Basic Concepts of Toxicology

The starting points for discussion of the basic concepts of toxicology are the definitions of hazard, exposure, and risk. These definitions are followed by an overview of ADME (absorption, distribution, metabolism, and excretion) of toxins. 

Hazard. Hazard is an inherent property or ability of a substance to cause an adverse effect or event. Classes of hazards include physical hazards (e.g., compressed gases, explosives, flammables, organic peroxides, pyrophorics, unstable and water-reactive materials) and health hazards (e.g., asphyxiants, irritants, systemic toxins, reproductive toxins, carcinogens). 

The hazards of a given substance are unaffected by concentration (e.g., an acid is capable of causing tissue destruction regardless of concentration) but dependent on chemical form (e.g., the hazards of elemental mercury differ from those of organic mercurial compounds). In the first example, it is important to recognize the distinction between the quantitative effect (the degree of the hazard) and the qualitative effect (the nature of the hazard)  

A substance may present an array of hazards, with the expression of one, some, or all hazards dependent on the conditions of exposure. The expressed hazards may be quite different (as exemplified by the central nervous system stimulation and depression associated with acute and chronic alcohol intake, respectively) or may represent a common underlying mechanism of action (as suggested by the involvement of lipid effects in local skin effects and in organ toxicity of certain organic solvents). 

Exposure. Exposure defines contact of a hazard with a specific set of conditions. For physical hazards, exposure defines the conditions under which the hazard will be expressed. For example, methanol must be exposed to temperatures at or above the flash point of 52°F (11°C) in order to express the hazard of flammability. 

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We have attempted to present the state of the art and scientific consensus in an unbiased way however, what is believed to be tme today may not hold tomorrow - politics may change, and science may progress. Fortunately, while methods and techniques are continuing to improve, the basic concepts of toxicological risk assessment remain stable and form the core in this book. 

To give some more depth on this subject, some basic concepts of toxicology and toxics are summarised in the Chapter 2. 

Once a toxic chemical is in contact with or enters the body, it can exert its effects. Whether a chemical produces any toxic effects is determined by the dose received over a period of time. This is called the dose rate. The quote by 16th century physician Paracelsus at the beginning of this section embraces the basic concept of toxicology that is commonly phrased as the dose makes the poison. Whether a chemical exerts its toxic effects depends on the amount or dose of the chemical that is received by the organism. Another critical factor that determines if a chemical is toxic is the time period over which the dose was received. 

From this point in history, substantial contributions to the fields of toxicology increased dramatically, and each contribution can be linked to a basic concept of toxicology (eg., mechanism of action) and/or a specialization in toxicology (e.g., forensic toxicology). A good source of additional... 

The various basic concepts of toxicology have been discussed. In applying them to the respirator user, we will try to correlate these basics with actual field problems. As a respirator is designed to protect the lungs and inhalation... 

A basic concept of toxicology is the statement of Paracelsus that the dose is the difference between a poison and a cure. To evaluate the level of danger from various substances, natural or synthetic, a risk assessment is made by exposing laboratory animals to the substances and monitoring the health effects. Often, doses very much greater than humans might ordinarily encounter are given to the test animals. 

The most basic concept in toxicology is that of the lethal dose. Paraselsus (1493-1541) said that All substances are poisons, there is none which is not a poison. The right dose... 

ALDRIDGE, W.N. (1996) Mechanisms and Concepts in Toxicology (London Taylor and Francis). GREGUS, Z. and KLAASSEN, C.D. (1996) Mechanisms of toxicity. In Cassarett and Doull s Toxicology, The Basic Science of Toxicology, edited by C.D.Klaassen, 5th edition (New York McGraw Hill). 

That a laboratory animal may qualitatively and quantitatively be extrapolated to man is a basic premise of toxicology (Paracelsus, 1493-1541). Paracelsus stated that, "All things are poisons, for there is nothing without poisonous properties it is only the dose which makes a thing poison" ( ). Inherent in this interpretation is the concept that quantitatively there will be an exposure level below which no discernable adverse effects occur. In addition, logical extrapolation of the premise of Paracelsus includes the concept that responses due to chemicals will be qualitatively similar in animals and man. 

It is essential that all laboratory workers understand certain basic principles of toxicology and learn to recognize the major classes of toxic and corrosive chemicals. The next sections of this chapter summarize the key concepts involved in assessing the risks associated with the use of toxic chemicals in the laboratory. (Also see Chapter 5, section 5.D.)... 

Concepts in Toxicology Presents the basic principles of toxicology, acute and chronic toxicities, metabolism, the language of toxicology, and factors that influence toxicity. 

This book is written by experts from disciplines as diverse as analytical chemistry, nuclear chemistry, environmental science, molecular biology, and medicinal chemistry in order to identify potential hot spots of metallomics and metalloproteomics. The scientific fundamentals of new approaches, like isotopic techniques combined with ICP-MS/ESI-MS/MS, the synchrotron radiation-based techniques. X-ray absorption spectroscopy, X-ray diffraction, and neutron scattering, as well as their various applications, with a focus on mercury, selenium, chromium, arsenic, iron and metal-based medicines are critically reviewed, which can help to understand their impacts on human health. The book will be of particular interest to researchers in the fields of environmental and industrial chemistry, biochemistry, nutrition, toxicology, and medicine. Basically, the book has two aims. The first deals with the educational point of view. Chapters 2 to 7 provide the basic concept of each of the selected nuclear analytical techniques and should be understandable by Master and PhD students in chemistry, physics, biology and nanotechnology. The... 

So far, we have discussed the basic concept of a dose-response relationship, how toxic effects are measured, and the types of toxic effects that can occur in a variety of organisms. This chapter introdnces mcmy of the core concepts of toxicology. We have seen that toxicity Ccm differ bcised on differences cunong species. The factors that result in these differences are farther discussed here. The majority of these factors affect toxicity across species in predictable ways. Children cmd the elderly are often considered most susceptible to toxic effects of chemicals the concepts presented here illustrate why this is so. 

Several textbooks and articles have been written on various aspects of the field of toxicology, most notably Casarett Doull s Toxicology The Basic Science of Poisons [7], which offers clear, concise descriptions of key concepts of toxicology. 

The explanation of the pharmacokinetics or toxicokinetics involved in absorption, distribution, and elimination processes is a highly specialized branch of toxicology, and is beyond the scope of this chapter. However, here we introduce a few basic concepts that are related to the several transport rate processes that we described earlier in this chapter. Toxicokinetics is an extension of pharmacokinetics in that these studies are conducted at higher doses than pharmacokinetic studies and the principles of pharmacokinetics are applied to xenobiotics. In addition these studies are essential to provide information on the fate of the xenobiotic following exposure by a define route. This information is essential if one is to adequately interpret the dose-response relationship in the risk assessment process. In recent years these toxicokinetic data from laboratory animals have started to be utilized in physiologically based pharmacokinetic (PBPK) models to help extrapolations to low-dose exposures in humans. The ultimate aim in all of these analyses is to provide an estimate of tissue concentrations at the target site associated with the toxicity. 

Three basic concepts for the description of toxicological action of mixture have been defined. 

This section provides a brief summary of the current knowledge of radiation-induced health effects together with certain basic elements of radiation toxicology needed to understand the concepts and terminology that are associated with this discipline. 

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. 

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