GENERAL PRINCIPLES OF TOXICOLOGY - dose-response relation as a bulwark of

toxicology
ANTIQUITY
• Ellenbog (circa 1480)
• animal venoms and plant extract
- warned the toxicity (Mercury, Lead)
- use for hunting, warfare, and assassination
- published On the Miners' Sickness and Other
• Ebers Papyrus (circa 1500 B.C.) Diseases Miners, 1567

- includes hemlock, aconite, opium, and metals • Bernardino Ramazzini

(lead, copper, and antimony)
- Discourse in the Disease of Workers, 1700
• Book of Job (circa 1400 B.C.)
• Percival Pott's (1775)
- poison arrow (Job 6:4)
- roled of soot in scrotal cancer (chimney sweeps)
• Hippocrates (circa 400 B.C.) - polyaromatic hydrocarbon carcinogenicity

- added a number of poisons and clinical AGE OF ENLIGHTENMENT

toxicology principles pertaining to
• Magendie (1783-1885), Orfila (1787-1853),
bioavailability in therapy and overdosage
Bernard (1813-1878)
• Theophrastus (370-286 B.C.)
- laid groundwork for pharmacology,
- includes numerous references to poisonous experimental therapeutics, and occupational
plants in De Historia Plantarum toxicology

• Dioscorides • Orfila

- Greek physicist - Spanish physician

- classify poisons (plant, animal, mineral) - used autopsy material and chemical analysis
- De Materia Medica contains 600 plants systematically as legal proof of poisoning

MIDDLE AGES • Magendie

• Moses ben Maimon, A.D. 1135-1204 - physician and experimental physiologist

- studied the mechanisms of action of emetine and
- include a treatise on the treatment of poisoning strychnine
from insects, snake, and mad dogs o determine the absorption and
- Treatise on Poison and Their Antidotes, 1198 distribution of these compounds in the
RENAISSANCE body

• Philippus Aureolus Theophrastus Bombastus • Claude Bernard

von Hohenheim-Paracelsus ( 1463-1541) - An Introduction to the Study of Experimental
- Pivotal Medicine
- physician-alchemist • Oswald Schmiedeberg (1838-1921)
- formulated many revolutionary views that
remain integral to the structure of toxicology, - trained student for laboratories of pharmacology
pharmacology, and therapeutics today and toxicology
- focused on chemical entity and held:
• Loius Lewin (1850-1929)
• experimentation
• identification between therapeutic and toxic - focused on narcotics, methanol, glycerol,
properties acrolein, and chloroform
• distinguishing dose of chemicals
• ascernity of degree of specificity of chemicals 20TH CENTURY TOXICOLOGY
and therapeutics or toxic effects • patented medicines
 • Wiley Bill in 1906
U.S. pure food and drug laws
• 1890's and early 1900's

- discovery of radioactivity and vitamins

- Led to bioassays (multiple animal studies)

• Archiv fur Toxikologie

- published in Europe for experimental toxicology

• National Institutes of Health

- response to tragic consequences of acute kidney

failure after taking sulfanilamide in glycol
solutions
Initial Federal Insecticide, Fungicide, and
Rodenticide Act 1947
- first major bill
Copeland bill, passed in 1938
- second major bill
AFTER WORLD WAR II
• The Delaney clause ( 1958)
• Tragic Thalidomide incident
Rachel Carson's Silent Spring 1962
• International Congress includes:
Europe
South America
Asia
Africa
Australia
21st CENTURY TOXICOLOGY
• Genetically Modified Organisms
• Toxicology

- study of the adverse effects of xenobiotics