LD50 by lorke 1983 is calulated as=the geometric mean of D0%xD100%, D100% is defined by some people as the least dose that produced mortality while some defines D100% as the first dose where 100% mortality was recorded. These two statements are different and I do not have the original document of Lorke. pls can someone tell me the statement that correctly defined D100. I will be very grateful.
Lowest dose that produced mortality is the D100. Now if you will agree with me, if rats of equal body weights are administered same toxic dose of a substance, you will expect to have similar effects. In other words, D100 is the lowest dose that produced 100% mortality.
because the Lorke method only uses one animal at each of the higher doses in the second phase, any mortality at a given dose means 100% mortality at that dose (1/1), so D100 means the lowest dose that an animal was killed (ie mortality occurred.) So the two statements in you question are not different..
thank you all for your response
@James Leigh. What if the mortality occurs in phase one where n=3 per group, how will you define D100?
Take for instance, that 1 animal died in group 1, 2 in group 2 and all in group 3. According to the first definition, D100 will be 10mg/ kg body weight(weight of extract administered to group 1 animals) and D100 will be 1000mg/kg body weight (weight of extract administered to group 3 animals). what can you say about this?
thank you all for your response
@James Leigh. What if the mortality occurs in phase one where n=3 per group, how will you define D100?
Take for instance, that 1 animal died in group 1, 2 in group 2 and all in group 3. According to the first definition, D100 will be 10mg/ kg body weight(weight extract administered to group 1 animals) and D100 will be 1000mg/kg body weight (weight of extract administered to group 3 animals). what can you say about this?
In this case , Lorke's method breaks down, as D0 is undefined. You would have to try again with a lower minimum dose. Then when you get a dose with no deaths,you have a D0. If you get any deaths at a phase 1 dose. then the lowest would become D100 and phase 2 would not be necessary. In this case you are correct and D100 would not equal 100% mortality. In your example D100 would be the group 1 dose where 1/3 died, but you would have to also have a group 0 of 3 where none died to define D0.
If mortality is recorded in phase 1, then you don't need to proceed to phase 2. Now, if you have 3 groups of 3 animals each, and you administered 10 mg/kg to group 1, and recorded no mortality, you administered in group 2,100 mg/kg and just one animal died, and in the third group, you administered 1000 mg/kg, and all animals died. Then 10 mg/kg does not defines your D0 (highest dose that caused no mortality) because you can also administer 20 to 90 mg/kg and still record no mortality. So you still need to test in between 10 mg/kg and 100 mg/kg I.e. 20 - 90 mg/kg. Same also applies to D100 (lowest dose that led to mortality), you still have to test in between 10 and 100 mg/kg, because mortality can still be recorded also in between 10 and 100 mg/kg I.e. 20 to 90 mg/kg may also lead to mortality. In science, one need not assume.
correct. you should always do a phase 2, with dosages based on the results of phase1.
then, the D100 is the first dose in phase 2 that the animal dies. and represents 100% mortality, see attached publn.
thank you all for your valueble contributions. @Leigh I have that publication. Is just that I needed the Lorke original article
@Oluwatobi Thank you so much
@Tobi with this I will like to react to your first post bc the present one was based on that understanding. you said and I quote "
Lowest dose that produced mortality is the D100. Now if you will agree with me, if rats of equal body weights are administered same toxic dose of a substance, you will expect to have similar effects. In other words, D100 is the lowest dose that produced 100% mortality".
Here, your expectation is that all the animals are expected to die if given the same dose.
What can you say when there is a case of identical twins who received same dosage of a drug based on their weight and ended up responding differently.
so the bottom line is that D100 is based on mortality not 100% because is assumed that the rats are same physically and genetically the same.
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