National Toxicology Program

The Draize rabbit eye test has been in use since 1944 to evaluate the risk of substances to cause irritation or corrosion to the eyes. This test presents the potential for pain and distress in rabbits after application of a severely irritating or corrosive substance. Alternative approaches have been proposed and developed to reduce the number of animals used or refine (reduce pain and suffering) these tests. In 2005, experts at a 2005 symposium Minimizing Pain and Distress in Ocular Toxicity Testing (see below) made the following recommendations:

• Topical anesthetics and systemic analgesics should routinely be administered before ocular testing to avoid or minimize pain and distress that might occur during and after the initial application of test articles.
• Systemic analgesics should routinely be administered when there is evidence of potentially painful ocular damage or when there are clinical signs indicative of pain or distress.
• Specific ocular injuries identified by the experts that would not be expected to reverse within 21 days could be used as humane endpoints to end a study early.

ICCVAM requested data (see Federal Register notice below) and then compiled available information on using topical anesthetics or systemic analgesics. An independent scientific peer review panel meeting in May 2009 will review the available information and comment on draft ICCVAM recommendations for the routine use of analgesics, anesthetics, and humane endpoints.

Federal Register Notice (Vol. 74, No. 60, page 14556-14557, March 31, 2009):
Announcement of an Independent Scientific Peer Review Panel on Alternative Ocular Safety Testing Methods; Availability of Draft Background Review Documents (BRD); Request for Comments

Federal Register Notice (Vol. 72, No. 89, page 26396, May 9, 2007):
Request for Data on the Use of Topical Anesthetics and Systemic Analgesics for In Vivo Eye Irritation Testing

NICEATM Presentations at 2007 Society of Toxicology and Sixth World Congress on Alternatives and Animal Use Meetings

Using data generated during testing of test substances to comply with regulatory requirements of governmental agencies, NICEATM staff conducted analyses evaluating of the effect of topical application of a tetracaine hydrochloride ophthalmic anesthetic solution on the irritancy potential of test substances evaluated using a sequential testing scheme. The results of these analyses were presented by NICEATM staff at two major scientific meetings in 2007.

Symposium on Minimizing Pain and Distress in Ocular Toxicity Testing

In May 2005, ICCVAM, NICEATM, and the European Centre for the Validation of Alternative Methods (ECVAM), organized a Symposium on Minimizing Pain and Distress in Ocular Toxicity Testing. The symposium was sponsored by ICCVAM, NICEATM, ECVAM, and the European Cosmetic, Toiletry and Perfumery Association. The goals of this symposium were to:

• Review current understanding of the sources and mechanisms of pain and distress in ocular toxicity testing
• Identify current best practices for preventing, recognizing, and alleviating ocular pain and distress
• Identify additional research, development, and validation studies necessary to support scientifically valid ocular toxicity testing procedures that avoid pain and distress

• Pre-treatment with topical or general anaesthesia should be used routinely to avoid pain from topical application of test substances
• Systemic analgesics should be administered prior to test article application and continued until injuries resolve or the study is terminated
• Ocular injuries predictive of severe or irreversible ocular damage should be used as earlier humane endpoints
• Objective, quantitative measurements should be collected during ocular studies to assist in identifying earlier, more humane endpoints. Data from these measurements are also critical to the development and validation of more predictive in vitro methods.

View information about the Symposium