]. Soc. Cosmet. Chem., 26, 397~409 (August 1975) Evaluation of Ocular Decongestants in Rabbits j. j. LOUX* and S. L. YANKELLt Presented April 1973, Federation [or Experimental Biology Spring Meeting, Atlantic City, N.I. Synopsis-A procedure has been developed for determining the minimum effective dose and the duration of activity of OCULAR DECONGESTANTS in RABBITS. A 5% sodium chloride solution causes a reproducible typeremic response, which can be abolished by OPHTHALMIC PREPARATIONS containing a VA'SOCONSTRICTOR. Dose range studies have been conducted to determine minimum effective doses of com- pounds proposed for use as ocular decongestants. INTRODUCTION Ocular irritation is assayed in most laboratories by employing the criteria and method proposed by Draize (1). This procedure was developed to assay the potential ocular irritation of substances which might accidentally get onto eye surfaces and cause untoward reactions. Four basic parameters are ap- praised: conjunctival redness or hyperemia edema or chemosis iritis and corneal opacity. While moderate to severe eye irritants can cause reactions in- volving all four of these categories, minor eye irritations are limited to a su- perficial conjunctival hyperemia associated with mild edema. Situations which can cause minor ocular irritations, objectively manifested by conjunctival redness, include allergy, eye fatigue, insomnia, intemperance, pollution, smoking, swimming, etc. In these cases, an ophthalmic deconges- tant preparation can afford symptomatic relief of an uncomfortable and cos- metically undesirable situation. *Cooper Laboratories, Research and Development Division, 110 E. Hanover Ave., Cedar Knolls, N.J. 07927. 'PMenly & James Laboratories, Ltd., 1500 Spring Garden Street, Philadelphia, Penn. 19101. 397

398 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The purpose of these investigations was to develop an assay using the scor- ing criteria of the Draize test, wherein a predictable and quantitative irrita- tion could be induced. Substances with known or suspected ocular deconges- tant activity could then be evaluated for their ability to alleviate this condi- tion in situ. METHODS Induction o[ Hyperemia Male albino rabbits weighing beween 2.0 and 2.5 kg were used. All eyes were examined prior to testing to exclude any preexisting overt ocular irrita- tion. Pupil size was measured in millimeters and recorded. Various concentra- tions of sodium chloride in aqueous solutions, ranging between 2 and 10% (w/v), were tested to determine the optimmn concentration necessary to produce a stable ocular hyperemia by placing 0.1 ml in the lower coniunctival sac. The eyelids were held shut for 1 min, after which the eye was graded for redness and edema. The grading of ocular reactions used throughout these investigations were as follows. Category Descriptions ø Score Redness Normal ocular tissues no evidence of hyperemia 0 Some definite engorgement of vessels 1 Tissues crimson red vessels not easily discernable 2 Tissues "beef red " individual vessels not discernable 3 Edema Normal ocular tissues no evidence of edema 0 Evidence of any slight edema 1 Tissues definitely edematous lids partially everted 2 •'A complete description of ocular irritation testing including illustrations of all types of irritancy is available in the Illustrated Guide [or Grading Eye Irritation btd Hazardous Substances, U.S. Dept. HEW, FDA, Washington, D.C. 20204. Other Agonists A 1:1000 histamine phosphate solution was tested to determine if suitable ocular irritation could be produced. Volumes ranged from 0.05 to 0.25 ml of the 1:1000 solution. Also, the use of water encountered in swimming activities was investigated as a potential agonist and included 0.1 ml volumes of Atlan- tic Ocean water (from Atlantic City, N.J. ) and athletic club pool water (from Philadelphia, Penn.). Standard Efficacy Test Efficacy assays were conducted using 5% sodium chloride solution as the standard agonist. To induce irritation, 0.1 ml of 5% (w/v) sodium chloride