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KEY POINTS

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  • A poison is any agent capable of producing a deleterious response in a biological system.

  • A mechanistic toxicologist identifies the cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms.

  • Toxicogenomics permits mechanistic toxicologists to identify and protect genetically susceptible individuals from harmful environmental exposures, and to customize drug therapies based on their individual genetic makeup.

  • A descriptive toxicologist is concerned directly with toxicity testing, which provides information for safety evaluation and regulatory requirements.

  • A regulatory toxicologist both determines from available data whether a chemical poses a sufficiently low risk to be marketed for a stated purpose and establishes standards for the amount of chemicals permitted in ambient air, industrial atmospheres, and drinking water.

  • Selective toxicity means that a chemical produces injury to one kind of living matter without harming another form of life even though the two may exist in intimate contact.

  • The individual or “graded” dose–response relationship describes the response of an individual organism to varying doses of a chemical.

  • A quantal dose–response relationship characterizes the distribution of responses to different doses in a population of individual organisms.

  • Hormesis, a “U-shaped” dose–response curve, results with some xenobiotics that impart beneficial or stimulatory effects at low doses but adverse effects at higher doses.

  • Descriptive animal toxicity testing assumes that the effects produced by a compound in laboratory animals, when properly qualified, are applicable to humans, and that exposure of experimental animals to toxic agents in high doses is a necessary and valid method of discovering possible hazards in humans.

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INTRODUCTION TO TOXICOLOGY

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Toxicology is the study of the adverse effects of chemicals on living organisms. A toxicologist is trained to examine the nature of those effects (including their cellular, biochemical, and molecular mechanisms of action) and assess the probability of their occurrence. Fundamental to this process is characterizing the relation of exposure (or dose) to the response. The variety of potential adverse effects from the abundant diversity of chemicals upon which our society depends often demands specialization in one area of toxicology.

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Different Areas of Toxicology

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A mechanistic toxicologist identifies the cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms (see Chapter 3 for a detailed discussion of mechanisms of toxicity). Mechanistic data may be useful in the design and production of safer chemicals and in rational therapy for chemical poisoning and treatment of disease. In risk assessment, mechanistic data may be very useful in demonstrating that an adverse outcome observed in laboratory animals is directly relevant to humans. Toxicogenomics permits the application of genomic, transcriptomic, proteomic, and metabolomic technologies to identify descriptive and mechanistic information that can protect genetically susceptible individuals from harmful environmental exposures, and to customize drug therapies based on their individual genetic makeup. Numerous genetic tests can identify susceptible individuals in advance of pharmacological treatment.

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A descriptive toxicologist is concerned ...

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