3.3. Eye Irritation

The eye can be exposed to cosmetic products and their ingredients, either through use of products that are meant to be used around the eyes (for example, mascaras, eye creams) or through accidental exposure to products that may enter the eye in diluted form during normal use, but are not meant to come into contact with the eye undiluted (for example, shampoos). An evaluation of eye irritation potential for a cosmetic product and its ingredients is therefore essential, to provide reassurance that a product is safe for consumers to use through intended and foreseeable uses or accidental exposure of the eyes. The conventional test for the irritant and corrosive potential of chemicals is the rabbit eye test, which was developed by Draize et al. (1) and which has become the international standard assay for acute ocular toxicity (OECD TG 405, 2; EC B.5, 3). The test material is applied to the conjunctival sac of the eye of the animal, and subsequent physiological responses are classified by careful visual examination of the cornea, iris and conjunctiva, and given a numerical score. A variety of different scoring systems for assessing the extent of injury to the corneal, the iridial and the conjunctival compartments are currently applied in different regulations, ranging from maximum single tissue scores to averaged weighed sum scores for all three tissues (c.f. 4–6). Whereas for the safety assessment of cosmetics, weighed sum scores, the maximum average score (MAS) and the modified maximum average score (MMAS, i.e. not including the results obtained 1 hour after treatment) are still in use, the OECD and the United Nations, together with other international regulatory authorities have recently agreed a Globally Harmonised System of Classification and Labelling of Chemicals (GHS; 7). This is based on averaged single tissue observations, taking into account reversibility of the observed effects. The Draize test serves four major goals: a) identification of severely irritant and corrosive substances (according to EU classification R41); b) testing moderate eye irritation potential (according to EU classification R36); c) safety assessment for cosmetics; and d) safety assessment for ophthalmic pharmaceuticals. The test can be very painful to the rabbits and has two other major shortcomings: subjectivity in the allocation of the respective scores, i.e. low interlaboratory reproducibility (8–10), and differences in sensitivity to tested substances between rabbits and humans (11). Some modifications have been proposed over the years, in order to reduce the pain to be endured by the animal and to achieve higher rates of recovery, such as in the low volume eye test (LVET), in which only a tenth of the sample volume used in the standard Draize test is applied to the cornea and the eyes are not held shut after instillation of the test material (12). Moreover, reduction and refinement approaches are now included in a sequential testing strategy published as a supplement to OECD TG 405 and EC B.5 (2, 3), whereby the in vivo rabbit eye test needs only to be performed as a last step, i.e. when the assessments in all the other tiers have produced negative results, to assess mildly to moderately irritant compounds. However, this strategy does not eliminate the need for an in vivo test, and there is potential for over-classification of the eye irritancy potentials of chemicals.