Up-and-down procedure

Acute oral toxicity Up-and-down procedure for acute oral toxicity testing EU... 

Bruce, R. (1985). An up-and-down procedure for acute toxicity testing. Fund. Appl. Tox. 5 151, 157. 

Acute Oral Toxicity Up-and-Down Procedure (Updated Guideline, adopted 20 December 2001) (Statistical software)... 

There are three US-EPA OPPTS Test Guidelines for acute toxicity testing. OPPTS 870.1100 is similar to OECD TG 425 (Acute Oral Toxicity Up-and-Down Procedure). OPPTS 870.1200 and OPPTS 870.1300 are similar to OECD TG 402 and 403, respectively. 

The guidance document offers a comparison of TG 420 (Fixed Dose Method), TG 423 (Acute Toxic Class Method), and TG 425 (Up-and-Down Procedure). The purpose of this Guidance Document is to provide information to assist with the choice of the most appropriate Guideline to enable particular data requirements to be met while reducing the number of animals used and animal suffering. The Guidance Document also contains additional information on the conduct and interpretation of test guidelines 420, 423, and 425. 

Spielmann H, Genschow E, Liebsch M, and Halle W (1999) Determination of the starting dose for acute oral toxicity (LD50) testing in the up-and-down procedure (UDP) from cytotoxicity data. ATLA 27 957-966. 

How close do the above estimates relate to the actual LD50 Studies have shown that the approximate lethal dose for 86% of those chemicals tested in this manner were within 30% of the known LD50 values determined by the classical approach. The method is not infallible for example, some 14% of chemicals were outside this range and no dose-response or slope information can be obtained. International agreement has been reached that the up-and-down procedure could replace the conventional acute toxicity test for the purposes of hazard classification and label (including color-coding) production. 

The run-down method was developed at Frankford Arsenal, Philadelphia, and produces a more complete frequency and probability of reaction curve [22]. Although a larger number of tests is used than in the up-and-down procedure, the method makes possible a better evaluation of the distribution of the population. Starting at a level expected to be between 0% and 100% reactions levels, 20-25 tests are made at each of several levels above and below the starting level until the 0% and 100% levels are reached. The increments between the levels normally are equal to or less than the expected standard deviation. A cumulative probability curve is then plotted from the results of the entire test which is considered to be the frequency distribution of the population. 

Organisation for Economic Co-operation and Development. OECD Guideline for Testing of Chemicals, 425. Acute oral toxicity—up-and-down procedure, 2001. 

Merkel, D.J. (2004) Acute oral toxicity up and down procedure in rats. Unpublished report prepared by the Product Safety Laboratories, Dayton, NJ, USA, for the Flavor and Extract Manufacturers Association, Washington, DC, USA. Submitted to WHO by the International Organization of the Flavor Industry, Bmssels, Belgium (Study No. 16114). 

Repeated dose 28-day oral toxicity in rodents (OPPTS 870.3050 or OECD 407) Acute oral toxicity (OPPTS 870.1100/OECD 401, or OECD 425 ["Acute Oral Toxicity Up-and-Down Procedure"])... 

OECD, 2001c, Test Guideline 425, Acute Oral Toxicity—Up-and-Down Procedure. 

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