Thiomersalate
Thiomersalate Uses, Dosage, Side Effects, Food Interaction and all others data.
Thiomersal (INN), commonly known in the U.S. as thimerosal, is an organomercury compound. This compound is a well-established and widely used antiseptic and antifungal agent.
Developed in 1927, thimerosal has been and is still being used as a preservative in some cosmetics, topical pharmaceuticals, and biological drug products, which includes vaccines. There has been significant concern regarding its safety and toxicity in the last several decades. Although thimerosal is banned in several countries, it continues to be included as a preservative in some vaccines in the United States and many vaccines in the developing world .
Thiomersalate is an organomercurial compound and derivative of thiosalicyclic acid with antibacterial and antifungal properties . Thiomersalate, which consists of approximately 50% mercury by weight, has been one of the most widely used preservatives in vaccines. It is metabolized/degraded to ethylmercury and thiosalicylate. Ethylmercury is an organomercurial that must be carefully distinguished from methylmercury, a closely related substance that has been the focus of many studies. Methylmercury is the type of mercury found in various species of fish . Experimental data demonstrates that the toxicokinetics of thimerosal (ethylmercury) is vastly different from that of methyl-mercury. Thus, methyl-mercury is not a suitable reference for assessing the risk from exposure to thimerosal-derived mercury .
| Trade Name | Thiomersalate |
| Generic | Thimerosal |
| Thimerosal Other Names | BTL-TML-COVID, BTL-TML-HSV, BTL-TML001, ethylmercurithiosalicylate sodium, ethylmercurithiosalicylic acid sodium salt, mercurothiolate, sodium ethylmercurithiosalicylate, sodium merthiolate, Thimerosal, Thiomersal, Thiomersalate, Thiomersalum, Tiomersal |
| Type | |
| Formula | C9H9HgNaO2S |
| Weight | Average: 404.81 Monoisotopic: 405.992720501 |
| Protein binding | 95 to 99% (depending on animal species and experimental conditions) of the mercury in plasma is bound to albumin (along with other plasma proteins). As significant proportion of albumin is filtered at the glomerulus . |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Used as preservative in some cosmetics, topical pharmaceuticals, and biological drug products, which includes vaccines .
Thiomersalate is also used to associated treatment for these conditions: Skin disinfection
How Thiomersalate works
Although its mechanism of action is not fully understood, thimerosal inhibits sulfhydryl-containing active site of various enzymes and binds to sulfhydryl compounds, including glutathione, cysteine, and sulfhydryl groups of proteins. In addition, thimerosal activates the InsP3 calcium channel on the endoplasmic reticular membrane, thereby triggering the release of intracellular calcium resulting in a calcium-induced calcium-influx of extracellular calcium. Therefore, thimerosal may induce or inhibit various cellular functions that are dependent on the signaling of calcium .
Ethylmercury is metabolized to inorganic mercury more rapidly than methylmercury. This difference in metabolism may account for kidney pathology that can result from toxic quantities. Also, whereas the increase in oxidative stress and induction of apoptosis observed in vitro with large doses (405 μg/L to 101 mg/L) of thimerosal may explain its damaging neurological effects. The effects of low-dose ethylmercury are not completely understood to date. It is known, however, that the shorter half-life of ethylmercury (the metabolite of thimerosal) allows for very limited opportunities of ethylmercury derived from thimerosal in vaccines .
Ethylmercury is a lipophilic cation that is capable of crossing the blood-brain barrier. The octanol/water partition coefficients of methyl and ethylmercury are 1.4 to 1.8, at intracellular pH and [Cl−], therefore, both organomercury compounds will primarily exist as intracellular lipophilic cations. It has been demonstrated that lipophilic cations accumulate inside mitochondria, in a Nernstian fashion, driven by the steady state membrane potential. As the typical mitochondrial membrane potential of astrocytes and neurons is between 140–170 mV, one would expect the concentration of these organomercury compounds within mitochondria to be approximately 1000 times greater than the cytosolic concentration .
Toxicity
Ld50 Oral: 75 mg/kg (mouse), 91 mg/kg (mouse)
Although methylmercury (meHg) is considered a hazardous substance that is to be avoided even at small levels when consumed in foods such as seafood and rice (in Asia), the World Health Organization considers small doses of thimerosal safe regardless of multiple/repetitive exposures to vaccines that are predominantly taken during pregnancy or infancy .
Food Interaction
No interactions found.Volume of Distribution
266 L in one study
Elimination Route
Less than 0.01% of an ingested dose is absorbed from the GI tract (rat study) .
Half Life
A study was done to study the pharmacokinetics of Thiomersalate in mice. Estimated half-lives (in days) were 8.8 for blood, 10.7 for brain, 7.8 for heart, 7.7 for liver and 45.2 for kidney .
The the long half-life of ethylmercury (~50 days on average in humans) results in accumulation that may be harmful to the developing fetal brain, as it is more susceptible to organomercurial compounds than the adult brain .
Clearance
The high concentrations of mercury identified in stool samples suggest that ethylmercury may be eliminated through the gastrointestinal tract .
Elimination Route
Gastrointestinal tract .
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