Download Introduction to toxicology

W507 – Introduction to
toxicology
Introduction to Toxicology
• Toxicity - the ability of a substance to cause harm to
a biological system
• Toxicology - the study of the potential of a substance
to produce adverse health effects on a living
organism and the likelihood that the effects might
occur under specified exposure conditions
“all substances are poisons; there
is none which is not a poison. The
right dose differentiates a poison
and a remedy…”
- Paracelsus, 1493 – 1541
Any chemical may be toxic if
the dose is high enough
Any chemical may be toxic if the
dose is high enough
• This concept is fundamental to understanding the
principles of toxicology
• It is also important when trying to protect workers
• However, it is often difficult to link the cause and
effect of a disease
Problems linking cause and effect
• The effect may not occur at time of exposure
• By the time it occurs the person may not be working
with the substance
• People vary in susceptibility (react differently)
• Variations may be due to age, gender, health status etc
• Complications of combined effects
• Exposure to different substances
• Exposure to alcohol, tobacco or prescribed drugs
• Detailed toxicological information is often not
available for many substances
Basic Toxicological Terms
• Acute effects
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Occur immediately on exposure or soon after
Usually from relatively high dose
Usually of short duration
Usually reversible
• Chronic effects
• Occur some time after exposure
• Usually from repeated lower doses over many months / years
• Usually irreversible
Basic Toxicological Terms
• Local effects
• Occur at the point of contact e.g.
• Xylene causes de-fatting of skin
• Sulphuric acid causes irritation / burns on skin
• Chlorine causes pulmonary inflammation
• Systemic effects
• Occur at target organ remote from point of contact e.g.
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Xylene causes dizziness / unconsciousness
Xylene causes damage to liver / CNS
Cadmium causes damage to kidney
Lead causes damage to blood forming process in bones
• Xenobiotic
• substance not normally found or produced in a person
Basic Toxicological Terms
• Stochastic – describes likelihood of an event taking
place – synonymous with random
• e.g. malignant disease such as cancer for which the probability
of an effect occurring is a function of dose without threshold
• Once it occurs consequence is independent of initiating dose
• Stochastic effects do not have a threshold dose
• Non-stochastic
• e.g. inflammatory and degenerative diseases
• severity and frequency of the effect varies with the dose
• have a threshold dose below which they do not occur
Main types of combined effects
Additive effect
Combined effect of two substances is equal to the sum of the individual effects
(1 + 3 = 4):
• Toluene and xylene – both are irritant and narcotic, similar chemicals,
affect the same target organs
• Organo-phosphorus insecticides – all organo-phosphorous pesticides
inhibit cholinesterase activity
Independent effects
Toxic effects of each substance are unaffected by simultaneous exposure
(1 + 2 = 1 + 2):
e.g. Lead and xylene
Main types of combined effects
Synergistic effects
Combined effect is greater than the sum of the individual effects if each
substance encountered alone e.g. (2 + 2 = 20):
• Carbon tetrachloride and ethanol – both are hepatoxic – but total liver
damage by combined exposure is much greater than expected
• Smoking and Asbestos – greatly increased lung cancer risk
(Also potentiation and antagonism)
Limitations of toxicity testing data
• Usually conducted on animals
• Are these relevant to humans?
• Difficult to extrapolate from high level doses to
lower level exposures
• Requires knowledge of absorption, distribution,
biotransformation and excretion
• Differences between animals and humans in how
they react to the substance
Physical forms of hazardous
substances
• Gas
• Vapour
• Gaseous phase of substance that is normally solid or liquid
at ordinary temperature and pressure
• Aerosol – dispersion of particles in air
• Dust
• Airborne solid particles (0.1 – 100 micron diameter)
• Fume
• Airborne solid particles generated by condensation from
gaseous state (usually less than 1 micron diameter)
• Mist
• Airborne liquid droplets
• Fibre