THE INTERNATIONAL VALIDATION-STUDY OF THE ACUTE TOXIC CLASS METHOD (ORAL)

An alternative to the oral LD(50) test, the acute toxic class (ATC) me thod (oral), was validated with 20 substances in an international coll aborative study with nine laboratories in five countries. The ATC meth od is a stepwise procedure with the use of three animals per step. It has been designed with three fixed doses (25, 200 and 2000 mg/kg). In general, this testing is sufficient for allocation to the toxicity cla sses of the majority of the international classification systems curre ntly in use. The selection of testing at additional fixed doses (5, 50 and 500 mg/kg) may be considered if further refinement is necessary o r for specific allocation to those international classification system s with a cut-off value of 5 mg/kg. On average, two to four steps are n ecessary to complete a test. With the ATC method substances can be ran ked in a similar or even better manner than with an LD(50) test but it uses up to 90% fewer animals, the average being 70% fewer. This also results in substantially fewer moribund/dead animals. The ATC method i s based on biometric evaluations that, together with the experimental results, demonstrate that this method is a sensitive and reliable alte rnative to the LD(50) test.