Thiomersal 221998 223658177 2008-07-05T03:18:54Z Eubulides 3573537 /* Autism */ Undo previous change, which was not supported by source. Source says "some doctors and scientists" and "many parents fervently believe there is a connection". It does not say "fringe". {{Chembox new | Name = Thiomersal | ImageFile = Thiomersal-2D-skeletal.png | ImageSize = 170px | ImageName = Thiomersal | ImageFile2 = Thiomersal-from-xtal-3D-balls.png | IUPACName = Ethyl(2-mercaptobenzoato-(2-)-O,S)<br />mercurate(1-) sodium | OtherNames = Mercury((o-carboxyphenyl)thio)ethyl sodium salt | Name = Thiomersal | Section1 = {{Chembox Identifiers | CASNo = 54-64-8 | RTECS = OV8400000 | EINECS = 200-210-4 }} | Section2 = {{Chembox Properties | Formula = [[carbon|C]]<sub>9</sub>[[hydrogen|H]]<sub>9</sub>[[Mercury (element)|Hg]][[sodium|Na]][[Oxygen|O]]<sub>2</sub>[[sulfur|S]] | MolarMass = 404.81 g/mol | Appearance = White or slightly yellow powder | Density = 500 kg/m³ | Solubility = 1000 g/l (20°C) | MeltingPt = 232&ndash;233°C (decomposition) | BoilingPt = | pKa = }} | Section4 = {{Chembox Thermochemistry | DeltaHf = }} | Section7 = {{Chembox Hazards | EUClass = | NFPA-H = 3 | NFPA-F = 1 | NFPA-R = 1 | RPhrases = {{R26/27/28}}{{R33}}{{R50/53}} | SPhrases = {{S13}}{{S28}}{{S36}}{{S45}}{{S60}}{{S61}} | FlashPt = 250°C | ExternalMSDS = [http://www.conncoll.edu/offices/envhealth/MSDS/neuroscience/thimerosal.pdf External MSDS] }} }} '''Thiomersal''' ([[International Nonproprietary Name|INN]]) (C<sub>9</sub>H<sub>9</sub>HgNaO<sub>2</sub>S), 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 1928 by the pharmaceutical corporation [[Eli Lilly and Company]] and has been used as a [[preservative]] in [[vaccine]]s, [[immunoglobulin]] preparations, [[Allergy#Diagnosis|skin test antigens]], [[antivenin]]s, [[ophthalmology|ophthalmic]] and nasal products, and [[tattoo]] inks. In the U.S., the [[European Union]], and a few other affluent countries, the compound is being phased out from vaccines routinely given to children.<ref name="drugsaf"/> Packaging the vaccines in single-dose vials eliminates the need for [[bacteriostatic]]s such as thiomersal.<ref>[http://www.fda.gov/cber/vaccine/thimfaq.htm Thimerosal in Vaccines: Frequently Asked Questions], from the [[United States Food and Drug Administration]]. Accessed [[March 9]] [[2008]].</ref> ==Use== Thiomersal's main use is as an antiseptic and antifungal agent. 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 [[inoculate]]d with a [[diphtheria]] vaccine that lacked a preservative.<ref name=T-in-vaccines/> Unlike other vaccine preservatives used at the time, thiomersal does not reduce the potency of the vaccines that it protects.<ref name=Baker>{{cite journal |journal= Am J Public Health |date=2008 |title= Mercury, vaccines, and autism: one controversy, three histories |author= Baker JP |doi=10.2105/AJPH.2007.113159 |pmid=18172138 |volume=98 |issue=2 |pages=244–53}}</ref> Thiomersal is not needed in more-expensive single-dose injectables. In the U.S., the European Union, and a few other affluent countries, thiomersal is no longer used as a preservative in routine childhood [[vaccination schedule]]s.<ref name="drugsaf">{{cite journal |journal= Drug Saf |year=2005 |volume=28 |issue=2 |pages=89–101 |title= Thiomersal in vaccines: balancing the risk of adverse effects with the risk of vaccine-preventable disease |author= Bigham M, Copes R |pmid=15691220 |doi= 10.2165/00002018-200528020-00001}}</ref> 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.<ref>{{cite web |title= Thimerosal in seasonal influenza vaccine |url=http://cdc.gov/FLU/ABOUT/QA/thimerosal.htm |date=2007-10-26 |accessdate=2008-04-02 |author= Coordinating Center for Infectious Diseases |publisher= Centers for Disease Control and Prevention}}</ref> 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.<ref name=T-in-vaccines>{{cite web |date=[[2007-09-06]] |url=http://www.fda.gov/cber/vaccine/thimerosal.htm |accessdate=2007-10-01 |title= Thimerosal in vaccines |publisher= Center for Biologics Evaluation and Research, U.S. Food and Drug Administration}}</ref> Also, four rarely used treatments for pit viper, coral snake, and black widow venom still contain thiomersal.<ref>{{cite web |date=[[2004-09-09]] |url=http://www.fda.gov/cber/blood/mercplasma.htm |accessdate=2007-10-01 |title= Mercury in plasma-derived products |publisher= U.S. Food and Drug Administration}}</ref> 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.<ref>{{cite web |title= Thiomersal and vaccines |author= Global Advisory Committee on Vaccine Safety |publisher= World Health Organization |url=http://www.who.int/vaccine_safety/topics/thiomersal/en/index.html |date=[[2006-07-14]] |accessdate=2007-11-20}}</ref> ==Toxicology== 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).<ref>{{cite web |url=http://chemdat.merck.de/documents/sds/emd/int/en/8170/817043.pdf |format=PDF |date=[[2005-06-12]] |accessdate=2007-10-01 |publisher=Merck |title= Thiomersal Ph Eur, BP, USP material safety data sheet}}</ref> In the body, it is metabolized or degraded to [[ethylmercury]] (C<sub>2</sub>H<sub>5</sub>Hg<sup>+</sup>) and thiosalicylate.<ref name=T-in-vaccines/> Few studies of the toxicity of thiomersal in humans have been performed. 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. 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.<ref name=Clarkson>Toxicology of thiomersal: *{{cite journal |journal=Environ Health Perspect |year=2002 |volume=110 |issue=S1 |pages=11–23 |title= The three modern faces of mercury |author= Clarkson TW |pmid=11834460 |url=http://www.ehponline.org/members/2002/suppl-1/11-23clarkson/clarkson-full.html}} *{{cite journal |journal= Crit Rev Toxicol |year=2006 |volume=36 |issue=8 |pages=609–62 |title= The toxicology of mercury and its chemical compounds |author= Clarkson TW, Magos L |doi=10.1080/10408440600845619 |pmid=16973445}}</ref> 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 turned out to be overly conservative.<ref name=Clarkson/> A 2008 study found that the half-life of blood mercury after vaccination averages 3.7 days for newborns and infants, much shorter than the 44 days for methylmercury.<ref>{{cite journal |journal=Pediatrics |date=2008 |volume=121 |issue=2 |pages=e208–14 |title= Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines |author= Pichichero ME, Gentile A, Giglio N ''et al.'' |doi=10.1542/peds.2006-3363 |pmid=18245396 |url=http://pediatrics.aappublications.org/cgi/content/full/121/2/e208 |laysource= University of Rochester Medical Center |laydate=2008-01-30 |laysummary=http://www.urmc.rochester.edu/pr/news/story.cfm?id=1848}}</ref> ===Allergies=== 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;<ref>{{cite journal |journal= Contact Dermatitis |year=2007 |volume=56 |issue=1 |pages=10–5 |title= Allergic contact sensitization in the general adult population: a population-based study from Northern Norway |author= Dotterud LK, Smith-Sivertsen T |doi=10.1111/j.1600-0536.2007.00980.x |pmid=17177703}}</ref> a higher prevalence of contact allergy (up to 6.6%) was observed in German populations.<ref name=Uter>{{cite journal |journal= J Clin Epidemiol |year=2004 |volume=57 |issue=6 |pages=627–32 |title= The prevalence of contact allergy differed between population-based and clinic-based data |author= Uter W, Ludwig A, Balda BR |doi=10.1016/j.jclinepi.2003.04.002 |pmid=15246132}}</ref> Thiomersal-sensitive individuals can receive [[Intramuscular injection|intramuscular]] rather than [[subcutaneous]] immunization,<ref>{{cite journal |journal= Contact Dermatitis |year=1991 |volume=24 |issue=1 |pages=6–10 |title= Vaccination despite thimerosal sensitivity |author= Aberer W |doi=10.1111/j.1600-0536.1991.tb01621.x |pmid=2044374}}</ref> so contact allergy is usually clinically irrelevant.<ref name=Uter/> Thiomersal allergy has decreased in Denmark, probably because of its exclusion from vaccines there.<ref>{{cite journal |journal= Contact Dermatitis |date=2007 |volume=57 |issue=5 |pages=287–99 |title= The epidemiology of contact allergy in the general population—prevalence and main findings |author= Thyssen JP, Linneberg A, Menné T, Johansen JD |doi=10.1111/j.1600-0536.2007.01220.x |pmid=17937743 |url=http://www.blackwell-synergy.com/doi/full/10.1111/j.1600-0536.2007.01220.x}}</ref> ===Autism=== {{main|Thiomersal controversy}} Many parents, and some scientists and doctors, believe there is a connection between thiomersal and [[autism]].<ref name=Sugarman/> More than 5,000 U.S. families have filed claims alleging autism was caused by vaccines, most implicating thiomersal; the majority of these claims are still being adjudicated, and no awards have been issued.<ref name=Sugarman>{{cite journal |journal= N Engl J Med |year=2007 |volume=357 |issue=13 |pages=1275–7 |title= Cases in vaccine court—legal battles over vaccines and autism |author= Sugarman SD |pmid=17898095 |url=http://content.nejm.org/cgi/content/full/357/13/1275 |doi= 10.1056/NEJMp078168}}</ref> Although there is no [[Evidence-based medicine|convincing evidence]] that thiomersal is a factor in the onset of autism, parents may first become aware of autistic symptoms in their child around the time of a routine [[vaccination]], and parental concern about vaccines has led to a decreasing uptake of [[childhood immunizations]] and an increasing likelihood of [[Measles#Public health|measles outbreaks]].<ref>Vaccines and autism: *{{cite web |title= Thimerosal in vaccines |publisher= Center for Biologics Evaluation and Research, U.S. Food and Drug Administration |url=http://www.fda.gov/CBER/vaccine/thimerosal.htm |date=2008-03-14 |accessdate=2008-03-21}} *{{cite journal |journal= Can J Neurol Sci |date=2006 |volume=33 |issue=4 |pages=341–6 |title= Immunizations and autism: a review of the literature |author= Doja A, Roberts W |pmid=17168158}} *{{cite journal |journal= Child Care Health Dev |year=2006 |volume=32 |issue=5 |pages=511–9 |title= Vaccines and the changing epidemiology of autism |author= Taylor B |doi=10.1111/j.1365-2214.2006.00655.x |pmid=16919130}}</ref> ==History== [[Morris S. Kharasch]], a [[chemist]] at the [[University of Maryland, College Park|University of Maryland]], filed a patent application for thiomersal in 1927;<ref>{{cite patent|US|1672615}}</ref> Eli Lilly was granted the patent for the compound under the trade name Merthiolate in 1928.<ref name=Baker/> [[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]]''.<ref name=Baker/> 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.<ref name=Baker/> Thiomersal's safety for its intended uses first came under question in the 1970s, when case reports demonstrated potential for neurotoxicity when given in large volumes as a topical antiseptic. At the time, the [[DPT vaccine]] was the only childhood vaccine that contained it; a 1976 [[FDA]] review concluded that this use of thiomersal was not dangerous.<ref name=Baker/> Concerns about mercury arising from [[Minamata disease]] and other cases of [[methylmercury]] poisoning led U.S. authorities to lower reference doses for methylmercury in the 1990s, about the same time that autism diagnoses began rising sharply. In 1999, a new FDA analysis concluded that infants could receive as much as 187.5 mg of ethylmercury during the first six months; lacking any standard for ethylmercury, it used methylmercury-based standards to recommend that thiomersal be removed from routine childhood vaccines in the U.S., which was done by 2001.<ref name=Baker/> Some parents of autistic children adopted thiomersal as an explanation for the increase in reported autism cases and sued vaccine makers; the mercury-autism hypothesis is accepted widely among parents of autistic children, despite scientific studies rejecting it.<ref name=Baker/> ==References== {{reflist|2}} {{vaccines}} {{Antiseptics and disinfectants}} [[Category:Mercury compounds]] [[Category:Carboxylic acids]] [[Category:Thiols]] [[Category:Eli Lilly and Company]] [[de:Thiomersal]] [[fr:Thiomersal]] [[it:Thimerosal]] [[nl:Thimerosal]] [[pl:Thiomersal]] [[pt:Timerosal]] [[ru:Мертиолят]] [[fi:Tiomersaali]] [[tr:Thiomersal]]