Estimated under- and over-classification rates for a 1-3 rabbit sequential Draize rabbit eye test

J Haseman¹, RR Tice², DG Allen², NY Choksi², WS Stokes³

1. Consultant, Raleigh, NC, USA
2. Integrated Laboratory Systems, Inc./NICEATM, RTP, NC, USA
3. NICEATM/NIEHS, RTP, NC, USA

ICCVAM is evaluating four in vitro assays for their ability to detect ocular corrosives/severe irritants in a weight-of-evidence tiered testing strategy. Ideally, this analysis would evaluate the ability of alternative assays and the Draize eye test to each correctly predict human ocular toxicity. However, the lack of appropriate human data only allows for a determination of how well alternative assays predict the rabbit response. In assessing the performance of alternative assays, information on the Draize eye test reliability would be useful but the paucity of repeat test data precludes an accurate estimate of inter- and intra-laboratory reproducibility. However, Draize eye test results can be used to estimate the likelihood of underclassifying a positive substance or overclassifying a negative substance using the current 1-3 rabbit sequential test. Data from Draize eye testing using 3-6 animals was obtained for ~900 substances from U.S. Federal regulatory agencies, published studies, and scientists and organizations. Ocular irritation categories were assigned based on the 2003 UN Globally Harmonized System of Classification and Labeling of Chemicals. Assuming either a homogeneous or a heterogeneous response among rabbits within a classification category, the distribution of individual rabbit responses was used to estimate the likelihood of under- and over-classification for a 1-3 rabbit sequential testing strategy. The estimated underclassification rate for corrosives/severe irritants that induced any severe response was <10%; rates were higher when this classification was based on only lesion persistence at day 21. Estimated overclassification rates will also be presented. Supported by NIEHS contract N01-ES 35504.

P162

Date: Tuesday, August 23, 2005, 13.00-14.00 h

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