Pg. Brantom et al., A SUMMARY REPORT OF THE COLIPA INTERNATIONAL VALIDATION-STUDY ON ALTERNATIVES TO THE DRAIZE RABBIT EYE IRRITATION TEST, Toxicology in vitro, 11(1-2), 1997, pp. 141-179
The principal goal of this study was to determine whether the results
from a set of selected currently available alternative methods as used
by cosmetics companies are valid for predicting the eye irritation po
tential of cosmetics formulations and ingredients and, as a consequenc
e, could be valid replacements for the Draize eye irritation test. For
the first time in a validation study, prediction models (PMs) that co
nvert the in vitro data from an assay to a prediction of eye irritatio
n were developed for each alternative method before the study began. T
he PM is an unequivocal description of the relationship between the bl
vitro and the in vivo data and allows an objective assessment of the
reliability and relevance of the alternative methods. In this study, 1
0 alternative methods were evaluated using 55 test substances selected
as representative of substances commonly used in the cosmetics indust
ry (23 ingredients and 32 formulations). Twenty of the single ingredie
nts were common to the European Commission/British Home Office (EC/HO)
eye irritation validation study (Balls et al., 1995b). The test subst
ances were coded and supplied to the participating laboratories. The r
esults were collected centrally and analysed independently, using stat
istical methods that had been agreed before the testing phase began. E
ach alternative method was then evaluated for reliability and relevanc
e in assessing eye irritation potential. Using the criteria of both re
liability and relevance as defined in the study, the preliminary resul
ts indicate that none of the alternative methods evaluated could be co
nfirmed as a valid replacement for the Draize eye irritation test acro
ss the full irritation scale. However, three alternative methods-the f
luorescein leakage test, the red blood cell assay (classification mode
l) and the tissue equivalent assay-each satisfied one criterion of rel
iability or relevance. Further investigation of the decoded data from
this study to explore more fully the relationship between the in vitro
data and the in vivo data is recommended. Such a review may allow the
development of new prediction models to be tested in a subsequent val
idation study. (C) 1997 Elsevier Science Ltd.