Toxicology: Principles, Effects, and Types of Exposure (PDF)

Toxicology has sometimes been described as the 'science of poisons'. However, this is a somewhat simplistic description. A more suitable definition of toxicology is: "Toxicology is the study of the potential of any substance to produce adverse health effects on a living organism and the likelihood...

Toxicology has sometimes been described as the 'science of poisons'. However, this is a somewhat simplistic description. A more suitable definition of toxicology is: "Toxicology is the study of the potential of any substance to produce adverse health effects on a living organism and the likelihood that such adverse effects might occur under specified exposure conditions". The principles of toxicology have been applied by humans for thousands of years. Early civilisations used a variety of materials because of specific effects ranging from medicinal (herbs and plant extracts) to harmful (cyanide extracted from peach kernels, aconite used on arrow tips for hunting). Paracelsus (1493-1541) is widely regarded as the father of modern toxicology and is one of the most important early pioneers of the subject. He recognised the relationship between dose and response and is credited with the statement, "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy..." This concept is fundamental to our understanding of the principles of toxicology and it is also important when trying to protect the health of workers who may be exposed to toxic substances. However, despite increases in our knowledge and understanding of toxicology it is often very difficult (or even impossible) to link the cause and effect of a disease. There are a number of reasons for this including the following: 4 - The health effect of concern may not occur at the time of exposure. Indeed, in many cases the effect may not be produced for a period of time after exposure (e.g. days or even years). For example asbestos or chromium-induced cancer may not manifest itself for many years after exposure has ceased - The person who develops the health effects may no longer work with the substance that caused the effects, and the link between the exposure and the health effect may not be noted - There may be a wide variation in genetic susceptibility between individuals to the effects of a hazardous substance. - The effects of exposure to hazardous substances may also vary widely depending on the persons age, gender and health status - There is also the added complication of combined effects of different substances. Exposure is rarely to only a single substance as a number of different substances may be present in the workplace and interactions between these different substances may significantly alter the severity of the effect on the person - The effects of the hazardous substance may be altered by alcohol, tobacco or any recreational or prescribed drugs that the person may be taking - Perhaps more surprisingly, there is also a lack of detailed toxicological information available for many of the materials commonly used industrially. 5 **2.2 SOME BASIC TOXICOLOGICAL TERMS AND CONCEPTS** **2.2.1 Acute and chronic effects** When a substance affects the body the effect may occur immediately or it may not manifest itself for a period of time. In toxicology, the terms that are used to describe how rapidly adverse responses to hazardous substances occur are acute effects and chronic effects. Acute effects occur very rapidly during or immediately after exposure and generally tend to be of short duration. The effects are generally developed in response to a relatively high dose or high exposure concentration of the substance. Symptoms of acute toxic effects vary from sudden death through to minor irritation of the skin, eyes, nose or throat. Examples of acute effects include the immediate eye and respiratory tract irritation to exposure to ammonia, burns to the skin caused by direct contact with strong acids or alkalis or narcosis from exposure to organic solvents. Chronic effects tend to occur after long-term, repeated exposure to lower levels of a hazardous substance. Chronic or long-term effects are long lasting and develop gradually over long periods of exposure, usually months or years. Recovery once exposure stops is extremely slow and often incomplete; in fact the effects are often permanent. Chronic effects include cancer, bronchitis, and dermatitis. Some examples of chronic toxicity are pneumoconiosis from (usually) long term exposure to coal dust and silicosis after exposures to quartz dusts. **2.2.2 Local and systemic effects** Hazardous substances may induce a toxic response either locally or systemically. - Local effects occur at the direct point of contact between the body and the substance, e.g. corrosive materials can cause burns; organic solvents can cause de-fatting of the skin; irritant gases such as chlorine can cause pulmonary inflammation. These are examples of 6 - An example of a chronic local effect is nasal cancer caused by exposure to wood dust. - Systemic effects occur when the material is absorbed into the body's systems and acts on organs remote from the point of contact of the body with the agent e.g. acute systemic effects from exposure to organic solvent vapours can include dizziness and unconsciousness. Examples of chronic systemic effects from exposure to lead (where the main route of entry is usually inhalation) include damage to the blood forming process in the long bones as well as harmful effects on the nervous system, kidneys and reproductive functions. Some hazardous substances may produce both local and systemic effects (e.g. organic solvents). **2.2.3 Xenobiotic** A xenobiotic is a chemical or substance which is not normally found or produced in a person or organism. They are also sometimes referred to as 'foreign' substances and include drugs, pesticides and many other synthetic chemicals. **2.2.4 Stochastic and non-stochastic** Stochastic is a term to describe the likelihood of an event taking place. It is synonymous with random i.e. the event can occur purely by chance. An example is the possibility of developing malignant diseases such as cancer for which the probability of cancer occurring is a function of dose. Once a stochastic effect occurs, the consequence is independent of the initiating dose. Stochastic effects do not have a threshold dose below which they cannot occur. In contrast, non-stochastic effects are characterized by a threshold dose below which they do not occur. Above the threshold dose, non-stochastic 7 effects have a clear relationship between the exposure and the magnitude of the effect. Examples include inflammatory and degenerative diseases. **2.2.5 Types of combined effects** It is common that people are exposed to more than one hazardous substance at a time. The different substances may interact such that one substance may alter the toxicity of one or more of the chemicals present. A number of possible interactions may occur: - Additive effects - Synergistic effects - Potentiation - Antagonism - Independent Additive effect -- the combined effect of two substances is equal to the sum of the individual effects if each substance was encountered alone, examples include: - Toluene and xylene -- where both are irritant and narcotic, are similar chemicals and affect the same target organs. - Organo-phosphorus insecticides -- all organo-phosphorus pesticides inhibit cholinesterase activity Synergistic effect -- the combined effect of two substances is greater than the sum of the individual effects if each substance was encountered alone, examples include: - Carbon tetrachloride and ethanol -- both chemicals are hepatoxic -- but total liver damage caused by combined exposures is much greater than expected. - Smoking and asbestos -- this leads to a greatly increased lung cancer risk Potentiation -- a substance has no toxic effect, but when simultaneous 8 exposure occurs with a second substance, the toxicity of the second chemical is enhanced. An example is: - Carbon tetrachloride and iso-propanol -- isopropanol alone is not hepatoxic, but it increases the hepatoxicity of carbon tetrachloride. Antagonism -- this is where the combined effect of two substances is less than the sum of the individual effects if each substance was encountered alone. An example is: - Phenobarbitone and paradoxon (an organo-phosphorous pesticide) - phenobarbitone increases the rate of metabolism of paradoxon and reduces its toxicity. Independent effect -- where none of the above effects occur the toxic effects of each substance are unaffected by simultaneous exposure. An example is: - Lead and xylene. **2.2.6 Limitations of toxicity testing data** Much of our current knowledge of how substances affect human health has been gathered from toxicity testing. Toxicity testing is usually conducted on animals, raising questions regarding how relevant these studies are to man. For example the dose or concentration of a substance required to kill 50% of rats may be very different to that required to kill 50% of say guinea pigs, or indeed humans. It is therefore very difficult to extrapolate toxicity tests to humans. The answer requires knowledge of absorption, distribution, biotransformation and excretion from the body. In predicting the adverse effects likely to be found in humans from the results of animal studies, reliance has to be placed on the many similarities in anatomy, biochemistry, physiology and reactions to poisons of other animals and humans. There are numerous examples of similar qualitative and quantitative responses in humans and animals but differences are common and it must never be assumed that people will react in the same 9 way as other animals. Equally, not every effect found in animals will necessarily occur in man. **2.3 PHYSICAL FORMS OF HAZARDOUS SUBSTANCES** Hazardous substances occur in many physical forms and knowledge of these is essential in understanding routes of entry, typical exposure scenarios as well as determining appropriate control methods. It is worthwhile, therefore, to define the different physical forms in which the hazardous substances may occur as follows: - **Gas -** a formless fluid that completely occupies the space of any enclosure at 25C and 760mm Hg. Examples include oxygen nitrogen and carbon dioxide. - **Vapour -** the gaseous phase of a material normally liquid or solid at ordinary temperature and pressure. Examples include benzene and mercury vapour from evaporation of the liquid forms. 1. **Aerosol -** a dispersion of particles of microscopic size in air; may be solid particles (dust, fume, fibre) or liquid particles (mist). **Dust -** airborne solid particles that range in size from 0.1 - 100μm in diameter. Examples include wood dust from cutting and sanding operations and quartz dust from crushing of rocks. **Fume -** airborne solid particles generated by condensation from the gaseous state. The particles that make up fumes are very small, usually less than 1 micron in diameter. In most cases the volatilised solid reacts with oxygen in the 10 1. igh temperature cutting or welding of metals. **Mist --** airborne liquid droplets generated by condensation from the gaseous state or by the break up of a liquid by splashing or atomising. Examples are oil mist produced during cutting and grinding operations, acid mists from electroplating, and paint spray mist from spraying procedures. **Fibre --** a thin and greatly elongated solid substance. Examples include asbestos and glass