Draize Rabbit Eye Test Replacement Milestone Welcomed

Press Release:

The Dr Hadwen Trust for Humane Research has welcomed news that international
acceptance of non-animal methods to replace the infamous and unreliable Draize
rabbit test for severe eye irritancy, has now been achieved. Thousands of rabbits
will now be spared procedures where chemical substances, including for household
products and cosmetics, are applied to their eyes [1]. The UK charity, which funds
the development of techniques to replace animal experiments, is proud to have funded
early-stage research work in the 1980s that has now resulted in one of the
replacement methods approved.

Developed in 1944, the Draize rabbit eye irritation test has been the standard
method for evaluating the ocular irritation/corrosion potential of a substance for
regulatory purposes. However its use has long been controversial. It has been
scientifically criticised for many decades for its poor reproducibility and lack of
relevance due to species differences between rabbits and humans [2]. The animal
suffering it can cause has also been highlighted for years. Some 4,500 rabbits are
used in the European Union each year in eye irritancy tests [3] during which they
can experience swollen, sore and weeping eyes. Global use is likely to be
considerably higher.

Acceptance by the Organisation for Economic Cooperation and Development (OECD) means
that guidance is finally in place on how to conduct the tests for severe eye
irritancy without using live rabbits [4]. Two test-tube methods for assessing eye
irritation have been accepted by the OECD, the BCOP (Bovine Corneal Opacity and
Permeability) test and the Isolated Chicken Eye (ICE) test, both for identifying
ocular corrosives and severe irritants [5]. The Draize test will continue to be
conducted for substances that are not severe eye-irritants.

It has taken at least thirty years for alternative tests to be approved, with
research starting in the 1980s, scientific approval by the European Centre for the
Validation of Alternative Methods (ECVAM) coming in 2007 and now OECD acceptance in
2009 meaning that the test can be used globally.

“The Draize eye test has been scientifically and ethically discredited for many
years,” says the Dr Hadwen Trust for Humane Research’s Science Director Dr Sebastien
Farnaud, “so to replace it with test-tube methods that produce reliable results and
don’t cause animal suffering, is very welcome. The Dr Hadwen Trust is proud that its
research has been a part of the history of efforts to replace the Draize test, but
we sincerely hope that the final chapter in its total replacement will be a far
swifter process.”

The Dr Hadwen Trust for Humane Research can share in the success so far as the
charity was one of the first-ever funders to support research to replace the Draize
test. In the 1980s DHT-funded innovative research at Leicester Polytechnic that
resulted in the very first eye irritation test and forerunner of the BCOP test that
has now achieved OECD approval [6]. The Dr Hadwen Trust no longer funds research
using animal tissues or cells, but our project represented a turning point in
international efforts to replace the Draize test.

It is highly regrettable that it has taken some thirty years to achieve
international acceptance of these replacement solutions. Whilst funding, industry
support for alternatives and consequently the speed of method development has
significantly improved in recent years, unnecessary delays in the validation process
remain a problem. A particular issue is that animal test data are still treated as
the ‘gold standard’ against which alternative tests are compared in order to achieve
scientific validation. However when animal data are of such poor and variable
quality such as the rabbit eye test, the process of replacing scientifically weak
animal methods can be delayed by years.

Notes:
1. Adult albino rabbits are most commonly used for eye irritancy tests because they
have eyes with a large surface area. At least three animals are used per test
substance. The test involves applying the substance directly into one eye (the other
eye acting as a control) and observing effects for up to 21 days.
2. For example Weil & Scala (1971) Toxicol.Appl.Pharmacol. 17,276-360; Freeberg et
al. (1986) J. Toxicol.Cut.Ocular Toxicol. 5, 115-123; Koch et al. (1989) J.Toxicol
Cut.Ocular Toxicol. 8, 17-22; Preliminary Evaluation of the Under-prediction Rate of
the In Vivo Dermal Irritation Test Method Part I: Introduction William S. Stokes,
D.V.M., D.A.C.L.A.M. Director, NICEATM Scientific Advisory Committee on Alternative
Toxicological Methods October 20, 2004, Research Triangle Park, NC.
3. Latest statistics available from the European Commission are for 2005

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2007:0675:FIN:EN:HTML

4. The OECD adopted the new methods on 7 September 2009

http://www.oecd.org/document/22/0,3343,en_2649_34377_43680406_1_1_1_1,00.html

5. The BCOP assay uses enucleated cow eyes that would otherwise be discarded at
slaughterhouses. The cornea is isolated from the rest of the eye and maintained in a
holder. A test substance is applied to this isolated cornea for a specified time
then removed, and the effect of the substance on the permeability of the cornea to
fluorescein (a coloured dye) and the increase in corneal opacity (transmission of
light through the cornea) are determined. The Isolated Chicken Eye assay uses
enucleated chicken eyes obtained from slaughterhouses. The eyes are placed in an
apparatus, kept moist and treated with the test substance. Three responses of the
cornea are evaluated: corneal swelling, corneal opacity and fluorescein retention.
The irritation potential of a substance is calculated from the mean values of these
measurements.
6. The Dr Hadwen Trust funded Dr Colin Muir, a research fellow at Leicester
Polytechnic. Dr Muir developed the ‘opacitometer’ which shines a light beam through
the isolated cornea enabling an objective measurement of changes in its opacity.
His publications between 1984 and 1987 are acknowledged as providing the essential
groundwork and inspiration for the BCOP test.

Filed under Uncategorized | Comment (1)