THE VALUE AND LIMITATIONS OF RECHALLENGE IN THE GUINEA-PIG MAXIMIZATION TEST

The guinea pig maximization test (GPMT) has played a primary role in t he evaluation of potential skin contact sensitizers for 25 years. In t he OECD Guideline 406 from 1993, it is specifically suggested that equ ivocal results from the initial challenge in the GPMT should be evalua ted further with a repeated challenge. However, there exist few publis hed rechallenge data and the guideline does not describe how rechallen ge data should be interpreted. In this paper, we have used examples fr om published results to illustrate both the positive value and the lim itations of repeated challenges, including cross challenge. Testing wi th modified concentrations may also help to indicate whether or not th e response is allergic in nature, particularly where there has been a low level of skin reaction observed in shamtreated controls, or where a low level of skin reaction is the dominant response in the test anim als. In conclusion, the data presented demonstrate that, as a tool for the investigation of skin sensitizing potential, the GPMT can benefit from an experienced scientific evaluation of rechallenge data, but th at this information should not be treated in a mechanistic fashion.