Are there any limitations of the up and down method? (mabye the broad of the LD50 and not an exact value)
in which cases should this test be performed?
And are there already better alternatives available or in development?
thank you in advance
Thank you very much for your answer.
So you test acute toxicity of medicines and chemicals? Or can you also use this procedure for other things? Do you need to do this test for each product before it comes on the market?
OECD guideline is this a law or just a directive?
Hi Laurence,
The employ of the measures like the LD50, CL50, etc. is very useful in toxicological studies. It does not work well when you´re testing a combination of active ingredients. In that case you should use Chou´s analysis...
Best regards
Ariel
Dear Laurence Vanderstraeten,
I wrote a whole page, but made a mistake and was not able to keep it.
Briefly:
1. LD50. Method - probit analysis. There are tables and formulas .
There are programs to calculate LD50 computer .
2. LD50. In determining in different laboratories (syngeneic rodents, male or female ) LD50 values in various laboratories around the world may be different 2 or more times. Even in the same laboratory for the determination of LD50 the figure for the highly toxic xenobiotics may differ by 1.5 times (or more).
3. The methods of determining the LD50 using even four animals.
Ask your question, please. For what purpose do you determine LD50?
There are so-called alternative methods which do not use of laboratory animals.
Hi Laurence, Up and Down Procedure (consisting of limit dose test and main test) as stipulated in OECD Guidelines on Acute Oral Toxicity Testing (425) remains the standard in vivo acute oral toxicity measures for determining approximate median LD50 of a chemical substance/chemical/drug with an unknown or closely related drugs of unknown LD50 value. It has the advantage of using few experimental animals which are dosed sequentially depending on its short-term and long-term outcome. This acute oral toxicity test also cuts cost since it involves the use of few experimental animals. However, it has its limitations which include:
1. The test is restricted to female, nulliparous mice and rats only;
2. The test requires close and long term close and strict monitoring for up to two weeks for each experimental animal for you to determine the short- and long-term outcomes;
3. Finally, the test requires an algorithm of strict steps which although simple but could be cumbersome;
4. It provides an estimated LD50 value and not the exact value
Overall, it remains the gold standard for determining the LD50 values of an orally administered substance/chemical/drug with an an unknown toxicity profile. You can check my published article using this procedure: Adeneye AA et al. Journal of Ethnopharmacology 105: 374-379 (see attached).
Best wishes!
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