By Dr Simon Elliott, Consultant Forensic Toxicologist
So what is toxicology and what does a toxicologist do? Toxicology can be described as the study of drugs and poisons, although it should be borne in mind that anything can be a poison it just depends on the dose. This is certainly the case with water, which at normal consumed amounts is a pre-requisite to normal body function, however, when consumed to excess it can result in organ swelling, dilution of body electrolytes and potentially death. In fact this particular example can and does occur in some “Ecstasy” (MDMA) poisoning/toxicity cases. The role of the toxicologist therefore lies in the detection, identification and measurement of drugs and poisons in human biological materials with subsequent interpretation based on knowledge of the physiological action of a substance. This is important as the involvement of drugs or poisons may not always be immediately obvious to investigators either at the scene of a crime/incident/death or through a lack of drug history for a particular individual (suspect or victim). Even in instances where there is significant evidence to suggest the use of drugs has occurred, the exact drug (or more usually drugs) may not be known. Furthermore, even if a drug has been detected, the interpretation of its presence or amount can depend on many factors.
As described above, dose is an important factor in toxicology and is especially important within medicine as it is necessary to ensure a patient receives the correct dose to be effective without being toxic. How a drug gets into the body (the route of administration) is also an important factor as the same dose taken by different routes (e.g. by mouth, “snorting”, injecting, etc) can result in different measured concentrations in the blood. In a clinical setting inappropriate doses or routes of administration can often be a source of iatrogenic poisoning but this is a consideration for any case when interpreting concentration data.
A question regularly asked of the toxicologist is to define a “normal” or “therapeutic” concentration usually in order to assist the Court in understanding what may constitute an “abnormal” concentration. Whilst this may be possible to an extent in life, it is more difficult in post-mortem situations. Dose and concentration data from pharmaceutical clinical trials (in life) cannot and do not often apply in post-mortem toxicology. Following on from this it is equally asked to determine what constitutes an “overdose” or fatal concentration, which consequently without knowing a “normal” concentration is indeed difficult to define, especially for a particular case circumstance. The term “overdose” itself can be described as a dose more than recommended and it should be understood that it does not necessarily have to take place as a single event, such an excessive dose can also occur as a result of continuous use, excessive or otherwise.
Probably the most important consideration in a post-mortem toxicological setting is the phenomenon of post-mortem redistribution. This occurs as a result of during life, drugs can be retained/stored within larger organs (e.g. heart, lung, liver) and following death, the processes keeping the drugs (and metabolites) in these areas cease and as changes in cellular biochemistry and autolysis proceed, drugs and other substances may be released from their binding sites in the tissues and major organs. Unabsorbed drug may also diffuse from the stomach or bladder. Drugs can move into the surrounding blood, elevating the concentration in blood close to these sites. Therefore, for more reliable and confident interpretation of toxicological findings, the sites and methods of blood sampling are important with the concentrations of some drugs more likely to be “falsely” elevated in blood obtained from thoracic and abdominal vessels rather than “peripheral” vessels such as femoral veins but this will still not necessarily represent the concentration at the time of death. The potential increase in blood concentration after death can be profound (sometimes more than ten-fold for some drugs) but it should also be known that the phenomenon does not affect all drugs (e.g. not paracetamol).
A further common request is to calculate the dose ingested (usually in terms of the number of tablets) from a blood concentration. Whilst a calculation can be made it is theoretical in nature using a person’s weight and theoretical volume of distribution of the drug. Apart from the volume of distribution as not being an exact known value (as it is often derived from within life clinical studies with variable results), in post-mortem casework, with changes after death as described above, the concentration cannot be relied upon to be exactly that at the time of death therefore any dose calculation would be highly inaccurate which can be misleading for the investigation.
Ultimately, the primary aim of the toxicologist is to provide the Court with the most appropriate and scientifically valid interpretation as possible, which may involve various alternative hypotheses. A summary of common considerations is as follows;
- Case information – the circumstances (how, when, where for case context), scene evidence.
- Submitted specimens – was an appropriate container used for sample collection (e.g. any preservative), nature/state of samples (e.g. clotting), anatomical site of collection (redistribution if post-mortem), timing (detection window for drug detection).
- Analysis – was the range of drugs analysed for appropriate with sufficient sensitivity. Does the laboratory have suitable accreditation to have confidence in the results, such as ISO17025 (the international standard for laboratory testing)?
- Tolerance – as the degree of tolerance possessed by an individual can profoundly affect the outcome of drug intake, the prescription or drug history of an individual is paramount.
- Pharmacogenomics – it is known that within the population some individuals metabolise drugs (including alcohol) at variable rates to the majority (i.e. slow or fast metabolisers).
- Drug combinations – intake of multiple drugs can cause a combinational or additive effect which may be toxic or produce particular effects.
- Drug stability – it is known that various drugs can be unstable in biological fluids such as blood which may reduce the measured concentration or cause them to be undetectable (e.g. cocaine, diltiazem, zopiclone).
- In vitro and post-mortem production – some drugs have been found to be produced either in a collected sample or in the body as part of natural processes (e.g. putrefaction), with alcohol and GHB (gamma-hydroxybutyrate) being common examples.
It is not unexpected therefore that the question be asked as to what a toxicologist can realistically say and on what basis? Certainly this is the case when determining the effect of a particular drug on a particular individual as it is not possible to be specific to that individual. Nevertheless, if documented and scientifically/clinically published effects are known (even in general terms) these can be conveyed in an appropriate report. This is common practice in drug-driving impairment casework whereby the toxicological findings and potential effects of a drug should be used in conjunction with any recorded witness or medical evidence at the time as to the demeanour and actions of an individual. In post-mortem cases, known results in fatalities involving alternative causes of death (e.g. not drug related) are useful for comparison with the results of other post-mortem cases where drug ingestion has been implicated in order to incorporate the possible impact of redistribution. Case experience of a toxicologist is therefore very important to enable a collation of knowledge of the results of many different drugs across many different case types and scenarios. The toxicologist also relies on published data but these can be skewed towards unusual cases which may involve abnormally high concentrations or cases with other interesting features that may not apply to the case in question. Compilations of drug concentrations exist but can be wide ranging or general with little information or detail about the specific cases involved. “Reference ranges” may be quoted based on a variety of different sources and thus can produce differences of opinion between toxicologists which is acknowledged to be frustrating to a Court but cannot be avoided due to the varying degree of experience amongst toxicologists. The toxicologist should therefore be keeping up with published work and coupled with case experience can provide relevant comments based on laboratory findings, however the extent and content of reports often varies between organisations and individuals but the wording should be clear and appropriate to the results and presented in a suitable toxicology report for the Court which can be supported as required by laboratory and/or oral evidence.
Whilst appropriate interpretation is a constant challenge for all drugs, something of significant pertinence to modern toxicological casework is the rise of the so-called “legal high” (the new and inappropriate name for an equally unfortunate term of “designer drug”). In simple terms, since the widespread use of “Ecstasy” (MDMA) in the late-1980s, many drugs often based on an evolving number of chemical frameworks have been developed either from former pharmaceutical research or experimental pharmacology to evade drug legislation or pursue particular desired effects. This has become tremendous particularly within the last decade and it is a major challenge for the toxicologist to keep up with this either analytically (i.e. actually detecting such drugs) or interpretatively (i.e. what is the significance of the presence or concentration of a drug when little is known about it?). Various toxicologists, laboratories (including this author) and organisations around the world have established expertise in this ever changing field and experiences and information is often shared at domestic (e.g. UK & Ireland Association of Forensic Toxicologists; UKIAFT) and international professional meetings (e.g. The International Association of Forensic Toxicologists; TIAFT).
Of greater pertinence to current UK toxicological casework and the Courts which Barristers may or may not be aware of is the present lack of available toxicological expertise and whilst some consultancy services or individuals may exist, they are typically not attached to a suitably accredited laboratory service. This has primarily been as a result of the closure of the Forensic Science Service and other changes within the forensic science sector whereby newly trained scientists and those with significant experience left the industry or the UK. This is coupled with many years of inadequate succession planning or no proactive training which is not helped by the lack of toxicology (forensic or otherwise) courses at graduate or post-graduate level. In an area of forensic science (as for many other areas) whereby opinion based on factual evidence is highly dependent on experience, this presents an existing and potentially dangerous situation for the criminal justice system, especially with the continued pressures of investigative expectations of timeliness and resourcing within a cost-cutting mandate of forensic procurement (both prosecution and defence), whilst maintaining a high quality level of evidence. Even globally there are fewer toxicologists than experts in other forensic disciplines; consequently, it is beneficial to all if the toxicological resource is used wisely and appropriately. Further benefits can be had if sufficient information is made available throughout the investigation and Court proceedings. This is of prime importance when further comments are required to assist the Court, especially in light of the relatively recent implementation of streamlined forensic reporting which requires co-operation across the criminal justice system.
In summary, despite the varying challenges, toxicology can be a useful and primary source of evidence that is important to various case types, particularly with correct utilisation and application.
Baselt’s Disposition of Toxic Drugs and Chemicals in Man (Biomedical Publications)
Clarke’s Analysis of Drugs and Poisons (Pharmaceutical Press)
Mason’s Forensic Medicine for Lawyers (Tottel Publishing)
Dr Simon Elliott, Consultant Forensic Toxicologist, Managing Director, ROAR Forensics, Malvern, UK.