Toxicology is the study of chemicals and similar items that can affect human health, or the environment.
The aim of this post is to describe the important aspects of toxicology, as they relate to an understanding of systems toxicology. Toxicology spans biology and chemistry, and can include politics, geography, economics, social science and much more. There are many good toxicology textbooks that describe this fascinating field in fuller detail.
What does toxicology cover?
The definition given above is very broad (“…chemicals and similar items that can affect human health, or the environment.”), and this reflects the wide scope of toxicology. The British Toxicology Society (BTS) website includes chemical, drug, biological, radiation or physical hazards in the purview of toxicology (http://www.thebts.org/Careers.aspx) and lists a number of disciplines found within ‘toxicology’: academic toxicology, regulatory toxicology, industrial toxicology, pharmaceutical toxicology, occupational toxicology, clinical toxicology, forensic toxicology and contract toxicology.
Substances of interest could include toxins, poisons, proteins, nanomaterials, gases and more. As well as commercially produced chemicals, there are naturally occurring chemicals and elements (for example mercury, cadmium), and the toxicity may arise here when human activity relocates or concentrates naturally occurring chemicals so that they adversely affect the environment or human health.
hazards and risks
In brief, a HAZARD is a property that something can have, for example being poisonous, flammable or corrosive, whilst a RISK is the probability that the hazard will actually affect e.g. a human.
For example corrosive chemicals are generally sold in child-proof bottles made of thick, resistant materials, clearly labelled as ‘corrosive’ and often with sales restricted to adults or professionals. In this example the hazardous chemical is of low risk.
A hazardous chemical is one that could cause a problem, but the chance of that problem occurring is usually driven by context, for example by dosage, co-exposures and timing. This is an area of much debate, for example whether it is helpful to label chemicals with their hazards, or if a useful estimate of risk would be more appropriate. Definitions of risk vary from person to person, and in different circumstances, and ideally should always be explicitly stated so that individuals and communities can understand the definition being used. Uncertainties in the assessment or prediction of risk can be large (and are themselves uncertain!) and need full consideration in discussions about toxicology.
Toxicological practice may have to respect boundaries set by legislators and authorities, and these can vary with different jurisdictions, for example differing between the US, Europe, the UK and other countries.
Paracelsus, often called the founding father of Toxicology, is usually paraphrased as having said
“the dose makes the poison”;
a fuller quote is
“All substances are poisons: there is none which is not a poison. The right dose differentiates a poison and a remedy.” Paracelsus (1493-1541).
It is interesting that the longer version implies (to my reading) that ‘everything’ is a poison, but take a small enough dose and ‘you’ll be OK’, and the shorter implies that there are ‘safe’ compounds, but even these become toxic if enough is taken. This one example illustrates the differences that can exist just in interpretations in toxicology! Of course, what is ‘OK’ will also be subjective and depend on many factors, which are rarely explictly stated.
aims of toxicology
Two common tasks in toxicology are 1) to assess the level of risk in a situation, for example at a site of contamination and 2) to set regulatory levels for a given chemical; for example the amount of pesticide residue permitted in a food item.
Special cases in toxicology include chemicals that are carcinogenic, cause mutations or affect reproduction (CMRs) or are particularly stable in the environment, in which case there is a greater risk of effect since exposures will be prolonged and hard to reverse. Such chemicals might be classed as PBT (Persistent, Bioaccumulative and Toxic) or vPvB (very Persistent, very Bioaccumulative); in the latter case, the need to show toxicity is relaxed because of the greater need for precaution with chemicals whose introduction into the environment will be essentially irreversible. In some instances, these classes define what can be done with a chemical, for example using a known carcinogen in a consumer product would be unacceptable, whilst using chemicals that are themselves hugely toxic can be acceptable in certain pharmaceuticals, if the possible benefit outweighs the risk. CMRs are an example of a hazard group, and debate is possible as to whether it is useful to place hazards in a hierarchy – this is referred to as a choice between hazard-based and risk-based assessment.
mixtures, and mixture toxicity (mixtox)
At the moment, there is increasing interest in ‘mixtures’, mixtures are most usefully defined as exposure to multiple chemicals, and including multiple routes of exposure. At present most chemicals are regulated on an individual basis, and there is a need to assess whether human health is adequately protected by this approach: the reason for concern is that more than one chemical in the human exposome can have a given adverse effect on health. Areas of interest remain how to regulate chemicals with mixture toxicology in mind (the subject of an ongoing research project at Brunel University: see mixtox.wordpress.com); accurate assessment of human exposure to mixtures (which chemicals, at which life stages, at what times, through which routes and, crucially, at what dose?), and which health effects can be considered and how do their risks relate to each other (are they independent or related?).
towards systems toxicology (SysTox)
The use of computing techniques and tools in toxicology is referred to as computational toxicology (e.g. Kavlock et al 2008), and systems toxicology (SysTox) is at the cutting edge of computational toxicology. The development of SysTox is the main focus of this blog. SysTox is developing rapidly and has huge potential, but will require intense activity and coordination to fulfill this potential.