The Dose Makes the Poison

1
The Dose Makes the Poison

• Dr Clifford Elcombe
• University of Dundee
• and
• CXR Biosciences

2
Father of Modern Toxicology PARACELSUS 1564
Dose THE KEY CONCEPT in Toxicology

• All things are poisonous, only the dose makes it
  non-poisonous.
• (Dose alone determines toxicity)

3

• Toxicology is arguably the oldest scientific
  discipline, as the earliest humans had to
  recognize which plants were safe to eat.
• Approximately 100,000 chemicals currently in use
  worldwide, 500 new chemicals enter the market-
  place annually.
• Humans are exposed to chemicals both deliberately
  and inadvertently. Most exposure of humans to
  chemicals is via naturally occurring compounds
  consumed in the diet from food plants.

4
A Selection of Natural Carcinogens
anise apples bananas brocolli brussel
sprouts cabbage carrots cauliflower celery cinnamo
n cloves cocoa comfrey tea fennel grapefruit
juice
honey dew melon horseradish kale mushrooms mustard
orange juice parsely parsnips peaches black
pepper pineapples radishes raspberries tarragon tu
rnips
5
The science of Toxicology helps people make
informed decisions and balance RISKS vs.
BENEFITS
The study found the highest levels of
pesticide residues in peaches, apples, pears.
AND Spinach.
6
Hazard and Risk

• Hazard
• the potential for harm
• Intrinsic property of the chemical
• Risk
• Risk is the chance (probability) that harm will
  actually occur
• Hazard x exposure (dose and time)

7
ALL Interactions between Chemicals and
Biological Systems follow a Dose-Response
Relationship
8
Dose-Response Relationship

• The quantitative relationship between the
  concentration of a xenobiotic in the body and the
  magnitude of the biological effect it produces.
• The magnitude of the effect of a xenobiotic is a
  function of the amount of xenobiotic a person is
  exposed to (i.e., The Dose Makes the Poison).

9
Dose Concepts

• The magnitude of the toxic response is
  proportional to the concentration (how much) of
  the chemical at the target site.
• The concentration of a chemical at the target
  site is proportional to the dose.
• Four important processes control the amount of a
  chemical that reaches the target site.
• Absorption
• Tissue distribution
• Metabolism
• Excretion

10

• Dose Determines Whether a Chemical Will Be
  Beneficial or Poisonous

Beneficial Dose Toxic Dose Aspirin 300 1,000
mg 1,000 30,000 mg Vitamin A 5000
units/day 50,000 units/day Oxygen 20 (Air) 50
80 (Air)
11
Dose-Response RelationshipThe Dose Makes the
Poison
12
Linearised Model
1,000,000
100,000
10,000
1,000
Risk per 1,000,000
100
10
1
1
10
100
1,000
10,000
100,000
Dose (ppm in diet)
VSD ("virtually safe dose")
13
Metabolic Saturation!
14
Concentration Analogies
One Part Per Million is

• one automobile in bumper-to-bumper traffic from
  Cleveland to San Francisco
• one minute in two years

15
Concentration Analogies
One Part Per Billion is

• one 4 inch hamburger in a chain of hamburgers
  circling the earth at the equator two-and-a-half
  times (4x10 9 inches)
• one second of time in 32 years

16
Which Results in the Largest Exposure?

• 1000 ng/mL
• 1 mg/mL
• 1 ppm
• 1000 ppb

17
Resources

• A Journalist's Handbook on Environmental Risk
  Assessment
• http//ruby.fgcu.edu/Courses/Twimberley/IDS3920/ma
  in.html
• http//www.agius.com/hew/resource/hazard.htm