Phenylmercuric salts

Thiomersal is employed as a preservative for eye-drops and in lower concentration, 0.001-0.004%, as a preservative for contact lens solutions. The phenylmercuric salts (0.002%) are also used for preservation of eye-drops but long-term use has led to... 

Mei curic cyanide or tliiocyanato. Alcoholic solution at 120°. Phenylmercuric salts. do. 

Pesci has shown that phenylmercuric salts react with ammonia to form salts of (CeHgHg)2NH—, these compounds yielding ammonia... 

As for other phenylmercuric salts see Phenylmercuric Nitrate. Solutions may be sterilized by autoclaving. 

Phenylmercuric salts are used as antimicrobial preservatives mainly in ophthalmic preparations, but are also used in cosmetics see Section 16), parenteral, and topical pharmaceutical formulations see Table I. 

Phenylmercuric salts are active over a wide pH range against bacteria and fungi and are usually used in neutral to alkaline solutions, although they have also been used effectively at slightly acid pH see Section 10. In acidic formulations, phenylmercuric nitrate may be preferred to phenylmercuric acetate or phenylmercuric borate as it does not precipitate. 

A number of adverse reactions to phenylmercuric salts have been reported and concern at the toxicity of mercury compounds may preclude the use of phenylmercuric salts under certain circumstances see Section 14. 

Activity is also increased in the presence of phenylethyl alcohol, and in the presence of sodium metabisulfite at acid pH. Activity is decreased in the presence of sodium metabisulfite at alkaline pH. When used as preservatives in topical creams, phenylmercuric salts are active at pH... 

The antimicrobial activity of phenylmercuric salts may be reduced in the presence of anionic emulsifying agents and suspending agents, tragacanth, starch, talc, sodium metabisul-fite, sodium thiosulfate, disodium edetate, and silicates... 

Phenylmercuric salts are incompatible with halides, particularly bromides and iodides, as they form less-soluble halogen compounds. At concentrations of 0.002% w/v precipitation may not occur in the presence of chlorides. Phenylmercuric salts are also incompatible with aluminum and other metals, ammonia and ammonium salts, amino acids, and with some sulfur compounds, e.g., in rubber. 

Phenylmercuric salts are absorbed by rubber stoppers and some types of plastic packaging components uptake is usually greatest to natural rubbers and polyethylene and least to polypropylene. ... 

Incompatibilities with some types of filter membranes may also result in loss of phenylmercuric salts following sterilization by filtration. ... 

Phenylmercuric nitrate and other phenylmercuric salts are widely used as antimicrobial preservatives in parenteral and topical pharmaceutical formulations. However, concern over the use of phenylmercuric salts in pharmaceuticals has increased as a result of greater awareness of the toxicity of mercury and other mercury compounds. This concern must, however, be balanced by the effectiveness of these materials as antimicrobial preservatives and the low concentrations in which they are employed. 

Phenylmercuric salts are irritant to the skin at 0.1% w/w concentration in petrolatum. In solution, they may give rise to erythema and blistering 6-12 hours after administration. In a modified repeated insult patch test, a 2% w/v solution was found to produce extreme sensitization of the skin. ° ... 

Included in the FDA Inactive Ingredients Guide (IM and ophthalmic preparations). Included in nonparenteral medicines licensed in the UK. In the UK, the use of phenylmercuric salts in cosmetics is limited to 0.003% (calculated as mercury, equivalent to approximately 0.0047% of phenylmercuric nitrate) as a preservative in shampoos and hair creams, which contain nonionic emulsifiers that would render other preservatives ineffective. Total permitted concentration, as mercury, when mixed with other mercury compounds is 0.007% (equivalent up to approximately 0.011% of phenylmercuric nitrate). Included in the Canadian List of Acceptable Non-medicinal Ingredients (ophthalmic, nasal and otic preparations only there must be no other suitable alternative preservative). 

Phenylmercuric salts should be used in preference to benzal-konium chloride as a preservative for salicylates and nitrates and in solutions of salts of physostigmine and epinephrine that contain 0.1% sodium sulfite. 

Organic Mercury. Case report studies suggest that dermal exposure to methylmercury or phenylmercury in humans can cause rashes and blisters on the skin (Hunter et al. 1940 Morris 1960). A 33-year-old male worker exposed to methylmercury nitrate dust for 2 years developed bums and blisters on his forearm (Hunter et al. 1940). These effects healed within 9 days. Sensitivity to phenylmercuric salts is shown by individuals who developed itchy, pruritic, papular eruptions or rashes on their skin following acute dermal exposure (Morris 1960). A 54-year-old woman with a family history of atopy was found to display erythema (at 30 minutes postexposure) and urticaria (at 60 minutes) when treated topically with a 0.01% solution of phenylmercuric acetate (Torresani et al. 1993). This positive reaction was associated with aggravation of facial edema and an attack of bronchospasm. The woman, who was a farmer, was believed to have been previously exposed to phenylmercuric acetate during contact with pesticides and herbicides used on farm crops. 

In vitro evidence suggests that organic mercury is also readily absorbed in the gastrointestinal tract and that methylmercuric chloride is absorbed to a greater extent than phenylmercuric chloride (Endo et al. 1989). Complexing of methylmercury with nonprotein sulfhydryls also may play a role in intestinal absorption and reabsorption (Urano et al. 1990). Phenylmercuric salt in the diet was completely... 

Morris G. 1960. Dermatoses from phenylmercuric salts. Arch Environ Health 1 53-55. 

Use Manufacture of phenylmercuric salts, fungicide, and germicide. Principal compound in manufacturing organic mercury derivatives, denaturant for alcohol. 

Classification Metallo-organic compd. phenylmercuric salt Empirical CeHyBHgOs Formula C6HsHgOB(OH)2 Properties Wh. cryst. powd. sol. in alcohol, glycerin si. sol. in water m.w. 338.56 m.p. 120-130 C... 

In aqueous solutions intended for the external auditory canal or the middle ear, where the active substance has no preservative properties, the combination of benzalkonium chloride 0.01 % and disodium edetate 0.1 % is the first choice the second choice is methyl parahydroxybenzoate 0.1 %. They are dealt with in Sect. 23.8. Phenylmercuric salts are not used in ear drops anymore, as the use of mercury and its salts is discouraged for reasons of protection of the environment and possible toxic effects. 

Phenylethanol alone is not routinely used as preservative in eye drops due to too low an antimicrobial activity especially against gram-positive bacteria. Moreover phenylethanol cannot be combined with other preservatives because of its potential to irritate the eye [101]. Hydroxybenzoic esters are also reported to cause a high incidence of eye irritation. Thiomersal is not routinely used due to low antimicrobial activity, allergic reactions and penetration of mercury into the eye. The same is also true but to a much lesser extent for phenylmercuric salts [102-104] (see also Sect. 23.8.4). 

Phenylmercuric borate is 0.08 % soluble in water. Mercury is in this compound covalently bound to the phenyl group. It is incompatible with many anions, including halides. However a 0.004 % solution is compatible with up to 0.7 % sodium chloride. The active concentration is 0.002 %, but a concentration up to 0.004 % may be used to compensate losses by adsorption on the membrane filter, etc. Eye drop bottles with chlorine and bromine butyl rubber droppers cannot be used with phenylmercuric salts, because a precipitate will be formed. An alternative is packaging the eye drops in a bottle with a polypropylene dropper (see Sect. 24.4.2). Phenylmercuric borate causes few hypersensitivity reactions, but with prolonged use, there might be a risk of mercury deposition in the lens. 

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