Improved up-and-down procedure for acute toxicity measurement with reliable LD50 verified by typical toxic alkaloids and modified Karber method

Background Up-and-down procedure (UDP) was recommended to replace traditional acute toxicity methods. However, it was limited due to the long experimental period (20-42 days). To improve UDP, an improved UDP method (iUDP) was developed by shortening observation time between sequence dosages. The aim...

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Published inBMC pharmacology & toxicology Vol. 23; no. 1; pp. 1 - 11
Main Authors Zhang, Yan-Yu, Huang, Yu-Feng, Liang, Jie, Zhou, Hua
Format Journal Article
LanguageEnglish
Published London BioMed Central Ltd 04.01.2022
BioMed Central
BMC
Subjects
Acute toxicity
Alkaloids
Berberine
Death & dying
Dosage
Hazardous materials
Improved up-and-down procedure
Laboratory animals
Lethal dose
Measurement
Median lethal dose
Methods
Modified Karber method
Mortality
Nicotine
Poisoning
Sinomenine hydrochloride
Toxicity
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Summary:Background Up-and-down procedure (UDP) was recommended to replace traditional acute toxicity methods. However, it was limited due to the long experimental period (20-42 days). To improve UDP, an improved UDP method (iUDP) was developed by shortening observation time between sequence dosages. The aim of this study was to test the reliability of iUDP to provide a reliable method for the acute toxicity measurement of valuable or minor amount compounds. Methods Oral median lethal dose (LD.sub.50) of nicotine, sinomenine hydrochloride and berberine hydrochloride were measured both by iUDP and modified Karber method (mKM). Results LD.sub.50 of the three alkaloids measured by iUDP with 23 mice were 32.71 [+ or -] 7.46, 453.54 [+ or -] 104.59, 2954.93 [+ or -] 794.88 mg/kg, respectively. LD.sub.50 of the three alkaloids measured by mKM with 240 mice were 22.99 [+ or -] 3.01, 456.56 [+ or -] 53.38, 2825.53 [+ or -] 1212.92 mg/kg, respectively. The average time consumed by the two methods were 22 days and 14 days respectively. Total grams of the alkaloids used by the two methods were 0.0082 and 0.0673 (nicotine), 0.114 and 1.24 (sinomenine hydrochloride), 1.9 and 12.7 (berberine hydrochloride). Conclusion iUDP could replace mKM to detect acute toxicity of substances with comparable and reliable result. And it is suitable for valuable or minor amount substances. Keywords: Acute toxicity, Improved up-and-down procedure, Median lethal dose, Modified Karber method, Nicotine, Sinomenine hydrochloride, Berberine hydrochloride
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ISSN:2050-6511
2050-6511
DOI:10.1186/s40360-021-00541-7