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Thiomersal (also called thimerosal, Chinese common name 硫柳汞) is an ethylmercury-containing organosulfur antiseptic and antifungal compound, primarily used for decades as a preservative in multi-dose vials of vaccines, antivenins, eye drops and other injectable biologic products to prevent dangerous microbial contamination that could cause severe adverse reactions in patients.
Key moments
The debunked claim that thiomersal causes autism has remained a core talking point in global anti-vaccine circles for more than 25 years, driving measurable declines in childhood vaccination rates across multiple regions, and leading to resurgences of previously well-controlled vaccine-preventable diseases like measles. Most of the public misunderstanding stems from a widespread failure to distinguish fast-metabolizing ethylmercury (the breakdown product of thiomersal) from the highly bioaccumulative, neurotoxic methylmercury commonly found in contaminated seafood.
While thiomersal has been almost completely removed from single-dose pediatric vaccines in high-income countries, the WHO continues to endorse its safe use in multi-dose vaccine formats for low and middle-income public health campaigns. It drastically reduces product spoilage, lowers cold chain distribution costs, and expands access to affordable immunizations for millions of underserved people, with no documented cases of clinical harm at standard authorized usage concentrations.
The 1999 voluntary phase-out of thiomersal from pediatric vaccines, implemented strictly as a public goodwill gesture rather than a response to proven safety risks, inadvertently created a false public impression that the compound must have been dangerous all along, amplifying the exact anti-vaccine fears that public health officials had originally sought to calm with the policy shift.
Thiomersal (INN), or thimerosal (USAN, JAN), also sold under the name merthiolate,[3] is an organomercury compound. It is a well-established antiseptic and antifungal agent.[4]
It has been used as a preservative in vaccines, immunoglobulin preparations, skin test antigens, antivenins, ophthalmic and nasal products, and tattoo inks.[5] Despite the scientific consensus that fears about its safety are unsubstantiated,[6][7][8]
Morris Kharasch, a chemist then at the University of Maryland, filed a patent application for thiomersal in 1927;[9] 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.
One of the earliest synthetic methods was a reaction between ethylmercury chloride and thiosalicylic acid in alkaline solution, with subsequent acidification.[10] Various minor modifications of this are possible, but the modern synthesis is essentially the same.
Thiomersal contains mercury(II) with a coordination number 2, i.e. two ligands are attached to Hg, the thiolate and the ethyl group. The carboxylate group confers solubility in water. Like other two-coordinate Hg(II) compounds, the coordination geometry of Hg is linear, with a 180° S-Hg-C angle. Typically, organomercury thiolate compounds are prepared from organomercury chlorides.[11]
Thiomersal's main use is as an antiseptic and antifungal agent, due to its oligodynamic effect. 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 vaccinated with a diphtheria vaccine that lacked a preservative. Unlike other preservatives at the time, such as phenol and cresol, thiomersal does not reduce the potency of the vaccines that it protects.[12] Bacteriostatics such as thiomersal are not needed in single-dose injectables.[13]
In the United States, the European Union, and a few other affluent countries, thiomersal is no longer used as a preservative in routine childhood vaccination schedules.[14] In the U.S., all vaccines routinely recommended for children 6 years of age and younger are available in formulations that do not contain thiomersal. Two vaccines (a TD and the single-dose version of the trivalent influenza vaccine Fluvirin) may contain a trace of thiomersal from steps in manufacture, at less than 1 microgram of mercury per dose.[15] The multi-dose versions of some trivalent and quadrivalent influenza vaccines can contain up to 25 micrograms of mercury per dose from thiomersal. Also, four rarely used treatments for pit viper, coral snake, and black widow venom contain thiomersal.[16]
Outside North America and Europe, many vaccines contain thiomersal; the World Health Organization reported no evidence of toxicity from thiomersal in vaccines and no reason on safety grounds to change to more expensive single-dose administration.[17] The United Nations Environment Program backed away from an earlier proposal of putting thiomersal on the list of banned vaccine compounds as part of its campaign to reduce mercury exposure.[18] It stated that eliminating it in multi-dose vaccines, primarily used in developing countries, would lead to high cost and a refrigeration requirement that developing countries could ill afford. At the Minamata Convention on Mercury in 2013, thiomersal was excluded from the treaty.[19]
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).[20]
In the body, it is metabolized or degraded to ethylmercury (C2H5Hg+) and thiosalicylate.[15]
Cases have been reported of severe mercury poisoning by accidental exposure or attempted suicide, with some fatalities.[21] Animal experiments suggest that thiomersal rapidly dissociates to release ethylmercury after injection; that mercury's disposition patterns are similar to those after exposure to equivalent doses of ethylmercury chloride; and that the central nervous system and the kidneys are targets. Loss of motor coordination is a common sign. Similar signs and symptoms have been observed in accidental human poisonings. The mechanisms of toxic action are unknown.[21]
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 by breakdown into other chemicals, including inorganic mercury.[22] The half-life of ethylmercury in the brains of infant monkeys is 14 days. Risk assessment for effects on the nervous system has been made by extrapolating from dose-response relationships for methylmercury. Methylmercury and ethylmercury distribute to all body tissues, crossing the blood–brain barrier and the placental barrier, and ethylmercury also moves freely throughout the body.[23]
Concerns based on extrapolations from methylmercury caused thiomersal to be removed from U.S. childhood vaccines, starting in 1999. Later it was reported 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.[24]
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;[25] a higher prevalence of contact allergy (up to 6.6%) was observed in German populations.[26] Thiomersal-sensitive individuals can receive intramuscular rather than subcutaneous immunization,[27] though there have been no large sample-sized studies regarding this matter to date. In real-world practice on vaccination of adult populations, contact allergy does not seem to elicit a clinical reaction.[26]
Thiomersal allergy has decreased in Denmark, probably because of its exclusion from vaccines there.[28]
The Center for Biologics Evaluation and Research (CBER) at the FDA initiated a formal risk assessment of thiomersal in vaccines beginning in 1998.[30] After determining the levels of ethylmercury exposure from the currently recommended vaccine schedule, the CBER found these amounts exceeded new standards for methylmercury exposure recently established by the Environmental Protection Agency.[12] On July 7, 1999, both the American Academy of Pediatrics and the US Public Health Service issued a statement calling for the removal of thiomersal-containing vaccines "as expeditiously as possible."[31][32] By March 2001, thiomersal-free versions of all the recommended childhood vaccines for children up to age 6 were available in the United States.[30]
On June 26, 2025, the Advisory Committee on Immunization Practices (ACIP) voted in favour of recommending that most Americans receive influenza vaccines that do not contain thiomersal.
Following the phasing out of thiomersal from most U.S. and European vaccines,[12][37] some parents saw 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.[12] The scientific consensus is that no evidence supports these claims, while the rate of autism continued to climb in children who did not take the thiomersal-preserved childhood vaccines.[7][38][6]
Scientific and medical bodies such as the Institute of Medicine[39]
