Toxicology is the study of adverse effects of chemicals on living organisms. It has evolved from ancient times when poisons were used for execution or murder. Key developments include Paracelsus' principle that "the dose makes the poison" in the 16th century and Mathieu Orfila establishing toxicology as a science in the 19th century. Toxicology now encompasses diverse areas like environmental, clinical, molecular and regulatory toxicology to study toxin effects and protect public health. Major events like thalidomide and Love Canal increased regulatory standards in the 20th century. Toxicology continues advancing our understanding of chemical safety.

1. HISTORY AND SCOPE
OF TOXICOLOGY
Prepared by : Sangar, Jaswant S.

3. Toxicology
Toxicologist
Poison

4. IMPORTANT TERMS IN
TOXICOLOGY
Toxicology
 defined as the study of the adverse effects xenobiotics and
thus is borrowing science that has evolved from ancient
poisoners.
 from the Greek word toxicos and logos
 historically it formed the basis of therapeutics and
experimental medicine.

5. Toxicant
 A poison that is made by humans or that is put into the
environment by human activities.
Toxicologists
 they are involved in the recognition, identification, and
quantification of hazards resulting from occupational
exposure to chemicals and the public health aspects of
chemicals in air, water, other parts of the environment,
foods, and drugs.
Poisons
 any substance that produces disease conditions,
tissue injury or otherwise interrupts natural life
processes when in contact with or absorbed into
the body.

6. TYPES OF TOXICOLOGISTS

7. Environmental
Toxicologist
Clinical
Toxicologist
Molecular
Toxicologist

8. 1. Environmental Toxicologists
 they study the effects of chemicals in flora and fauna.
2. Molecular Toxicologists
 study the mechanisms by which toxicants modulate
cell growth and differntiation and cell respond to
toxicants at the level of gene.
3. Clinical Toxicologists
 develop antidotes and treatment regimes to
ameliorate poisonings and xenobiotic injury.

9. Regulatory
Toxicologist
Forensic
Toxicologist

10. 4. Regulatory Toxicologists
 has the responsibility for deciding on the basis provided by
descriptive and mechanistic toxicologists, whether a drug
or another chemical poses a sufficiently low risk.
5. Forensic Toxicologists
 concerned mainly with the medicolegal aspects of the
harmful effects of chemicals in humans and animals.

11. Science of Toxicology
 defined as the observational and data-gathering
phase.

13. History of Toxicology
Aureolus Philippus Theophrastus Bombastus Von
Hohenheim (Paracelsus)
 Father of Modern Toxicology
 “ The dose makes the Poison”
Mathieu Joseph Buenaventura Orfila (April 24,
1787 - March 12, 1853)
 was a spanish born french toxicologist and
chemist
 the founder of the science of toxicology
 often called the father of toxicology

14. HISTORY OF TOXICOLOGY
(ANTIQUITY)

15. Ebers Papyrus (circa 1500 B.C.)
 contains information pertaining to many
recognized poisons
Examples of Poisons :
• Hemlock (the state poison of the Greeks)
• Aconite (a chinese arrow poison)
• Opium (used as both a poison and an antidote)
• Metals ((arsenic lead, copper, and antimony

16. Hemlock
Aconite
Opium

18. Hippocrates (Circa 400 B.C.)
 added a number of poisons and clinical toxicology
principles pertaining to bioavailability in therapy and
overdosage.
Book of Job (Circa 400 B.C.)
 speaks of poison arrows (Job 6:4).
Theophrastus (370- 286 B.C.)
 student of Aristsotle, included numerous
references to poisonous plants in De
Historica Plantarum.

19. Socrates (470-399 B.C.)
 used recipient of poisons as a state method of
execution
 his cup of hemlock extract was apparently estimated to
be the proper dose.
Dioscorides
 a greek physician in the court of the roman emperor
Nero, made the first attempt at a classification of
poisons, which was accompanied by descriptions and
drawings.

20. Cleopatra (69-30 B.C.)
 use knowledge of naural primitive toxicology
permmitted her to use the more genteel method of
falling on her asp
King Mithridates VI of Pontus
 Experimented on criminals and himself.
 He would drink a poison cock-tail (36 ingredients!) to
protect himself from his enemies.
 When ultimately captured, he had to resort to using
his sword.
 Known as the “King of Poisons”

21. Nicander of Colophon( 204-135 B.C.)
 deals with poisonous animals; his poem
Alexipharmaca was about antidotes.
Lex Cornelia ( circa 82 B.C.)
 the first law against poisoning in Rome and later
became a regulatory statue directed at careless
dispensers of drugs.
Nero (A.D. 37-68)
 used poisons to do way with his stepbrother
Brittanicus and employed his slaves as food
tasters to diferentiate edible mushrooms
from their more poisonous kin

22. HISTORY AND SCOPE OF
TOXICOLOGY – MIDDLE AGES

23. BEFORE RENAISSANCE
Maimonides (Moses ben Maimon, AD 1135-
1204)
 he included a treatise on the treatment of
poisoning from insects, snakes, and mad dogs (
poisons and their Antidotes, 1198).
 he wrote on the subject of bioavailability, noting
that milk, butter, and cream could delay
intestinal absorption.

24. EARLY RENAISSANCE
Italians
 brought the art of poisoning to its zenith.
Prisoner
 became an integral part of the political science.
Council of Ten of Venice
 contain ample testimony about the political use of poisons.
Toffana
 prepared arsenic-containing cosmetics (Aqua Toffana) and
perfumes

25. Aqua Toffana

26. Hieronyma Spara
 provided a new fillip by directing her activities toward
specific marital and monetary objectives.
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, site of action), and the
complaints of the victim (clinical signs and symptoms)
Catherine Deshayes
 a midwife sorceress who earned the title " La Voisin"
 she represented the culmination of practice in France by the
Commercialization of the service.

27. Catherine de Medici Catherine Deshayes

28. HISTORY AND SCOPE OF
TOXICOLOGY – AGE OF
ENLIGHTENMENT

29. Philippus Aureolus Theophrastus Bombastus von
Hohenheim-Paracelsus (1493–1541).
 formulated many revolutionary views that remain an integral
part of the structure of toxicology, pharmacology, and
therapeutics today
 Responsible for the most famous saying in all of toxicology:
All substances are poisons; there is none which is not a
poison. The right dose differentiates a poison from a
remedy.
 focused on the importance of the ‘toxicon’—a primary toxic
agent and a single chemical entity

30. • Experimentation is essential in the examination of
responses
• There is a difference between the therapeutic and toxic
properties
• The above are not easily determined, except by dose
• It is possible to ascertain a degree of specificity of
chemicals and their therapeutic or toxic effects.

31. On the Miners: Sickness and Other Diseases of
Miners (1567),
 was published by Paracelsus
 This treatise addressed the ethiology of miners’ disease,
along with treatment and prevention strategies.
Discourse on the Diseases of Workers (1700)
 by Bernardino Ramazzini
 Set the standard for occupational medicine
 included information about miners,
midwives, printers, weavers and potters

32. Percival Pott (1714–1788)
In 1825
 phosgene (COCl 2) and mustard gas (bis[β-
chloroethyl]sulfi de) had been synthesized. These 2
agents, along with chlorine gas, were used by the
German forces in World War I as chemical warfare agents.
In 1880
 10,000 organic compounds had been synthesized including:
 Chloroform
 carbon tetrachloride
 diethyl ether
 carbonic acid
 and petroleum and
 coal gasifi cation

33. Magendie (1783–1885), Orfila (1787–1853),
and Bernard (1813–1878)
Orfila
 a Spanish physician in the French court,
 was the first toxicologist to use autopsy material
and chemical analysis systematically as legal
proof of poisoning.
Magendie
 studied the mechanisms of action of emetine,
strychnine, and “arrow poisons”

34. Oswald Schmiedeberg ( 1838 - 1921)
 His research focused on the synthesis of hippuric acid
in the liver and the detoxification mechanisms of the
liver in several animal species (Schmiedeberg and
Koppe, 1869).
Kurt Lewin (1850-1926)
 contibuted on the chronic toxicity of narcotics
and other alkaloids
 published much of the early work on the toxicity
of methanol, glycerol, acrolein, and chloroform
(Lewin, 1920, 1929).

35. HISTORY AND SCOPE OF
TOXICOLOGY - THE SECOND HALF
OF THE 19TH CENTURY

36. Formalization of the experimental program for the testing
of food, drug and cosmetic safety in 1955
 Updated by the FDA in 1982
 Basically states that any chemical found to be carcinogenic in
lab animals or humans cannot be added to the US food supply.
Toxicology and Applied Pharmacology started around
1958
 First journal dedicated to toxicology

37. Major Events in 1960s:
1. Thalidomide babies –Silent Spring by Rachel Carson
 Highlighted the ecological effects of pesticide usage
2. Equipment available for detecting parts per billion (ppb)
 Genetic assays for point mutations (Ames assay)

38. Two major discoveries (1948):
1. Paper chromatography for chemical separation.
2. Use of blood and urine for testing presence of
various chemical metabolites (biomarkers).

39. In 1970s :
1. Discovery of Love Canal as a major dumping site for toxic
chemicals.
2. Push for toxicology to consider exposures to complex mixtures.

40. HISTORY AND SCOPE OF
TOXICOLOGY - 20th Century
Toxicology : The awakening of
Understanding

41. “Doctor” Munyan versus Harvey Wiley, MD (1844–1930)
 a classic battle between the federal government and the most
infamous purveyor of patent medicines, over mislabeling,
false advertisement, lack of efficacy, and serious toxicity led
to further Congressional action.
Dow, Union Carbide, and Du Pont
 The major chemical manufacturers in the United States
 established internal toxicology research laboratories to help
guide decisions on worker health and product safety.

42. During 1890s and early 1990s
Becquerel, Roentgen, and the Curies
 The european scientists reported the
discovery of radioactivity and x-rays.
vitamins, or “vital amines,”
 led to the use of the first large-scale bioassays (multiple
animal studies) to determine whether these new synthetic
chemicals were beneficial or harmful to laboratory
animals, and by extension to humans.

43. The discovery by Paul Ehrlich (1854–1915) of arsenicals for the
treatment of syphilis (arsenicals had been used in agriculture since
the mid-19th century) resulted in acute and chronic toxicity.
triorthocresyl phosphate (TOCP)
 was a recent gasoline additive, caused a syndrome that became
known as “ginger-jake” walk, a spastic gait resulting from
drinking ginger beer adulterated with TOCP.
Methanol
 used as a cheap ethanol substitute, blinded and killed many
unsuspecting people (see Poisoners Handbook , 2011).

44. 1. Dodds’s work on the bioactivity of the estrogenic
compounds resulted in the synthesis of
diethylstilbestrol (DES), hexestrol, other stilbenes,
and bisphenol A (BPA) and the discovery of the
strong estrogenic activity of substituted stilbenes.
2. Development of neurotoxicity field due to the
production of bootleg liquor by- products (methanol &
lead).
3. Toxicology of metals due to the production of ‘the
bomb’.

45. POST WORLD WAR II
Discovery of organophosphates (OPs) as
cholinesterase inhibitors.
• Today used as non-bioaccumulating pesticides
Production of quinine as an antimalarial. Based on
derivative of chincona bark
Discovery of mixed-function oxidases (MFOs) –Prelude to
latter work on P450s

46. HISTORY AND SCOPE OF
TOXICOLOGY – 21ST CENTURY

47. REFERENCES :
Casarett and Doull’s TOXICOLOGY The Basic Science of Poisons
Eighth Edition
"Mammalian Toxicology: History & Principles Lecture 1, Fall
2006. Retrieved from : https://slideplayer.com/slide/7233196/