‘The Dose Makes the Poison’
Dr Clifford Elcombe
University of Dundeeand
CXR Biosciences
Father of Modern Toxicology Father of Modern Toxicology PARACELSUS — — 1564
“All things are poisonous, only the dose makes it non-poisonous.”(Dose alone determines toxicity)
Dose
THE KEY CONCEPT in Toxicology
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.
aniseapplesbananasbrocollibrussel sproutscabbagecarrotscauliflowercelerycinnamonclovescocoacomfrey teafennelgrapefruit juice
honey dew melonhorseradishkalemushroomsmustardorange juiceparselyparsnipspeachesblack pepperpineapplesradishesraspberriestarragonturnips
A Selection of Natural Carcinogens
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.
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)
ALL Interactions between
Chemicals and Biological Systems follow a
Dose-Response Relationship
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”).
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
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)
Dose-Response Relationship“The Dose Makes the Poison”
An
ima
ls S
lee
pin
g (
%)
Phenobarbital (mg/kg) Log Scale
An
ima
ls K
ille
d (
%)
ED50LD50
Effective Dose Lethal Dose100
60
80
40
20
100
60
80
40
20
10 20 30 50 1001 2 3 5 7 10
Linearised Model
110 100 1,000 10,000 100,000
1
10
100
1,000
10,000
100,000
1,000,000
Dose (ppm in diet)
Ris
k p
er 1
,000
,000
VSD ("virtually safe dose")
Metabolic Saturation!
Concentration Analogies
one automobile in bumper-to-bumper traffic from Cleveland to San Francisco
one minute in two years
One Part Per Million 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
Concentration Analogies
One Part Per Billion is :
Which Results in the Largest Exposure?
• 1000 ng/mL
• 1 g/mL
• 1 ppm
• 1000 ppb
Resources
A Journalist's Handbook on Environmental Risk Assessment
http://ruby.fgcu.edu/Courses/Twimberley/IDS3920/main.html
http://www.agius.com/hew/resource/hazard.htm
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