Thimerisol

Thimerosal/thimerisol is an organomercury compound used as an antifulgal and antiseptic agent. It is most commonly used in vaccines, nasal products, skin test antigens, tattoo inks, and certain kinds of makeup such as mascara. It is made up of mercury a thiolate and an ethyl group (coordinated), along with a carboxylate group uncoordinated which confers solubility in water. Thimerisol is one of the most common allergies, and is toxic by inhalation, ingestion, and contact with skin. It has also recently been linked with autism and it has been taken out of eye products such as eye drops, and many other antiseptics since it has been found to be toxic. 

Use in Life
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;a higher prevalence of contact allergy (up to 6.6%) was observed in German populations.Thiomersal-sensitive individuals can receive intramuscular rather than subcutaneous immunization,so contact allergy is usually clinically irrelevant.Thiomersal allergy has decreased in Denmark, probably because of its exclusion from vaccines there.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 5 years before the study, while further immunizations were performed with new thiomersal-free vaccines.

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 is not coordinated, but confers solubility in water. Like other two-coordinate Hg(II) compounds, the coordination geometry is linear, with a 180° S-Hg-C angle. Typically, organomercury thiolate compounds are prepared from organomercury chlorides.[2]

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). In the body, it is metabolized or degraded to ethylmercury (C2H5Hg+) and thiosalicylate.

Few studies of the toxicity of thiomersal in humans have been performed. Cases have been reported of severe poisoning by accidental exposure or attempted suicide, with some fatalities. 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-life of about 18 days in adults. 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. Methylmercury and ethylmercury distributes to all body tissues, crossing the blood-brain barrier and the placental barrier, and ethylmercury also moves freely throughout the body.] 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. 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.

History
Morris Kharasch, a chemist at the University of Maryland, filed a patent application for thiomersal in 1927; Eli Lilly later marketed the compound under the trade name Merthiolate 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 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.



Thimerisol is a mercury-containing organic compound. Since the 1930s, it has been widely used as a preservative in a number of biological and drug products, including many vaccines, to help prevent potentially life threatening contamination with harmful microbes. Over the past several years it has been added to the infant immunization schedule, concerns about the use of thimerosal in vaccines and other products have been raised. Indeed, because of these concerns, the Food and Drug Administration has worked with, and continues to work with, vaccine manufacturers to reduce or eliminate thimerosal from vaccines. However, there is no evidence suggesting that thimerisol in vaccines causes any health issues in children or adults other that hypersensitivity like redness and swelling at the injection site.