The files listed below include the program and associated documentation for conducting the Up-and-Down Procedure, an alternative acute toxicity test that provides a way to determine the toxicity of chemicals with fewer test animals by using sequential dosing steps.

The up-and-down method is used in the Series 870 Health Effects Test Guidelines for acute toxicity testing and by the Organisation for Economic Co-operation and Development member nations. It replaces the traditional acute oral toxicity test formerly used to characterize industrial chemicals, pesticides, and their mixtures.

This method maintains the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test.

• AOT425StatPgm (Executable)(1 pg, 2 MB)  

The AOT425StatPgm program to perform calculations required to implement the OECD Acute Oral Toxicity Test Guideline 425 procedure (OECD TG 425). The program calculates:

• the doses for the test animals;
• when to stop dosing animals; 
• the specified LD50; and
• a confidence interval for the LD50.

• AOT Test Data Set (Zip file)(1 pg, 117 K)

This is a self-extracting zip file that will install the program on your computer in two steps.

Note: This is to confirm that use of the computer program, AOT425StatPgm, developed by Westat for EPA, is freely given, and there are no licensing restrictions in connection with its use. The user is cautioned to read the User Documentation regarding any limitations and applicability and hardware requirements.

OPPTS Harmonized Test Guideline 870.1100 Acute Oral Toxicity

• User Documentation for the Acute Oral Toxicity (Guideline 425) Statistical Program (AOT425StatPgm) (PDF)(28 pp, 10 MB)
• OECD Test Guideline 425: Acute Oral Toxicity - Up-and-Down Procedure (PDF)(26 pp, 422 K)
• QA Testing for the AOT425StatPgm Program (PDF)(34 pp, 959 K)
• Simulation Results for the AOT425StatPgm Program (PDF)(183 pp, 1 MB)
• Toxicology Guidance: Performance of the Up-and-Down Procedure (PDF)(7 pp, 106 K)
• Crosswalk of Paragraphs: OPPTS 870.1100 versus OECD 425 Acute Oral Toxicity: Up-and-Down Procedure (PDF)(3 pp, 13 K)