Dose-response studies of contact allergens using 3 guinea pig models

A multi-dose-response induction protocol for the guinea pig maximization te st (GPMT), including a statistical computer program, has earlier been devel oped to improve the power of predictive tests for identification of contact allergens. This dose-response protocol, with 2 modifications (i.e., increa sed number of animals in each group and increased number of challenge conce ntrations) was evaluated in the GPMT, the cumulative contact enhancement te st (CCET) and the Freund's complete adjuvant test (FCAT), using potassium d ichromate and hydroxycitronellal as model contact allergens. Application of the dose-response protocol on the CCET and the FCAT resulted in either mon otone or non-monotone curves with significant dose-response. However, appli cation of the dose-response protocol on the GPMT gave curves with no signif icant dose-response. The protocol makes it possible to obtain an EC50 value , thus improving the possibility of ranking contact allergens, which is of substantial use for risk assessments. The dose-response protocol could bene fit from a few adjustments: a wider span in the induction doses; change to simultaneous increase in intradermal and topical induction doses to obtain a proper dose-response for the GPMT the addition of further challenge conce ntrations. In addition the computer program should allow calculation of thr eshold concentration for sensitization and EC50 value for a non-monotone cu rve.