Abstract
Based on 364 LD50 determinations in mice and rats after intravenous and oral administration of drugs, the reliability of an “approximate LD50” was retrospectively tested.
The difference between “approximate LD50” and LD50 is — independent of species and route of administration — not greater than ± 20% of the LD50 in 90% of the cases.
Four to five doses — uniformly distributed over the dose-mortality range can suffice in reliably determining the “approximate LD50”.
The probability is 10% that an “approximate LD50” and LD50 are significantly different from each other.
152 parallel studies on male and female animals show that the LD50 or “approximate LD50” must not be determined for both sexes. It is sufficient to test a dose near the LD50 in the opposite sex. A 50–75% reduction of expenditure in animal material is possible in most of LD50 determinations.
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References
Balazs T (1970) Measurement of akute toxicity. In: Methods in toxicology. Blackwell Scientific Publications. Oxford Edinburgh, pp 49–81
Balazs T (1976) Assessment of the value of systemic toxicity studies in experimental animals. In: Mehlmann M, Shapiro RE, Blumenthal H (eds) New concepts of safety evaluation. John Wiley and Sons, New York London Sydney Toronto, pp 141–153
Bliss CI (1939) The calculation of the dose-mortality curve. Ann Appl Biol 22: 134–167
Behrens B, Kärber G (1935) Wie sind Reihenversuche für biologische Auswertungen am zweckmäßigsten anzuordnen? Arch Exp Pathol Pharmacol 177: 379–388
Buck W (1976) Der U-Test nach Uleman. EDV Med Biol 7:65–75
Deichmann WB, LeBlanc TJ (1943) Determination of the approximate lethal dose with about six animals. J Ind Hyg Toxicol 25:415–417
Deichmann WB, Mergard EG (1948) Comparative evaluation of methods employed to express the degree of toxicity of a compound. J Ind Hyg Toxicol 30: 373–378
Gaddum JH (1933) Reports on biological standards III methods of biological assay depending on a quantal response. MRC Spezial Report M.S.O. London, Ser No. 183
Hackenberg U, Bartling H (1959) Messen und Rechnen im pharmakologischen Laboratorium mit einem speziellen Zahlensystem (WL24-System). Arch Exp Pathol Pharmacol 235:437–463
Horn HJ (1956) Simplified LD50 (or ED50) calculations. Biometrics 12: 311–322
Hunter WJ, Lingk W, Recht P (not dated) An intercomparison study conducted by the Commission Communicated by the Health and Safety Directorate. Commission of the European Communities (unpublished document)
Litchfield JT Jr, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96: 99–113
Miller LC, Tainter ML (1944) Estimation of the ED50 and its error by means of logarithmic probit graph paper. Proc Soc Exp Biol Med 57: 261–264
Sperling F (1976) Nonlethal parameters as indices of acute toxicity: inadequacy of the acute LD50. In: Mehlmann M, Shapiro RE, Blumenthal H (eds) New concepts of safety evaluation. John Wiley and Sons, New York London Sydney Toronto pp 177–191
Tattersall ML (1982) Statistics and the LD50 study. Arch Toxicol (in press)
Thompson WR (1947) Use of moving averages and interpolation to estimate median effect dose. Bacteriol Rev 11: 115–145
Thompson WR, Weil CS (1952) On the construction of tables for moving average interpolation. Biometrics 8: 51–54
Weil CS (1952) Tables for convenient calculation of median-effective dose (LD50 or ED50) and instructions in their use. Biometrics 8:249–263
Winne D (1968) Zur Planung von Versuchen: Wieviel Versuchseinheiten? Arzneim Forsch 18:1611–1618
Zbinden G (1973) Acute toxicity. Progress in toxicology, special topics. Vol 1. Springer, Berlin Heidelberg New York, pp 23–27
Zbinden G, Flury-Roversi M (1981) Significance of LD50-test for the toxicological evaluation of chemical substances. Arch Toxicol 47:77–99
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Müller, H., Kley, H.P. Retrospective study on the reliability of an “approximate LD50” determined with a small number of animals. Arch Toxicol 51, 189–196 (1982). https://doi.org/10.1007/BF00348852
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DOI: https://doi.org/10.1007/BF00348852