JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The small amount of available evidence supports the use of chlorocresoI 0.05% for use with intact, but not damaged eyes. The considerable volume of work on chlorbutol has shown that almost all workers have found it to be consistently an effective, but relatively slow, sterilizing agent. It would seem that formulation aspects of this agent have been adequately investigated (36,54). The mercurials have been shown to be effective sterilizing agents by nearly all workers. Riegelman et al (11) found 0.01% P.M.N. required longer than a week to sterilize a heavy inoculum of Ps.aeruginosa, but Kohn et al (24), using several strains and similar procedures to those of Riegelman and his co-workers, found that sterilization was effected in 6 hr. It has been asserted that these mercurials may give rise to mercurial sensitization ("mercurialentis"), and that mercury may deposit on the lens capsule (6,26). There is little published evidence to support these assertions. Ridley (16) found very few cases of dermatitis medicamentosa with P.M.N. preservation. These few cases were with drops used for a long period of time, and in every case the reaction was slight. Work is in progress in our laboratory to elucidate this situation. Rabbits' eyes have been irrigated with mercurial solution, subsequently sectioned, and examined with an electron probe microanalyser. It is hoped that these procedures will provide useful information about local concentrations of mercury. The available evidence offers little support for the use of phenylethyl alcohol as an ophthalmic preservative. The existence of resistant Ps.aerug- inosa strains would not appear to be the result of inadvertent training due to faulty procedures. The evidence about quaternary ammonium compounds is clouded by numerous quotations of opinions, assertions unsupported by data, and even errors in quoting the literature. A literature search has revealed very few instances where resistance to benzalkonium chloride has been demonstrated. Murphy et al (36) and Riegelman et al (11) have shown the existence of highly resistant strains of Ps.aeruginosa. On the other hand, it has been shown that faulty procedures may enable contaminants to acquire resis- tance, particularly to quaternary ammonium compounds (55). The available evidence supports the conclusion of Riegelman and Vaughan (1) "with all its limitations, benzalkonium chloride is among the most effective and rapidly acting preservatives when the conditions of its use are properly controlled."

THE PRESERVATION OF OPHTHALMIC PREPARATIONS 385 There is no evidence of resistance by Ps.aeruginosa to polymyxin B sulphate. This antibiotic is limited by its relatively low activity against gram-positive organisms, and some species of Proteus (47). The U.S.P. XI suggests the use of a combination of 1000 units/ml polymyxin B sulphate and 0.01% benzalkonium chloride. The newer recommended ophthalmic preservatives include several promising compounds, nearly all of which require more work before their acceptance. Chlorhexidine is an exception in that it has been introduced into the Australian Pharmaceutical Formulary, and experience in practice has been gained. Nevertheless there are problems of compatibility with this compound, and it is not uniformly satisfactory with all ophthalmic solutions (50). When suitably formulated, the following compounds have reasonable scientific support for their use as ophthalmic preservatives in some in- stances: 0.05% Chlorocresol, 0.5% chlorbutol, 0.01% benzalkonium chloride, 0.005% chlorhexidine. Experimental evidence is required about mercury deposition on the lens before the mercurials may be used with confidence. Little attention has been paid to the use of combinations of agents. The recommendation of a combination of polymyxin B sulphate and benzalkonium chloride by U.S.N.F. XI would seem to be based on attain- ing broad spectrum activity rather than an expectation of synergism against any particular organism. Attention has been drawn to the dangers of indiscriminately combining antimicrobial agents (56,57). Preliminary work has shown synergism between phenylethyl alcohol and the organic mercurials (58). It would appear that the future lies more in the understanding of the nature of the resistance of Ps.aeruginosa to chemical inactivation than in the discovering of other new agents. The literature possesses several monuments to the capacity of this beast, literally to eat the agents used against it. The acquired resistance to a quaternary ammonium compound has been eliminated in the presence of E.D.T.A. (59), and the U.S.N.F. XI has suggested its use for that purpose. It has been shown that cells grown in the presence of Tween 80 are much less resistant to the action of several agents than are cells grown in plain broth (60,61). It has been suggested that the resistance of Ps.aeruginosa is connected with its slime production and its membrane permeability, both of which may be affected by Tween 80. The problems of sterilization and preservation have for too long been