This test is found in the main body of the document.
The rabbit is the preferred model.
When the test material is to be tested directly, the sample preparation is performed according to an associated annex. If the potential for irritation is suspected, start with one initial pre-screening animal. If there is not a well defined reaction in the first animal, 2 more animals for direct or 2 more animals per extract are subsequently dosed.
Three, 2 kg or greater rabbits of either sex from a single strain are used. Shaving of the fur is performed 4 to 24 hours before dosing. Depilatories are permitted if used by trained personnel and the process is validated in the laboratory. Based upon the clinical use of the test material, there is the possibility of repeated exposure up to 21 days.
The test materials is delivered as a dose of 0.5 ml or 0.5 grams, moistened if necessary. The test material is applied to both sides of each animal. The test material is applied for a 4 hour exposure. Any residual material is removed.
Observations (scoring) is made one hour and at 24, 48, and 72 hours post-removal. Scoring may be made out to 14 days if necessary based on the results observed. The skin is graded on a 5 point scale ranging from no(0), very slight(1), well-defined(2), moderate(3), to severe(4) for both erythema and edema. Only the 24, 48, and 72 hour scores are used for overall calculation.
How to calculate the score is explained as an overall mean score from all animals, all scoring observations and both scoring categories.
The final scoring determination is an irritation grade called the Primary Irritation Index which has scoring ranges including negligible, slight, moderate and severe with corresponding numerical scores from 0.0 to 8.0 with 8.0 being the maximum possible score for a single time point at any given site. Therefore the calculation of the primary irritation index is the overall mean score for all sites of all animals.
The rabbit is the preferred model.
When the test material is to be tested directly, the sample preparation is performed according to an associated annex. If the potential for irritation is suspected, start with one initial pre-screening animal. If there is not a well defined reaction in the first animal, 2 more animals for direct or 2 more animals per extract are subsequently dosed.
Three, 2 kg or greater rabbits of either sex from a single strain are used. Shaving of the fur is performed 4 to 24 hours before dosing. Depilatories are permitted if used by trained personnel and the process is validated in the laboratory. Based upon the clinical use of the test material, there is the possibility of repeated exposure up to 21 days.
The test materials is delivered as a dose of 0.5 ml or 0.5 grams, moistened if necessary. The test material is applied to both sides of each animal. The test material is applied for a 4 hour exposure. Any residual material is removed.
Observations (scoring) is made one hour and at 24, 48, and 72 hours post-removal. Scoring may be made out to 14 days if necessary based on the results observed. The skin is graded on a 5 point scale ranging from no(0), very slight(1), well-defined(2), moderate(3), to severe(4) for both erythema and edema. Only the 24, 48, and 72 hour scores are used for overall calculation.
How to calculate the score is explained as an overall mean score from all animals, all scoring observations and both scoring categories.
The final scoring determination is an irritation grade called the Primary Irritation Index which has scoring ranges including negligible, slight, moderate and severe with corresponding numerical scores from 0.0 to 8.0 with 8.0 being the maximum possible score for a single time point at any given site. Therefore the calculation of the primary irritation index is the overall mean score for all sites of all animals.
