2. Definition:
LD stands for "Lethal Dose". LD50 is the amount of a dose, given all at once,
which causes the death of 50% (one half) of a group of test animals. The LD50 is
one way to measure the acute toxicity of a material.
Toxicologists can use many kinds of animals but most often testing is done with
rats.
The LD50 can be found for any route of entry or administration but dermal
(applied to the skin) and oral (given by mouth) administration methods are the
most common.
Initially introduced by J.W. Trevan in 1927.
3. Importance:
It is an initial step in the assessment and evaluation of the toxicity of a
substance.
To determine the therapeutic index (TI) i.e. ratio between the median lethal
dose and the effective dose in the same strain and species (LD50/ED50). The
greater the index, safer is the compound.
The test is used to measure acute systemic toxicity.
The smaller the LD50 value, the more toxic is the drug and larger the LD50
value, lower is the toxicity of that particular drug.
4. Limitations of LD50:
Only for acute toxicity.
Cannot provide information on chronic, or long term, toxicity;
Example: lead will build in the body over time and result in poisoning when
concentration becomes too high.
5. Scales Used:
Two most common scales used are the ;
Hodge and Sterner Scale
Gosselin, Smith and Hodge Scale
6.
7.
8. Methods of LD50:
Two most common methods used;
Arithmetical method:
Graphical Method:
9. Factors Affecting LD50:
Species, age, sex, bodyweight, general health condition, diet, nutritional status
and number of animals used in the test.
Route of administration (oral route differ from parenteral route)
Environmental Conditions (lab conditions) i.e. intra and inter laboratory
conditions.
Experimental procedures and Dosage Formulations.