Accumulation of Toxic Agent in Biological Systems – The Storage Depots

Toxic agents are usually concentrated and stored in specific tissues or organs within a biological system. These tissues or organs can be thought of as storage depots for the chemical agent concerned and the phenomenon is known as bio-accumulation which may at times involve active absorption of the chemical agent from food or from the surrounding environment.

While within the storage depot, a toxic agent does not cause much harm to biological system. Therefore, these storage depots can also be considered as protective devices which prevent excessive concentration of the toxic agent being achieved at the site of its action. Lead for example is stored in bones while the toxicity of this element is due to its action on soft tissues. Accumulation of lead in bones results in a decrease in its plasma concentration and as a consequence the intensity of lead toxicity is moderated.

However, there are many chemicals which attain their maximum concentration at the site of their action and for these cases there is no such moderating mechanism available. For example, carbonmonoxide accumulates or achieves its highest concentration in blood as it has a great affinity for haemoglobin which is the site of its toxic action.

The concentration of toxic agent in storage depots and in the blood plasma usually remains in equilibrium with each other. As the process of detoxification and excretion brings about a diminution in the concentration of toxic agents in the plasma, more and more toxic material is drawn out into the blood stream from the storage depots.

Thus almost a constant concentration of the toxic agent in the plasma is maintained as long as the toxic agent persists in storage depots. These storage depots may be confined to certain specific anatomic locations such as liver, kidney or bones, or they may be diffused and located throughout the body of the organism. Following are the major storage sites for toxic agents in an organism.

1. Plasma Protein as Storage Depots:

In blood plasma, probably the most important protein, to which many of the foreign chemicals are bound to, is albumen. Beta-globulin, transferrin, ceruloplasmin, alfa and beta-lipoproteins are some of the other proteins which acting cumulatively are capable of binding many foreign chemical agents which gain entry into the blood plasma. The binding usually involves reversible bonds like hydrogen bond, van der Walls forces and ionic bonds.

The toxic agent bound to protein molecules thus constitutes a pool or storage depot diffusedly located throughout the body of the organism, from where toxicants can be released later. There is a great variation in the extent upto which different foreign chemicals are bound to protein molecules in the blood plasma. Drugs like antipyrine are not bound at all, while about 50% of thyroxin administered is present in bound form in blood plasma.

There exists equilibrium between the bound form and the free form of the toxic agent. It is only the free form which is available for distribution and detoxification. The decrease in concentration of the free form in blood plasma brings about release of the toxic agent from the storage depots. Another feature of considerable importance is the displacement of one chemical agent by another from the protein molecules.

This result in the release of the chemical which had hitherto existed in bound state. In this way the administration of a chemical agent which selectively binds or competes with another toxicant absorbed earlier in the system can release it in sufficient quantities to cause toxic responses. For example, sulphonamides selectively bind to plasma protein displacing antidiabetic drugs. Its administration may cause hypoglycemic coma due to the release of antidiabetic drug in large quantities.

2. Liver and Kidney as Storage Depots:

Both liver and kidney are capable of concentrating more toxic agents than any other part of the body. The rapidity with which liver stores foreign chemicals is evident from the fact that only half an hour after administration of lead; its concentration is about 50 times higher in liver as compared to its concentration in blood plasma.

The high concentrations of various toxicants usually met with in liver and kidney might be related to the fact that these organs are instrumental in their elimination. Both liver and kidney are capable of excreting foreign chemicals while liver has a high capacity to metabolise them.

The possible mechanism by which liver and kidney remove toxic material so efficiently from blood plasma appears to be active transport and protein binding. It has been suggested that intra-cellular protein binding could be an important factor in concentration of toxic agents as several intracellular proteins of liver and kidney have been shown to have high affinity for various chemical agents, carcinogens, metal ions etc.

3. Fats as Storage Depots:

Accumulation of toxic agents in fatty or adipose tissues of a biological system depends on the ability of the toxicant to dissolve in lipids and fats. Lipid solubility is an important factor in absorption of the toxic agent and their movement across various membrane systems and so it is natural that this property is helpful in distribution of chemical agent in various Toxic Material in Environment and Exposure Risk Assessment fatty tissues within a biological system.

In an athletic individual fats constitute about 20% of the body weight while in an obese individual it could make as much as 50% of the total body weight. Thus, there is enough fat for many of the toxic agents to get stored without causing any appreciable damage. It is the process of natural diffusion and dissolution which appears to be responsible for storage of the toxic agent in fatty tissues of a biological system.

4. Bones as Storage Depots:

Bones which are made up of relatively inert tissues may be used as storage depots for many foreign chemicals such as tetracycline, lead etc. As much as 80-90% lead present in mammalian system is found deposited in bones wherein it probably substitutes for calcium in crystal lattices.

Toxic agents deposited in bones are not toxic but the fact that they may be released in the blood stream again appears to be a feature of serious concern. This may be accomplished by administration of another foreign chemical or a drug. For example, osteolyses caused by drugs like prothormone results in the release of lead and thereby a quick rise in plasma level of this element is observed.