Fixed-dose procedure

The Fixed Dose Procedure (FDP), proposed in 1984 by the British Toxicology Society, is a method to assess a substance's acute oral toxicity.^[1] In this procedure the test substance is given at one of the four fixed-dose levels (5, 50, 500, and 2000 mg/kg) to five male and five female rats. The objective is to identify a dose that produces clear signs of toxicity but no mortality (22). Depending on the results of the first test, either no further testing is needed or a higher or lower dose is tested: If mortality occurs, retesting at a lower dose level is necessary (except if the original dose chosen is 5 mg/kg). If no signs of toxicity occur at the initial dose, it is necessary to retest at a higher dose level. The results are thus interpreted in relation to animal survival and evident toxicity (5) and it becomes possible to assign the chemical to one of the OECD classification categories.^[2]

In comparison to the older LD₅₀ test developed in 1927, this procedure produces similar results while using fewer animals and causing less pain and suffering.^[3] As a result, in 1992 this test was proposed as an alternative to the LD50 test by the Organisation for Economic Co-operation and Development under OECD Test Guideline 420.^[4] However, the U.S. Food and Drug Administration has begun to approve non-animal alternatives in response to research cruelty concerns and the lack of validity/sensitivity of animal tests as they relate to humans.^{[5] [6]}

See also

• Up-and-down procedure

References

1. Stallard, N.; A. Whitehead (1995). "Reducing animal numbers in the fixed-dose procedure". Human & Experimental Toxicology. 14 (4): 315–323. doi:10.1177/096032719501400401. Retrieved 10 Feb 2010.
2. Walum E (1998). "Acute oral toxicity". Environ. Health Perspect. Brogan &#38. 106 (Suppl 2): 497–503. doi:10.2307/3433801. JSTOR 3433801. PMC 1533392. PMID 9599698.
3. van den Heuvel MJ, Clark DG, Fielder RJ, et al. (1990). "The international validation of a fixed-dose procedure as an alternative to the classical LD₅₀ test". Food Chem. Toxicol. 28 (7): 469–82. doi:10.1016/0278-6915(90)90117-6. PMID 2210519.
4. Stallard, N.; A. Whitehead; P. Ridgway (2002). "Human & Experimental Toxicology". Human & Experimental Toxicology. 21 (4): 183–196. doi:10.1191/0960327102ht239oa.
5. "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX® and BOTOX® Cosmetic (onabotulinumtoxinA)". Source: Allergan, Inc. News Provided by Acquire Media. 24 June 2011. Retrieved 2011-06-26.
6. "In U.S., Few Alternatives To Testing On Animals". Washington Post. 2 April 2008. Retrieved 2011-06-26.

Further reading

• Stallard, N.; Whitehead, A. (1995). "Reducing animal numbers in the fixed-dose procedure". Human & Experimental Toxicology. 14 (4): 315. doi:10.1177/096032719501400401.