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]
^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. PMID2210519.
^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. PMID12099620. S2CID45430481.
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. PMID1628867.
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. PMID7896233.
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. PMID2040488.
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. PMID8962748. S2CID78559.
