Chapter 1

• Toxicology is the study of the adverse effects of xenobiotics on living systems.
• Toxicology assimilates knowledge and techniques from biochemistry, biology, chemistry, genetics, mathematics, medicine, pharmacology, physiology, and physics.
• Toxicology applies safety evaluation and risk assessment to the discipline.

Modern toxicology goes beyond the study of the adverse effects of exogenous agents by assimilating knowledge and techniques from most branches of biochemistry, biology, chemistry, genetics, mathematics, medicine, pharmacology, physicology, and physics and applies safety evaluation and risk assessment to the discipline. In all branches of toxicology, scientists explore the mechanisms by which chemicals produce adverse effects in biological systems. Activities in these broad subjects complement toxicologic research, thereby contributing to the application of this knowledge to the science and art of toxicology.

### Antiquity

Knowledge of animal venoms and plant extracts for hunting, warfare, and assassination presumably predate recorded history. One of the oldest known writings, the Ebers Papyrus (circa 1500 b.c.), contains information pertaining to many recognized poisons, including hemlock, aconite, opium, and metals such as lead, copper, and antimony. Whereas the Book of Job (circa 1400 b.c.) speaks of poison arrows (Job 6:4), Hippocrates (circa 400 b.c.) added a number of poisons and clinical toxicology principles pertaining to bioavailability in therapy and overdosage. Theophrastus (370–286 b.c.), a student of Aristotle, included numerous references to poisonous plants in De Historia Plantarum. Dioscorides, a Greek physician in the court of the Roman emperor Nero, made the first attempt at classifying poisons into plant, animal, and mineral poisons in his book De Materia Medica, which contains reference to some 600 plants.

One legend tells of Roman King Mithridates VI of Pontus, who was so fearful of poisons that he regularly ingested a mixture of 36 ingredients as protection against assassination. On the occasion of his imminent capture by enemies, his attempts to kill himself with poison failed because of his successful antidote concoction. This tale leads to use of the word mithridatic as an antidote or protective mixture. Because poisonings in politics became so extensive, Sulla issued the Lex Cornelia (circa 82 b.c.), which appears to be the first law against poisoning and later became a regulatory statute directed at careless dispensers of drugs.

### Middle Ages

The writings of Maimonides (Moses ben Maimon, a.d. 1135–1204) included a treatise on the treatment of poisonings from insects, snakes, and mad dogs (Poisons and their Antidotes, 1198). Maimonides described the subject of bioavailability, noting that milk, butter, and cream could delay intestinal absorption. In the early Renaissance and under the guise of delivering provender to the sick and the poor, Catherine de Medici tested toxic concoctions, carefully noting the rapidity of the toxic response (onset of action), the effectiveness of the compound (potency), the degree of response of the parts of the body (specificity and site of action), and the complaints of ...

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