quick reference for general toxicology history and co-evolution of plants & animals along with environment since the dawn of the evolution.

1. INTRODUCTION TO VETERINARY
TOXICOLOGY
Dr. Sindhu K.
MVSc scholar, Dept of VPT,
COVAS, Pookode.

2. POISON
A POISON is any substance which, when ingested, inhaled, absorbed, or when
applied to, injected into, or developed with in the body, in relatively small
amounts, may cause damage to body structure or disturbance of function through
its chemical action.
Poison & poisonous animals have been of interest to humans since the dawn of
creation.
Toxicology = the study of poisons.
Bio toxicology = the study of poisons
from living organisms.
Zoo toxicology = the study of poisonous animals.

3. ETYMOLOGY
TOXIN
Toxon (Greek)  for bow & arrow
Toxicon  poison dipped arrow
POISON
Poi  to drink & becoming potare in Latin
(potion)
 Venomous nature derived from wen to win, & led
to venus/venerate through “love potions” (venin)

4. I. TOXICOLOGY IN ANTIQUITY
Medicine is an ancient science.
The use of plant & animals substances
to heal disease is as old as the diseases themselves.
Early practitioners of medicine were priests or
magicians/physicians, & it was commonly thought
that guilty of a crime would be affected by a
poison.

5. PREHISTORIC MAN
The historical development
of toxicology began with early
cave dwellers who recognized
poisonous plants and animals
and used their extracts for
HUNTING or in warfare.

6. FIRST “MENTION” (3100-3000 B.C.)
Egyptian pharaoh of the 1st dynasty
United the lower & upper Egypt.
Founded Memphis as capital
Founder of many new cults & temples
Cultivated & studied effects of poisons &
medicinal plants.

7. MESOPOTAMIA
The development of human civilization
is thought to have originated in the
fertile crescent which is now occupied
by Iraq, Syria, Israel & Egypt, but was
known as Babylon & Assyria
historically.
Medicine had its beginnings in this
region.

8. The code of Hammurabi was
chiseled into stone, providing
evidence for future generations
of the expected behavior of
physicians.

9. Bites & stings from venomous animals occurred & were
treated with scarification, bloodletting (cut & suction), the use
of incantations, & a procedure called Cupping
Cupping = use of animal horn to neutralize the poison.

10. EGYPT
The Egyptian civilization developed at
approximately the same time as those of
Babylon & Assyria.
Writing paper was manufactured from the
papyrus plant, Cyperus papyrus-sedge
family- Cyperaceae, which is reed like plant
that grows in shallow water.
Modern humans have learned of the
prescriptions & medicine used for treating
ailments through various papyri.

11. One Egyptian picture story depicts a
puffer fish, Tetraodon sp. Which was
recognized as a poisonous fish.
The Smith papyrus (1600 B.C.) lists
charms for use against snakebite.
The Hearst Medical papyrus provides
numerous prescriptions, some of
which were prescribed for animal
bites.

12. 1STWRITTEN RECORD (2700 B. C.)
Shen Nung Pen ts’ao ching – divine
Husbandman’s material medica.
Contained list of poisonous &
medicinal plants and drugs
Enlisted the effects & antidotes
viz., iodine, opium, cannabis,
mercury.

13. THE VEDAS (900 B. C.)
Hindu scriptures  ATHARVA
VEDA
• First Indian text dealing with
medicine
• Mention of poisoning for use in
warfare
I. Arrows with ducts
II. Castor bean poison
III. Poisoned nets
IV. Hook traps

14. ISRAEL
Ancient Hebrew people were guided in every
aspect of their lives by the old Testament.
Strict dietary laws were imposed on the people,
presumably to maintain health & prevent disease.
Eg: trichinosis in pork.
Early Israelites were admonished not to eat items
from the water that had neither fins nor scales
(Deuteronomy 14:9-10). Fish with neither of these
structures tend to be the most poisonous & thus
should be avoided.

15. • One of the plagues pronounced on the Egyptians by Moses was the
earliest account of red tide caused by dinoflagellates (the water turned
to blood, killing all the fish– Exodus 7:19-20)

16. CHINA
Ancient & modern Chinese medicine rely
heavily on natural products for healing
disease (herbal medicine, rhinoceros horn
& gall bladders).
Medical practitioners recognized scale less
fish as being toxic & 1st report of ciguatera
toxicosis was described from ingestion of
yellowtail tuna (ca A.D. 700)

17. GREECE (500 B.C TO A.D. 500)
Modern medicine had its genesis in the Greek civilization, from 500 B.C to A.D.
500.
Medicine became separated from myth, magic, & religion.

18. • Homer (600 B.C.) Odysseus obtains poison for his arrows

19. HIPPOCRATES (460 – 355 B.C).
The father of medicine.
Introduced principles of clinical toxicology
related to bioavailability of toxicants.
knew of the toxicity of sea urchin spines.
Oath to ‘not poison’.
“to please no one will I prescribe a deadly
drug nor give advice which may cause his
death”.

20. ARISTOTLE (384 – 322 B.C.)
Aristotle (384 – 322 B.C.) knew of the
stinging of jellyfish.
Alexander the great forbade his troops
to eat fish, presumably because of
concern for toxicity.

21. THEOPHRASTUS
(370-286 B. C.)
Born in Eresus, on the island of Lesbos.
Student of Aristotle.
Authored De Historia Plantarum.
Included numerous references to poison
plants.
Considered as “The Father of Botany”.

22. SOCRATES (469 – 399 B.C.)
Was a classical Greek (Athenian) philosopher credited as one of the
founders ofWestern philosophy.
Execution/Suicide death of by hemlock (Conium maculatum).
The term, "Socratic paradox" can also refer to a self-referential paradox,
originating in Socrates' utterance, as “I know that I know nothing”.
• No one desires evil.
• No one errs or does wrong willingly or knowingly.
• Virtue—all virtue—is knowledge.
• Virtue is sufficient for happiness.

24. DEMOSTHENES (385 –
322 B. C.)
Demosthenes was a prominent Greek
statesman and orator of ancient Athens.
His famous saying – “ All speech is vain &
empty unless it be accompanied by action.”
Suicide by poisoned pen.

25. NICANDER (197 – 130 B. C.)
Nicander of Colophon (2nd century B.C.), Greek poet, physician and grammarian, was
born at Claros (Ahmetbeyli in modern Turkey), near Colophon, where his family held
the hereditary priesthood of Apollo. He flourished under Attalus III of Pergamum.
He wrote a number of works both in prose and verse, of which two survive complete.
The longest, Theriaca, is a hexameter poem (958 lines) on the nature of venomous
animals and the wounds which they inflict.
The other, Alexipharmaca, consists of 630 hexameters treating of poisons and
their antidotes.
The works of Nicander were praised by Cicero (De oratore, i. 16), imitated
by Ovid and Lucan, and frequently quoted by Pliny and other writers
(e. g. Tertullian in De Scorpiace, I, 1).

26. ALEXIPHARMACA: THE WORKS OF NICANDER

27. CLEOPATRA (LATE 69 BC– AUGUST 12, 30 BC)
Cleopatra VII Philopator , known to history as Cleopatra,
was the last active pharaoh of Ancient Egypt,
only shortly survived by her son, Caesarion as pharaoh.
The ancient sources, particularly the Roman ones, are in general agreement that
Cleopatra killed herself by inducing an Egyptian cobra to bite her.
 The oldest source is Strabo, says that there are two stories: that she applied a toxic
ointment, or that she was bitten by an asp on her breast.
Several Roman poets, writing within ten years of the event, all mention bites by two
asps, as does Florus, a historian, some 150 years later.
Velleius, sixty years after the event, also refers to an asp.

29. MITHRIDATES (120 – 63 B.C.)
The king of Pontus, Mithridates VI,
was one of the 1st to advance the art & science of poisons & antidotes.
He experimented to attempt development of a universal antidote, including
numerous substances in his concoctions, which were called “mithridates”.
Even today, the term “mithridates” or “shotgun treatment” is used to describe a
situation in which multiple drugs are prescribed, in the hope that one of the
drugs will be effective against the ailment suffered by the patient.
Mithridates philosophy was followed for many centuries in treating all kinds of
diseases, including poisoning & envenomination.

31. FIRST POISON LAW: CIRCA
82 B. C.
Dictator Lucius Cornelius Sulla – Lex
Cornelia.
Growing conspiracy to kill men for profit.
Provisions for both the poisoner and the
provider of the poison.

32. PEDANIUS DIOSCORIDES (A.D. 50 - 100)
• was a physician, pharmacologist and
botanist, the author of De Materia
Medica—a 5-volume encyclopedia about
herbal medicine and related medicinal
substances (a pharmacopeia), which
served the medical profession for 1600
years.
• Classified poisons for 1st time into plants,
minerals / animal poisons.
• He described treatment for various
marine animal intoxications, including
the stingray & “sea vipers”.

33. AQUA TOFFANA
Arsenic containing perfumes were
prepared by lady named Toffana
Such cosmetics are termed Aqua
toffana, were used to kill the foes.

34. ARUM MACULATUM
Arum or Cuckoo-Pint
Ancient physicians called this plant  the
Drakontaia Mikre/ “small dragon” because central
stalk resembles a serpant.
According to Dioscorides, its shape revealed its
purpose as an antidote for snakebite.
Rubbing one’s hands with Arum root was supposed
to make one unbiteable.

35. PLINY THE ELDER (A.D. 29 - 79)
wrote the classic Naturalis Historcia, a
comprehensive encyclopedia of the
natural world, which was the natural
history “bible” until the Renaissance.
Pliny wrote one section devoted to De
Venenalis Marinus (marine poisons).

36. NERO (37 – 68 A. D.)
Mother (Agrippina) consults with skilled
poisoner (Locusta) to poison Emperor
Claudius such that her son from a previous
marriage (Nero), seize power & cleverly
poisoned step-brother Brittanicus.
Used slaves as food tasters to differentiate
poisonous mushrooms from edible ones.

37. GALEN (129 – 199 A. D.)
Claudius Galen of Pergamum
Greek physician, Philosopher
Believed therapeutics should be in the hands
of physicians rather than herbalists
Galena : a remedy/anti-dote for poison

39. ISLAMIC COUNTRIES
Moslem countries provided little
original contribution to the field of
toxicology until a Persian by the name
of Geber ibn Hajan (ca. A.D. 750 - 760)
wrote a long treatise on poisons,
including venoms & their antidotes.

40. II. MEDIEVAL PERIOD
The collapse of the Roman empire
ushered in a period of intellectual
stagnation(Dark Ages).
Many of us have the impression that
nothing was accomplished in the
science during this time; but in reality,
the printing press & gun powder, among
other things, were invented during dark
ages.
A few physicians wrote about
venomous animals, but little original
toxicologic thought arose in this era.

41. MOSES BEN MAIMON (1135-
1204 AD)
was a preeminent medieval Spanish,
Sephardic Jewish philosopher,
astronomer and one of the most
prolific and influential Torah scholars
and physicians of the Middle Ages.
Wrote a book “Poisons and Their
Antidotes” describing the treatment of
poisoning from insects, snakes & mad
dogs.

42. With the Renaissance came
the age of scientific inquiry, &
numerous naturalists,
physicians, missionaries,
explorers, & historians began
to document the prevalence of
intoxication of humans by
animals & plants.

43. EARLY RENAISSANCE
Little was known about the
nature of the venoms/poisons.
The provincialism of European &
Mediterranean country writers was
overcome as explorers returned
from far-flung expeditions with
factual & fanciful tales of the
tropical region of the world.

44. Captain James Cook of H.M.S. Resolution nearly died of tetradotoxin
poisoning after consuming fish in New Caledonia.

45. CATHERINE DE MEDICI
In France, a lady along with
Marchioness de Brinvillers used the
most effective poisons on sick & poor
people in the name of treating them &
killed several people!!
Catherine was given the tittle of ‘La
Voisine’
Later she was convicted of many
poisonings including over 2000 infants.

46. CARL VON LINNE (LINNAEUS)
The Swedish naturalist, made a
monumental contribution to biology &
toxicology.
He introduced the system of binomial
naming & classification of plants &
animals, Systema Naturae, 1758.
His system enabled scientists from around
the world to communicate about plants &
animals without having to know all the
local, common names.

47. PARACELSUS (1493 - 1541)
Famous German physician who
distinguished a poison from a remedy.
He gave the great statement “All substances
are poisons; there is none which is not
poison. The right dose differentiates a
poison & a remedy”.
This statement laid the foundation of the
modern concept of the ‘dose-response
relationship’ & the ‘therapeutic index’
developed later.

48. IV. MODERN ERA OF TOXICOLOGY
Relatively young science based on the scientific works carried out by
numerous dedicated researchers & scientists.
It’s the outcome of rational thinking, experimentation, relationship
between dose & therapeutics as compared with toxic, and response to
chemicals.

49. FRIEDRICH SERTURNER (1783-
1841)
German pharmacologist who isolated the
specific narcotic substance from opium & named
it morphine after Morpheus, the Roman god of
sleep.
Its isolation allowed physicians to prescribe
painkiller's in regulated dose.

50. M. J. B. ORFILA (1787-1853)
Spanish physician considered as ‘Father of Toxicology’.
He established toxicology as a discipline distinct from others & defined
toxicology as the study of poisons.
In 1813, he published the results of many toxicological experiments under the
tittle of “toxicologic Generale”
He advocated the necessity of chemical analysis for medicolegal cases.
Orfila became very proficient in the chemistry of crime scene investigation &
was an early promoter of chemical evidence in the courtroom.

51. FATHER OF
TOXICOLOGY

52. FRANCOIS MAGENDIE (1783-
1855)
A pioneer French experimental physiologist &
toxicologist who researched the different motor
functions of the body in relation to the spine, as
well as nerves within it.
He also described the effects & uses of
morphine, emetine, quinine, strychnine, & other
alkaloids, for which he is also called the “Father
of Experimental Pharmacology”.

53. 19TH CENTURY
Scientific disciplines began to
proliferate viz., chemistry,
physiology, pharmacology &
toxicology.
Scientific meetings provided a
forum for expounding theories, &
professional publications spread
information throughout the
world.

54. Biologists studied natural history of plant & animals.
Anatomists dissected & described the venom apparatus.
Biochemists studied venoms & poisons, & much was learned in the
19th century about chemical structure and pharmacologic effects.
Textbooks on toxicology were published in German, French,
Japanese, English & other languages.
Toxicology became a required course in most medical & veterinary
schools

55. • The field of toxicology became so broad that scientists began to
narrow their fields of interest further: into plant poisoning,
marine biotechnology, or pesticide toxicology.
• Scientists of the 20th century continued & intensified the study of
poisons.

56. JAMES MARSH 1832
Developed the first chemical test for
identifying arsenic, called Marsh test.
Hugo Reinsch 1842
Developed a series of tests for
detecting arsenic & mercury.

57. THEODORE G. WORMLEY (1869)
Wrote the 1st
American book -
‘Microchemistry
of poisons’ ,
dedicated to
poisons.

58. LOUIS LEWIN (1854-1929)
A German scientist who took up the task of
classifying drugs & plants in accordance to
their psychological effects.
He also published many articles & books
dealing with toxicology of methyl alcohol,
ethyl alcohol, chloroform, opium, & other
chemicals.
His important publications are;
Toxicologist’s view of world history.
A text book of toxicology.

59. FDA, 1930.
• Food & Drug Administration was founded to regulate the content
and safety of consumer drugs & foods.

60. PAUL HERMANN MULLER (1899-1965)
He discovered the insecticidal properties of
DDT in 1939 & along with his team
introduced other chlorinated hydrocarbon
insecticides.
He was awarded the Nobel prize in
physiology/medicine in 1948 for his
discovery of “the high efficiency of DDT as a
contact poison against several arthropods”.

61. GERHARD SCHRADER (1903-1990)
A German chemist who accidentally developed
the toxic nerve agents viz., sarin, tabun, soman,
cyclosarin while attempting to develop new
insecticides.
Schrader & his team, thus, introduced a new
class of synthetic insecticides, the
organophosphorous insecticides & defined the
structural requirements for insecticidal activity
of anticholinesterase compounds.
He is also called the “Father of the nerve agents”

62. K. K. CHEN (1934)
• Demonstrated antagonist effect of
sodium nitrite & sodium
thiosulphate in cyanide poisoning.

63. R. A. PETERS, L. A. STOCKEN, & R. H. S. THOMPSON.
(1945)
• Developed dimercaprol as an antidote to arsenic containing war
gases {lewisite}.

64. THALIDOMIDE DISASTER 1959-1960’s
 was first marketed in 1957 in West Germany under the trade-name Contergan.
 The German drug company Chemie Grünenthal (now Grünenthal) developed
and sold the drug.
 Primarily prescribed as a sedative or hypnotic, thalidomide also claimed to cure
“anxiety, insomnia, gastritis, and tension".
 Afterwards, it was used against nausea and to alleviate morning sickness in
pregnant women.
 Thalidomide became an over the counter drug in Germany on October 1, 1957.
 Shortly after the drug was sold in Germany, between 5,000 and 7,000 infants
were born with phocomelia (malformation of the limbs).
 Only 40% of these children survived.
 Throughout the world, about 10,000 cases were reported of infants with
phocomelia due to thalidomide.

66. RACHEL CARSON (1962)
• Started crusade against the use of DDT & published the great book
“silent spring”.

67. LOUIS J. CASARETT & JOHN DOULL (1971)
• published the 1st modern
Toxicology textbook titled
“Toxicology: The basic
science of poisons”.

68. NUCLEAR ACCIDENTS AT THREE MILE ISLAND NEAR
HARRISBURG, PENNSYLVANIA. (1979)
• The accident began with failures in the non-nuclear
secondary system, followed by a
stuck-open pilot-operated relief valve in the
primary system, which allowed large
amounts of nuclear reactor coolant to escape.
• The partial meltdown resulted in the release
of unknown amounts of radioactive gases and
radioactive iodine into the environment.

69. BHOPAL GAS DISASTER, (1984)
 occurred due to accidental release of methyl isocyanate killing
thousands & injuring hundred’s of people.

70. CHERNOBYL NUCLEAR POWER PLANT ACCIDENT (1986)
Occurred in Soviet Union spreading radioactive debris over several
countries.

71. LATTER HALF OF THE 20TH CENTURY
A noteworthy achievements led to better understandings of the ecology
of poisons & venoms.
Some answers have been discovered to such puzzling questions as:
1. Why are plants & animals poisonous/venomous ?
2. What have poisons contributed to evolution ?
3. How can an understanding of poisons & venoms contribute to the
management of both free-ranging wild animal populations & domestic
animals ?

72. COEVOLUTION??
Plants & herbivorous animals (insects) coevolved in an adversarial
relationship.
Plant population developed various strategies for coping with
herbivores that could potentially destroy them!
Mechanical means  thorns, spines, harsh outer coats of stems/leaves.
Chemical deterrents  PSM’s bitter tasting, offensively odorous,
poisonous or have antinutitional effects.
As plants became more efficient in producing PSM’s  animals,
likewise improved their own methods of coping.

73. The case of coevolution of plants & insects
is easily demonstrated, while evidence for
plant/mammal coevolution is more elusive.
Seems logical ??
1) Insects & plants have shared the earth for
approximately 250 million years
(Carboniferous Period, Paleozoic Era).
2) Primitive mammals have been on earth
only for 100 million years (Cretaceous
Period, Mesozoic Era).

74. The progenitors of large, wild herbivorous animals viz.,
cattle/horse/bison/antelope didn’t appear until 40 million
years ago.
All domestic animals arose from their wild counterparts less
than 12,000 years ago!!!

75. Even though mammalian herbivores may not have coevolved with
plants like insects, there is sound evidence that plant (dietary) selection
is determined by the presence & quantity of PSM’s in the part of the
plant consumed viz., leaves, stem, fruit & seeds.

76. ANIMAL TOXIN ECOLOGY
Animal toxin & venoms are used to obtain
• Food
• Deter predation
• Regulate population
• Aid in exploiting a territory
• Aid in defense against enemies.
Just as in plants, the end products of sec. metabolites are channeled to storage
sites within or upon the animals body, where there is slow turnover.
The slow turnover minimizes the necessity of excessive expenditure of
precious energy & chemical resources to this function.

77. CONCLUSIONS
Poisons & venoms have served a vital role in the evolution of plants &
animals.
• The pharmacological effects of plants & animals = PSM (Plants
Secondary Metabolites).
• The determining factor of whether a substance is a medicine or a
poison may be a matter of dosage.
Scientists are just beginning to unravel many of the mysteries of
plant/animal/animal interactions.

78. DISCUSSIONS

79. REFERENCES.
Murray E. Fowler: Veterinary Zootoxicology. (CRC press).
Sandhu H. S. & Brar R. S: Text Book of Veterinary Toxicology.
Garg S. K: Veterinary Toxicology.
Matham V. K: Essentials of Toxicology.
Wikipedia & Google images.