Objective To evaluate the operability and results consistency among four acute oral toxicity testing methods and analyze the application value of these methods to acute oral toxicity assessment.
Methods Traditional Horn's procedure and three alternative methods including fixed dose procedure (FDP), up-and-down procedure (UDP), and acute toxic class method (ATC) were applied to assess the acute oral toxicity of selected chemicals of P-phenylenediamine, hydroquinone, and boracic acid to rats. The consistency of results, manipulation of experimental animal, dose selection, and observed indicators were compared among these four procedures.
Results The Globally Harmonized System (GHS) grades of the three alternative methods are consistent with those of Horn's. The three alternative methods with sequential principle used less experimental animals but required a longer testing period. FDP and ATC methods did not provide accurate LD50 values and not take animal death as final result judgment standards; therefore, the two methods reduced the mortality rate of experimental animals and improved animal welfare. UDP was similar with Horn's method in terms of relatively fixed dose progression factor, taking animal death as an important result judgment indicator, and providing exact LD50 values and corresponding confidence intervals, but UDP was more suitable for the evaluation of acute toxicity resulting in death within 48 h after exposure.
Conclusion According to the properties and available data of test substances, we could adopt appropriate alternative method to replace Horn's method for acute oral toxicity assessment.
DownLoad: