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Principles of Toxicology

History of Toxicology

Michael J. Hooper

The Environmental Toxicology Department Texas Tech University Lubbock, Texas

History of Toxicology Antiquity ­ Animal venoms, plants, minerals Rome and the dark ages ­ modification and manipulation to improve potency/utility Age of Enlightenment ­ foundations of toxicology Chemical and Industrial Revolutions ­ syntheses galore 20th Century ­ Chemical soup

Egyptians The Ebers Papyrus Earliest cultures developed knowledge of drugs and poisons Egyptians ­ The Ebers Papyrus Chinese ­ Pen Ts'ao Ts' Hindus ­ Rig-Veda RigDated to 1500 BCE, compiles material back to 3000 BCE Named for Egyptologist Georg Moritz Ebers (1837(18371898) 20 m scroll with 700 drugs in 900 formulas ­ Indications, dosages and appropriate spells and incantations.



Topics - intestinal disease, helminthiasis, ophthalmology, helminthiasis, dermatology, gynecology, obstetrics, pregnancy diagnosis, contraception, dentistry, and the surgical treatment of abscesses, tumors, fractures and burns. Drugs made of plant, animal and mineral sources in beer, wine, milk, honey vehicles Poisons noted: Plant - Opium, hellbore, aconite, hyoscayamus, hemlock hellbore, hyoscayamus, Mineral - Lead, antimony, copper Insect and animal venoms In general ­ physicians combined biological/chemical materials with mysticism to cure their patients.

Pen Ts'ao - the Great Herbal or Chinese Materia Medica Ts' 2735 BCE by Shen Nung ­ father of Chinese medicine Lists of poisonous and medicinal plants (together!) as well as antidotes Includes: Iodine, aconite (and its use as an arrow poison), opium, cannabis, rhubarb, alum, camphor, iron, sulfur and mercury

The Greeks Hindus The Rig-Veda - 1500 and 1200 BCE RigMany references to alchemy, science and magic Medicinal and poisonous plants, antidotes to snake bite Susruta-Samhita ­ 100 BCE Susruta760 indigenous medicinal plants Kalpa Sthana ­ toxicology section primarily antidotes for bites and stings and as aphrodisiacs Homer (~600 BCE) Odysseus obtained poison for his arrows Socrates (470-399 BCE) Forced to drink (470hemlock, the state poison, due to his vocal disapproval of current society


Dioscorides (surgeon in Nero's court; 40-90 ACE) Nero' 40Other Greeks Hippocrates (460-355 BCE) Scientific method, sound (460observation and logical reasoning. Environmental factors can cause disease ­ purification can cure ­ emetics, cathartics and enema for removal of poisons Defined ideas of bioavailability and dose De Historia Plantarum (300 BCE) - Theophrastus (student of Aristotle) ­ Documented medical and poisonous plants ­ beginnings of botany Wrote the Materia Medica (5 volumes) documenting over 600 medicinal plants he encountered while traveling with the Roman military, as well as earlier compilations of Roman and Greek knowledge Classification of poisons into plant, animal and mineral sources It was the authoritative reference well into the 17th century

1547 translation

Arabic version of Mat. Med. C1334. Cumin and dill

Pedanius Dioscorides

King Mithridates VI of Pontus (120-63 BCE) (120Studied poisoning and its prevention using slaves and prisoners from his lifelong battles against the Romans Took daily doses of poisons, increasing levels to develop polyvalent tolerance. Mithridatium ­ a concoction containing a collection of materials to prevent poisoning When capture loomed, couldn't couldn' poison himself and had to have one of his guard hold a sword for him to fall upon

Aulus Cornelius Celsus describes this complex antidote, named Antidotum Mithridaticum, in his De Medicina: Mithridaticum, Medicina: But the most famous antidote is that of Mithridates, which that king is said to have taken daily and by it to have rendered his body safe safe against danger from poison. It contains costmary 1.66 grams, sweet sweet flag 20 grams, hypericum, gum, sagapenum, acacia juice, Illyrian iris, hypericum, sagapenum, cardamon, 8 grams each, anise 12 grams, Gallic nard, gentian root cardamon, and dried rose-leaves, 16 grams each, poppy-tears and parsley, 17 rosepoppygrams each, casia, saxifrage, darnel, long pepper, 20.66 grams each, casia, storax 21 grams, castoreum, frankincense, hypocistis juice, myrrh and castoreum, opopanax, 24 grams each, malabathrum leaves 24 grams, flower of opopanax, round rush, turpentine-resin, galbanum, Cretan carrot seeds, 24.66 turpentinegrams each, nard and opobalsam, 25 grams each, shepherd's purse opobalsam, 25 grams, rhubarb root 28 grams, saffron, ginger, cinnamon, 29 grams grams each. These are pounded and taken up in honey. Against poisoning, a poisoning, piece the size of an almond is given in wine. In other affections an affections amount corresponding in size to an Egyptian bean is sufficient.

The Last King, Michael Curtis-Ford (2005) ISBN 0-312-93615-X (Book V, 23:3) King, Curtis0- 312- 93615-


Uses of poisons Suicides ­ Poison was often the easier alternative Demosthenes (382-322 BCE) Greek orator who (382spoke against Macedonians ­ When summoned before Alexander, he chose poison in his pen over torture

Murder 400-300 BCE ­ Livy describes Roman wives (later 400widows) poisoning their husbands for monetary gains 1300 AD ­ Toffana and Heironyma Spara Developed As containing cosmetics ­ used for marital and monetary gain ­ came with instructions 1503 AD ­ Alexander VI and the Borgias The pope poisoned rich cardinals to return their money to the papacy 1500-1700 AD - Catherine de Medici, Marchioness do 1500Brinvillers and Catherine Deshayes ­ used sick, poor and orphans to hone poisoning skills ­ Documented onset times, specificity, potency, age dependence, signs and symptoms

Cleopatra (30 BCE) Rather than falling on her sword, she chose to... to... "fall on her asp" asp"

Theophrastus Phillippus Aureolus Bombastus von Hohenheim a.k.a., Paracelsus (1493-1541)

Paracelsus Medical doctor with a wide breadth of interests ­ focused on disease causation rather than spiritual basis Focused on the Toxicon or toxic agent Believed experimentation was crucial to understanding responses to chemicals Chemicals can have both therapeutic and toxic effects, properties that were indistinguishable except by dose "The Dose Makes the Poison" Poison" There is a specificity of chemicals in therapeutic and toxic actions Documented a variety of miner's diseases miner'

The Father of Toxicology


Occupational poisoning 1480 ­ Recognition of Hg and Pb poisoning in the gold smithing industry 1556 ­ Agricola publishes De Re Metallica, documenting health effects of miners

"If the dust has corrosive qualities, it eats away the lungs, and implants consumption in the body; hence in the mines of the Carpathian Mountains women are found who have married seven husbands, all of whom this terrible consumption has carried off to a premature death." De Re Metallica Georgius Agricola, 1556.

1775 ­ Sir Percival Potts documents the first occupational cancer Otherwise healthy young men who were chimney sweeps in England had elevated occurrence of squamous cell carcinoma of the scrotum. Came from exposure to coal tar in the chimneys. Scrotal tissue particularly susceptible because of thin nature of skin that allows for easy penetration of the coal tar. Polynuclear aromatic hydrocarbons (PAHs)

The Chemical Revolution of the 1800s Organic chemistry makes giant advances By 1880, over 10,000 organic chemicals have been synthesized

1800's 1800' Development of Autopsy and Analytical Chemistry and an understanding of Mechanism of Action Arrow poisons, strychnine, carbon monoxide Orfila Bernard Magendie


1900-1920 1900Curies (Marie, Pierre and Irene) discover radium and radioactivity and their toxicities Wiley Bill ­ First pure food and drug law ­ in response to Upton Sinclair's The Jungle, about Sinclair' Jungle, the meat packing industry Vitamins ­ the vital amines ­ first major use of animal models ­ development of purified lines of laboratory animals World War I ­ Chlorine gas, mustard gas and other "human" pesticides human" 1920s Arsenicals developed to treat syphillis Ginger Jake ­ TOCP, Pb and Hg from bootlegging Discovery of DDT Androgens, estrogens and DES (diethyl stilbestrol)

1950-1970 19501930s ­ 1950 Expansion of radioactivity research Lange and Schrader - Development of organophosphates for humans and insects Widespread DDT use Elizabeth and James Miller ­ Carcinogenesis mechanisms The Delaney Clause Society of Toxicology and TAP 1962 ­ Rachel Carson's Silent Spring and the beginning Carson' of the environmental movement Analytical capabilities to PPB (part per billion) levels Minimata Bay and Hg poisoning Dioxin (TCDD) in Agent Orange ­ Operation Ranchhand


1970s Love Canal, New York Hooker Chemical Co.

1970s Dioxin Contamination Times Beach, Missouri Seveso, Italy Seveso, US EPA Environmental Protection Agency established NCTR ­ National Center for Toxicological Research NIEHS ­ National Institute of Environmental Health Sciences DDT and other OCs banned



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