BENZOYL PEROXIDE FORMULATIONS 539 Table IV Conjunctival Swelling for Rabbits After Single Topical Ocular Instillation of Benzoyl Peroxide 10 Per Cent Test Formulation Wash Conj unctival Swelling Time •' 1 h 24 h 48 h 72 h 7 day 14 day 21 day A 20 sec A 5 min A 24h C 20 sec C 5 min C 24h Day 0 Controls Day 0 Day 1 Controls Day 1 Untreated Controls -- •a 3.7 2.0 2.0 1.7 0.0 0.0 0.0 Inc? 6/6 6/6 5/6 5/6 0/6 0/6 0/6 • 3.7 3.3 3.3 3.3 1.3 1.3 0.0 Inc. 6/6 6/6 6/6 6/6 4/6 3/4 0/4 - x 4.0 3.3 3.3 3.3 1.0 0.7 0.3 Inc. 6/6 6/6 6/6 6/6 3/6 2/6 1/6 • 3.7 3.3 3.7 3.0 2.3 0.7 0.3 Inc. 6/6 6/6 6/6 5/6 5/6 2/6 1/6 • 4.0 4.3 5.3 4.7 3.7 2.7 1.7 Inc. 6/6 6/6 6/6 6/6 6/6 6/6 5/6 d x 3.7 3.7 4.0 4.3 3.0 2.7 1.3 Inc. 6/6 6/6 6/6 6/6 6/6 4/6 3/6 • 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Inc. 0/6 0/6 0/6 0/6 0/6 0/6 0/6 • 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Inc. 0/6 0/6 0/6 0/6 0/6 0/6 0/6 • 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Inc. 0/6 0/6 0/6 0/6 0/6 0/6 0/6 aMaximum score: Swelling = 8. Mean score calculated by summing individual number of observations. bNumber of eyes with response/number of eyes in test groups. elnterval of time after dosing until eye was washed. dNumber less than 6 indicates mortality not related to treatment. scores and dividing by the 72-h observation periods with minimal conjunctival discharge at a low incidence being observed on days 7 and 14 and discharge being absent on Day 21. Moderate con- junctival discharge at a high incidence was observed for the 1-h observation period for eyes which received benzoyl peroxide formulations. Moderate to severe conjunctival discharge at a high incidence was observed at the 24-, 48-, and 72-h and Day 7 observation periods for all treatment groups. Minimal con- junctival discharge at a moderate incidence was observed on Days 14 and 21 for the 20-sec wash group for eyes which received 10 per cent benzoyl peroxide formulations. Moderate conjunctival discharge at a moderate incidence was observed on Day 14 for the 5-min and 24-h wash groups, while discharge had diminished to a minimal intensity at a moderate incidence by Day 21. The second instance of minimal conjunctival dis- charge was observed at the 1-h observation period for the Day 0 controls thereafter, the eyes in this treatment group did not exhibit discharge in the remainder of this 21- day test period. Discharge was not observed for the Day 1 controls and untreated con- trols (Table V). Formulation A after the 24-h treatment had minimal discharge com- pared to formulation C. All eyes were normal relative to light reflex (pupillary response and lens) for eyes receiving benzoyl peroxide formulations and control formulations.

540 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table V Conjunctival Discharge for Rabbits After Single Topical Ocular Instillation of Benzoyl Peroxide 10 Per Cent Test Wash Conjunctival Discharge Formulation Time ½ ! h 24 h 48 h 72 h 7 day 14 day 2 ! day A 20sec •a 3.7 4.7 2.7 2.0 0.0 0.0 0.0 Inc? 6/6 6/6 5/6 5/6 0/6 0/6 0/6 A 5min • 4.3 5.3 5.0 4.7 2.7 0.5 0.0 Inc. 6/6 6/6 6/6 6/6 4/6 1/4 d •4 d A 24h • 3.7 4.3 4.7 4.7 1.0 0.3 0.0 1 Inc. 6/6 6/6 6/6 6/6 2/6 1/6 0/6 C 20sec • 3.0 5.0 5.3 5.3 4.0 1.0 0.7 Inc. 6/6 6/6 6/6 6/6 5/6 3/6 2/6 C 5min • 4.3 6.0 6.0 6.0 5.3 3.3 2.0 Inc. 6/6 6/6 6/6 6/6 6/6 5/6 4/6 - c 24h x 3.3 5.7 6.0 6.0 5.0 4.0 2.3 Inc. 6/6 6/6 6/6 6/6 6/6 4/6 4/6 Day 0 Controls Day 0 • 0.3 0.0 0.0 0.0 0.0 0.0 0.0 Inc. 1/6 0/6 •6 •6 0/6 0/6 0/6 Day 1 Controls Day 1 • 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Inc. 0/6 0/6 •6 0/6 0/6 0/6 •6 Untreated Controls -- • 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Inc. 0/6 0/6 0/6 0/6 0/6 •6 0/6 aMaximum score: discharge = 6. Mean score calculated by summing individual scores and dividing number of observations. •Number of eyes with response/number of eyes in test group. CInterval of time after dosing until eye was washed. aNumber less than 6 indicates mortality not related to treatment. by the Relative to flare, a single incidence of minimal aqueous flare was observed at the 24-h observation period for the 20-sec wash group. Flare was not observed in the remainder of the 21-day period for all treatment groups (benzoyl peroxide formulations). Minimal aqueous flare at a low to moderate incidence was observed at the 1-, 24-, and 48-h observation periods for the 5-min wash group for eyes which received benzoyl peroxide formulations thereafter, aqueous flare was not observed in the remainder of the 21-day test period for this treatment group. Minimal aqueous flare at a low to moderate incidence was observed at 1, 24, and 48 h for the 24-h wash group for eyes which received benzoyl peroxide formulations thereafter, aqueous flare was not ob- served in the remainder of the 21-day test period. Minimal aqueous flare at a low to high incidence was observed at the 1-, 24-, and 48-h observation periods for the 20-sec wash group for the eyes receiving various benzoyl peroxide preparations thereafter, aqueous flare was not observed during the remainder of the 21-day test period. Minimal aqueous flare at a low to high incidence was observed at l, 24, 48, and 72 h for the 5-min and 24-h wash groups for eyes which received some of the benzoyl peroxide formulations thereafter, aqueous flare was not observed for the remainder of the 21- day test period. Aqueous flare was not observed for the control eyes. Flare in general was minimal in all benzoyl peroxide formulations.