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Toxicology has expanded its scope to include biological mechanisms of toxicity and host defences (or resistance) against toxicity from its early preoccupation with particularly toxic chemicals, from which it gained its essential definition as a science of poisons. In the 20^th century, momentum for its development as an independent discipline has come from food safety, chemical warfare defence, product safety, radiation biology, pesticide research, environmental medicine, and immunology. Toxicology has become highly specialized in the area of risk assessment, which identifies the level of hazard peculiar to a particular chemical exposure and the limits of acceptably safe exposure.

For convenience in terminology, all substances not normally present in the body and introduced from outside are referred to as “xenobiotics” (from the Greek xeno-, meaning foreign). Xenobiotics may be drugs, food constituents, natural chemical exposures, or anthropogenic environmental chemical exposures.

Toxicology plays a central role in medical geology. The scientific principles of toxicology are applied to medical geology in three broad areas: clinical toxicology, risk assessment, and hazard control and monitoring. Risk assessment is the identification and characterisation of the level of risk resulting from exposure of hazards, including the uncertainties. Toxicology plays an essential role in risk assessment both in characterising the potential toxicity of a chemical hazard, the first step in the process, and in proving the conceptual framework upon which quantitative risk assessment is based.

Regardless of their effect or origin, the behaviour of xenobiotics in the body can be described by general terms and models reflecting the mechanisms by which exposure occurs and the body handles the chemicals. From the standpoint of evolutionary biology, it is supposed that these mechanisms developed in response to selection pressures indicating either of two biological needs: to detoxify and excrete harmful substances ingested in foods and to metabolize endogenous chemical compounds (such as steroid hormones).

Four terms describe the disposition of xenobiotics: absorption, distribution, metabolism, and excretion. Modelled together, the terms indicate the entry, local and overall accumulation, transformation, and removal from the body of the xenobiotic. Because tissue level depend on transport of the xenobiotic to the target organ and the degree to which the xenobiotic partitions or is sequestered into the tissue, the kinetics of the xenobiotics determines the presentation of the xenobiotic to the target organ at the receptor level, where the toxic effect occurs (see Fig.).

Xenobiotics may enter the body through any of several “portals” or routs of entry. By far the most common opportunities for exposure are skin contact and breathing in the agent. Ingestion, resulting from eating or placing objects (e.g. cigarettes) in the mouth in a situation where the object or the hands may have been contaminated, or in suicide attempts, is not a common problem in environmental medicine, but appears from time to time. Other routs of exposure, such as intravenous infusion or implantation of soluble agents, are artificial and seldom seen outside of medical care and experimental studies.

Once the xenobiotic is absorbed and enters the organism, it is transported to capillary level in tissues of the body where it becomes available for uptake by the target organ. After one pass through the circulation the xenobiotic is uniformly mixed in arterial blood regardless of its entry. When a bolus is absorbed, the peripheral tissues are therefore presented with an increasing concentration in the blood which peaks and then declines as the xenobiotic is distributed to tissues throughout the body and removed by metabolism, excretion, or storage.

Many xenobiotics are substrates for intracellular enzyme systems which transform it from the original compound to a series of stable metabolites, often through intermediate unstable compounds. These transformations may have the effect of either “detoxifying”, by rendering the agent toxicologically inactive, or of “activation”, by converting the native agent into a metabolite that is more active in producing the same or another toxic effect.

The xenobiotic or its metabolite would accumulate and remain within the body, if there were no mechanisms for excretion. Elimination is the term used for removal of xenobiotic from the bloodstream, whether by excretion, metabolism, or sequestration (storage).

Date: 2016-01-14; view: 955