History and scope of Toxicology

1
Chapter 1

• History and scope of Toxicology

2
Learning Objectives

• Define toxicology
• Areas of science that contribute to toxicology
• Overview of the history of toxicology

3
Overview of Important Areas Discussed in this book

• Definition of toxicology
• The study of the adverse effect of xenobiotics on
  living systems
• Vertebrates, Invertebrates, Plants
• Drugs, environmental contaminants
• Found in food, water, air or soil
• Metals, Inorganic and Organic chemicals
• All chemicals are potentially toxic

4
(No Transcript)
5
(No Transcript)
6
Toxicologist

• Multidisciplinary subject
• Apply basic biochemical, chemical, pathological,
  and physiological knowledge
• Most be able to understand why certain substances
  cause the disruption in a biological system and
  leads to toxic effects
• What do toxicologist do?
• Research
• Teach
• Product safety evaluation
• Public Service, Regulatory Affairs, Consulting

7
Environment and Chemical

• Approximately 65,000 chemical are currently
  produced in US
• 500- 1000 new chemical added each year.
• Must have some knowledge of the toxic effects of
  these chemicals.

8
Assimilating many branches of science

• Biochemistry
• Biology
• Chemistry
• Genetics
• Mathematics
• Medicine
• Pharmacology
• Safety and physic
• Etc.

9
Historical Aspects

• What is a poison?
• Range from natural plant alkaloid to synthetic
  nerve gas
• Definitions
• A poison is any substance which has a harmful
  effect on a living system
• Depends on use
• http//www.asmalldoseof.org/historyoftox/Milestone
  s_06Final_screen.pdf

10
Penicillin vs Phosgene gas

• Penicillin is a poison to bacteria.
• Phosgene gas inhalation can kill humans
• Chemical formula for phosgene CL2CO
• CO Cl2 ? COCl2
• Used in WWI as chemical weapon
• Disrupts gas exchange in lungs following
  hydrolysis- suffocation
• Used now as pesticide, industry

11
Poisons

• In the past, the study of poisons were a
  practical art utilized by murderers and
  assassins.
• No one wants to be the enemy of a toxicologist.

12
Natural Poisons (Antiquity)

• Primitive man used natural poisons from animals
  and plants as weapons, hunting, and
  assassinations
• Toxicon a poisonous substance into which an
  arrow head was dipped
• Ebers Papyrus (1500 B.C.)
• Earliest collection of medical records with
  references and recipes for poisons

13
Ebers Papyrus

• Egyptians distilled prussic acid from peach
  kernels
• What is prussic acid?
• Opium, lead, copper, etc
• Book of Job (speaks of poison arrows)
• curare

14
Ebers Papyrus
15
Plants with Cyanogenic Potential

• Apple
• Apricot
• Cherry
• Flax
• Lima Bean
• Peach
• White Clover

16
Cyanogenic compound

• Prussic acid is a potent, rapidly acting poison.
• Signs of prussic acid poisoning can occur within
  15 to 20 minutes
• Excitement, rapid pulse, and generalized muscle
  tremors occur initially, followed by rapid and
  labored breathing, staggering, and collapse.

17
Prussic acid

• The mucous membranes are usually bright pink, and
  the blood will be a characteristic bright cherry
  red.
• Cytochrome C oxidase of electron transport chain
• Cellular respiration

18
Hindu and Chinese medicine (900 B.C.)

• Arsenic
• Allosteric inhibition of essential metabolic
  enzymes, multi-system organ failure
• Opium
• Narcotic, paralyze
• Aconite (wolfsbane)
• Chinese herb (neurotoxin)

19
Hippocrates and Nicander

• Hippocrates (400 B.C.)
• Treatment of poisoning by influencing absorption
• Nicander (150 B.C.)
• Used condemned criminals as subjects to
  experiment with poisons
• Write books on antidotes to poisons

20
King Mithridates and Dioscorides

• Mithridates
• King ingested mixture of chemical to protect
  himself against poisons
• Used criminals to search for antidotes to venon
  and poisonous substances
• Mithridatic means antidote
• Dioscorides
• Classification of poison (animal, plant, mineral)
• Emetics in the treatment of poisons

21
Mithridates
)                                              
22
Socrates

• Committed suicide with hemlock
• Conium
• Coniine is a neurotoxin
• Neuromuscular junction
• Respiratory paralysis

23
Borgias

• Family in Italy that mastered the art of
  poisoning
• Toffana
• Aqua toffana
• Prepared cosmetics containing arsenic
• Removed enemies, husbands, etc.

24
Catherine de Medici

• Tested poisons on poor and sick of France
• Keep a record of clinical signs and symptoms

25
Catherine de Medici

• Tested toxic concoctions
• Noting the toxic response
• Potency
• Effects on different parts of the body
• Complaints of victims

26
Paracelsus (Most Important Concept of Toxicology)
(1400s)

• All substances are poisons, there is none which
  is not a poison. The right dose differentiates a
  poison and a remedy
• Understood chemistry
• Poison in the body would be cured by a similar
  poison (dose important)
• Salts as treatments

27
Other important figures

• Orfila (1800s)
• Forensic toxicology- detect poisons in body
• Bernard
• Effects on biological systems. Site of action of
  curare
• Peters
• Mechanism of action of war gases like arsensic

28
Modern Toxicology

• 1850s
• Anesthetics and disinfectant
• Introducing governmental laws and bill
• Food and Drug Administration (FDA)

29
Public Awareness (after WWII)

• Rachel Carson
• Silent Spring
• Description of the devastating effects of
  pesticides on the environment.
• Hazard and risk assessments and value judgments
  became important
• How many of you have seen the following movies?
• Erin Brochovich and Rachel Carson
• Inconvenient Truth by Al Gore
• Bhopal and Chernobyl

30
Industrial Disasters

• Knowledge of effective and rapid treatments
  important
• Bhopal in 1984
• One of the worst industrial disasters
• Methyl isocyanate

31
Types of toxic substances

• Drugs
• Designed to be highly potent in biological
  systems and many are potentially toxic
• Overdose
• Adverse effect
• Foreign substance that human ingest intentionally

32
Food Additives

• Added to food to alter flavor or color, prevent
  spoilage, taste
• Naturally occurring in food
• Cooking
• Veterinary drugs
• Ingested daily

33
Industrial Chemicals

• Contribute Environmental pollution
• Direct hazards in workplace
• Solvents

34
Environmental Pollutants

• Industrial processes and the deliberate release
  into the environment
• Pesticides
• Smoke, etc.
• Released into air, river, sea water, on land.
• Also sprayed on crops

35
Natural Toxins and Household Poisons

• Natural Toxins
• Animal, plants, bacterial origin
• Some individuals believe natural is safe Not
  always true
• Household Poisons
• Cleaning agens

36
Types of Exposure

• Gases and vapors
• Liquids
• Acute poisoning single episode of accidental
  exposure
• Chronic poisoning long-term exposure

37
Types of exposure (continued)

• Intentional ingestion
• Food additive, alcohol, cigarette
• Chronic effects, allergies
• Occupational exposure
• Inhalation or skin
• Lung disease and dermatitis
• Acute and chronic
• Environmental exposure
• Gases (sulfur dioxides, carbon monoxide)
• Acute and Chronic exposure

38
Types (continued)

• Accidental poisoning
• Acute poisoning
• Drugs, pesticides, household products
• Intentional poisoning
• Suicide
• Homicide