Mechanisms and Concepts in Toxicology by W. Norman Aldridge

By W. Norman Aldridge

Makes a speciality of study approaches in toxicology, aiming to demonstrate recommendations and kinds of toxicity from a mechanistic standpoint. Examples of chemical intoxicants are used to demonstrate mechanisms in each one degree of toxicity.

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Most of the steps in each stage may be characterised by affinity (K) or rate constants (k), Michaelis constants (Km) and maximum rates (Vmax) derived from studies of the effects of concentration of intoxicant, time and sometimes temperature. g. rates of penetration, detoxification pathways, bioactivation, reaction with target, etc. 1)—the biological cascade—are biology-related and may involve many factors such as rates of loss and recovery of activity of an enzyme or receptor, rates of macromolecular resynthesis, cell turnover, 26 MECHANISMS AND CONCEPTS IN TOXICOLOGY recruitment of other cells, etc.

Rapid penetration of chemicals is best achieved when the substance has both lipophilic and hydrophilic properties. Oils penetrate the skin and, provided they or their solutes have sufficient solubility in water, reach the blood and are generally distributed throughout the body. Oils as solvents of other substances are used as a reliable way of administering substances. Drug administration via absorption through the skin is now often used (for example, the use of patches applied to the skin in order to supply a small dose of nicotine to those who are trying to break the habit of smoking).

Thus, provided DDT reaches the nervous system, toxicity appears. If the animal does not die, recovery is complete with no histopathological changes. e. an intoxication which can be produced rapidly and from which, dependent on the exposure, complete recovery is possible. The administration can be by many routes and can be by a single exposure, a few exposures or even by a slow uptake over a long time. Provided the toxic chemical reaches and accumulates at its site of action or reacts to cause a persistent chemical change, signs or symptoms of poisoning will appear.

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