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'''Thiomersal''' ([[International Nonproprietary Name|INN]]), or '''thimerosal''' ([[United States Adopted Name|USAN]], [[Japanese Accepted Name|JAN]]), is an [[organomercury]] compound. It is a well-established [[antiseptic]] and [[antifungal agent]].
'''Thiomersal''' ([[International Nonproprietary Name|INN]]), or '''thimerosal''' ([[United States Adopted Name|USAN]], [[Japanese Accepted Name|JAN]]), is an [[organomercury]] compound. It is a well-established [[antiseptic]] and [[antifungal agent]].


The pharmaceutical corporation [[Eli Lilly and Company]] gave thiomersal the trade name '''Merthiolate'''. It has been used as a [[preservative]] in [[vaccine|vaccines]], [[immunoglobulin]] preparations, [[Allergy#Diagnosis|skin test antigens]], [[antivenin]]s, [[ophthalmology|ophthalmic]] and nasal products, and [[tattoo]] inks.<ref>{{Cite journal |last1=Sharpe |first1=M. A. |last2=Livingston |first2=A. D. |last3=Baskin |first3=D. S. |title=Thimerosal-Derived Ethylmercury is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA |doi=10.1155/2012/373678 |journal=Journal of Toxicology |volume=2012 |pages=1–12 |year=2012 |pmid=22811707 |pmc=3395253 |quote="...widely used in medical products, including as a preservative in vaccines, immunoglobulin preparations, skin test antigens, antivenins, ophthalmic and nasal products, and tattoo inks..."|doi-access=free }}</ref> In spite of the [[scientific consensus]] that fears about its safety are unsubstantiated,<ref>{{cite book|last=Immunization Safety Review Committee, Board on Health Promotion and Disease Prevention, Institute of Medicine |title=Immunization Safety Review: Vaccines and Autism |year=2004 |publisher=The National Academies Press |location=Washington, DC |isbn=978-0-309-09237-1 }}</ref><ref>{{cite journal |last1=Doja |first1=Asif |last2=Roberts |first2=Wendy |title=Immunizations and autism: a review of the literature |journal=[[Canadian Journal of Neurological Sciences|Can J Neurol Sci]] |date=November 2006 |volume=33 |issue=4 |pages=341–46 |pmid=17168158 |doi=10.1017/s031716710000528x |doi-access=free }}</ref><ref name="CDC concerns">{{Cite web |title=Vaccines Do Not Cause Autism |url=https://www.cdc.gov/vaccinesafety/concerns/autism.html |website=cdc.gov |access-date=29 November 2015 }}</ref><ref>{{cite journal |last1=Gołoś |first1=A |last2=Lutyńska |first2=A |title=Thiomersal-containing vaccines - a review of the current state of knowledge |journal=Przeglad Epidemiologiczny |date=2015 |volume=69 |issue=1 |pages=59–64, 157–61 |pmid=25862449 }}</ref> its use as a vaccine preservative was [[Thiomersal controversy|called into question]] by [[vaccine hesitancy|anti-vaccination]] groups, and it was phased out from routine childhood vaccines in the United States, the European Union, and a few other countries in response to popular fears.<ref name=drugsaf/>
The pharmaceutical corporation [[Eli Lilly and Company]] gave thiomersal the trade name '''Merthiolate'''. It has been used as a [[preservative]] in [[vaccine|vaccines]], [[immunoglobulin]] preparations, [[Allergy#Diagnosis|skin test antigens]], [[antivenin]]s, [[ophthalmology|ophthalmic]] and nasal products, and [[tattoo]] inks.<ref>{{Cite journal |last1=Sharpe |first1=M. A. |last2=Livingston |first2=A. D. |last3=Baskin |first3=D. S. |title=Thimerosal-Derived Ethylmercury is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA |doi=10.1155/2012/373678 |journal=Journal of Toxicology |volume=2012 |pages=1–12 |year=2012 |pmid=22811707 |pmc=3395253 |quote="...widely used in medical products, including as a preservative in vaccines, immunoglobulin preparations, skin test antigens, antivenins, ophthalmic and nasal products, and tattoo inks..."|doi-access=free }}</ref> In spite of the [[scientific consensus]] that fears about its safety are unsubstantiated,<ref>{{cite book|last=Immunization Safety Review Committee, Board on Health Promotion and Disease Prevention, Institute of Medicine |title=Immunization Safety Review: Vaccines and Autism |year=2004 |publisher=The National Academies Press |location=Washington, DC |isbn=978-0-309-09237-1 }}</ref><ref>{{cite journal |last1=Doja |first1=Asif |last2=Roberts |first2=Wendy |title=Immunizations and autism: a review of the literature |journal=[[Canadian Journal of Neurological Sciences|Can J Neurol Sci]] |date=November 2006 |volume=33 |issue=4 |pages=341–46 |pmid=17168158 |doi=10.1017/s031716710000528x |doi-access=free }}</ref><ref name="CDC concerns">{{Cite web |title=Vaccines Do Not Cause Autism |url=https://www.cdc.gov/vaccinesafety/concerns/autism.html |website=cdc.gov |access-date=29 November 2015 }}</ref><ref>{{cite journal |last1=Gołoś |first1=A |last2=Lutyńska |first2=A |title=Thiomersal-containing vaccines - a review of the current state of knowledge |journal=Przeglad Epidemiologiczny |date=2015 |volume=69 |issue=1 |pages=59–64, 157–61 |pmid=25862449 }}</ref> its use as a vaccine preservative has been [[Thiomersal controversy|called into question]] by [[vaccine hesitancy|anti-vaccination]] groups. Due to this public pressure the substance was phased out of routine childhood vaccines in the United States, the European Union, and a few other countries in response to popular fears.<ref name=drugsaf/> It remains in use as a preservative for annual [[Influenza vaccine|flu vaccines]].<ref>{{Cite web |last=Nast |first=Condé |date=2015-02-08 |title=Not Immune |url=https://www.newyorker.com/magazine/2015/02/16/immune-3 |access-date=2022-10-02 |website=The New Yorker |language=en-US}}</ref>


==History==
==History==

Revision as of 22:57, 2 October 2022

Thiomersal
Thiomersal
Names
IUPAC name
Ethyl(2-mercaptobenzoato-(2-)-O,S) mercurate(1-) sodium
Other names
Mercury((o-carboxyphenyl)thio)ethyl sodium salt, sodium ethylmercurithiosalicylate
Identifiers
3D model (JSmol)
8169555
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.192 Edit this at Wikidata
EC Number
  • 200-210-4
1677155
KEGG
RTECS number
  • OV8400000
UNII
  • InChI=1S/C7H6O2S.C2H5.Hg.Na/c8-7(9)5-3-1-2-4-6(5)10;1-2;;/h1-4,10H,(H,8,9);1H2,2H3;;/q;;2*+1/p-2 checkY
    Key: RTKIYNMVFMVABJ-UHFFFAOYSA-L checkY
  • InChI=1/C7H6O2S.C2H5.Hg.Na/c8-7(9)5-3-1-2-4-6(5)10;1-2;;/h1-4,10H,(H,8,9);1H2,2H3;;/q;;2*+1/p-2/rC9H10HgO2S.Na/c1-2-10-13-8-6-4-3-5-7(8)9(11)12;/h3-6H,2H2,1H3,(H,11,12);/q;+1/p-1
    Key: RTKIYNMVFMVABJ-TYXNQWANAP
  • [Na+].[O-]C(=O)c1ccccc1S[Hg]CC
Properties
C9H9HgNaO2S
Molar mass 404.81 g/mol
Appearance White or slightly yellow powder
Density 2.508 g/cm3[1]
Melting point 232 to 233 °C (450 to 451 °F; 505 to 506 K) (decomposition)
1000 g/L (20 °C)
Pharmacology
D08AK06 (WHO)
Hazards
GHS labelling:
GHS06: ToxicGHS08: Health hazardGHS09: Environmental hazard
Danger
H300, H310, H330, H373, H410
P260, P273, P280, P301, P302, P304, P310, P330, P340, P352[2]
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g. calciumSpecial hazards (white): no code
3
1
1
Flash point 250 °C (482 °F; 523 K)
Lethal dose or concentration (LD, LC):
75 mg/kg (oral, rat)[3]
Safety data sheet (SDS) External MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Thiomersal (INN), or thimerosal (USAN, JAN), is an organomercury compound. It is a well-established antiseptic and antifungal agent.

The pharmaceutical corporation Eli Lilly and Company gave thiomersal the trade name Merthiolate. It has been used as a preservative in vaccines, immunoglobulin preparations, skin test antigens, antivenins, ophthalmic and nasal products, and tattoo inks.[4] In spite of the scientific consensus that fears about its safety are unsubstantiated,[5][6][7][8] its use as a vaccine preservative has been called into question by anti-vaccination groups. Due to this public pressure the substance was phased out of routine childhood vaccines in the United States, the European Union, and a few other countries in response to popular fears.[9] It remains in use as a preservative for annual flu vaccines.[10]

History

Morris Kharasch, a chemist then at the University of Maryland filed a patent application for thiomersal in 1927;[11] Eli Lilly later marketed the compound under the trade name Merthiolate.[12] In vitro tests conducted by Lilly investigators H. M. Powell and W. A. Jamieson found that it was forty to fifty times as effective as phenol against Staphylococcus aureus.[12] It was used to kill bacteria and prevent contamination in antiseptic ointments, creams, jellies, and sprays used by consumers and in hospitals, including nasal sprays, eye drops, contact lens solutions, immunoglobulins, and vaccines. Thiomersal was used as a preservative (bactericide) so that multidose vials of vaccines could be used instead of single-dose vials, which are more expensive. By 1938, Lilly's assistant director of research listed thiomersal as one of the five most important drugs ever developed by the company.[12]

Structure

Thiomersal features mercury(II) with a coordination number 2, i.e. two ligands are attached to Hg, the thiolate and the ethyl group. The carboxylate group confers solubility in water. Like other two-coordinate Hg(II) compounds, the coordination geometry of Hg is linear, with a 180° S-Hg-C angle. Typically, organomercury thiolate compounds are prepared from organomercury chlorides.[1]

Uses

Thiomersal's main use is as an antiseptic and antifungal agent, due to the oligodynamic effect. In multidose injectable drug delivery systems, it prevents serious adverse effects such as the Staphylococcus infection that, in one 1928 incident, killed 12 of 21 children vaccinated with a diphtheria vaccine that lacked a preservative.[13] Unlike other vaccine preservatives used at the time, thiomersal does not reduce the potency of the vaccines that it protects.[12][clarification needed] Bacteriostatics such as thiomersal are not needed in single-dose injectables.[14]

In the United States, countries in the European Union, and a few other affluent countries, thiomersal is no longer used as a preservative in routine childhood vaccination schedules.[9] In the U.S., the only exceptions among vaccines routinely recommended for children are some formulations of the inactivated influenza vaccine for children older than two years.[15] Several vaccines that are not routinely recommended for young children do contain thiomersal, including DT (diphtheria and tetanus), Td (tetanus and diphtheria), and TT (tetanus toxoid); other vaccines may contain a trace of thiomersal from steps in manufacture.[13] The multi-dose versions of the influenza vaccines Fluvirin and Fluzone can contain up to 25 micrograms of mercury per dose from thiomersal.[16][17] Also, four rarely used treatments for pit viper, coral snake, and black widow venom still contain thiomersal.[18] Outside North America and Europe, many vaccines contain thiomersal; the World Health Organization has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on safety grounds to change to more expensive single-dose administration.[19] The United Nations Environment Program backed away from an earlier proposal of putting thiomersal, when used as a component in vaccines, on the list of banned compounds, in its campaign to reduce exposure to mercury worldwide.[20] Citing that eliminating the preservative in multi-dose vaccines, primarily used in developing countries, would lead to high cost and a requirement for refrigeration which the developing countries can ill afford, the UN's final decision at the Minamata Convention on Mercury in 2013 was to exclude thiomersal from the treaty.[21]

Toxicology

General toxicity

Thiomersal is very toxic by inhalation, ingestion, and in contact with skin (EC hazard symbol T+), with a danger of cumulative effects. It is also very toxic to aquatic organisms and may cause long-term adverse effects in aquatic environments (EC hazard symbol N).[22] In the body, it is metabolized or degraded to ethylmercury (C2H5Hg+) and thiosalicylate.[13]

Cases have been reported of severe mercury poisoning by accidental exposure or attempted suicide, with some fatalities.[23] Animal experiments suggest that thiomersal rapidly dissociates to release ethylmercury after injection; that the disposition patterns of mercury are similar to those after exposure to equivalent doses of ethylmercury chloride; and that the central nervous system and the kidneys are targets, with lack of motor coordination being a common sign. Similar signs and symptoms have been observed in accidental human poisonings. The mechanisms of toxic action are unknown.[23]

Fecal excretion accounts for most of the elimination from the body. Ethylmercury clears from blood with a half-life of about 18 days in adults by breakdown into other chemicals, including inorganic mercury.[24] Ethylmercury is eliminated from the brain in about 14 days in infant monkeys. Risk assessment for effects on the nervous system have been made by extrapolating from dose-response relationships for methylmercury.[25] Methylmercury and ethylmercury distribute to all body tissues, crossing the blood–brain barrier and the placental barrier, and ethylmercury also moves freely throughout the body.[26]

Concerns based on extrapolations from methylmercury caused thiomersal to be removed from U.S. childhood vaccines, starting in 1999. Since then, it has been found that ethylmercury is eliminated from the body and the brain significantly faster than methylmercury, so the late-1990s risk assessments turned out to be overly conservative.[25] Though inorganic mercury metabolized from ethylmercury has a much longer half-life in the brain, at least 120 days, it appears to be much less toxic than the inorganic mercury produced from mercury vapor, for reasons not yet understood.[25]

As an allergen

Patch test

Thiomersal is used in patch testing for people who have dermatitis, conjunctivitis, and other potentially allergic reactions. A 2007 study in Norway found that 1.9% of adults had a positive patch test reaction to thiomersal;[27] a higher prevalence of contact allergy (up to 6.6%) was observed in German populations.[28] Thiomersal-sensitive individuals can receive intramuscular rather than subcutaneous immunization,[29] though there have been no large sample sized studies regarding this matter to date. In real-world practice on vaccination of adult populations, contact allergy does not seem to elicit clinical reaction.[28]

Thiomersal allergy has decreased in Denmark, probably because of its exclusion from vaccines there.[30] In a recent study of Polish children and adolescents with chronic/recurrent eczema, positive reactions to thiomersal were found in 11.7% of children (7–8 y.o.) and 37.6% of adolescents (16–17 y.o.). This difference in the sensitization rates can be explained by changing exposure patterns: The adolescents have received six thiomersal-preserved vaccines during their life course, with the last immunization taking place 2–3 years before the mentioned study, younger children received only four thiomersal-preserved vaccines, with the last one applied five years before the study, while further immunizations were performed with new thiomersal-free vaccines.[31]

Disproven autism hypothesis

Main article: Thiomersal and vaccines

Following a review of mercury-containing food and drugs mandated in 1999, the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics asked vaccine manufacturers to remove thiomersal from vaccines as a purely precautionary measure, and it was rapidly phased out of most U.S. and European vaccines.[12][32] Many parents saw the action to remove thiomersal—in the setting of a perceived increasing rate of autism as well as increasing number of vaccines in the childhood vaccination schedule—as indicating that the preservative was the cause of autism.[12] The scientific consensus is that there is no evidence supporting these claims, and the rate of autism continues to climb despite elimination of thiomersal from routine childhood vaccines.[7][33][34][35] Major scientific and medical bodies such as the Institute of Medicine[35] and World Health Organization,[36][37] as well as governmental agencies such as the Food and Drug Administration[13] and the CDC[38] reject any role for thiomersal in autism or other neurodevelopmental disorders.[39] This controversy has caused harm due to parents attempting to treat their autistic children with unproven and possibly dangerous treatments, discouraging parents from vaccinating their children due to fears about thiomersal toxicity,[40] and diverting resources away from research into more promising areas for the cause of autism.[41] Thousands of lawsuits have been filed in a U.S. federal court to seek damages from alleged toxicity from vaccines, including those purportedly caused by thiomersal.[42]

See also

  • Nitromersol – Organomercury antiseptic and antifungal agent, a related antimicrobial
  • Phenylmercuric nitrate - an organomercury compound with powerful antiseptic and antifungal effects

References

  1. ^ a b Melnick, J. G.; Yurkerwich, K.; Buccella, D.; Sattler, W.; Parkin, G. (2008). "Molecular Structures of Thimerosal (Merthiolate) and Other Arylthiolate Mercury Alkyl Compounds". Inorg. Chem. 47 (14): 6421–26. doi:10.1021/ic8005426. PMID 18533648.
  2. ^ "Thimerosal T5125".
  3. ^ Chambers, Michael. "ChemIDplus – 54-64-8 – RTKIYNMVFMVABJ-UHFFFAOYSA-L – Thimerosal [USP:JAN] – Similar structures search, synonyms, formulas, resource links, and other chemical information". chem.sis.nlm.nih.gov. Retrieved 3 April 2018.
  4. ^ Sharpe, M. A.; Livingston, A. D.; Baskin, D. S. (2012). "Thimerosal-Derived Ethylmercury is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA". Journal of Toxicology. 2012: 1–12. doi:10.1155/2012/373678. PMC 3395253. PMID 22811707. ...widely used in medical products, including as a preservative in vaccines, immunoglobulin preparations, skin test antigens, antivenins, ophthalmic and nasal products, and tattoo inks...
  5. ^ Immunization Safety Review Committee, Board on Health Promotion and Disease Prevention, Institute of Medicine (2004). Immunization Safety Review: Vaccines and Autism. Washington, DC: The National Academies Press. ISBN 978-0-309-09237-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
  6. ^ Doja, Asif; Roberts, Wendy (November 2006). "Immunizations and autism: a review of the literature". Can J Neurol Sci. 33 (4): 341–46. doi:10.1017/s031716710000528x. PMID 17168158.
  7. ^ a b "Vaccines Do Not Cause Autism". cdc.gov. Retrieved 29 November 2015.
  8. ^ Gołoś, A; Lutyńska, A (2015). "Thiomersal-containing vaccines - a review of the current state of knowledge". Przeglad Epidemiologiczny. 69 (1): 59–64, 157–61. PMID 25862449.
  9. ^ a b Bigham, M; Copes, R (2005). "Thiomersal in vaccines: balancing the risk of adverse effects with the risk of vaccine-preventable disease". Drug Saf. 28 (2): 89–101. doi:10.2165/00002018-200528020-00001. PMID 15691220. S2CID 11570020.
  10. ^ Nast, Condé (8 February 2015). "Not Immune". The New Yorker. Retrieved 2 October 2022.
  11. ^ U.S. patent 1,672,615 "Alkyl mercuric sulphur compound and process of producing it".
  12. ^ a b c d e f Baker, JP (2008). "Mercury, Vaccines, and Autism: One Controversy, Three Histories". Am J Public Health. 98 (2): 244–53. doi:10.2105/AJPH.2007.113159. PMC 2376879. PMID 18172138.
  13. ^ a b c d "Thimerosal in vaccines". Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. 3 June 2008. Retrieved 25 July 2008.
  14. ^ "Thimerosal in Vaccines: Frequently Asked Questions". Food and Drug Administration. Retrieved 9 March 2008.
  15. ^ Coordinating Center for Infectious Diseases (26 October 2007). "Thimerosal in seasonal influenza vaccine". Centers for Disease Control and Prevention. Archived from the original on 11 April 2008. Retrieved 2 April 2008.
  16. ^ "Seasonal Influenza Vaccine Supply for the U.S. 2016-2017 Influenza Season | Seasonal Influenza (Flu) | CDC". cdc.gov. Retrieved 16 March 2017.
  17. ^ Grohskopf, Lisa A.; Sokolow, Leslie Z.; Broder, Karen R.; Olsen, Sonja J.; Karron, Ruth A.; Jernigan, Daniel B.; Bresee, Joseph S. (2016). "Prevention and Control of Seasonal Influenza with Vaccines". MMWR. Recommendations and Reports. 65 (5): 1–54. doi:10.15585/mmwr.rr6505a1. ISSN 1057-5987. PMID 27560619.
  18. ^ "Mercury in plasma-derived products". U.S. Food and Drug Administration. 9 September 2004. Archived from the original on 29 September 2007. Retrieved 1 October 2007.
  19. ^ Global Advisory Committee on Vaccine Safety (14 July 2006). "Thiomersal and vaccines". World Health Organization. Archived from the original on 20 August 2003. Retrieved 20 November 2007.
  20. ^ Hamilton, Jon (17 December 2012). "Doctors Argue Against Proposed Ban on Vaccine Preservative". NPR. Retrieved 25 February 2013.
  21. ^ Sulaski Wyckoff, Alyson (22 January 2013). "Global ban on mercury grants exception to thimerosal-containing vaccines". AAP News. American Academy of Pediatrics. Retrieved 24 August 2019.
  22. ^ "Safety data sheet, Thiomersal Ph Eur, BP, USP" (PDF). Merck. 12 June 2005. Retrieved 1 January 2010.
  23. ^ a b Clarkson, TW (2002). "The three modern faces of mercury". Environ Health Perspect. 110 (S1): 11–23. doi:10.1289/ehp.02110s111. PMC 1241144. PMID 11834460. Archived from the original on 6 September 2008.
  24. ^ Magos, L. (2003). "Neurotoxic character of thimerosal and the allometric extrapolation of adult clearance half-time to infants". Journal of Applied Toxicology. 23 (4): 263–269. doi:10.1002/jat.918. PMID 12884410. S2CID 20703489. Retrieved 19 January 2021.
  25. ^ a b c Clarkson, TW; Magos, L (2006). "The toxicology of mercury and its chemical compounds". Crit Rev Toxicol. 36 (8): 609–62. doi:10.1080/10408440600845619. PMID 16973445. S2CID 37652857.
  26. ^ Clarkson, TW; Vyas, JB; Ballatori, N (2007). "Mechanisms of mercury disposition in the body". Am J Ind Med. 50 (10): 757–64. doi:10.1002/ajim.20476. PMID 17477364.
  27. ^ Dotterud, LK; Smith-Sivertsen, T (2007). "Allergic contact sensitization in the general adult population: a population-based study from Northern Norway". Contact Dermatitis. 56 (1): 10–15. doi:10.1111/j.1600-0536.2007.00980.x. PMID 17177703. S2CID 25765635.
  28. ^ a b Uter, W; Ludwig, A; Balda, BR (2004). "The prevalence of contact allergy differed between population-based and clinic-based data". J Clin Epidemiol. 57 (6): 627–32. doi:10.1016/j.jclinepi.2003.04.002. PMID 15246132.
  29. ^ Aberer, W (1991). "Vaccination despite thimerosal sensitivity". Contact Dermatitis. 24 (1): 6–10. doi:10.1111/j.1600-0536.1991.tb01621.x. PMID 2044374. S2CID 43264826.
  30. ^ Thyssen, JP; Linneberg, A; Menné, T; Johansen, JD (2007). "The epidemiology of contact allergy in the general population – prevalence and main findings". Contact Dermatitis. 57 (5): 287–99. doi:10.1111/j.1600-0536.2007.01220.x. PMID 17937743. S2CID 44890665.
  31. ^ Czarnobilska, E; Obtulowicz, K; Dyga, W; Spiewak, R (2011). "The most important contact sensitizers in Polish children and adolescents with atopy and chronic recurrent eczema as detected with the extended European Baseline Series". Pediatr Allergy Immunol. 22 (2): 252–56. doi:10.1111/j.1399-3038.2010.01075.x. PMID 20969635. S2CID 22195669.
  32. ^ "Thimerosal in vaccines: frequently asked questions (FAQs)". Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. 7 June 2007. Retrieved 22 July 2008.
  33. ^ DeStefano, F (2007). "Vaccines and autism: evidence does not support a causal association". Clin Pharmacol Ther. 82 (6): 756–59. doi:10.1038/sj.clpt.6100407. PMID 17928818. S2CID 12872702.
  34. ^ Doja, A; Roberts, W (2006). "Immunizations and autism: a review of the literature". Can J Neurol Sci. 33 (4): 341–46. doi:10.1017/s031716710000528x. PMID 17168158.
  35. ^ a b Immunization Safety Review Committee, Board on Health Promotion and Disease Prevention, Institute of Medicine (2004). Immunization Safety Review: Vaccines and Autism. Washington, DC: The National Academies Press. ISBN 978-0-309-09237-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
  36. ^ World Health Organization (2006). "Thiomersal and vaccines: questions and answers". Archived from the original on 12 October 2003. Retrieved 19 May 2009.
  37. ^ WHO. "Statement on thiomersal". www.who.int. Archived from the original on 29 October 2012. Retrieved 3 April 2018.
  38. ^ Centers for Disease Control (8 February 2008). "Mercury and vaccines (thimerosal)". Archived from the original on 18 April 2018. Retrieved 19 May 2009.
  39. ^ Sugarman, SD (2007). "Cases in vaccine court – legal battles over vaccines and autism". N Engl J Med. 357 (13): 1275–77. doi:10.1056/NEJMp078168. PMID 17898095.
  40. ^ Harris, G; O'Connor, A (25 June 2005). "On autism's cause, it's parents vs. research". New York Times. Retrieved 11 March 2016.
  41. ^ Offit, PA (2007). "Thimerosal and vaccines – a cautionary tale". N Engl J Med. 357 (13): 1278–79. doi:10.1056/NEJMp078187. PMID 17898096.
  42. ^ Autism cases in vaccine court:
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