320 JOURNAL OF COSMETIC SCIENCE p-values less than or equal to 0.05 at the 95% confidence level. The intensity values were given as means ± SEM. RESULTS AND DISCUSSION Ocular tissues consisting of palpebral conjunctiva, bulbar conjunctiva, cornea, and ca­ runcle respond to cosmetic exposure with different severity, pattern, and/or onset of symptoms, with respect to inflammation, abnormalities, and/or observed tissue abrasion. Figure 1 depicts ocular irritation induced by instillation of a cosmetic or consumer product. Moderate inflammation of the conjunctivae at a level 3 (Figure lA) punctate fluorescein staining patterns of the palpebral conjunctivae at an area level 3 with a density level 2 (Figure lB) superficial punctate keraropathy at an area level 3 with a density level 3 (Figure lC) and punctate staining of the caruncle at an area level 4 with a density level 3 (Figure 1D) were observed. INCIDENCE OF UNEXPECTED ADVERSE EVENTS IN HUMAN OCULAR INSTILLATION TESTS Studies on humans proceed only after a potentially suitable formulation has been iden­ tified as a result of irritation tests in animals and in vitro (4), minimizing the potential of unexpected adverse events during in vivo studies. The frequency of occurrence of adverse events was minimal in human ocular instillation studies. Of 205 human subjects who participated in ocular instillation studies from 1998 to 2003, only one subject Figure 1. Representative illustrations of ocular irritation induced by a cosmetic product.

ASSESSMENT OF OCULAR IRRITANCY 321 experienced an adverse event. This event, which occurred prior to test material instil­ lation, was unrelated to the test material or to the study procedures. Other evidence of the safety of this methodology is provided by the repeated willingness of subjects to enroll in these studies as well as the resolution of all observed ocular irritation during the course of the studies. SUBJECTIVE IRRITATION Average maximum score levels of subjective irritation (Figure 2), including stinging, burning, itching, dryness, and/or foreign body sensation, demonstrated that mascara and powder eye shadow exhibited mild to moderate irritation (2.8 ± 0.102 and 2.45 ± 0.182, respectively), which was statistically higher (p 0.05) than for the remaining product types, except for baby wash and eye makeup remover as compared to powder eye shadow. Liquid makeup with an average maximum score level of 0.5 ± 0.088 elicited significantly lower levels of reported subjective irritation than all other products (p 0.05). OBJECTIVE IRRITATION (SLIT LAMP BIOMICROSCOPE EXAMINATION) Objective ophthalmic evaluation consisted of examination of lacrimation, eyelid inflam­ mation, palpebral and bulbar conjunctiva! inflammation, and corneal abnormalities. No lacrimation, eyelid inflammation, or corneal abnormalities were observed for all product types. The average maximum score levels of combined palpebral and bulbar conjunctiva! inflammation scores (maximum combined score of 8) were significantly higher (p 0.05) for shampoo and baby wash, with scores of 4.075 ± 0.126 and 4.1 ± 0.16, respectively, than for liquid makeup, eye make�p ·remover, mascara, powder eye shadow, and facial 4 3.5 " 3 .J t 2.5 8 2 ,,, G) ! 1.5 G) 0.5 0 Liquid makeup Shampoo Baby wash Eye makeup remover Mascara Powder eye Facial cleanser shadow Figure 2. Average maximum levels of subjective irritation.