Тимерозал

Химические свойства

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

Использование

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.

Определение

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

Методы производства

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

Общее описание

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

Реакции воздуха и воды

Water soluble.

Профиль реактивности

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.

Опасность

Toxic by ingestion, inhalation.

Пожароопасность

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

Фармацевтические приложения

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.

Контактные аллергены

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.

Профиль безопасности

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.

Экологическая судьба

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.

хранилище

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.

Методы очистки

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

Несовместимости

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.

Регуляторный статус

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.