I am conducting a pain-induction model using acetic acid 0,9% at a dose of 1500 mg/kg. However, in a book written by a well-known author from my country, it is mentioned that experimental doses should range between 1/20 and 1/5 of the LD50. When I performed the toxicity test at a concentration of 5000 mg/kg, no mice died, meaning the LD50 could not be determined (following the OECD 423 guidelines).
My professor stated that the 1500 mg/kg dose is too high and violates regulations. I am wondering whether there are any specific rules for determining experimental doses after conducting toxicity tests. Are there any references I could consult to justify this matter?
Thank you for your help, I truly appreciate it.
Dear Viet Ha,
The doses for determining LD50 can be any (to a smaller or larger ‘side’ of the estimated LD50, a minimum of 3 doses, the more they are, the more accurately you will determine the LD50. The mean lethal toxic substance doses depending on species, sex of animals, time of year, etc. can differ from author to author by a factor of 2 or even 4.
Check out my articles, especially the early ones, they will be helpful to you.
https://www.researchgate.net/profile/Pf-Zabrodskii
And also this article in Russian.
https://cyberleninka.ru/article/n/statisticheskaya-obrabotka-rezultatov-farmakologicheskih-issledovaniy
There are many methods for determining the average lethal dose:
https://en.wikipedia.org/wiki/Median_lethal_dose
https://ru.wikipedia.org/wiki/%D0%9B%D0%9450
I think you can find the formulas on the Internet if you want.
https://dommedika.com/farmakology/588.html
The Behrens method I can send you.
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