Toxicity factor, dose-time relationship

The most important factor is the dose-time relationship. The dose-time relationship forms the basis for distinguishing between two types of toxicity acute and chronic. Acute toxicity of a chemical refers to its ability to inflict systemic damage as a result (in most cases) of a one-time exposure to relative large amounts of the chemical. In most cases, the exposure is sudden and results in an emergency situation. 

The most important factor is the dose-time relationship. The amount of a substance that enters or contacts a person is called a dose. An important consideration in evaluating a dose is body weight. Dose is the quantity of a chemical substance that a surface, plant, or animal is exposed to. Time means how often one is exposed to or the duration of exposure to a chemical substance. In simple terms, the dose-time relationship provides information on how much of the test substance is involved and how often the exposure to the test substance occurs. This relationship gives rise to two different types of toxicity of a chemical substance—namely, acute toxicity and chronic toxicity. 

Organophosphates illustrate several points. First, repeated exposure can be a problem not only because of accumulation of the substance (as can occur with other substances such as aspirin) but also because of accumulation of the effect, if it is irreversible. Therefore the dose-time relationship is important as weU as the dose-response relationship. Secondly, understanding the mechanism allows effective detection and treatment thirdly, other factors such as decomposition and exposure to other chemicals can have a large impact on toxicity and finally the dose is crucial, and it would seem, at least from the information available at present, that OPs can be used safely if they are used sparingly and carefully. 

This entry presents a discussion of the principles of respiratory toxicology including (1) an historical perspective, (2) approaches used to evaluate respiratory responses to inhaled chemicals, (3) classification of airborne chemicals, (4) concepts of dose-time relationships, (5) factors influencing toxicity of airborne substances, (6) the basic biology of the respiratory system with emphasis on those structures and functions that are involved in toxicological responses, (7) biomarkers of pulmonary effects, (8) toxicological response associated with inhaled chemicals, and (9) assessing the human risk of airborne chemicals. 

It is natural to consider one or another of these trans-species dose prescriptions for scaling dose-response relationships in carcinogenesis. But in any chronic effect, such as carcinogenesis, another parameter enters namely, time. Whereas the LDjo describes the acutely toxic properties of a chemical, the relevant dose for carcinogenesis is usually accumulated over a long time. One must consider, therefore, the relationship between daily dose, total lifetime dose, and body weight. The difference in life spans between man and mouse—70 years versus 2 years—amounts to a factor 35. Most analyses, however, consider that it is the daily dose that is more relevant, and that the shorter lifetime of the mouse represents the effects of its higher metabolic rate. The difference between these various interspecies dose conversion schemes is illustrated in Thble 8.1. 

Toxicology is the study of the potential of a substance to cause a harmful effect to animals and humans by describing the effect and the conditions under which the effect takes place. Simply stated, toxicology is the study of the nature and action of poisons. A substance is said to be toxic if it has the ability to produce injury at a susceptible site on or in the body. Toxicology is concerned with several factors that influence the toxicity and mode of action of a toxic substance. The most important factors are the dose-response relationship, the route of entry of the substance into the body, and the time course of exposure. 

However, there are other major factors in determining the dosing regimen, such as the nature of the concentration-response relationship for both efficacy and toxicity (therapeutic window) and commercial/ compliance factors. There are additional reasons why caution should be applied in assuming an efficacy-time profile from a given plasma concentration-time profile. Some reasons why the time course of drug concentration and effect may differ are given in Table 5.1. 

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