Guinea Pig Maximization Test

In the GPMT, three groups of animals are used with 20-25 animals in each group. One group receives intradermal injections of Freund's complete adjuvant (FCA). The second group receives an intradermal bolus of the test material. The induction group is immunized with both FCA and the test material at a dose that causes mild to moderate skin irritation. After 7 days, the animals receive an epicutaneous application of test material in petrolatum. This challenge dose is usually the highest nonirritating concentration. To promote contact with the skin, the material is covered with a surgical dressing for 48 hr. Twenty-one days after the initial exposure, the animals are challenged for 24 hr with a topical application of the test material and the intensity and duration of the skin reactions are determined relative to controls (Burrell etal., 1992).

The GPMT method has several disadvantages (Robinson et al., 1989) and does not provide an absolute standard. The method bypasses the skin barrier that normally prevents chemical penetration. By bypassing the skin barrier at induction, the GPMT can overstate the sensitization risk of epicutaneous exposure to weak sensitizers (Robinson et al., 1989) and can understate the risk to very strong sensitizers possibly through tolerance induction (Buehler and Ritz, 1985). Also, the method gives false-negative responses with weaker contact allergens (Goodwin etal., 1981).

Because the FCA is a potent immune system stimulator, caution should be used in the interpretation of data from sensitization methods using FCA (Buehler, 1996). FCA increases responses to the vehicle. It is also possible that FCA increases hyperreactivity to several alternate vehicles. Nonspecific hyperreactivity in the vehicle control group may contribute to the poor reproducibility in repetitive testing studies (Marzulli and McGuire, 1982).

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