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]

References

^ 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.
^ 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.
^ 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.
^ 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.
^ "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.
^ Gaul, Gilbert M. (12 April 2008). "In U.S., Few Alternatives To Testing On Animals". The Washington Post.

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.

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[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.

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Fixed-dose procedure

See also

References

Further reading