Thimerosal

from Wikipedia, the free encyclopedia
Structural formula
Structure of thimerosal
General
Non-proprietary name Thimerosal
other names
  • THIMEROSAL ( INCI ) ( USP )
  • Merfamin
  • Merthiolate
  • Sodium 2- (ethylmercurithio) benzoate
  • Mercury ethyl sodium thiosalicylate
  • 2- (Ethylmercuriosulfanyl) benzoic acid sodium salt
Molecular formula C 9 H 9 HgNaO 2 S
Brief description

beige odorless powder

External identifiers / databases
CAS number 54-64-8
EC number 200-210-4
ECHA InfoCard 100,000.192
PubChem 16682923
ChemSpider 10772045
DrugBank DB11590
Wikidata Q411046
Drug information
ATC code

D08 AK06

Drug class

antiseptic

properties
Molar mass 404.81 g · mol -1
Physical state

firmly

density

0.5 g cm −3

Melting point

234 ° C (decomposition)

solubility

easy in water (1000 g l −1 at 20 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary
06 - Toxic or very toxic 08 - Dangerous to health 09 - Dangerous for the environment

danger

H and P phrases H: 300 + 310 + 330-373-410
P: 260-273-280-301 + 310 + 330-302 + 352-310-304 + 340 + 310
Toxicological data

75 mg kg −1 ( LD 50 ,  mouse ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Thimerosal (also: Thimerosal in US space) is the sodium salt of an organic mercury compound , used as a preservative in cosmetic and pharmaceutical products, in order to protect against microbial spoilage. It is effective even in very low concentrations. The minimum inhibitory concentration is 0.2 micrograms per milliliter (e.g. against Staphylococcus aureus ) to 128 micrograms per milliliter (e.g. against Aspergillus niger ) , depending on the germ . Thimerosal has a broad spectrum of activity, but is not effective against spore-forming germs.

It was synthesized by Morris S. Kharasch and patented in 1928.

Extraction and presentation

Thiomersal is synthesized by reacting thiosalicylic acid with ethyl mercury chloride in the presence of sodium hydroxide solution.

Mechanism of action

Thimerosal is metabolized in the organism to thiosalicylate and ethyl mercury. The ethyl mercury cation blocks the activity of enzymes by binding to thiol groups in the protein structures . This results in the antimicrobial effect in low doses and a neurotoxic and kidney toxic effect ( neurotoxicity , nephrotoxicity ) in high doses . Depending on the pH value, thimerosal kills bacteria ( bactericidal ) or inhibits the growth of bacteria and fungi ( bacteriostatic and fungistatic ).

The metabolically formed ethyl mercury has a half-life of 3 to 7 days in the human body - in the blood . It is excreted in the stool. Ethyl mercury does not accumulate in the blood; the original blood values ​​are restored within 30 days.

Use in cosmetics

In the EU, according to Regulation (EC) No. 1223/2009, thimerosal is permitted in concentrations of up to 0.007% (calculated as mercury) for the preservation of eye products.

Use in tattoo ink

Thimerosal can also be found in tattoo inks as a preservative .

Use in medical devices

Thimerosal is used to preserve cleaning and storage solutions for contact lenses . A number of hypersensitivity reactions have been reported in contact lens wearers who have used thimerosal-containing care products on their lenses.

Use in medicines

Medicinal products for external use

Thimerosal can be used to preserve eye drops in multi-dose containers, for which preservation is mandatory, of nose and ear drops and of topical preparations. The concentration range is between 0.001% and 0.01% depending on the dosage form. As an active ingredient for disinfecting rinsing solutions (in concentrations of around 0.1%), thimerosal no longer plays a role due to its toxicity in higher doses and its environmental pollution.

Injection drugs

Injection drugs can also be preserved with thiomersal . In particular, vials for multiple withdrawal of an injection dose make preservation imperative due to legal regulations. That is why preparations for pre-pandemic and pandemic vaccinations (ie special vaccines in the event of a pandemic, such as influenza vaccines , "swine flu" vaccines ) sometimes contain thimerosal; namely when they are filled in multi-dose containers. If the vials were pierced several times, germs could get into them, the multiplication of which is suppressed by thiomersal. Under certain circumstances, however, preservation may also be necessary for single dosage forms that cannot be sterilized using standard methods.

At the end of the 1990s, doubts arose about the harmlessness of thimerosal: on the one hand due to the increasing number of reports of undesirable effects , in particular hypersensitivity reactions, and on the other hand because of the accumulated mercury exposure of children through routine child vaccinations, due to which neurological disorders such as e.g. B.  Autism were feared. As a precautionary measure, the authorities in the USA and Europe recommended that thimerosal and other organic mercury compounds should be removed from vaccines for infants and young children as far as possible without any specific evidence of neurological toxicity. Since 2002, vaccines that do not contain thimerosal have only been used in children under the age of six in the USA. Overall, in the US, all single-dose vaccines no longer contain thimerosal as a preservative additive. Two of these vaccines, a Td vaccine and a flu vaccine, contain traces of thiomersal (less than 1 μg thiomersal per dose) due to the manufacturing process (as of 2018) - for comparison: the amount of thiomersal in multi-dose containers is around 25 μg thiomersal per dose.

In 2004 the Committee of the European Medicines Agency revised the evaluation of thimerosal in vaccines. The evaluation of epidemiological studies had led to the conclusion that there was no connection between neurodevelopmental disorders and thimerosal in vaccines. Nevertheless, the development of vaccines without mercury-containing auxiliaries should continue, also for ecological reasons. The agency emphasized that the benefits of vaccinations far outweigh the theoretical risks of thiomersal.

After an evaluation of several pharmacokinetic and epidemiological studies as well as the evaluation of a risk model, the Advisory Committee on Vaccination Safety of the WHO also confirmed in 2012 that the amounts of thimerosal used in vaccinations do not reach toxic values ​​even in premature infants and babies with low birth weights, which means neurodegenerative damage Thiomersal are implausible.

As a result of technical progress, aseptic production has been improved in such a way that single-dose formulations can be produced without preservatives. As of 2020, all vaccines approved in Germany - with the exception of the pandemic vaccines mentioned in multi-dose containers - are therefore free of thimerosal.

Thimerosal is still used in animal vaccines.

Labelling

Medicinal products containing thiomersal must include warnings about possible hypersensitivity reactions and sensitizations in the package insert, the instructions for use and the label.

Allergies

Vaccinations with vaccines containing thiomersal can cause contact allergies. In many cases the benefit of the vaccination is far greater than the low risk of a contact allergic reaction at the vaccination site. In addition, a comparison of patients with a positive skin test for thiomersal showed that they do not have any more vaccine reactions than in a control group with patients with a negative skin test.

controversy

Thimerosal has been linked to the occurrence of autism by some scientists, vaccine opponents, and some parents of autistic children - especially in the United States. Based on epidemiological studies, a connection between thimerosal and the occurrence of autism is now considered disproved. Numerous scientific and medical institutions, such as the FDA , the Public Health Agency of Canada, and the American Medical Association, followed suit .

The Robert Koch Institute writes about the connection between thimerosal and autism in children alleged by two US doctors:

"The World Health Organization WHO , the US Institute of Medicine , and the European Medicines Agency have now independently come to the conclusion that the available studies speak against such a connection."

In addition, if thimerosal in vaccines had been omitted from vaccines, the number of diagnosed cases of autism in children should have decreased or decreased if the thimerosal in vaccines had actually had something to do with the occurrence of autism - but this did not happen.

Individual evidence

  1. ↑ Entry on THIMEROSAL in the CosIng database of the EU Commission, accessed on May 11, 2020.
  2. ↑ a b c d e f Entry on sodium 2- (ethylmercurithio) benzoate in the GESTIS substance database of the IFA , accessed on February 22, 2017(JavaScript required) .
  3. ↑ Not explicitly listed in Regulation (EC) No. 1272/2008 (CLP) , but with the specified labeling it falls under the group entry organic compounds of mercury with the exception of those specified elsewhere in this Annex in the Classification and Labeling Inventory of the European Chemicals Agency ( ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
  4. ^ Entry on thiomersal in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  5. ↑ a b c Handbook of Pharmaceutical Excipients, 5th Edition (2006). Ray C. Rowe (Editor), Paul J. Sheskey (Editor), PJ Weller (Editor).
  6. ↑ Patent US1672615 : Alkyl mercuric sulfur compound and process of producing it. Published June 29, 1927 , inventor: Kharasch Morris Selig. ‌
  7. ↑ a b c WHO (Ed.): Weekly epidemiological record . tape 87 , no. 30 , July 27, 2012, p. 277-288 ( who.int [PDF]).
  8. ↑ Annex V Regulation (EG) No. 1223/2009
  9. ↑ Thiomersal - an overview | ScienceDirect Topics. Retrieved January 10, 2020 .
  10. ↑ Dr Thomas Schmitz and Sven Siebert: Plain text: Vaccination! - An educational book to protect our health . 1st edition. HarperCollins, 2019, ISBN 978-3-95967-884-1 , pp. 56 .
  11. ↑ Thiomersal keratoconjunctivitis, frequency, clinical spectrum and diagnosis. N. Wilson-Holt N, JK Dart in: Eye 1989; 3 (Pt 5): 581-7. PMID 2630335 Immunological complications of soft contact lenses. BJ Mondino et al. in: J Am Optom Assoc. 1987 Oct; 58 (10): 832-5. PMID 3316352 Allergic and toxic reactions of soft contact lens wearers. BJ Mondino et al. in: Surv Ophthalmol. 1982 May-Jun; 26 (6): 337-44. PMID 6810487 Allergic reactions to contact lens solutions. AA Fisher in: Cutis. 1985 Sep; 36 (3): 209-11. PMID 3931986 .
  12. ↑ Paul Ehrlich Institute : Technical information for doctors and pharmacists: Pandemic vaccines in pregnancy ( Memento from March 16, 2010 in the Internet Archive ), s. Section 3.3.1 Other substances .
  13. ↑ Statement by the European Medicines Agency on medicinal products containing thimerosal , July 1999 (English, PDF; 28 kB).
  14. ↑ Thimerosal in Vaccines Thimerosal | Concerns | Vaccine Safety | CDC. December 12, 2018. Retrieved January 6, 2019 (American English).
  15. ↑ Timeline: Thimerosal in Vaccines (1999-2010) Thimerosal | Concerns | Vaccine Safety | CDC. December 12, 2018. Retrieved January 6, 2019 (American English).
  16. ↑ a b FDA (ed.): Thimerosal and Vaccines . February 1, 2018 ( fda.gov [accessed January 10, 2020]).
  17. ↑ Statement by the European Medicines Agency on the use of thiomersal in vaccines for use on humans (PDF; 100 kB) March 2004 (English).
  18. ↑ Alice Echtermann: No, flu vaccines in Germany do not contain mercury. In: corrective . October 11, 2019, accessed March 4, 2020 .
  19. ↑ PEI vaccination and mercury / thiomersal - answers to critical questions. Retrieved November 29, 2018 .
  20. ↑ Database on Allergology. ( online ).
  21. ↑ J. Liese and M. Prelog: Vaccinations and allergies . In: Heinz Spiess, Ulrich Heininger, Wolfgang Jilg (Eds.): Impfkompendium . 8th edition. Georg Thieme Verlag, 2015, ISBN 978-3-13-498908-3 , p. 311 .
  22. ↑ K. Weisser, K. Bauer, P. Volkers and B. Keller-Stanislawski (2004): Thiomersal and vaccinations. In: Federal Health Gazette - Health Research - Health Protection . Vol. 47, pp. 1165-1174. doi: 10.1007 / s00103-004-0943-z . Full text ( memento of April 21, 2017 in the Internet Archive ) on the PEI website.
  23. ↑ Statement on thiomersal , WHO, 2006.
  24. ↑ Thomas Verstraeten et al .: Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases . In: Pediatrics . tape 112 , no. 5 , November 2003, p. 1039-1048 , PMID 14595043 .
  25. ↑ Anders Hviid et al .: Association between thimerosal-containing vaccine and autism . In: JAMA . tape 290 , no. 13 , October 1, 2003, p. 1763-1766 , doi : 10.1001 / jama.290.13.1763 , PMID 14519711 .
  26. ↑ Eric Fombonne et al .: Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations . In: Pediatrics . tape 118 , no. 1 , July 2006, p. e139-150 , doi : 10.1542 / peds.2005-2993 , PMID 16818529 .
  27. ↑ Michael Shevell and Eric Fombonne: Autism and MMR vaccination or thimerosal exposure: an urban legend? In: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques . tape 33 , no. 4 , November 2006, pp. 339-340 , doi : 10.1017 / s0317167100005278 , PMID 17168157 .
  28. ^ F. DeStefano: Vaccines and autism: evidence does not support a causal association . In: Clinical Pharmacology and Therapeutics . tape 82 , no. 6 , December 2007, pp. 756-759 , doi : 10.1038 / sj.clpt.6100407 , PMID 17928818 .
  29. ↑ Deutscher Ärzteverlag GmbH, editorial office of Deutsches Ärzteblatt: No developmental damage to children due to thimerosal in vaccines. September 27, 2007, accessed January 6, 2019 .
  30. ↑ Thimerosal in vaccines . Center for Biologics Evaluation and Research, US Food and Drug Administration. September 6, 2007. Retrieved October 1, 2007.
  31. ↑ National Advisory Committee on Immunization: Thimerosal: updated statement. An Advisory Committee Statement . In: Can Commun Dis Rep . 33, No. ACS-6, 2007, pp. 1-13. PMID 17663033 .
  32. ^ American Medical Association : AMA Welcomes New IOM Report Rejecting Link Between Vaccines and Autism . May 18, 2004. Retrieved July 23, 2007.
  33. ↑ Robert Koch Institute in Vaccinations - 20 Objections and Answers from the Robert Koch Institute and the Paul Ehrlich Institute .
  34. ↑ Lindzi Wessel: Vaccine myths . In: Science . tape 356 , no. 6336 , April 28, 2017, p. 368-372 , doi : 10.1126 / science.356.6336.368 , PMID 28450594 .

See also

Web links