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
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. This page was last updated May 9, 2007 Contact the webmaster Return to the NICEATM/ICCVAM Home Page |