W507 – Introduction to toxicology

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. “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