Lecture 1 - Introduction To Toxicology

Question 1

What is toxicology?

Answer 1

• The study of the adverse effects of xenobiotics on biological and ecological systems.
• Includes drugs, food additives, pesticides (all 3 of which are highly regulated), cosmetics, environmental toxins, and natural toxins
• Toxicologists specifically study the undesired effects of exposure to a poison, etc., whereas pharmacologists study a desired effect
• Less funding in tox than in pharma because tox=”the ugly truth” (funding primarily from government)
• For many years, tox and pharma had the same source - the Materia Medica

Question 2

Materia Medica

Answer 2

Used collectively for pharma and tox

Started 4000 years ago (2735 BC) by father of Chinese medicine (Emperor Shen Nung)

Question 3

Cleopatra

Answer 3

Tested pistons on criminals (heavy metals)

Question 4

Ebers Papyrus

Answer 4

First Western tox document (Chinese medicine Medica was the first one)
Egypt, 1500
Recognized poisons such as hemlock, aconite, arrow poison, opium…

Question 5

Hippocrates

Answer 5

• First to articulate concept of bioavailability, clinical toxicology, and overdose
• First to believe that disease came from nature and not punishment
• 400BC Greece

Question 6

King Mithridates VI

Answer 6

132 BC
Did toxicity poison experiments on criminals - then gave them antidotes to see what would happen
Treated himself with antidotes, claimed to have discovered antidotes of toxicants
Mithridatic=antidotal, protective mixture
Died of poisoning himself

Question 7

Maimonides

Answer 7

• wrote Poisons and their Antidotes
• first to systematically describe treatment for poisonings
• noted that milk/butter/cream can decrease/slow down intentional absorption (less toxic)
• 1200s

Question 8

De Medici

Answer 8

1500s
Obtained evdience for most effective poisons
She carefully noted onset of action, potency, specificity, clinical symptoms

Question 9

Paracelsus

Answer 9

1400s-1500s 
Father of modern toxicology 
Responsible for:
-DR curve
-toxicon concept: primary toxic substance is a chemical entity, not a mixture 
-used animal studies

Question 10

Who was the first to identify link between occupation and toxicity?

Answer 10

Pott, 1775: first association of soot causing scortal cancer in chimney csweeps –> first report of PAH toxicity
OR ellenberg?

Question 11

Ellenberg, 1480

Answer 11

Warned of the toxicity of mercury and lead in goldsmith industry

Question 12

Orfila, 1818

Answer 12

First to use autopsies for legal proof of poisoning

Question 13

Magendie

Answer 13

1800s: showed how a chemical can work as a poison by discovering mechanism of action of strychnine.

Question 14

How did Paracelsus articulate the dose-response relationship?

Answer 14

1. Need experimentation
2. Need to disntguish between lethal and effective doses
3. These properities are sometimes, but not always, distinguishable by dose
4. Can measure the degree of specificities

Question 15

Clause Bernard (1800s)

Answer 15

• mechanism of action of curare

- mechanism of action for carbon monoxide and how it can be used as a poison or drug (anesthesia)

Question 16

What developments in the 20th century led to an explosion in the field of toxicology?

Answer 16

1. Rapid development of organic chemistry
2. The misuse of drugs and elixirs led to numerous toxic reactions
3. The development of chemical warfare agents and pesticides, insectidices, etc
4. Creation of govenrment regulation agencies such as FDA 1938
5. Natural products and their claims
6. Recognition of toxicology as a field on its own, with national societies and agencies and scientific publications
7. A blend of gov, industry and research (each hacving their own agenda) –> this is distinct from neuro conferences, for example, where ~all neuroscientists

Question 17

What developments in the 21st century led to the expansion of toxicology?

Answer 17

• OMICS: ex: proteomics, genomics, toxicogenomics
• epigenetics - we know how that chemicals that modify our genes and mark our DNA can contribute to toxicity
• transgenerational toxicilogy: DOHAD idea
• computational toxicology
• predictive toxicology: can we predict whether a chemical will be toxic or not
• environmental toxicology

Question 18

What are examples off branches of toxicology?

Answer 18

• clinical tox: hospitqlsetting
• forensic tox: medical examiners office
• regulatory tox: industry and govenrment setting (ex: FDA)
• industrial tox: ever company has a toxicologist that provides advice and guidelines on how to reduce exposure and toxicity etc
• environmental tox: health canada, FDA
• biochemical and molecular tox: university-based
• Product development toxicology: corporate setting; when new products are made