Fixed-dose procedure

The fixed-dose procedure (FDP), proposed in 1992 by the British Toxicology Society, is a method to assess a substance's acute oral toxicity. ^{[1] [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.; Whitehead, A. (2 July 2016). "Reducing animal numbers in the fixed-dose procedure". Human & Experimental Toxicology. 14 (4): 315–323. doi:10.1177/096032719501400401. PMID   7598991. S2CID   37663587.
2. Walum, E (April 1998). "Acute oral toxicity". Environmental Health Perspectives. 106 (Suppl 2): 497–503. doi:10.1289/ehp.98106497. JSTOR   3433801. PMC   1533392 . PMID   9599698.
3. van den Heuvel, M.J.; Clark, D.G.; Fielder, R.J.; Koundakjian, P.P.; Oliver, G.J.A.; Pelling, D.; Tomlinson, N.J.; Walker, A.P. (January 1990). "The international validation of a fixed-dose procedure as an alternative to the classical LD50 test". Food and Chemical Toxicology. 28 (7): 469–482. doi:10.1016/0278-6915(90)90117-6. PMID   2210519.
4. Stallard, N; Whitehead, A; Ridgway, P (2 July 2016). "Statistical evaluation of the revised fixed-dose procedure". Human & Experimental Toxicology. 21 (4): 183–196. doi:10.1191/0960327102ht239oa. PMID   12099620. S2CID   45430481.
5. "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX® and BOTOX® Cosmetic (onabotulinumtoxinA)" (Press release). Allergan. June 24, 2011. Retrieved May 19, 2020.
6. Gaul, Gilbert M. (12 April 2008). "In U.S., Few Alternatives To Testing On Animals". The Washington Post.

Further reading

• Whitehead, A.; Curnow, R.N. (April 1992). "Statistical evaluation of the fixed-dose procedure". Food and Chemical Toxicology. 30 (4): 313–324. doi:10.1016/0278-6915(92)90009-a. PMID   1628867.
• Lipnick, R.L.; Cotruvo, J.A.; Hill, R.N.; Bruce, R.D.; Stitzel, K.A.; Walker, A.P.; Chu, I.; Goddard, M.; Segal, L.; Springer, J.A.; Myers, R.C. (March 1995). "Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures". Food and Chemical Toxicology. 33 (3): 223–231. doi:10.1016/0278-6915(94)00136-c. PMID   7896233.
• Yam, J.; Reer, P.J.; Bruce, R.D. (January 1991). "Comparison of the up-and-down method and the fixed-dose procedure for acute oral toxicity testing". Food and Chemical Toxicology. 29 (4): 259–263. doi:10.1016/0278-6915(91)90023-Z. PMID   2040488.
• Stallard, Nigel; Whitehead, Anne (9 April 2019). "A Statistical Evaluation of the Fixed Dose Procedure". Alternatives to Laboratory Animals. 32 (2_suppl): 13–21. doi: 10.1177/026119290403202s05 . PMID   15601221. S2CID   46160911.
• Stallard, N.; Whitehead, A. (2 July 2016). "The fixed-dose procedure and the acute-toxic-class method: a mathematical comparison". Human & Experimental Toxicology. 14 (12): 974–990. doi:10.1177/096032719501401206. PMID   8962748. S2CID   78559.
• Stallard, Nigel; Whitehead, Anne; Indans, Ian (2 July 2016). "Statistical evaluation of an acute dermal toxicity test using the dermal fixed dose procedure". Human & Experimental Toxicology. 23 (8): 405–412. doi: 10.1191/0960327104ht465oa . PMID   15346722. S2CID   26925263.
• Ellard, GA (November 1999). "The evaluation of rifampicin bioavailabilities of fixed-dose combinations of anti-tuberculosis drugs: procedures for ensuring laboratory proficiency". The International Journal of Tuberculosis and Lung Disease. 3 (11 Suppl 3): S322-4, discussion S351-2. PMID   10593711.