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

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

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 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. 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