Reduction of animal use with improved procedure for acute tolerance assessment.
A retrospective evaluation of previously conducted acute tolerance tests in rats and mice, following oral and intravenous routes of administration, and a review of the literature indicated that a minimum of three animals per group was adequate to characterize acute tolerance. Limited exploratory testing, using six compounds for which classical LD50 tests had been performed previously, indicated that fewer numbers of rats gave comparable results. A method is proposed by which the acute tolerance of a compound may be adequately characterized in both sexes using approximately 30 animals instead of the 70 to 100 used in the classical LD50 test. The objective of the testing procedure is identification of the maximum nonlethal dose or the minimum lethal dose, rather than determination of the LD50.
Fabian
R
R
Drug Safety Assessment, Sterling Winthrop Pharmaceuticals Research Division, Rensselaer, New York 12144.
Fetrow
N
N
Greener
Y
Y
Zelinger
D
D
Olson
H
H
Dean
J
J
D000284:Administration, Oral; D000827:Animal Welfare; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010146:Pain / Q000517:prevention & control / Q000662:veterinary; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D051381:Rats; D012189:Retrospective Studies; D013312:Stress, Physiological / Q000517:prevention & control / Q000662:veterinary
D004364:Pharmaceutical Preparations