Oral acute toxic class method: a successful alternative to the oral LD50 test

• Published in: Regulatory toxicology and pharmacology Vol. 42; no. 1; pp. 15 - 23
• Main Authors: Schlede, Eva, Genschow, Elke, Spielmann, Horst, Stropp, Gisela, Kayser, Detlev
• Format: Journal Article
• Language: English
• Published: Netherlands 01.06.2005
• Subjects: Administration, Oral; Animals; International Agencies - trends; International Cooperation; Lethal Dose 50; Toxicity Tests - methods; Toxicity Tests - trends; Toxicity Tests, Acute - methods
• ISSN: 0273-2300
• DOI: 10.1016/j.yrtph.2004.12.006

The oral acute toxic class method (ATC method) was developed as an alternative to replace the oral LD50 test. The ATC method is a sequential testing procedure using only three animals of one sex per step at any of the defined dose levels. Depending on the mortality rate three but never more than six animals are used per dose level. This approach results in the reduction of numbers of animals used in comparison to the LD50 test by 40-70%. The principle of the oral ATC method is based on the Probit model and it was first evaluated on a biometric basis before a national and subsequently an international ring study were conducted. The results demonstrated an excellent agreement between the toxicity and the animal numbers predicted biometrically and observed in the validation studies. The oral ATC method was adopted as an official test guideline by OECD in 1996 and was slightly amended in 2001. The ATC method has been successfully used in Germany and in 2003 >85% of all tests on acute oral toxicity testing was conducted as oral ATC tests. In member states of the European Union the ATC method is used in the range of 50% of all tests conducted. Meanwhile the oral LD50 test has been deleted by OECD, by the European Union and by the USA, making the use of alternatives to the oral LD50 test mandatory.