Reducing the number of rabbits in the Draize eye irritancy test: A statistical analysis of 155 studies conducted over 6 years*1

Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*1

“…Currently, eye irritation assays use a systematic numeric scoring system to quantify irritation in the albino rabbit (4,6,13). Although in vivo eye irritation tests provide important and useful information, they have been criticized for their subjectivity (4,26), their lack of repeatability (4,38), and their overprediction of human responses (4,17,31) and by animal welfare advocates because they require the use of animals (4,35). Thus, there is great interest in developing alternative methods to allow ocular safety assessments to be made more accurately and without the use of animals (4)(5)(6).…”

Soaps and Detergents: Alternatives to Animal Eye Irritation Tests

“…One is that the rabbit eye differs from the human eye in that it has a thinner cornea, a nictitating membrane (third eyelid), a different tearing mechanism, and a higher pH of the aqueous humor; thus, the rabbit eye is usually more sensitive to chemical insult than the human eye. Furthermore, the relevance of the test to human hazard evaluation is questionable because most testing protocols require application of the chemical into the lower everted eyelid and subsequent closure of the eyelids for 1-2 s. Such exposure is not representative of the typical human exposure to eye irritants (Talsma et al, 1988). Finally, the Draize eye irritation test is costly in terms of time and resources, uses significant numbers of animals, and may be painful to the test animals.…”

“…Primary dermal irritation tests are not reliable substitutes for in vivo ocular irritation assays (Gilman et al, 1983). Talsma et al (1988) reported that highly accurate testing could be performed with fewer animals than the usually required six and that sample size could be reduced to three and still preserve very good accuracy. Topical ophthalmic anesthetics were proposed to lessen pain in test animals, but their use was not found to be entirely satisfactory (Seabaugh et al, 1993).…”

Using fewer animals to identify chemical eye hazards: Revised criteria necessary to maintain equivalent hazard classification

“…Results from DeSousa et al (1984) and Talsma et al (1988) showed that using 3 rabbits per test provided accuracy of up to 94% in predicting a 6-animal test (using subsets of 3 animals). Springer et al (1993) also conducted analyses to determine if the standard group size of 6 rabbits for ocular safety testing could be reduced in order to use fewer animals and concluded that a 3-animal test and a decision rule requiring at least 2 positive animals to classify a substance as an irritant yielded accuracy of 98%.…”