Fixed-dose procedure

Fixed dose procedure for acute oral toxicity testing Fixed dose procedure for acute oral toxicity testing EU... 

Fixed Dose Procedure. The fixed dose design (Figure 5.7) was proposed by the British Toxicology Society (1984). It is designed to supply the data needed for classification or labeling purposes. It is essentially a three-step limit test. 

FIGURE 5.7. British Toxicology Society fixed dose procedure. 

The fixed dose procedure is relatively new and apparently results in a large decrease in animal usage. It is also noteworthy in that it utilizes not only lethality but also evident toxicity, which, in all likelihood, refers to obvious signs of CNS effect, such as seizures or prostration. Whether or not this protocol design becomes widely accepted by various regulatory agencies remains to be established. 

TABLE 5.2. Comparison of Toxicity Classification Based on LD50 versus Fixed Dose Procedure... 

Acute Inhalation Toxicity - Fixed Dose Procedure, Draft Revised Guideline (June 2004)... 

The following draft guidelines are being developed by the OECD TG 433 (Acute Inhalation Toxicity-Fixed Concentration Procedure), TG 434 (Acute Dermal Toxicity-Fixed Dose Procedure),... 

B.lbis Acute oral toxicity - Fixed dose procedure 2004... 

As mentioned above, a NOAEL is usually not derived in acute toxicity smdies. It is more usual that the only numerical value derived is the LD50 or LC50 value. The LD50 or LC50 values (or the discriminating dose if the Fixed Dose Procedure was used or the result of the Acute Toxic Class Method) give an indication of the relative lethal potency of a substance. The slope of the dose-response curve is a particularly useful parameter as it indicates the extent to which reduction of exposure will reduce the lethality the steeper the slope, the greater the reduction in response for a particular finite reduction in exposure. 

LD50 = 50% lethal dose. It should be emphasized (even in a book for organic chemists) that the LD50 test is now outdated because of the large number of mammals necessary to carry out such tests (see Zbinden, 1981). The European Community issued a statement (Anonymous, 1990) of its intention to replace the LD50 test by the so-called Fixed Dose Procedure. 

OECD, 2001a, Test Guideline 420, Acute Oral Toxicity—Fixed Dose Procedure. 

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