“Toxicology and Ecotoxicology in Chemical Safety Assessment.”
Blackwell Publishing Ltd 2005 and Edited by Dr. Ian Thorn.

"...brings together a large amount of up-to-date information that probably never has been brought together in one place.
This is not a book for the professional toxicologist, but for those who need to use toxicology professionally."
Chemistry & Industry, Issue 10 May 2005

Introduction From The Book

Toxicology can be defined as the study of poisons, which to many probably conjures up images of witches hovering around a cauldron, cooking up a lethal potion for some unsuspecting victim!

Therefore, perhaps a better and more appropriate definition for the purpose of this book is:

“Toxicology is the study of adverse effects of chemicals on living organisms”

Owing to the strict legislation that operates in most countries, chemical companies wishing to introduce their products onto the market have to assess firstly the hazards associated with them. (In this context, hazards mean adverse health effects.) Toxicity can be defined as the inherent capacity of a chemical to cause adverse health effects'. Therefore, with relevance to humans, toxicologists are employed to investigate the potential adverse effects and associated mechanisms of toxicity arising from exposure to chemicals.

For toxicity to occur there has to be exposure to the chemical and there are three main ways in which this can occur: inhalation, skin contact and ingestion. Some chemicals cause toxicity directly whereas others require conversion to a more reactive form. Once exposure has taken place a chemical can cause local effects such as irritation at the site of contact, otherwise it may be absorbed into the bloodstream and distributed to other parts of the body which could result in systemic affects. Note that it is not uncommon for a chemical to cause both local and systemic effects.

Toxicity testing
In order to protect the general population, many countries have strict requirements for the hazardous nature of chemicals to be established prior to their use. The aim of toxicological testing is to predict the toxicity in man by using animals or cell cultures as surrogates. The tests themselves aim to mimic as closely as possible the likely exposure scenario that a human being would face, using the most appropriate animal model (or in some cases, cell cultures). There are standard test procedures, which can be used for toxicological evaluations and some of these procedures use animals, whilst others use cultured cells and other in vitro techniques.

Different species of animals are used in toxicity testing because there is no one animal that is satisfactory for use in the evaluation of all toxicological effects. The choice will depend on the type of toxicity to be investigated, although other factors such as availability, cost and reliability in their response will also influence the choice. Both sexes are usually employed although in some cases tests may be gender-specific. In tests where more than one dose level is used, they are selected in order to establish a dose- response relationship and threshold level of effect.

Many people perceive all chemicals as being bad in some way or another. The expression “toxic chemicals' is often used in everyday life, and questions concerning whether or not one particular chemical can cause more harm than another are frequently raised. These were studied as far back as the sixteenth century by a Swiss scientist named Paracelsus and the results of his work are now considered to be an underlying theme in the field of toxicology. He concluded that in sufficient quantities everything has the potential to cause adverse health effects and that the only thing that differentiates something from being harmful or not is the dose. In other words, “it is the dose which makes the poison'. This may seem like a strange concept as many of us have the idea that when dealing with a toxic chemical', its mere presence in our vicinity can cause harm to us. But this is not the case and, as was written by Paracelsus, it depends on the exposure dose as there will be a dose level below which this “toxic chemical' will not cause harm. (There are exceptions, however – Genotoxic carcinogens are believed to be active at all dose levels.)

For some chemicals such as arsenic, which features in so many murder suspense movies, this dose level is very low, whereas for other chemicals such as sugar, the dose level is much higher because it is less toxic. Conversely, so-called 'harmless' chemicals, which are around us all the time, such as water, oxygen and even those which we may daily use in the kitchen such as table salt, have the potential to cause us harm should the amount to which we are exposed be sufficiently high.

Acute and chronic toxicity
There are two main types of toxicity that need to be taken into consideration when studying the adverse effects of chemicals. These are acute toxicity and chronic toxicity. Acute toxicity describes the adverse health effects following a single or limited number of exposures.

Chronic toxicity describes the adverse health effects resulting from continuous or intermittent exposure over a lifetime. An example of chronic toxicity is organ damage, such as liver cirrhosis arising from long-term alcohol abuse.

Both acute and chronic toxicities are very different with respect to how they occur, i.e. the target organs involved and also the resulting adverse effects.

For example, acute effects tend to appear quickly and can be reversible, whereas chronic effects usually take a longer time to appear and are often irreversible.

Therefore, it is not possible to predict the chronic toxicity of a particular compound based on its acute toxicity, or vice versa - which is a question that is often asked! In fact, both these forms of toxicity can be considered to be extremes of each other, the differences being based on the dose levels experienced and the exposure period.