Selective toxicity can be defined as the property of a toxic agent to harm or eradicate one species without affecting the other even if the two species are in a very close association. Selective toxicity of a chemical agent is evaluated by using selectivity co-efficient which is the ratio between LD50 of the two species concerned:
Chemicals having selectivity co-efficient considerably higher than unity are said to be highly specific or selective in their action. As this value approaches unity the selective action of the toxic agent diminishes, both the species involved are harmed equally.
As a matter of fact, selective action of a toxic agent on different species or organisms forms the very basis of Economic Toxicology. It is the property of a chemical agent to harm one species while inflicting little or nominal damage to other species which is used to protect the desired species against the harmful action of undesired ones. The selective action of chemical agent may be due to following reasons:
1. Due to differences in the process of absorption, distribution and accumulation the toxic agent may attain toxic concentrations in some species while in others it remains well below the toxic level. Thus, only those species are harmed which can absorb more toxic agent.
The low toxicity of fungicide Captan to plants can be explained by the fungicide's lower capacity to penetrate the plant cells while in cells of the fungus it readily enters and kills them. Simply, a large surface area as compared to unit weight may at times result in greater absorption of the toxic chemical in some species. Insects for example, have a greater surface area per unit weight as compared to plants or mammals. This causes a number of insects to absorb much more insecticide than plants or mammals do. The effectively of radio-active iodine in the treatment of hyperthyroidism is due to its selective uptake by tissues of the thyroid gland.
2. Rapid detoxification and excretion of chemical agent in one species while a slower rate or total absence of these processes in another may result in attainment of toxic levels in the latter. The relatively low toxicity of Organophosphate insecticide Malathion in mammals is due to its decomposition into harmless compounds while in insects this process is much slower and results into a large concentration of the insecticide which becomes toxic to the insect.
3. Selective toxicity of many chemicals is due to the fact that they are capable of disturbing certain specific structure or bio-chemical processes which may not be present or are not very significant in the desired species. For example, chemicals acting on Central Nervous System (like most of the insecticides) affect only animals while causing no damage to plants as a nervous system is absent in plants.
Organophosphate insecticides do not harm plants because they act on the process of synaptic transmission of nerve impulses. Herbicides like Carbamate derivatives have little action on animal life as they selectivity inhibit the process of photosynthesis which does not occur in animals. Antibiotics like Penicellin, Cephalosporine etc. inhabit cell wall formation in bacteria due to which they are killed while no adverse effects occur in man in whose body these bacteria live as there are no cells similar to bacteria. Like-wise Bacteria synthesise Folic acid from p-amino-l benzoic acid, glutamic acid and pterdine.
Sulphonamide drugs which resemble p-arainol benzoic acid in both charge and dimensions antagonise the incorporation of p-amino-l benzoic acid and therefore inhabit folic-acid synthesis. It is due to lack of folic acid anil bacteria disappear. The chemical pathway is absent in humans which have to absorb folic I acid from intestines - from the food which we eat. Sulphonamide drugs therefore do not harm humans.
Factors which influence the toxicity of a chemical agent introduced deliberately or accidentally inside a living being are as follows:
1. Age is an important factor which determines the toxcity of various chemical agents. It assumes great significance at the extremes of life, i.e., new borns and very elderly individuals. In many cases the intensity of the effect of various chemicals can be traced to the inability of the system to detoxify and excrete it. In very young individuals this machinery is not well developed while in elderly persons it is impaired or incapacitated due to the old age.
2. Vitality or state of physical health plays an important role. In weak and feable persons small quantities of chemical agent cause toxicity while in stronger individuals a similar amount produces no response.
3. Weight of an individual also plays an important role. It is actually the amount of toxic agent present per unit weight of the organism (the biological material) which determines the degree of toxicity of a chemical agent. It is obvious that only half of the chemical agent shall be required to produce toxicity in a 40 kg individual as compared to the amount needed to produce similar symptoms in an individual weighing 80 kg.
4. Responses to toxic agent in different sexes are not always similar. Women usually require smaller doses of drugs than man but certain chemicals are needed in greater amounts to produce effects similar to those seen in males. No satisfactory explanation of the phenomenon is available.
5. Presence of food in the stomock and intestine at the time of administration of chemical agent influences the intensity of toxic action the chemical causes as absorption of the chemical is much faster from empty intestines. It is well known fact that alcohol produces very intense and quick action if taken on empty stomock. The presence of food in stomock delays its absorption.
6. under the conditions of stomock upsets and diarrhoea which is characterised by gastrointestinal hypermotility, toxic action of chemical agents is weaker because active motion of the contents of stomock and intestines reduces absorption.
7. Organisms may respond to various chemical agents in an unusual way in the presence of underlying pathology. Diseased liver or kidney often fails to detoxify and excrete chemical agents which may subsequently accumulate in toxic concentrations. In addition, the pathological state sometimes changes the responsiveness of tissues in such a way as to result either in toxic reactions or resistance to various chemicals.
For example, drugs like thiopental may cause unexpectedly deep unconsciousness or even death from respiratory failure in patients suffering from liver ailments. In patients with impaired kidney activity, antibiotics like streptomycin and gentamycin which are excreted via kidney are accumulated and may cause serious damages.
8. The intensity of action of chemical agent may be affected by genetic factors also. Some individuals are rapid in activators of certain chemical agents while susceptible to others. These genetically controlled characteristics are usually brought into effect by intermediation of certain defective enzyme systems.
9. Immunological factors may sometimes determine the intensify of action of chemical agents in individuals. First exposure of the organism to chemical agents stimulates immunological mechanisms as a result of which antibodies are formed. Any subsequent administration of the same or similar chemical causes severe reactions which range from breathing difficulty to disorders of skin, joints and circulatory system.
10. Tolerance which can be defined as reduced responsiveness to certain chemicals or groups of chemicals is sometimes responsible for reduced toxic action of some chemical agents. Tolerance to drugs in patients often requires a physician to prescribe higher doses.
The tolerance to a chemical agent may be congenital or acquired. Congenital tolerance can be seen in Negroes who are tolerant to mydriatic action of sympathomimetics like ephedrine. Eskimoes have tolerance to high fat diets which causes acidosis in others. Repeated administration of some chemicals results in gradual development of resistance to its effects and in order to produce the same symptoms increasingly larger amounts are required.
This type of tolerance to chemical agent is known as acquired tolerance which may either be due to poor absorption of the chemical agent or its rapid detoxification and excretion or acclimatization of the target tissues.