‘All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy’ – Paracelsus
Toxicity as such is a relative phenomenon. The dose of a substance has an impact on its toxicity and not the toxic material present in it. The dose- response relationship is perhaps the most important relationship in toxicology. It basically establishes the relationship between exposure to chemicals and observed effects on the human system.
For all types of toxicity barring allergic responses , knowing the dose-response relationship is a necessary part of understanding the cause and effect relationship between chemical exposure and illness
Dose- Response Relationship
The dose of a poison is going to determine the degree of effect it produces. The following example illustrates this principle. Suppose you are in a bar and you ordered 1 pint of beer. You will probably not feel drunk. But after four or five pint, you may start feeling a little tipsy. After six or eight pint you start feeling very drunk and may feel nauseating. Now is your body response to the dose. Another friend of yours who may have had the same amount of beer, may not have any impact on him.
The effect measured in this example is getting drunk. Individual sensitivity to alcohol varies, as does individual sensitivity to other toxic substances. There is a dose level at which none of the individuals in the group may get drunk (NOEL- no observable effect level). There is also a dose level at which all of the individuals will get drunk.
The dose level at which 50 percent of the individual gets drunk is known as the ED50, which means effective dose for 50 percent of the humans tested. The ED50 of any poison varies depending on the effect measured. In general, the less severe the effect measured, the lower the ED50 for that particular effect.
Poisons are not tested in humans as such . Instead, animals are used to predict the toxicity that may occur in humans.
Dose – Response Common Terms
Let us now understand the common terms used in Dose- response relationship in a scientific manner.
Toxic dose low (TDLO): The lowest dose of a substance introduced by any route, other than inhalation, over any given period of time, and reported to produce any toxic effect in humans.
Toxic concentration low (TCLO): The lowest concentration of a substance in air to which humans or animals have been exposed for any given period of time that has produced any toxic effect in humans.
Lethal dose low (LDLO): The lowest dose, other than LD50 of a substance introduced by any route, other than inhalation, which has been reported to have caused death in humans or animals.
Lethal dose fifty (LD50): A calculated dose of a substance which is expected to cause the death of 50 percent of an entire defined experimental animal population. It is determined from the exposure to the substance by any route other than inhalation.
Lethal concentration low (LCLO): The lowest concentration of a substance in air, other than LC50, which has been reported to cause death in humans or animals.
Lethal concentration fifty (LC50): A calculated concentration of a substance in air, exposure to which for a specified length of time is expected to cause the death of 50 percent of an entire defined experimental animal population.
TD 50 – The dose which is toxic to 50 per cent of the population of organisms exposed to the substance or a 50 per cent toxic response in a biological system exposed to the substance.
The normal way to determine and represent the dose response relation is to determine the
percentage of the animals or cells in a particular dosage or concentration group which show the response. This response is then plotted against the dosage or concentration resulting in a typical sigmoid curve.
Comparison of the LD50 or TD50 with the ED50 affords an indication of the margin of safety of the compound and it is quantified as the therapeutic index
LD50/ED50 (In animals)
TD50 /ED 50 (In humans)
The larger the number the greater is the margin of safety for use of the compound.
For example, if the TD50 is 300 and the ED50 is 30 mg, the TI would be 10.
TI= TD50/ED50 = 300/30 = 10
Dose means the total amount of a substance administered to an organism whereas the term dosage includes a characteristic of the organism, typically body weight or surface area