Comparison of dose-responses of contact allergens using the guinea pig maximization test and the local lymph node assay

The guinea pig maximization test (GPMT) has been used as a method for the p rediction of skin sensitizing potential for over 30 years. Besides hazard i dentification, risk assessment of sensitizing chemicals requires the assess ment of potency. For the determination of potency based on lowest effective dose levels, dose-response studies are required. In the standard GPMT a si ngle concentration is used for intracutaneous and topical induction and the assay provides a qualitative assessment of allergenicity. This paper prese nts data derived from quantitative evaluation of the sensitizing potency of chemicals in the GPMT, based on multiple concentrations. We performed the GPMT in accordance with the original procedure of Magnusson and Kligman; an d included in this procedure a range of intradermal and topical concentrati ons for induction. Three allergens with different sensitizing potencies, di ethylamine (DEA), tetramethyl thiuram disulfide (TMTD) and zinc dimethyl di thiocarbamate (ZDMC) were tested. The data obtained with this test procedur e were compared to data we previously obtained using the local lymph node a ssay (LLNA). Both the GPMT and the LLNA showed dose response relationships for the three chemicals tested. For the chemicals tested, both tests differ ed in the relative potencies based on benchmark concentrations. While both tests ranked DEA as the least potent allergen, the GPMT ranked ZDMC more po tent than TMTD, the reverse being found in the LLNA. The nature of the data provided in the LLNA makes it likely that benchmarks as defined with this test are more reliable than that defined in the GPMT. However, further vali dation with human data is necessary. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.