The 21-day human cumulative irritation test can be reduced to 14 days without loss of sensitivity

The 21-day cumulative irritation test for assessing the irritancy of topical products and chemicals is a venerable procedure that appears to have become the gold standard for manufacturers. Berger and Bowman in 1982 (1) showed that reducing the exposure to 14 days was less traumatic to the volunteers, less costly, less arduous, and did not affect reliability or the capacity to place the test agents in the proper rank order of irritancy. In the current study we compared (a) the 21-day cumulative irritation test, (b) the 14-day cumulative irritation test, and (c) the 14-day test with every-other-day patching. Additionally, ten-day, seven-day and four-day data from the 21-day test were compared. Forty-one subjects completed this study of six test materials. Two sets of patches were applied to each subject' lower back. One set had 21 consecutive applications of the test articles. The second set was applied, and removal of the test articles occurred Monday, Wednesday, and Friday for 14 days. The 21-day test fully differentiated the test materials from each other. Using only the first 14 days of the 21-day test also fully differentiated the test materials. Every-other-day patching rank ordered the test materials the same as the everyday patching, but full differentiation of the test materials was not obtained. We conclude that the 14-day cumulative irritancy test is as reliable and sensitive as the 21-day test, along with the obvious advantages in time, cost, and minimization of trauma to the test subjects.