Information about Thiomersal

Thiomersal
IUPAC name	Ethyl(2-mercaptobenzoato-(2-)-O,S) mercurate(1-) sodium
Other names	Mercury((o-carboxyphenyl)thio)ethyl sodium salt
Identifiers
CAS number	54-64-8
EINECS number	200-210-4
RTECS number	OV8400000
Properties
Molecular formula	C9H9HgNaO2S
Molar mass	404.81 g/mol
Appearance	White or slightly yellow powder
Density	500 kg/m³
Melting point	232 - 233 °C (decomposition)
Solubility in water	1000 g/l (20 °C)
Hazards
MSDS	External MSDS
NFPA 704	1 3 1
R-phrases	R26/27/28R33R50/53
S-phrases	S13S28S36S45S60S61
Flash point	250 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 C, 100 kPa)

Thiomersal (INN) (C₉H₉HgNaO₂S), formerly and still commonly known in the United States as thimerosal, is an organomercury compound (approximately 49% mercury by weight) used as an antiseptic and antifungal agent.

It was developed and registered under the trade name Merthiolate in 1929 by the pharmaceutical company Eli Lilly and Company, and has been used as a preservative in vaccines, immune globulin preparations, skin test antigens, antivenins, ophthalmic and nasal products, and tattoo inks.

The compound has been phased out from most childhood vaccinations in Europe and North America. Packaging the vaccines in single-dose vials eliminates the need for bacteriostatics such as thiomersal.

Use

Thiomersal's main use is as an antiseptic and antifungal agent. In multi-dose injectable drug delivery systems, it prevents serious adverse effects such as the Staphylococcus infection that in one 1928 incident killed 12 of 21 children inoculated with an diphtheria vaccine that lacked a preservative.^[] It is not needed in more-expensive single-dose injectables.

In North America and Europe, thiomersal is no longer used as a preservative in most vaccines and other medications. In the U.S., the only exceptions among vaccines routinely recommended for young children are most formulations of the inactivated influenza vaccine. Several vaccines not routinely recommended for young children contain thimerosal, 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.^[0] Also, four rarely-used treatments for pit viper, coral snake, and black widow venom still contain thimerosal.^[2] Outside North America and Europe, many vaccines contain thiomersal; the World Health Organization has concluded that there is no evidence of harm from thimerosal in vaccines and no reason to change to more-expensive single-dose administration.^[3]

Toxicology

Thiomersal is very toxic by inhalation, ingestion, and in contact with skin (EC hazard symbol T+), with 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).^[4] In the body, it is metabolized or degraded to ethylmercury (C₂H₅Hg⁺) and thiosalicylate.^[0]

Few studies of the toxicity of thiomersal in humans have been performed. Animal experiments suggest that thimerosal 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. Fecal excretion accounts for most of the elimination from the body. Ethylmercury clears from blood with a half-time of about 18 days, and from the brain in about 14 days. Inorganic mercury metabolized from ethylmercury has a much longer clearance, at least 120 days; it appears to be much less toxic than the inorganic mercury produced from mercury vapor, for reasons that are not understood.^[5] Risk assessment for effects on the nervous system have been made by extrapolating from dose-response relationships for methylmercury, which is why thiomersal was removed from U.S. childhood vaccines starting in 1999. However, since then it has been found that ethylmercury is cleared from the body and the brain significantly faster than methylmercury, so the late-1990s risk assessments were overly conservative.^[5]

Allergies

Thiomersal is used in patch testing for people who have dermatitis, conjunctivitis and other potentially allergic reaction. A 2007 study in Norway found that 1.9% of adults had a positive patch test reaction to thiomersal.^[6] A higher prevalence of contact allergy (up to 6.6%) was observed in German populations. It is usually clinically irrelevant;^[7] thiomersal-sensitive individuals can receive intramuscular rather than subcutaneous immunization.^[8]

Autism

Main article: Thiomersal controversy

Some doctors and scientists, and many parents, believe there is a connection between thiomersal and autism. More than 5000 U.S. families have filed claims alleging autism was caused by vaccines, most implicating thiomersal; most claims are still being adjudicated and no awards have been given.^[9] There is no convincing evidence that thiomersal helps cause autism, but parents may first become aware of autistic symptoms in their child around the time of a routine vaccination, and parental concern has led to a decreasing uptake of childhood immunizations and the increasing likelihood of measles outbreaks.^[10]

History

Thiomersal was developed by Dr. Morris S. Kharasch, a chemist and Eli Lilly and Company fellow at the University of Maryland and then at the University of Chicago.

A patent for the alkyl mercuric sulfur compound, which was felt to have possibilities as an antiseptic and antibacterial product, was filed in the 1920s. Eli Lilly and Company registered the compound under the trade name Merthiolate in 1929. It was used to kill bacteria and prevent contamination in antiseptic ointments, creams, jellies, and sprays used by consumers and in hospitals. Thiomersal was used in many such products (e.g. nasal sprays, eye drops, contact lens solutions, immunoglobulins, and vaccines).

Thiomersal was first put in vaccines in 1931 by Eli Lilly Corporation and used as a preservative (bactericide) so multi-dose vials of vaccines could be used instead of single dose vials, which are more expensive.

References

•  • [ e] Vaccination/Vaccine (and Immunization, Inoculation. See also List of vaccine topics and Epidemiology)
Development	Adjuvants • Cancer vaccines • DNA vaccination • HIV • Live vector vaccine • Models • Timeline • Trial
Administration	ACIP • GAVI • VAERS • Vaccine court • Vaccination policy • Vaccination schedule • VSD
Live vaccines	Anthrax • BCG • Flu • MMR • MMRV • Polio(OPV) • Smallpox • Varicella
Inactivated/toxoid vaccines	inactivated virus: Flu • HAV • Polio(IPV) •• inactivated bacteria/toxoid: DPwT •• conjugate: Hib • PCV
Other vaccines	subunit: Anthrax • DPaT • HPV •• recombinant DNA: HBV •• other: Anthrax • PPV
Controversy	A-CHAMP • Controversy • NCVIA • Pox party • Safe Minds • Simpsonwood • Thiomersal • Vaccine injury

•  • [ e] Antiseptics and disinfectants (D08)
Acridine derivatives	Ethacridine lactate - Aminoacridine - Euflavine
Biguanides and amidines	Dibrompropamidine - Chlorhexidine - Propamidine - Hexamidine - Polihexanide
Phenol and derivatives	Hexachlorophene - Policresulen - Phenol - Triclosan - Chloroxylenol - Biphenylol
Nitrofuran derivatives	Nitrofurazone
Iodine products	Iodine/octylphenoxypolyglycolether - Povidone-iodine - Diiodohydroxypropane
Quinoline derivatives	Dequalinium - Chlorquinaldol - Oxyquinoline - Clioquinol
Quaternary ammonium compounds	Benzalkonium - Cetrimonium - Cetylpyridinium - Cetrimide - Benzoxonium chloride - Didecyldimethylammonium chloride
Mercurial products	Mercuric amidochloride - Phenylmercuric borate - Mercuric chloride - Mercurochrome - Thiomersal - Mercuric iodide
Silver compounds	Silver nitrate
Others	Hydrogen peroxide - Eosin - Propanol - Tosylchloramide sodium - Isopropanol - Potassium permanganate - Sodium hypochlorite - Ethanol