Minimizing pain and distress in ocular safety testing: Current best practices and research needs

WS Stokes¹, K Gupta², D Lowther³, W Chambers³, M Wind², M Snyder⁴, A Jacobs³, R Bronaugh³, DG Allen⁵, RR Tice⁵, J Merrill³, LM Schechtman³

1. NIEHS, NICEATM, RTP, NC, USA
2. U.S. CPSC, Bethesda, MD, USA
3. U.S. FDA, Rockville, MD, USA
4. NIH, Bethesda, MD, USA
5. Integrated Laboratory Systems, Inc./NICEATM, RTP, NC, USA

Rabbit eye testing has been used effectively for over 60 years to safeguard human health by identifying and classifying chemicals and products that have the potential to cause temporary or permanent eye damage. However, pain and distress may occur in such testing from the initial application of the test substance and from subsequent chemically-induced damage to ocular tissues. Current test guidelines attempt to avoid and minimize animal pain and distress by allowing ocular hazard decisions to be made in some situations without the use of animals, and requiring only 1-3 animals in most situations where animals must be used. Current guidelines also seek to minimize pain and distress by allowing the use of pre-application treatment with topical anesthetics. However, regulatory guidelines state that such agents should not interfere with the outcome of the study. The lack of information about potential interference has precluded the routine use of pre- and post-application analgesics and topical anesthetics. Current guidelines also seek to reduce the duration of pain and distress by allowing for humane euthanasia of animals that develop severe ocular lesions or that exhibit severe and enduring signs of pain and distress. If identified, predictive biomarkers could serve as humane endpoints for terminating studies in order to avoid potential pain and distress. Additional research is needed to support the identification and use of humane endpoints, analgesics, and topical anesthetics that will further minimize or eliminate pain and distress in routine ocular toxicity testing. Related recommendations from a recent ICCVAM-NICEATM-ECVAM symposium will be discussed.

Date: Wednesday, August 24, 2005, 14.00Ð16.00 h, ECC Hall D

5.5 Session: Advancements and Needs for Developing and Validating Alternatives for Ocular Irritancy and Corrosivity Testing