Acute Toxic Class Methods: Alternatives to LD/LC50 Tests

Abstract

The Acute Toxic Class (ATC) methods for the oral, dermal and inhalation routes were developed as alternatives to the respective LD/LC50 Tests. The ATC methods use at least 40% (and up to 90%) fewer animals and their reliability with respect to classification probabilities into one of several toxicity classes is in the same order of magnitude or even better in comparison to the LD/LC50 Tests. The ATC methods are stepwise procedures with the use of three fixed starting doses/concentrations, three animals per step and a maximum of 6 animals per dose/concentration. The outcome (numbers of dead or moribund animals) will determine if further testing is necessary or if the test is terminated. Like the previous tests the biometric basis of the ATC methods is the Probit model. The oral ATC method is already an official Test Guideline of the OECD and the EU and it is widely used for the notification of new chemicals in the EU. This oral ATC method was validated by two animal ring studies together with biometric evaluations. With respect to classification probabilities and expected animal numbers the agreement between animal data and biometric evaluations was very good. Therefore for the dermal and inhalation routes of administration the ATC methods were entirely developed on a biometric basis. These two methods have still to be adopted by OECD. However, in view of the recently agreed Global Harmonisation System (GHS) of classification for acute toxicity all three ATC methods have to be revised in order to include these new classification systems.