Toxicology

Practice
Dr.Shahad
Lab:5
Date:21/3/2023

Acute Toxicity Study, Determination

Of LD50
4th stage
Assistant lecturer: Shahad Salah.aldeen
Department of pharmacology and toxicology
March -2023

Median Lethal dose (LD50)

The amount of a toxic agent (as a poison, virus, or radiation) that is sufficient to
kill 50 percent of a population of animals usually within a certain time

Expressed as milligrams of substance per kilogram of body mass(mg/kg)

Compare the toxic potency or intensity of different chemicals

A measure of acute toxicity

Only used in animal study

Median Lethal Concentration (LC50)

• The concentration of a chemical in (air or water ) which produces

death in 50% of an exposed population of test animals in a specified
time frame .

• Normally expressed as milligrams of substance per liter (mg/l) of air

or water (or as ppm).

Median Toxic Dose -TD50

• Is the dose that produces a toxic response in 50% of the population
It is used to calculate the drug safety in humans

Median Effective Dose (ED50)

• the dose of a drug required to produce a therapeutic or
pharmacological response in 50% of the population (humans and
animals)
Drug Safety
• Drug safety can be determined by
1. Therapeutic index or therapeutic ratio (TI)

2. Certain safety factor (CSF)

Therapeutic index

• Is a comparison between the amount of a drug that causes the

therapeutic effect and the amount that causes death (in animal studies)
or toxicity (in human studies).
• Therapeutic index=LD50/ED50. In Animal Studies.

• Therapeutic index=TD50/ED50 In Human Studies

Drug safety in human study

Drug safety in animal study

Cont..
• The wider TI the more the drug is safe ie: a patient would have to take a much
higher dose of such a drug to reach the lethal/toxic threshold than the dose
taken to elicit the therapeutic effect.

• Drug with narrow TI required dosage adjusted according to measurements of

the actual blood levels achieved in the person or animal taking it. This may be
achieved through therapeutic drug monitoring (TDM) protocols.

Certain Safety Factor (CSF)

• Drug safety could be better assessed by using the following ratio
which is
Certain safety factor=LD1/ED99
LD1 : dose of drug that cause lethality in 1% of test animals
ED99: dose of drug that produce therapeutic effect in 99% of test animals

• The wider the margin between the ED99 and the LD1, the safer the
drug.
Cont..

This ratio could also be expressed as a percentage value, and is called

"standard safety margin". This value expresses the % dose-increase
between the ED99 and LD1.

Standard safety margin (%)= (LD1/ED99)-1 × 100

Drug-response Relationship
• There are 2 types of drug-response relationship:
1. Graded drug-response relationship, the magnitude or the intensity of
response is relatively proportional to the effective drug concentration
ex:. The response elicited by pentobarbital (sleeping time) can be
measured on a continuous scale.

2. Quantal drug-response relationship , in contrast, is an all-or-non

response, e.g. anaesthesia or no anaesthesia, the dose of a drug either
produces or fails to produce a specified effect
0 0
0 0

0 0

0 0

0 0