The dermal acute toxic class method: test procedures and biometric evaluations.

Abstract

A dermal acute toxic class (ATC) method is presented with the use of significantly fewer animals in comparison with the classical dermal 50% lethal dose (LD50) test. The principle of the dermal ATC method is based on the oral and the inhalation ATC method. The method was developed for three fixed starting doses. Depending on the dermal LD50, the slope, the classification system and the starting dose on average 40 to 90% fewer animals will be used in comparison to at least 30 animals with the dermal LD50 test. The method was biometrically evaluated by using the Probit model for dose-response relationships. At present, there are eight different international classification systems based on dermal LD50 values. The test procedures and the calculations of the classification probabilities demonstrate that the dermal ATC method is a reliable alternative to the dermal LD50 test with the use of significantly fewer animals. Classification probabilities are presented for all classification systems currently in use, and expected numbers of experimental and of moribund/dead animals are demonstrated for the system of chemicals in the European Union for all three starting doses. The conclusion is justified that, similarly to the inhalation ATC method, there is no need to validate the dermal ATC method with the use of experimental animals.