Toxicology

1. GOMATHI’S
TOXICOLOGY

2. 

TOXICOLOGY – STUDY OF POISONS
(GREEK WORDS)
TOXICAN – POISON
?
LOGOS – STUDY

5. ………..

“All substances are poisons; there is none
which is not a poison. The right dose
differentiate a poison and a remedy”
- Paracelsus (Grand Father of Toxicology)

6. INTRODUCTION

Toxic – the chemical/physical
agent/substances having the characteristic of
producing an undesirable or adverse health
effects.

Toxicity – the ability of a toxic to cause
adverse effects in living organisms.

7. DEFINITION - TOXICOLOGY

The science that deals with the study of the
adverse effects chemicals/physical agents
may produce in living organisms under
specific conditions of exposure.

It is the science that attempts to qualitatively
identify all the hazard as well as to
quantitatively determine the exposure
conditions.

8. “The science that experimentally investigates the
occurrence, nature, incidence, mechanism and risk
factors for the adverse effects of toxic substances.”

9. HISTORY
The knowledge of poison substance (venom
& plant extracts) –ancient periods – hunting.
 Poisons such as
Hemlock (blood of Socrates)


10. 4,000 BC – Opium poppy – alkaloids such as
morphine, codeine, Laudanum are all
narcotics.
 Morphine the very first medicinal compound
ever isolated in pure form.


11. 
In 9th century Dioscorides, a Greek physician
– classified poison
1. Plant poisons
2. Animal poisons
3. Mineral poisons

12. Paracelsus (1493) - contributed greatly to
the fields of medicine and toxicology - the
use of chemicals and minerals in
medicine, (First Coined “Zinc”)
 Certain illnesses of the body had chemical
remedies that could cure them.
 He was, therefore, a precursor to modernday medicine and to the use of vitamins and
minerals to maintain health.


13. Mathieu Orfila - Modern father of toxicology
 First formal treatment – experimental
toxicology laid down great success to
pharmacology in 1813.
 In 1815 Magendia - done atopsy & chemical
toxicants and explain the mechanism of
action of emitine & strychine –
absorption, distribution of the compounds.


14. 1850’s- advent of anesthetics & disinfectants
began to understand.
 During 1900, discovery of radioactivity &
vitamins.
 NIH- National Institute of Health assigned NIDA –
National Institute of Drug Abuse.

FDA ASSIGNED U.S PESTICIDE ACT – 1947
 1950’S additives of food, drugs, cosmetics Act
passed.
 Many toxicological
journals, professional, governmental & other
scientific organizations begins to broadcast


15. TOXICOLOGIST
Identify the toxic materials
 Mechanism of toxins
 Exposure assessment
RESEARCH
 Experimentally prove the toxicants
 Risk characterization
 Safety measures


IMPLEMENTATION / AWARENESS

16. 
TOXICITY DEPENDS UPON,

17. MEASURES OF TOXICITY
 Toxicity
is measured as clinical
“endpoints” which include
 Mortality
(death)
 Teratogenicity (ability to cause birth
defects)
 Carcinogenicity (ability to cause cancer)
 Mutagenicity (ability to cause heritable
change in the DNA)

18. Toxic dose low (TDLO): The lowest
dose of a substance introduced by any
route, other than inhalation, over any
given period of time, and reported to
produce any toxic effect in humans or
to produce tumorigenic or reproductive
effects in animals.
Toxic concentration low (TCLO):
The lowest concentration of a
substance in air to which humans or
animals have been exposed for any
given period of time that has produced
any toxic effect in humans or produced
tumorigenic or reproductive effects in
animals.
Lethal dose low (LDLO): The lowest
dose, other than LD50 of a substance
introduced by any route, other than
inhalation, which has been reported to
have caused death in humans or
animals.
Lethal dose fifty (LD50): A calculated
dose of a substance which is
expected to cause the death of 50
percent of an entire defined
experimental animal population. It is
determined from the exposure to the
substance by any route other than
inhalation.
Lethal concentration low (LCLO):
The lowest concentration of a
substance in air, other than
LC50, which has been reported to
cause death in humans or animals.
Lethal concentration fifty (LC50): A
calculated
concentration
of
a
substance in air, exposure to which
for a specified length of time is
expected to cause the death of 50
percent of an entire defined
experimental animal population.

19. ROUTES OF ENTRY
ABSORPTI
ON

20. MECHANISM OF
TOXICANTS
Allergic response
or
Hypersensitivity
Biological pathways
changes,
Receptors, Ion
channel, Enzyme mediated
toxicity
Example: The cyanide
ion (CN−) blocks cellular
respiration by inhibiting
an enzyme in the
mitochondria
called cytochrome c
oxidase.
Organ directed toxicity
Mutagenesis
Carcinogenesis
Teratogenesis

21. R

22. INGESTION
ABSORPTIO
N
Gastrointestinal
tract
LUNGS
DISTRIBUTIO
N
EXTRACELLULAR
FLUIDS
METABOLIS
M
LIVER
BILE
BLOOD &
LYMPH
KIDNEY
DERMAL
CONTACT
INHALATION
LUNGS
ORGANS
OF
BODY
SOFT
TISSUES OR
BONES
SECRETI
ON OF
GLANDS
BLADDER
FAECES
URINE
EXPIRED AIR
FATS
SECRETION
EXCRETI
ON

24. ABSORPTION
Passive diffusion - Diffusion occurs through the
lipid membrane.
 Filtration - Diffusion occurs through aqueous
pores.
 Special transport - Transport is aided by a carrier
molecule.
 Endocytosis - Transport takes the form of


25. Large surface are for absorption of toxicants in
small intestine.
 Lipophilic toxicants highly absorbed than
hydrophilic substances


26. LUNGS – ALVEOLAR ABSORPTION

27. EXAMPLES OF RESPIRATORY TRACT TOXICANTS

28. SKIN

Absorbs
lipophilic
compounds of
low molecular
weight very
quickly and also
hydrophilic
substances.

29. KINETICS OF ABSORPTION





Rate of absorption of toxic depends upon the nature
of chemicals and their site of administration.
Rate of absorption more for lipid – soluble molecules
and slow for strong acids and bases.
First order process: at low doses, rate of reaction is
directly proportional to the amount of toxicant
present.
Zero order process: as the concentration of
substances increase, a point may be reached at
which there is no further increase in rate of
absorption.
Extent of absorption depends on the bioavailability of
the substance.

30. INGESTION
ABSORPTIO
N
Gastrointestinal
tract
LUNGS
DISTRIBUTIO
N
EXTRACELLULAR
FLUIDS
METABOLIS
M
LIVER
BILE
BLOOD &
LYMPH
KIDNEY
DERMAL
CONTACT
INHALATION
LUNGS
ORGANS
OF
BODY
SOFT
TISSUES OR
BONES
SECRETI
ON OF
GLANDS
BLADDER
FAECES
URINE
EXPIRED AIR
FATS
SECRETION
EXCRETI
ON

31. DISTRIBUTION
Rate of distribution is rapid in plasma but slow
in tissues.
 Extent of distribution related to apparent
volume of distribution (V).
V = Ab
C
 Ab – total quantity of toxicants in the body
 C – plasma concentration
 Volume of distribution actual space in which
toxicants distributed.
Vd = D (dose
administered)
Cp


32. INGESTION
ABSORPTIO
N
Gastrointestinal
tract
LUNGS
DISTRIBUTIO
N
EXTRACELLULAR
FLUIDS
METABOLIS
M
LIVER
BILE
BLOOD &
LYMPH
KIDNEY
DERMAL
CONTACT
INHALATION
LUNGS
ORGANS
OF
BODY
SOFT
TISSUES OR
BONES
SECRETI
ON OF
GLANDS
BLADDER
FAECES
URINE
EXPIRED AIR
FATS
SECRETION
EXCRETI
ON

33. EXCRETION
Rate of excretion is determined by apparent
volume of distribution (V) and clearance (CL).
Rate of elimination of chemicals
 CL =
Plasma concentration
 Plasma clearance = sum of the clearance of
metabolism (CLM), renal excretion
(CLR), biliary excretion (CLB).
 Metabolic clearance cannot measured easily
so the total clearance(CL) = CLM + CLR
CLM = CL - CLR


34. WHY WE NEED TO STUDY TOXICOLOGY

36. NOT FOR………….