In vitro alternatives to the use of animals in ocular toxicology testing

Chemical substances, including household products, industrial chemicals, and cosmetics, must be tested for ocular toxicity or irritancy so that the public can be assured of their safety or warned of dangers associated with their use. The in vivo Draize test is the standard method used to meet this requirement; however, this test is coming under increasing criticism on scientific and ethical grounds. This has led to the development of a large number of proposed in vitro tests, some of which are routinely used to screen chemicals in toxicology laboratories. This review addresses regulations governing ocular irritancy testing and the current status of the movement toward use of alternative methods. Such methods include the use of cultured cells, hen's eggs, isolated animal eyes and corneas, human corneal epithelial cell lines, and the recently developed in vitro corneal equivalent models. The protocols for these methods are outlined, and their endpoints are described with respect to prediction of in vivo responses. The tests are evaluated in the context of the outcomes of validation studies and acceptance by regulatory agencies. While several of these tests yield useful information concerning ocular irritancy, to date, no in vitro alternative test has been validated as a replacement for the Draize test. If the goal of replacing the in vivo test while protecting the public from chemical eye injury is to be achieved, further development and improvement of alternative tests, as well as establishment of a human ocular toxicity data base, are required.