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Ullmann's Industrial Toxicology WOLFGANG DEkANT, Institute of Toxicology, University of Wuerzburg, .. rate science and wrote the first book devoted ex-. Toxicology is the science of poisons, embracing the physical and chemical study of all the known poisonous substances, as well as the. “Toxicology is the study of the adverse physicochemical effects of chemical, physical or biological agents on living organisms and the ecosystem, including the.
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Request Username Can't sign in? Forgot your username? Types of toxic substance His contribution to medicine and toxicology was enormous although not recognized until after his death in Indeed Claude Bernard — believed that the study of the effects of substances on biological systems could enhance the understanding of those systems.
More recently, in , Sir Rudolph Peters studied the mechanism of action of arsenical war gases and so was able to devise an effective antidote known as British Anti-Lewisite for the treatment of soldiers exposed to these gases.
Toxicology has now become much more than the use of poisons for nefarious purposes and the production of antidotes to them. It has also created the need for the organized study of toxic substances by the industries manufacturing them and for legislation to control them. This has in turn resulted in the establishment of government regulatory agencies to implement the resulting legislation. This knowledge is essential for the development of effective and rapid treatment of the toxic effects, just as it is essential for the treatment of overdoses and accidental poisonings.
For example, one of the worst industrial disasters occurred at Bhopal in India in where a factory manufacturing the insecticide carbaryl leaked a large amount of the extremely noxious compound methyl isocyanate Figure 1. Little was known of the toxicity of this compound and consequently treatment of the victims was uncertain and possibly inadequate.
This will then enable decisions to be made about marketing and labelling. So we are exposed to toxic or potentially toxic compounds in many ways in our daily lives and toxicology is clearly a subject of great importance in society.
This becomes apparent when we look at the types of poisons and the ways in which we are exposed to them. Indeed, the categories cover virtually all the chemicals one might expect to encounter in the environment. Headline from The Sunday Times, 1 December , with permission. Drugs used in veterinary practice must also be considered here and in the next section as humans may consume meat from or other food derived from animals treated with these drugs. Drugs, however, have usually been designed to be highly potent in biological systems and consequently many are potentially toxic.
Drug toxicity may be due either to an overdose or it may be a rare and unusual adverse effect, and examples of both of these will be considered in detail in Chapter 5. Drugs vary enormously in chemical structure and possess a wide variety of biological activities. They are probably the only foreign substances of known biological activity that man ingests intentionally.
Included in this category are alcohol and the active principles in cigarettes, both of which are used because of their food additives This is the second category of foreign substances which are directly ingested. However, food additives are usually of low biological activity. Veterinary drugs and their breakdown products may also be found in foodstuffs as indicated above. In many cases they are ingested daily for perhaps a lifetime and the numbers of people exposed is very large.
Although reliable data are still scarce, there certainly seems to be evidence that at least some additives may be associated with adverse effects. There is a huge range of chemical types and many different industries may involve the use or manufacture of hazardous chemicals. Although in general exposure is controlled by law, often by the setting of control limits, realistic levels may still prove to be hazardous in the long term and acute exposure due to accidents will always occur. Factories may also produce and emit more potent substances in smaller quantities although the level of these is generally controlled.
Environmental pollutants may be released into the air, river or sea water or dumped onto land. Car exhaust fumes with several known toxic constituents constitute a major source of pollution. Pesticides are deliberately sprayed onto crops or agricultural land with the potential for exposure either via the crop itself or through contamination of drinking water or air.
With pesticides a major problem is persistence in the environment and an increase in concentration during passage through the food chain. Natural toxins may feature in poisoning via contamination in food, by accidental ingestion of poisonous plants or animals, and by stinging and biting.
The most visible pollutant, but perhaps not the These may include some of the substances in the other categories such as pesticides, drugs and solvents. Exposure to these types of compounds is usually acute rather than chronic.
Many of the household substances used for cleaning are irritants and some are corrosive. Some of the drugs and pesticides which are widely available and consequently often found in the home are also very toxic.
For example, gases and vapours lead to inhalation exposure whereas liquids give rise to problems associated with skin contact.
Many industrial chemicals are often associated with chronic effects due to long-term exposure whereas household substances are usually involved in acute poisoning following a single episode of accidental exposure.
This form of exposure is usually chronic but there have been isolated accidents at factories where acute exposure of humans outside the factory occurs such as at Bhopal and Seveso. Environmental exposure is also important in relation to pesticides contaminating air, water and food. Large-scale spraying means that most people are exposed to pesticides or their residues both within their food and directly via the air.
The exposure to these compounds, especially repeated or chronic exposure, may be associated with adverse responses such as allergic reactions. Alcohol and cigarettes are used by many people, often on a long-term basis, and these may lead to chronic toxic effects.
Occupational exposure to toxic compounds is mainly chronic, continual exposure. The route of exposure is either via inhalation or skin contact. Consequently lung disease and dermatitis are common industrial diseases. Acute exposure may occur in the event of an accident such as an explosion, spillage or leakage or because of bad working practices.
Cleaning out reactor vessels which have contained solvents may lead to acute toxicity due to excessive exposure for example. Drugs, pesticides, household Dose—response relationship products and natural poisons may all be involved in this type of exposure, and children and the elderly are most commonly involved. Drugs are commonly used but household products occasionally feature; both types are usually taken by mouth in these circumstances. It encompasses the differences in susceptibility to toxic effects between different species of animal or plant or between different cells, such as between tumour cells and normal cells.
It is in many cases a useful attribute which is utilized in the design of antibacterial drugs, pesticides or anti-cancer drugs.
It is also of relevance to the prediction of toxicity in humans based on studies in another species. The reasons for selective toxicity are various but can be divided into those due to differences in the absorption, distribution, metabolism and excretion of a chemical toxicokinetics or those due to biochemical differences affecting the presence of a receptor or target molecule toxicodynamics.
For example the insect is more susceptible to the toxicity of DDT than mammalian organisms for two reasons. Firstly, the insect cuticle allows DDT to penetrate more readily than the mam- 9 malian skin. Secondly, the insect has a greater surface area to volume ratio and therefore absorbs relatively more DDT.
Insects are more susceptible to some organophosphorus insecticides because the compound is metabolized by oxidative desulphuration to a compound that inhibits acetylcholinesterase, whereas in mammals enzymatic hydrolysis produces a metabolite that is more readily excreted but is not an inhibitor of acetylcholinesterase.
The rodenticide norbormide is active against rats because they possess a receptor in smooth muscle whereas humans, cats and dogs do not. Therefore after the oral ingestion of a poisonous chemical the rat is unable to rid itself of the substance by simply vomiting.
Penicillin is active against certain bacteria because it interferes with synthesis of the cell wall in multiplying bacteria but mammalian cells do not have a cell wall and therefore are not affected. This relationship between the dose of a compound and the response it elicits is a fundamental concept in toxicology.
The toxic response that is simplest to observe is death but this is a crude parameter to measure. A more precisely measured response is a biochemical, pharmacological or chemical change.
In both cases there will be a dose at which there is no measurable effect and an upper dose where there is a maximal response. However, it is often important to know the limits of dosing in practical terms. Although it is not always necessary to know the lethal dose, it is important to know whether toxicity occurs at the dose or a multiple of the dose likely to be encountered by man or animals.
It should be noted that strictly speaking the word dose means the total amount of a substance administered to an organism whereas the term dosage includes a characteristic of the organism, typically body weight or surface area. We can therefore talk about dosage—response relationships. This response is then plotted against the dosage or concentration resulting in a typical sigmoid curve as illustrated in Figure 1.
By using probit analysis the data can be plotted as a straight line. When the response is a graded one the actual values measured are plotted against the dosage or concentration giving the same type of curve Figure 1. There are, however, a few well understood receptor toxicant interactions such as that between the aryl hydrocarbon hydrolyase Ah receptor and a number of aromatic compounds such as dioxin TCDD.
It is possible that many toxic responses do not involve direct interactions with receptors in the pharmacological sense. It is more likely Figure 1.
Dose—response relationship Figure 1. This graph shows the relationship between these parameters.