5.2.2 OECD Test Guideline 425 — Up-and-Down Procedure (UDP)

The Up-and-Down Procedure dispenses with fixed group dosing in favour of sequential dosing of individual animals, with each subsequent animal's dose...

The Up-and-Down Procedure dispenses with fixed group dosing in favour of sequential dosing of individual animals, with each subsequent animal's dose adjusted upward or downward depending on whether the preceding animal survived. The starting dose is selected from the best available literature estimate of LD50 for the chemical class in question. A maximum of approximately fifteen animals is typically required — substantially fewer than either the traditional Lorke method or the classical LD50 determination it superseded. Dedicated statistical software (the US-EPA's AOT425 program) calculates the LD50 point estimate together with its 95% confidence interval from the resulting dose-response sequence. Because it achieves a valid LD50 estimate with markedly fewer animals, OECD 425 is preferred over older methods by both OECD and CDSCO, in direct alignment with the Reduction principle of the 3Rs.