It is the concentration of toxic agent which is the most important factor in evaluation of toxicity of chemicals. A small amount of some chemical may cause intense toxic effects where as for others a larger quantity may be needed to affect a biological system adversely.
Even the most innocuous and safe chemical may be harmful if administered in very high doses. The toxic effects of a substance are, therefore, evaluated by the concentration at which the deleterious response appears. The indices commonly used for the purpose are: threshold dose, sub-lethal doses and toxic lethal dose or concentration.
1. Threshold Dose:
The, minimum or the smallest dose of a substance which causes adverse change in an organism, as determined by the most sensitive biochemical and physiological methods even if no external indication of such a change is present, is known as the threshold dose. In other words, the threshold dose of chemical agent is the dose at which its toxic action just starts.
Threshold limit is the limit marked by this concentration. Below this limit the use of the chemical agent in a biological system is considered relatively safe.
2. Toxic Lethal Dose or Concentration:
The dose of a chemical agent which causes an individual to be killed is known as Toxic lethal dose. As the toxicity of most of the chemical agent vary from individual to individual and factors like strain, age, weight, type of feed, caging, pre-trail fasting, volume and type of suspension medium, method of administration etc. affect the toxic action considerably, it is not possible to estimate toxic lethal dose accurately on an individual. It is usually assessed on groups of individuals.
The different doses of toxic agent are administered to groups of individuals randomly selected from a natural population and dose related mortality is plotted as given in Fig. 21.6, or the data is converted to probit units to straighten the regression line and plotted against rising dose levels (See under Evaluation of toxicity above). It is from the regression line that percent mortality or mortality in probit units at any desired dose is determined.
In order to evaluate, the toxicity of a chemical agent it is often unnecessary to deal with quantities which result in cent per cent mortality within the groups examined. The dose which can kill about 50% of the individuals of the group can very well serve our purpose. It is for this reason that the term Median Lethal Dose is used.
A medium lethal dose of a toxic agent is the dose which can kill 50% or half of the organisms in the group examined. This toxicity is denoted by the symbol LD50. Similarly, LD1 indicates the dose which kills only 1% and LD99 denotes the dose which can cause 99% mortality.
3. Sub-lethal Dose or Effective Dose:
Toxic sub-lethal dose is the amount of chemical agent required to cause the appearance of some observable symptom or visible manifestation of toxicity without resulting into death of the test organisms. Any dose of toxic agent between the threshold dose and the lethal toxic dose which usually manifests itself in the form of certain responses the organism under observation exhibits but death does not occur can be referred to as a sub-lethal or effective dose.
Any of the response exhibited by the organism consequent upon the administration of a sublethal dose may be selected to determine the Effective dose which is another index of toxicity denoted by the symbol ED. It is also determined on group of individuals by a method similar to that used for determination of toxic lethal dose. Here instead of number of individuals killed, the appearance of a particular response in the individuals of the group is the final parameter used to calculate the percentages. Like LD50, Median effective dose or ED50 is the dose effective on 50% of the organisms.
Chemical agents used in practice of therapeutic medicine upto a certain concentration produce desirable responses. The dose response curve plotted for the appearance of any desirable symptom is termed as Therapeutic dose-response curve which is smaller to toxic dose response curve.
The term concentration instead of dose is usually used in case of aquatic systems or air in which organism lives. In such cases, it is not possible to determine the amount of chemical agent absorbed by the organisms^ The dose or quantity of toxic agent absorbed by an organism may vary which depends upon a number of factors. However, the concentration of toxic agent in air or water can be determined accurately. It is therefore, considered better to use the term concentration rather than dose under the conditions, which is at least accurate.