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Retrospective study on the reliability of an “approximate LD50” determined with a small number of animals

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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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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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