middaugh JP. Balancing fish consumption benefits with mercury exposure. Science 1997; 278(5345): 1904–5

    Article  PubMed  CAS  Google Scholar 

  14. Halsey NA. Limiting infant exposure to thimerosal in vaccines and other sources of mercury. JAMA 1999; 282(18): 1763–6

    Article  PubMed  CAS  Google Scholar 

  15. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines. Pediatrics 2001; 107(5): 1147–54

    Article  PubMed  CAS  Google Scholar 

  16. US Food and Drug Administration. Thimerosal in vaccines [online]. Available from URL:http://www.fda.gov/cber/vaccine/thimerosal.htm [Accessed 2002 May 29]

  17. US Centers for Disease Control and Prevention. Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and Public Health Service. MMWR Morb Mortal Wkly Rep 1999; 48 (26): 563–5

    Google Scholar 

  18. US Centers for Disease Control and Prevention. Joint statement concerning removal of thimerosal from vaccines [online]. Available from URL:http://www.cdc.gov/nip/vacsafe/concerns/thimerosal/joint_statement_00.htm [Accessed 2000 Nov 21]

  19. US Centers for Disease Control and Prevention. Notice to readers: summary of the joint statement on thimerosal in vaccines. MMWR Morb Mortal Wkly Rep 2000; 49 (27): 622, 631

    Google Scholar 

  20. The European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit. EMEA public statement on thiomersal containing medicinal products: 8 July 1999; EMEA/20962/99 [online]. Available from URL:http://www.eudra.org/emea.html [Accessed 2004 Jan 13]

  21. The European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit. EMEA Position Statement - Recent developments concerning thiomersal in vaccines: 29 June 2000; /EMEA/CPMP1578/00 [online]. Available from URL:http://www.eudra.org/emea.html [Accessed 2004 Jan 13]

  22. US Centres for Disease Control and Prevention. Mercury and vaccines [online]. Available from URL:http://www.cdc.gov/nip/vacsafe/concerns/thimerosal/default.htm [Accessed 2004 Jan 12]

  23. US Centres for Disease Control and Prevention. Thimerosal content in some US licensed vaccines [online]. Available from URL:http://www.vaccinesafety.edu/thi-table.htm [Accessed 2004 Jan 12]

  24. World Health Organization. Global Advisory Committee on Vaccine Safety, 2003 Jun 11–12. Wkly Epidemiol Rec 2003; 32: 282–4

    Google Scholar 

  25. World Health Organization. WHO Guidelines on regulatory expectations related to the elimination, reduction or replacement of thiomersal in vaccines: technical report series (unnumbered), 2003 [online]. Available from URL:http://www.who.int/biologicals/Thimerosal_final.pdf [Accessed 2004 Jan 12]

  26. World Health Organization. Global Advisory Committee on Vaccine Safety: statement on thiomersal, 2003 Aug [online]. Available from URL:http://www.who.int/vaccine_safety/topics/thiomersal/statement200308/en/index.html [Accessed 2004 Jan 12]

  27. World Health Organization (WHO). Thiomersal as a vaccine preservative. Wkly Epidemiol Rec 2000; 75 (2): 9–16

    Google Scholar 

  28. Knezevic I, Griffiths E, Reigel F, et al. Thiomersal in vaccines: a regulatory perspective WHO consultation, Geneva, 2002 Apr 15-16. Vaccine 2004; 22: 1836–41

    Article  PubMed  CAS  Google Scholar 

  29. Institute of Medicine. Immunization safety review. In: Stratton K, Gable A, McCormick MC, editors. Thimerosal-containing vaccines and neurodevelopmental disorders. Washington (DC): National Academy Press, 2001

  30. Centers for Disease Control and Prevention. Recommended childhood and adolescent immunization schedule — United States, 2004 Jan-Jun [online]. Available from URL:http://www.cdc.gov/nip/recs/child-schedule.pdf [Accesssed 2004 Jan 12]

  31. Centers for Disease Control and Prevention. Vaccinations for Adults [online]. Available from URL:http://www.cdc.gov/nip/recs/adult-schedule.htm [Accessed 2004 Jan 12]

  32. World Health Organization (WHO). State of the world’s vaccines and immunization: 2002; 1–97. Available from URL:http://www.who.int/vaccines-documents/DocsPDF02/www7-18.pdf [Accessed 2004 Feb 7]

  33. Madsen KM, Lauritsen MB, Pedersen CB, et al. Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Pediatrics 2003; 112(3): 604–6

    Article  PubMed  Google Scholar 

  34. Stehr-Green P, Tull P, Stellfeld M, et al. Autism and thimerosal-containing vaccines. Am J Prev Med 2003; 25(2): 101–6

    Article  PubMed  Google Scholar 

  35. Institute of Medicine. Immunization safety review: vaccines and autism. Washington (DC): National Academies Press, 2004

  36. Heron J, Golding J, ALSPAC Study Team. Thimerosal exposure in infants and developmental disorders: a prospective cohort study in the United Kingdom does not support a causal association. Pediatr 2004; 114: 577–83

    Article  Google Scholar 

  37. Andrews N, Miller E, Grant A, et al. Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United Kingdom does not support a causal association. Pediatr 2004; 114: 584–91

    Article  Google Scholar 

  38. Health Canada. National Advisory Committee on Immunization Statement on Thimerosal. Can Commun Dis Rep 2003; 29 (ACS–1): 1–10

    Google Scholar 

  39. Magos L, Brown AW, Sparow S, et al. The comparative toxicology of ethyl- and methylmercury. Arch Toxicol 1985; 57(4): 260–7

    Article  PubMed  CAS  Google Scholar 

  40. Summary and Conclusions. Joint FAO/WHO Expert Committee on Food Additives: 61st Meeting, Rome, 2003 Jan 10–19 [online]. Available from URL:http://www.who.int/ipcs/food/jecfa/summaries/en/summary_61.pdf [Accessed 2004 Jan 13]

  41. US Environmental Protection Agency (EPA). Mercury report to Congress Volumes 1–8. EPA–452/R–97–003 to EPA–452/R–97–010; 1997[online]. Available from URL:http://www.epa.gov/oar/mercury.html [Accessed 2004 Jan 13]

  42. Food and Drug Administration. Action level for mercury on fish, shellfish, crustaceans and other aquatic animals. Federal Register 1979; 44 (14): 3990–93

    Google Scholar 

  43. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Mercury (Update). 1999; 1-617 [online]. Available from URL:http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf

  44. Magos L. Review on the toxicity of ethylmercury, including its presence as a preservative in biological and pharmaceutical products. J Appl Toxicol 2001; 21: 1–5

    Article  PubMed  CAS  Google Scholar 

  45. World Health Organization. Global Advisory Committee on Vaccine Safety, 2002 Jun 20–21: safety of thiomersal-containing vaccines. Wkly Epidemiol Rec 2002; 77: 389–404

  46. Magos L. Neurotoxic character of thimerosal and the allometric extrapolation of adult clearance half-time to infants. J Appl Toxicol 2003; 23: 263–9

    Article  PubMed  CAS  Google Scholar 

  47. Clements CJ. The evidence for the safety of thiomersal in newborn and infant vaccines. Vaccine 2004; 22: 1854–61

    Article  PubMed  CAS  Google Scholar 

  48. Davidson PW, Myers GJ, Cox C, et al. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment: outcomes at 66 months of age in the Seychelles Child Development Study. JAMA 1998; 280: 701–7

    Article  PubMed  CAS  Google Scholar 

  49. Davidson PW, Palumbo D, Myers GJ, et al. Neurodevelopmental outcomes of Seychellois children from the pilot cohort at 108 months following prenatal exposure to methylmercury from a maternal fish diet. Environ Res 2000; 84(1): 1–11

    Article  PubMed  CAS  Google Scholar 

  50. Grandjean P, Weihe P, White RF, et al. Cognitive performance of children prenatally exposed to ‘safe’ levels of methylmercury. Environ Res 1998; 77: 165–72

    Article  PubMed  CAS  Google Scholar 

  51. Grandjean P, Weihe P, White RF, et al. Cognitive deficits in 7-year old children with prenatal exposure to methylmercury. Neurotoxicol Teratol 1997; 19(6): 417–28

    Article  PubMed  CAS  Google Scholar 

  52. Crump KS, Kjellstrom T, Shipp AM, et al. Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Risk Anal 1998; 18(6): 701–13

    Article  PubMed  CAS  Google Scholar 

  53. Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions. Contact Dermatitis 1988; 18(4): 229–33

    Article  PubMed  CAS  Google Scholar 

  54. Pless R, Risher JF. Mercury, infant neurodevelopment, and vaccination. J Pediatr 2000; 136(5): 571–3

    Article  PubMed  CAS  Google Scholar 

  55. Bigham M, Copes R. Exposure to thimerosal in vaccines used in Canadian infant immunization programs, with respect to risk of neurodevelopmental disorders. Can Commun Dis Rep 2002; 28(9): 69–80

    PubMed  CAS  Google Scholar 

  56. Goncalo M, Figueiredo A, Goncalo S. Hypersensitivity to thimerosal: the sensitivity moiety. Contact Dermatitis 1996; 34: 201–3

    Article  PubMed  CAS  Google Scholar 

  57. Van’t Veen A-J. Vaccines without thimerosal: why so necessary, why so long coming? Drugs 2001; 61(5): 565–72

    Article  Google Scholar 

  58. Stajich GV, Lopez GP, Harry SW, et al. Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants. J Pediatr 2000; 136: 679–81

    Article  PubMed  CAS  Google Scholar 

  59. Katsunuma H, Suzuki T, Nishi S, et al. Four cases of occupational organic mercury poisoning. Rep Inst Sci Lab 1963; 61: 33–40

    Google Scholar 

  60. Zhang J. Clinical observations in ethyl mercury chloride poisoning. Am J Ind Med 1984; 5(3): 251–8

    Article  PubMed  CAS  Google Scholar 

  61. Cox C, Clarkson TW, Marsh DO, et al. Dose-response analysis of infants prenatally exposed to methylmercury: an application of single compartment model to single strand hair analysis. Environ Res 1989; 49(2): 318–32

    Article  PubMed  CAS  Google Scholar 

  62. Marsh DO, Clarkson TW, Cox C, et al. Fetal methylmercury poisoning: relationship between concentration in single strands of maternal hair and child effects. Arch Neurol 1987; 44(10): 1017–22

    Article  PubMed  CAS  Google Scholar 

  63. Cranmer M, Gilbert S, Cranmer J. Neurotoxicity of mercury: indicators and effects of low-level exposure: overview. Neurotoxicology 1996; 17(1): 9–14

    PubMed  CAS  Google Scholar 

  64. Crump KS, Kjellstrom T, Shipp AM, et al. Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Risk Anal 1998; 18(6): 701–13

    Article  PubMed  CAS  Google Scholar 

  65. The European Agency for the Evaluation of Medicinal Products, Committee for Veterinary Medicinal Products, Veterinary Medicines Evaluation Unit. Thiomersal and timerfonate summary report EMEA/MRL/140/96-FINAL, 1996 Oct [online]. Available from URL:http://www.eudra.org/emea.html [Accessed 2004 Feb 7]

  66. Health Canada, Dir Gen, Food Directorate. Memo to F/P/T Committee on Food Safety Policy. 1998 Jun 22

  67. US Food and Drug Administration. Action level for mercury in fish, shellfish, crustaceans and other aquatic animals: withdrawal of proposed rulemaking. Fed Regist 1979; 44 (14): 3990–3

    Google Scholar 

  68. Galal-Gorchev H. Dietary intake, levels in food and estimated intake of lead, cadmium, and mercury. Food Addit Contam 1993; 10: 115–28

    Article  PubMed  CAS  Google Scholar 

  69. American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Environmental Health. Thimerosal in vaccines: an interim report to clinicians (RE9935). Pediatrics 1999; 104 (3): 570–4

    Google Scholar 

  70. Mahaffey KR. Methylmercury: a new look at the risks. Public Health Rep 1999; 114: 397–413

    Article  Google Scholar 

  71. Halsey NA, Goldman LR. Mercury in infants given vaccines containing thiomersal [letter]. Lancet 2003; 361: 698–9

    Article  PubMed  Google Scholar 

  72. US Centers for Disease Control and Prevention. National Center for Health Statistics. Girls weight-for-age percentiles [online]. Available from URL:http://www.cdc.gov/nchs/data/nhanes/growthcharts/set1clinical/cj41l018.pdf [Accessed 2004 Feb 7]

  73. Schoeny R. Use of genetic toxicology data in US EPA risk assessment: the mercury study report as an example. Environ Health Perspect 1996; 104Suppl. 3: 663–73

    PubMed  CAS  Google Scholar 

  74. Sundberg J, Oskarsson A. Placental and lactational transfer of mercury from rats exposed to methylmercury in their diet: speciation of mercury in the offspring. J Trace Elem Exp Med 1992; 5(1): 47–56

    CAS  Google Scholar 

  75. Sakamoto M, Kubota M, Matsumoto S-i, et al. Declining risk of methylmercury exposure to infants during lactation. Environ Res 2002; 90: 185–9

    Article  PubMed  CAS  Google Scholar 

  76. Gundacker C, Pietschnig B, Wittmann KJ, et al. Lead and mercury in breast milk. Pediatr 2002; 110(5): 873–8

    Article  Google Scholar 

  77. Sandborgh-Englund G. Mercury exposure in utero and during pregnancy. J Toxicol Environ Health A 2001; 63: 317–20

    Article  PubMed  CAS  Google Scholar 

  78. Dorea JG, Barbosa AC. Maternal mercury transfer. Environ Res 2003; 93: 113–4

    Article  PubMed  CAS  Google Scholar 

  79. Abadin HG, Hibbs BF, Pohl HR. Breast-feeding exposure of infants to cadmium, lead and mercury: a public health viewpoint. Toxicol Ind Health 1997; 134: 495–517

    Google Scholar 

  80. Dorea JG. Mercury and lead during breast-feeding. Br J Nutr 2004; 92: 21–40

    Article  PubMed  CAS  Google Scholar 

  81. World Health Organization (WHO). Global strategy for infant and young child feeding: the optimal duration of exclusive breastfeeding. 2001; Document A54/INF.DOC./4 [online]. Available from URL:http://www.who.int/gb/EB_WHA/PDF/WHA54/ea54id4.pdf [Accessed 2004 Feb 7]

  82. World Health Organization. Minor and trace elements in human milk: report of a joint WHO/IEAE collaborative study. Geneva: WHO, 1989

  83. Canadian Medical Association. Complete book of mother & baby care. Montreal (QC): Readers Digest Association (Canada) Ltd, 1992: 102

  84. World Health Organization (WHO). Environmental Health Criteria 101: Methylmercury, 1990. WHO: Geneva [online]. Available from URL:http://www.inchem.org/documents/ehc/ehc101.htm [Accessed 2003 Dec 31]

  85. World Health Organization (WHO). The World Health Report 2003. Geneva: World Health Organization, 2003: 1–184 [online]. Available from URL:http://www.who.int/whr/2003/en/[Accessed 2004 Feb 7]

  86. World Health Organization (WHO). Immunization coverage among infants by WHO Region by vaccine, 2002 [online]. Available from URL:http://www.who.int/vaccines-surveillance/graphics/htmls/covreg.htm [Accessed 2004 Jan 12]

  87. World Health Organization (WHO). Geographic pattern of hepatitis B prevalence, 1997 [online]. Available from URL:http://www.who.int/vaccines-surveillance/graphics/htmls/hepbprev.htm[Accessed 2004 Jan 13]

  88. World Health Organization (WHO). Global status of countries using hepatitis B vaccine in their national infant immunization system, 2003 [online]. Available from URL:http://www.who.int/vaccines-surveillance/graphics/htmls/hepb.htm [Accessed 2004 Jan 13]

  89. Global Alliance for Vaccines and Immunization (GAVI) [online]. Available from URL:http://www.vaccinealliance.org [Accessed 2004 Feb 7]

  90. The European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products. Points to consider on the reduction, elimination or substitution of thiomersal in vaccines: 2001 Apr 26; EMEA/CPMP/BWP2517/00 [online]. Available from URL:http://www.emea.eu.int/pdfs/human/bwp/251700en.pdf [Accessed 2004 Jan 12]

  91. World Health Organization (WHO). Report of the Strategic Advisory Group of Experts (SAGE); 2002 Jun 14–15; Geneva. Document WHO/V&B/03.06 [online]. Available from URL:http://www.who.int/vaccines-documents/DocsPDF03/www7-20.pdf [Accessed 2004 Jan 12]

  92. World Health Organization (WHO). The use of opened multi-dose vials of vaccine in subsequent immunization sessions. WHO Policy Statement: document WHO/V&B/00.09, 2000 [online]. Available from URL:http://www.who.int/vaccines-documents/DocsPDF99/www9924.pdf [Accessed 2004 Jan 12]

  93. Drain PK, Nelson CM, Lloyd JS. Single-dose versus multi-dose vaccine vials for immunization programmes in developing countries. Bull World Health Organ 2003; 81(10): 726–31

    PubMed  Google Scholar 

  94. Hutubessy RCW, Bendib LM, Evans DB. Critical issues in the economic evaluation of interventions against communicable diseases. Acta Trop 2001; 78: 191–206

    Article  PubMed  CAS  Google Scholar 

  95. Prakash C. Crucial factors that influence cost-effectiveness of universal hepatitis B immunization in India. Int J Technol Assess Health Care 2003; 19(1): 28–40

    Article  PubMed  Google Scholar 

  96. World Bank. Immunization at a glance [online]. Available from URL:http://wbln0018.worldbank.org/HDNet/hddocs.nsf/c84-0b59b6982d2498525670c004def60/86eca35fe03389328525-6a42005e0dc6?OpenDocument [Accessed 2004 Feb 7]

  97. Kane MA. Global status of hepatitis B immunization. Lancet 1996; 348: 696

    Article  PubMed  CAS  Google Scholar 

  98. Bigham M, Scheifele D, Dobson S. Impact of the media on vaccine uptake in British Columbia’s grade 6 hepatitis b immunization program. Can Commun Dis Rep 1999; 25(10): 89–93

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors received no funding for the preparation of this review and have no conflicts of interest directly relevant to its content.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark Bigham.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bigham, M., Copes, R. Thiomersal in Vaccines. Drug-Safety 28, 89–101 (2005). https://doi.org/10.2165/00002018-200528020-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200528020-00001

Keywords

Navigation