Guidelines for poison control
II. Technical guidance - 4. Analytical toxicology and other laboratory services
Laboratory services are an essential component of a poison control programme. They should be capable of undertaking toxicological analyses of both biological and non-biological materials, as well as relevant biomedical analyses, on an emergency basis. In some instances this would necessitate a round-the-clock service. Each laboratory service should develop its analytical capabilities in partnership with physicians dealing with poisoning cases. Furthermore, treatment of poisoning requires cooperation between laboratory services and those who interpret the analytical data. Laboratory services also have an important role in the surveillance of populations exposed to toxic substances, e.g. rural workers exposed to pesticides.
Analytical toxicology and other laboratory services may be provided within the context of a general hospital laboratory that also conducts routine biomedical analyses but should preferably have their own specific equipment and support. A specialized analytical toxicology laboratory may also be envisaged; this would normally be associated with a multifunctional poison centre and could also provide further services to the community, such as forensic toxicology, monitoring drugs of abuse and therapeutic drugs, and biological monitoring of occupational and environmental chemical exposure.
Functions of an analytical toxicology service
The main functions of an analytical toxicology service are to provide:
*emergency qualitative and/or quantitative assays for certain common poisons, especially where knowledge of the amount of poison absorbed may influence treatment (a 24-hours-a-day service may be essential for such assays);
*more complex analyses, such as "unknown" screening for cases where the cause of illness is unknown but may involve a poison; these analyses should be available, even if not provided on an emergency basis;
*analyses to monitor the efficacy of certain treatment or elimination techniques (e.g. haemoperfusion, haemodialysis);
*analyses for the biological monitoring of populations exposed to chemicals occupationally or environmentally;
*advice on the collection, storage, and transport of specimens, and on the interpretation of results of analyses;
*research into toxicokinetics and mechanisms of toxicity, in collaboration with clinical services and poison information centres.
Depending on local circumstances, it may be cost-effective to add other functions, such as monitoring of therapeutic drugs, surveillance of drug abuse, and analysis of occupational and environmental chemicals, since these activities require similar equipment and expertise. Training is essential for staff performing toxicological analysis. A central service for analytical toxicology may provide training in the subject for other hospital laboratory staff and - for physicians who treat poisoned patients - in the interpretation of analytical data.
Location, facilities, and equipment
The ideal location for an analytical toxicology laboratory is within, or close to, clinical services where poisoned patients are treated. This may facilitate the rapid transport of samples and consultation on specific cases between clinicians and analysts.
The availability of basic equipment, including balances, centrifuges, vortex mixer, water-bath, refrigerator, freezer, and fume cupboard, is assumed. Although the analytical equipment available will inevitably depend on local requirements and circumstances, certain basic equipment for techniques such as colorimetry, spectrophotometry, and thin-layer chromatography will normally be available, even if only at the local hospital laboratory. Attention is drawn to the recent IPCS manual on simple analytical toxicological tests.1 However, it should be emphasized that, even where the appropriate equipment is available, an experienced analytical toxicologist is still needed to provide an effective service.
1 Basic analytical toxicology. Geneva, World Health Organization, 1995.
The use of more sophisticated analytical techniques such as immunoassay, gas chromatography, mass spectrometry, high-performance liquid chromatography, and atomic absorption spectrophotometry requires specialized back-up facilities (servicing and consumables). A high degree of operator expertise in both the use and maintenance of such equipment is also essential. It is therefore recommended that the purchase and use of equipment for the following techniques should be undertaken only as part of a comprehensive programme for the development of analytical facilities:
simple "spot" tests
UV/visible recording spectrophotometer
thin-layer chromatography - qualitative
thin-layer chromatography - quantitative
gas chromatography - packed columns
gas chromatography - capillary columns
gas chromatography - flame ionization detection
gas chromatography - nitrogen-phosphorus detection
gas chromatography - electron-capture detection
gas chromatography - mass spectrometry
high-performance liquid chromatography - UV detection
high-performance liquid chromatography - fluorescence detection
high-performance liquid chromatography - mass spectrometry
high-performance liquid chromatography - electrochemical detection
high-performance liquid chromatography - diode array UV detection
atomic emission spectrometry
atomic absorption spectrometry (flame)
electrothermal atomic absorption spectrometry
inductively coupled plasma source spectrometry
radioimmunoassay - counting
enzyme immunoassay (e.g. enzyme-multiplied immunoassay technique)
enzyme-linked immunosorbent assay
The availability of pure reference compounds is essential for any analytical toxicology service. These can be purchased from some chemical suppliers or may be provided with commercial kits. In some instances, reference solutions may also be obtained from other laboratories, either locally or internationally.
Reagents and consumables
Special chemicals are required to perform many colorimetric assays and to prepare reagents for thin-layer chromatography. Particular attention should be given to ensuring a reliable supply of such chemicals. Availability of consumables for chromatographic and other techniques must be guaranteed if equipment is to be used to full advantage.
A list of reference books on laboratory investigations is given in Section 9.
The analytical data provided by laboratory services must be reliable, and this can best be ensured by employing certain basic quality assurance procedures:
* Internal quality control. Internal quality control involves the analysis of samples known to contain a poison of interest at the same time as clinical samples. For qualitative work, this procedure ensures the viability of the test reagents and the assay conditions. For quantitative work, specimens containing known concentrations of the poison should be analysed together with clinical samples in order to validate the procedure.
* External quality control. Some countries operate quality assurance programmes in which samples of known composition are regularly circulated from a central laboratory to a number of different laboratories. The receiving laboratory may be notified of the poison present and asked to determine its concentration. Alternatively, the exercise may involve the detection, identification, and subsequent measurement of unknown poison(s). Results are returned to the central coordinating laboratory and the performance of the receiving laboratory is assessed.
The training and participation of analytical toxicologists in both these aspects of quality assurance are crucial to the maintenance of good analytical performance. In addition, analysts should be made aware of, and encouraged to adopt, the principles of good laboratory practice.1
Analytical staff may be at risk both from the toxic effects of chemicals with which they work and from diseases associated with biological samples (particularly viral hepatitis B and HIV infection). Appropriate educational and safety measures are essential. Attention is drawn to a recent IUPAC/IPCS monograph dealing with the safe use and disposal of chemicals in laboratories.2
The staff required by a laboratory service will depend on the volume and type of toxicological and other tests to be performed, which in turn will depend on local circumstances. Every toxicological laboratory must have at least one experienced toxicological analyst and one laboratory assistant. However, a central analytical toxicology service requires a considerably larger number of staff because of the wide range of clinical and research needs it has to cover. It will also require administrative staff and possibly a documentalist.
1 Good laboratory practice in the testing of chemicals: final report of the Group of Experts on Good Laboratory Practice. Paris, Organisation for Economic Co-operation and Development, 1982.
2 Chemical safety matters. Cambridge, Cambridge University Press, 1992.
Laboratory assistants should have been educated in one or more science subjects and have practical analytical experience such as can be gained by working in a general chemistry laboratory. The number employed will depend upon local circumstances and particular situations, such as the need to provide an emergency service. Rotation of these personnel with, for example, the staff of a local hospital laboratory could help in establishing a pool of experience. Laboratory assistants should continue in part-time education in chemistry, biochemistry, or related subjects, in addition to receiving practical in-house instruction in analytical techniques.
An analytical toxicologist should possess a university degree, or the equivalent, in chemistry, biochemistry, or a related subject such as experimental toxicology, pharmacy, or pharmacology, and have a good understanding of analytical chemistry. A further qualification, such as a doctorate, plus relevant experience that includes a high standard of practical analytical work, would be an advantage for the head of an analytical toxicology laboratory. Wider knowledge of aspects of toxicology other than analytical toxicology is also desirable. Since many basic reference works are published in English, a knowledge of that language is important. It is of paramount importance that individuals recruited for analytical toxicology posts are committed to their work; a career structure should be provided to encourage them to remain in their posts when trained and to pass their experience on to others.
The training of senior analytical toxicology staff for a central analytical toxicology service must be considered in the context of the circumstances in the country concerned. For an individual with the basic qualifications outlined in the previous paragraph, the training period would normally be a minimum of six months in total, which could be spread over several years. During this period the staff member should acquire both practical and theoretical knowledge of the following, depending on the needs of the service and the equipment and facilities available:
*liquid- and solid-phase extraction techniques
*qualitative colour tests
*scanning ultraviolet/visible spectrophotometry
*immunochemical assays (radioimmunoassay, enzyme-multiplied immunoassay, fluorescence polarization immunoassay)
*gas chromatography (flame ionization, electron capture, and nitrogen/phosphorus detection)
*high-performance liquid chromatography
*flame and electrothermal atomic absorption spectrophotometry
*toxicokinetics, metabolism, and human toxicology of the substances analysed, with emphasis on the interpretation of results
*basic pathology as far as this relates to clinical toxicology
*laboratory management (choice, handling, and storage of specimens, reporting and recording of results)
*good laboratory practice and quality assurance procedures
*teaching and oral presentation of cases and reviews of the literature and the results of research projects.
Wherever possible, the training should lead to a recognized diploma. The analyst will continue to gain practical on-the-job experience, particularly as the work of the analytical toxicology service expands. Continuing education, such as participation in research and development projects, case presentations, and attendance at international meetings, should be encouraged. Membership of national and international toxicological and pharmacological societies should also be encouraged.
The training required by the head of a laboratory will also depend on local circumstances. If a country does not yet have a suitable training programme, help should be sought from countries with well established analytical toxicology services, which should be encouraged to provide training fellowships. In a country that already has an analytical toxicology service, but needs additional expertise in particular fields, visiting experts from other countries may be invited to provide the necessary training. Sample criteria for laboratories providing training in analytical toxicology are given in Table 3.
Laboratory staff should be encouraged to participate in regular meetings within a multifunctional poison control centre in order to:
*review case reports and, in particular, discuss the medical interpretation of analytical results with the clinical personnel
*review developments in analytical toxicology published in the literature
*examine results of research carried out in the laboratory and identify areas for cooperative investigation or further research
*discuss laboratory management in relation to the overall work on poison control.
Laboratory staff should also be encouraged to present papers at, and participate in, scientific meetings of relevance to their work.