title: Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.
abstract: The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.
authors.affiliation: US Environmental Protection Agency, Washington, DC, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Rispin
authors.forename: David
authors.initials: D
authors.lastname: Farrar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Margosches
authors.forename: Kailash
authors.initials: K
authors.lastname: Gupta
authors.forename: Katherine
authors.initials: K
authors.lastname: Stitzel
authors.forename: Gregory
authors.initials: G
authors.lastname: Carr
authors.forename: Michael
authors.initials: M
authors.lastname: Greene
authors.forename: William
authors.initials: W
authors.lastname: Meyer
authors.forename: Deborah
authors.initials: D
authors.lastname: McCall
mesh_terms: D000826:Animal Testing Alternatives; D000827:Animal Welfare; D000818:Animals; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D015233:Models, Statistical; D051381:Rats; D023382:Toxicity Tests, Acute / Q000379:methods*; D015262:Xenobiotics / Q000633:toxicity
chemical_list: D015262:Xenobiotics