Thiomersal

| Section2 = {{Chembox Properties | Formula = C₉H₉HgNaO₂S | MolarMass = 404.81 g/mol | Appearance = White or slightly yellow powder | Density = 2.508 g/cm³

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 inoculated with a diphtheria vaccine that lacked a preservative. Bacteriostatics like thiomersal are not needed in more-expensive single-dose injectables.

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. 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. 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. Also, four rarely used treatments for pit viper, coral snake, and black widow venom still contain thiomersal. 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.

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). In the body, it is metabolized or degraded to ethylmercury (C₂H₅Hg⁺) and thiosalicylate. 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 clears from the brain in about 14 days in infant monkeys. 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 not yet understood.

Risk assessment for effects on the nervous system have been made by extrapolating from dose-response relationships for methylmercury. 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 cleared from the body and the brain significantly faster than methylmercury, so the late-1990s risk assessments turned out to be overly conservative. 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.

It was voted Allergen of the Year in 2002 by the American Contact Dermatitis Society.

Autism

Following a mandated review of mercury-containing food and drugs, the Centers for Disease Control (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. Many parents took 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. The current scientific consensus is that no convincing scientific evidence supports these claims, based on various lines of evidence including the observation that the rate of autism continues to climb despite elimination of thiomersal from routine childhood vaccines. and World Health Organization as well as governmental agencies such as the Food and Drug Administration reject any role for thiomersal in autism or other neurodevelopmental disorders. Despite this, many parents, and some scientists and doctors, believe there is a connection. 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 and diverting resources away from research into more promising areas for the cause of autism. 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.

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.

See also

Mercurochrome

References

Category:Thiolates Category:Eli Lilly and Company Category:Organomercury compounds Category:Excipients Category:Sodium compounds Category:Benzoates