Thimerosal Chemical Properties

Melting point:

234-237 °C (dec.)(lit.)

Flash point:

250 °C

storage temp. 

Store at RT.

solubility 

methanol: 0.1 g/mL, ≤ 10 TE CF

form 

Powder

color 

white to off-white

PH

6.0～8.0 (10g/L, 25℃)

Water Solubility 

1 G/ML (20 ºC)

Merck 

13,9389

BRN 

8169555

Stability:

Stable. May degrade in sunlight. Incompatible with strong acids, strong bases, strong oxidizing agents, iodine, heavy metal salts.

InChI

InChI=1S/C7H6O2S.C2H4.Hg.Na/c8-7(9)5-3-1-2-4-6(5)10;1-2;;/h1-4,10H,(H,8,9);1H,2H3;;/q;-1;2*+1/p-1

InChIKey

RTKIYNMVFMVABJ-UHFFFAOYSA-L

SMILES

O=C1[O-][Hg+2]([CH-]C)[SH-]C2=CC=CC=C12.[Na+]

CAS DataBase Reference

54-64-8(CAS DataBase Reference)

EPA Substance Registry System

Thimerosal (54-64-8)

Safety Information

Hazard Codes 

T+,N,T

Risk Statements 

26/27/28-33-50/53

Safety Statements 

13-28-36-45-60-61-28A

RIDADR 

UN 2025 6.1/PG 3

WGK Germany 

3

RTECS 

OV8400000

F 

8

TSCA 

Yes

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

29310095

Hazardous Substances Data

54-64-8(Hazardous Substances Data)

Toxicity

LD50 s.c. in rats: 98 mg/kg (Mason)

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS

Thimerosal Usage And Synthesis

Description

Since the 1930s, thimerosal (sodium ethylmercury thiosalicylate) has been used in the manufacture of vaccines to prevent fungal or bacterial contamination of multidose preparations. The single-dose vaccines are much more expensive and thus the use of the preservative significantly reduces the cost of vaccination. There is controversy as to whether the use of thimerosal in vaccines is an etiological factor in autism and other neurodevelopmental disorders such as attention deficit hyperactivity disorder. It has been estimated that children exposed to mercury-containing vaccines could be exposed to levels of mercury far beyond those considered safe by the US Food and DrugAdministration (FDA) standards. Therefore, in 1999, theUS Public Health Service agencies urged vaccine manufacturers to stop or limit the use of the preservative in vaccine formulations. Today, the vaccines on the US Recommended Childhood and Adolescent Immunization Schedule are thimerosal-free although some formulations of the influenza vaccine still contain the mercury-containing preservative. The Centers for DiseaseControl and Prevention (CDC) has discounted an association between exposure to this organic ethylmercury compound and autism. This is based on studies showing that the risk of autism is not increased in children treated with vaccines containing the preservative compared with children who were vaccinated with thimerosal-free formulations. Furthermore, in Denmark, the use of the preservative was discontinued after 1992. After removal of thimerosal, there was a continued rise in new cases of autism.

Chemical Properties

Slightly beige powder

Chemical Properties

Thimerosal is a light cream-colored crystalline powder with a slight, characteristic odor.

Originator

Timeolate,Lifar

Uses

Thimerosal is used as ophthalmie preservative; topieal anti-infective; topical veterinary antibacterial and antifungal agent; bacteriostat; fungistat; preservative in vaccines, antitoxins, skin-testing allergens, antiseptics, contact-Iens solutions, and cosmetic products like eye makeup.

Uses

Pharmaceutic aid (preservative).

Uses

Thiomersal is an organomercury compound that is used as an antiseptic and antifungal agent It is used as a vaccine preservative. During cell culture, thiomersal is used to prevent overgrowth in fibroblast cells 1. It has been used to preserve Atovaquone 2.

Uses

antifungal, antimicrobial

Uses

nootropic Anti-Alzheimer’s drug main ingredient of Neupramir derived from Piracetam but 8-30 times more potent

Definition

ChEBI: An alkylmercury compound (approximately 49% mercury by weight) used as an antiseptic and antifungal agent.

Production Methods

Thimerosal is prepared by the interaction of ethylmercuric chloride, or hydroxide, with thiosalicylic acid and sodium hydroxide, in ethanol (95%).

Manufacturing Process

To a solution or suspension in alcohol of 0.1 mole of methyl mercuric chloride is added 0.1 mole of sodium hydroxide in water and 0.1 mole of thiosalicylic acid in ethanol. The product is poured into water, whereupon; the methyl mercurithiosalicylic acid is precipitated, since it is insoluble in water. This precipitate can be collected on a filter, and washed well with water to remove all the alcohol, salts, and free inorganic acids. The washed precipitate may then be dissolved in a water solution of sodium hydroxide, or, better, in a water solution of sodium bicarbonate. This produces the water-soluble salt of the methyl mercurithiosalicylic acid.The methyl mercurithiosalicylic acid is a white solid which melts at about 171°C. It is soluble in alcohol and in ether. It is soluble in either sodium bicarbonate or sodium hydroxide solution, to form the corresponding salt; which is suitable for intravenous injection.
The alkali metal salts, such as the sodium and potassium salts, of this acid, are readily a soluble in water; so are its ammonium salts, and many (probably all) of its alkyl-ammonium salts; but the alkaline earth salts, such as the calcium salt, are insoluble in water.

brand name

Thiomersal is INN and BAN;Thiobactal.

Therapeutic Function

Antiseptic, Pharmaceutic aid

General Description

Light cream-colored crystalline powder with a slight odor: pH (1% aqueous solution) 6.7. Slight odor.

Air & Water Reactions

Water soluble.

Reactivity Profile

Thimerosal is incompatible with strong oxidizing agents and strong bases. The oxidation of Thimerosal is greatly accelerated by traces of copper ions. Incompatible with acids, iodine, heavy metal salts and many alkaloids. Can be absorbed by rubber caps. . Stable in air, but not sunlight. May discolor on exposure to light. Dilute aqueous solutions are fairly stable to heat but sensitive to light. Solutions are less stable to heat when acidic than when alkaline. Solutions are most stable to light at pH 5 to 7. Solutions are unstable to heat but not to light in the presence of copper, iron or zinc ions but not in the presence of calcium or magnesium ions.

Hazard

Toxic by ingestion, inhalation.

Fire Hazard

Flash point data for Thimerosal are not available; however, Thimerosal is probably combustible.

Pharmaceutical Applications

Thimerosal has been used as an antimicrobial preservative in biological and pharmaceutical preparations since the 1930s.
It is used as an alternative to benzalkonium chloride and other phenylmercuric preservatives, and has both bacteriostatic and fungistatic activity. Increasing concerns over its safety have, however, led to questions regarding its continued use in formulations.
Thimerosal is also used in cosmetics and to preserve soft contact lens solutions.
Therapeutically, thimerosal is occasionally used as a bacteriostatic and fungistatic mercurial antiseptic, which is usually applied topically at a concentration of 0.1% w/w. However, its use is declining owing to its toxicity and effects on the environment.

Contact allergens

Thiomersal is an organic mercury salt prepared by react- ing ethylmercuric chloride (or ethylmercuric hydroxide) with thiosalicylic acid. It is still used as a disinfectant and a preservative agent, but less commonly than previ- ously, especially in contact lens fluids, eyedrops, and vaccines. The ethylmercuric moiety is the major aller- genic determinant, sometimes associated with mercury sensitivity. Thiomersal is an indicator of photosensitiv- ity to piroxicam, through its thiosalicylic moiety.

Safety Profile

Poison by ingestion, subcutaneous, and intravenous routes. Experimental teratogenic and reproductive effects. An eye irritant. Questionable carcinogen with experimental neoplastigenic data. Mutation data reported. An ophthalmic preservative, a topical anti-infective, topical veterinary antibacterial and antifungal agent. An FDA over-the-counter drug. When heated to decomposition it emits very toxic fumes of Hg, Na2O, and SOx. See also MERCURY COMPOUNDS.

Safety

Thimerosal is widely used as an antimicrobial preservative in parenteral and topical pharmaceutical formulations. However, concern over the use of thimerosal in pharmaceuticals has increased as a result of a greater awareness of the toxicity of mercury and other associated mercury compounds. The increasing number of reports of adverse reactions, particularly hypersensitivity, to thimerosal and doubts as to its effectiveness as a preservative have led to suggestions that it should not be used as a preservative in eye drops or vaccines. In both Europe and the USA, regulatory bodies have recommended that thimerosal in vaccines be phased out.
More recent studies assessing the safety of thimerosal in vaccines have, however, suggested that while the risk of hypersensitivity reactions is present, the relative risk of neurological harm in infants is negligible given the quantities of thimerosal present in vaccines. Regulatory bodies in Europe and the USA have therefore updated their advice on the use of thimerosal in vaccines by stating that while it would be desirable for thimerosal not to be included in vaccines and other formulations the benefits of vaccines far outweigh any risks of adverse effects associated with their use.
The most frequently reported adverse reaction to thimerosal, particularly in vaccines, is hypersensitivity, usually with erythema and papular or vesicular eruptions. Although not all thimerosal-sensitive patients develop adverse reactions to vaccines containing thimerosal, there is potential risk. Patch testing in humans and animal experiments have suggested that 0.1% w/v thimerosal can sensitize children. The incidence of sensitivity to thimerosal appears to be increasing; a study of 256 healthy subjects showed approximately 6% with positive sensitivity.
Adverse reactions to thimerosal used to preserve contact lens solutions have also been reported. Reactions include ocular redness, irritation, reduced lens tolerance, and conjunctivitis. One estimate suggests that approximately 10% of contact lens wearers may be sensitive to thimerosal.
Thimerosal has also been associated with false positive reactions to old tuberculin, ototoxicity, and an unusual reaction to aluminum in which a patient suffered a burn 5 cm in diameter at the site of an aluminum foil diathermy electrode after preoperative preparation of the skin with a 0.1% w/v thimerosal solution in ethanol (50%). Investigation showed that considerable heat was generated when such a solution came into contact with aluminum. An interaction between orally administered tetracyclines and thimerosal, which resulted in varying extents of ocular irritation, has been reported in patients using a contact lens solution preserved with thimerosal.
Controversially, some have claimed a connection between the use of thimerosal in vaccines and the apparent rise in the incidence of autism. However, recent studies have shown no association between thimerosal exposure and autism.
Serious adverse effects and some fatalities have been reported following the parenteral and topical use of products containing thimerosal. Five fatal poisonings resulted from the use of 1000 times the normal concentration of thimerosal in a chloramphenicol preparation for intramuscular injection.
Ten out of 13 children died as a result of treatment of umbilical hernia (omphaloceles) with a topical tincture of thimerosal. It has therefore been recommended that organic mercurial disinfectants should be restricted or withdrawn from use in hospital since absorption occurs readily through intact membranes.
In a case of attempted suicide, a 44-year-old man drank 83 mg/kg of a thimerosal-containing solution. Despite spontaneously vomiting after 15 minutes, gastric lavage and administration of chelating agents on hospital admission, serious symptoms ultimately ending in coma occurred. The patient survived and after 5 months treatment made a full recovery except for sensory defects in two toes.
LD50 (mouse, oral): 91 mg/kg
LD50 (rat, oral): 75 mg/kg
LD50 (rat, SC): 98 mg/kg

Environmental Fate

Thimerosal is a cream-colored crystalline powder; it is water soluble and thus the compound can leach into groundwater. Aquatic toxicity has been demonstrated at relatively high concentrations.

storage

Thimerosal is stable at normal temperatures and pressures; exposure to light may cause discoloration.
Aqueous solutions may be sterilized by autoclaving but are sensitive to light. The rate of oxidation in solutions is increased by the presence of trace amounts of copper and other metals. Edetic acid or edetates may be used to stabilize solutions but have been reported to reduce the antimicrobial efficacy of thimerosal solutions.
The solid material should be stored in a well-closed container, protected from light, in a cool, dry place.

Purification Methods

Recrystallise this antibacterial from EtOH/Et2O. HIGHLY TOXIC. [Trikojus Nature 158 472 1940, Beilstein 10 III 213.]

Toxicity evaluation

Not much is known about the toxic effects of ethylmercury and most toxicologists have assumed that the toxicity is similar to that caused by MeHg. However, because of the differences in the toxicokinetic profiles of the organic mercury salts (see above), this may not be a valid comparison. Methylmercury is a known neurotoxin. However, the neurotoxicity is very complex and depends on the duration of exposure, dose, and the age of the individual. Mercury salts have a strong affinity for thiol groups and this is likely to play a role in mediating their neurotoxicity. Glutathione depletion has been observed after exposure to ethylmercury. Some in vitro studies indicate that oxidative stress leading to lipid peroxidation and DNA damage may play a role in the mechanism of toxicity. Organic mercury salts may exert their toxicity by multiple diverse pathways that have yet to be precisely defined.

Incompatibilities

Incompatible with aluminum and other metals, strong oxidizing agents, strong acids and bases, sodium chloride solutions, lecithin, phenylmercuric compounds, quaternary ammonium compounds, thioglycolate, and proteins. The presence of sodium metabisulfite, edetic acid, and edetates in solutions can reduce the preservative efficacy of thimerosal.
In solution, thimerosal may be adsorbed by plastic packaging materials, particularly polyethylene. It is strongly adsorbed by treated or untreated rubber caps that are in contact with solutions.
When it was used with cyclodextrin, the effectiveness of thimerosal was reduced; however, this was related to the lipid nature of the other ingredients in the preparation.

Regulatory Status

Included in the FDA Inactive Ingredients Database (IM, IV, and SC injections; ophthalmic, otic, and topical preparations). Included in nonparenteral and parenteral medicines licensed in the UK. In the UK, the use of thimerosal in cosmetics is limited to 0.003% w/w (calculated as mercury) as a preservative in shampoos and haircreams, which contain nonionic emulsifiers that would render other preservatives ineffective. The total permitted concentration (calculated as mercury) when mixed with other mercury compounds is 0.007% w/w. Included in the Canadian List of Acceptable Nonmedicinal Ingredients.

Thimerosal(54-64-8)Related Product Information

• Diclofenac sodium
• Diethylaminosulfur trifluoride
• Salicylic acid
• Sodium alginate
• Sodium benzoate
• Sodium acetate
• Sodium hydroxide
• Sodium salicylate
• Orphenadrine citrate
• Sodium citrate
• Sodium bicarbonate
• Trisodium phosphate
• Sodium chloride
• 8-CHLOROADENOSINE-3',5'-CYCLIC MONOPHOSPHOROTHIOATE, RP-ISOMER SODIUM SALT
• MERCURIC THIOCYANATE
• SODIUM MERCURY AMALGAM
• Thiosalicylic acid
• Mercury
• Merthiolate
• Thiomersal