1. W507 – Introduction to toxicology

2. 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

3. Any chemical may be toxic if the dose is high enough
“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

4. 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

5. 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

6. Basic Toxicological Terms
Acute effects
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

7. 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.
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

8. 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

9. 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

10. 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)

11. 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

12. 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