REDUCING THE NUMBER OF RABBITS IN EYE AND SKIN IRRITANCY TESTS

Reduction in the number of rabbits used for acute testing of irritatio n in the eye and skin is a worthwhile goal, and some recent publicatio ns have supported such reduction from six to three animals. In anticip ation of making such reductions in our laboratory, data from 185 eye a nd 179 skin irritation tests performed in-house were evaluated within the framework of several schemes of classification. Mean scores for ir ritation in all possible two, three, four, and five-rabbit subsets wer e compared to scores with all six rabbits. Parameters included mean we ighted Draize scores (eye) and Occupational Safety and Health Administ ration (OSHA) primary irritation index (skin). Classification of irrit ants is often based on scales with two or more categories of relative severity (e.g., nonirritating, mild, moderate, severe). Therefore, irr itation scores of each subset were grouped into two, three,four, or ri ve categories of irritation. Overall agreement of rankings for the sub sets was closer to rankings with six rabbits when fewer categories wer e used with greater numbers of animals in the subset. Mean agreement a cross all categories was >90% with three rabbits and four categories f or both eye and skin irritation. However, agreement within a given cat egory across subsets was best with nonirritants and least among irrita nts; eye irritants with mean weighted Draize scores of 16-35 had only approximately 76% agreement with 3 rabbits/subset. Comparisons were al so made between subsets of three rabbits and the original six rabbits using both the European Community (EC) system of mean values for eve i rritation and the OSHA system based on the number of individuals with ''positive'' scores. Agreement was better with the EC system. To maint ain accuracy within the framework of American guidelines, our laborato ry will continue to use six rabbits for regulatory studies. Other inve stigators should carefully evaluate the effect on accuracy of results before reducing the numbers of animals used per acute study.