Download PDF Principles of Biochemical Toxicology Fourth Edition by John A. Timbrell

Sinopsis

Toxicology is the subject concerned with the study of the noxious effects of chemical substances on living systems. It is a multidisciplinary subject, as it embraces areas of pharmacology, biochemistry, chemistry, physiology, and pathology; although it has sometimes been considered as a subdivision of some of these other subjects, it is truly a scientific discipline in itself.

Toxicology may be regarded as the science of poisons; in this context, it has been studied and practiced since antiquity, and a large body of knowledge has been amassed. The ancient Greeks used hemlock and various other poisons, and Dioscorides attempted a classification of poisons. However, the scientific foundations of toxicology were laid by Paracelsus (1493–1541), and this approach was continued by Orfila (1787–1853). Orfila, a Spanish toxicologist working in Paris, wrote a seminal work, Trait des Poisons, in 1814 in which he said toxicology should be founded on pathology and chemical analysis.

Today, highly sensitive and specific analytical methods are used and together with the new methods of molecular biology have a major impact on the development of the science. Interactions between chemicals and living systems occur in particular phases. The first is the exposure phase where the living organism is exposed in some way to the chemical and which may or may not be followed by uptake or absorption of the chemical into the organism. This precedes the next phase in which the chemical is distributed throughout the organism. Both these phases may require transport systems. After delivery of the chemical to various parts of the organism, the next phase is metabolism, where chemical changes may or may not occur, mediated by enzymes. These phases are sometimes termed “toxicokinetics,” whereas the next phase is the toxicodynamic phase in which the chemical and its metabolites interact with constituents of the organism. The metabolic phase may or may not be a prerequisite for the final phase, which is excretion.

This sequence may then be followed by a phase in which pathological or functional changes occur. Ability to detect exposure and early adverse effects is crucial to the assessment of risk as will be apparent later in this book. Furthermore, understanding the role of metabolites rather than the parent chemical and the importance of concentration in toxic effects are essential in this process. Therefore, toxicology has of necessity become very much a multidisciplinary science. There are difficulties in reconciling the often-conflicting demands of public and regulatory authorities to demonstrate safety with pressure from animal rights organizations against the use of animals for this purpose. Nevertheless, development of toxicology as a separate science has been slow, particularly in comparison with subjects such as pharmacology and biochemistry, and toxicology has a

much more limited academic base. This may in part reflect the nature of the subject, which has evolved as a practical art, and also the fact that many practitioners were mainly interested in descriptive studies for screening purposes or to satisfy legislation.

Content

1. Fundamentals of Toxicology and Dose-Response Relationships
2. Factors Affecting Toxic Responses: Disposition
3. Factors Affecting Toxic Responses: Metabolism
4. Factors Affecting Metabolism and Disposition
5. Toxic Responses to Foreign Compounds
6. Biochemical Mechanisms of Toxicity: Specific Examples

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