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    UNITED NATIONS ENVIRONMENT PROGRAMME
    INTERNATIONAL LABOUR ORGANISATION
    WORLD HEALTH ORGANIZATION


    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY



    GUIDELINES FOR POISON CONTROL













        The issue of this document does not constitute formal publication.
    It should not be reviewed, abstracted, or quoted without the written
    permission of the Manager, International Programme on Chemical Safety,
    WHO, Geneva, Switzerland.

    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.


    Guidelines for poison control





    First draft prepared at the National Institute of Health Sciences,
    Tokyo, Japan, and the Institute of Terrestrial Ecology, Monk's Wood,
    United Kingdom


    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization


    World Health Organization
    Geneva, 1997

         The International Programme on Chemical Safety (IPCS) is a joint
    venture of the United Nations Environment Programme, the International
    Labour Organisation, and the World Health Organization. The main
    objective of the IPCS is to carry out and disseminate evaluations of
    the effects of chemicals on human health and the quality of the
    environment. Supporting activities include the development of
    epidemiological, experimental laboratory, and risk-assessment methods
    that could produce internationally comparable results, and the
    development of manpower in the field of toxicology. Other activities
    carried out by the IPCS include the development of know-how for coping
    with chemical accidents, coordination of laboratory testing and
    epidemiological studies, and promotion of research on the mechanisms
    of the biological action of chemicals.

    WHO Library Cataloguing in Publication Data



    Guidelines for poison control



    1.Poisoning - prevention & control  2.Poison control centres
    3.Guidelines


    ISBN 92 4 154487 2  (NLM Classification: QV 600)


         The World Health Organization welcomes requests for permission to
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    (c) World Health Organization 1997

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    Contents

    Preface

    Acknowledgements

    Introduction

    I.   Policy overview

    1.   Poison information centres: their role in the prevention and
         management of poisoning

         History
         Functions
         Benefits
         Conclusions and recommendations

    II.  Technical guidance

    2.   Information services

         Organization and operation
         Location, facilities, and equipment
         Staff
         Financial aspects
         Research

    3.   Clinical services

         Introduction
         Clinical toxicology units
         Staff
         Recommendations

    4.   Analytical toxicology and other laboratory services

         Introduction
         Functions of an analytical toxicology service
         Location, facilities, and equipment
         Staff

    5.   Toxicovigilance and prevention of poisoning

         Introduction
         Toxicovigilance and prevention programmes
         Recommendations

    6.   Response to major emergencies involving chemicals

         Introduction
         Information
         Treatment
         Contingency planning
         Education and training
         Follow-up studies
         Financial support
         Collaboration between centres

    7.   Antidotes and their availability

         Introduction
         Scientific aspects
         Technical aspects
         Economic aspects
         Registration and administrative requirements
         Considerations of time and geography
         Special problems of developing countries
         Antidotes for veterinary use
         Improving availability

    8.   Model formats for collecting, storing, and reporting data

         Substance records
         Product records
         Communications records
         Annual reports

    9.   Library requirements for poison information centres

         Books
         Journals
         Publications of international organizations
         Computerized databases
         Educational material

    Annexes

    1.   Summary description of the IPCS INTOX Package

    2.   Classified lists of antidotes and other agents

    3.   Example of a substance record: chemical

    4.   INTOX product record

    5.   INTOX communication record and miniform

    6.   Proposed format for a poison centre annual report

    7.   Environmental Health Criteria series
    
    Preface

         The International Programme on Chemical Safety (IPCS) was
    established in 1980 as a collaborative programme of the International
    Labour Organisation (ILO), the United Nations Environment Programme
    (UNEP), and the World Health Organization (WHO) in order to provide
    assessments of the risks to human health and the environment posed by
    chemicals, so that all countries throughout the world might develop
    their own chemical safety measures. The IPCS provides guidance on the
    use of such assessments and seeks to strengthen the capacity of each
    country to prevent and treat the harmful effects of chemicals and to
    manage emergencies involving chemicals. In its different activities,
    the IPCS collaborates with various international organizations and
    professional bodies. Its work on prevention and treatment of poisoning
    is undertaken in collaboration with the World Federation of
    Associations of Clinical Toxicology Centres and Poison Control
    Centres1 and its member associations. The aims of the European
    Commission (EC) in the field of poison control are similar to those of
    the IPCS and many activities are undertaken jointly by the two bodies.

         Poisoning by chemicals is a significant risk in all countries
    where substantial quantities and increasing numbers of chemicals are
    being used in the development process. Some countries already have
    well established facilities for the prevention and control of
    poisoning, many wish to establish or strengthen such facilities, and
    others have not yet fully recognized the extent of the risk.

         The need for advice on poison control, particularly with a view
    to encouraging countries to establish poison information centres, was
    recognized at a joint meeting of the World Federation, the IPCS, and
    the EC, held at WHO headquarters, Geneva, from 6 to 9 October 1985. At
    this meeting it was recommended that guidelines be prepared on poison
    control and particularly on the role of poison information centres. It
    was also recommended  inter alia that antidotes and other substances
    used in the treatment of poisoning should be evaluated, comparable
    information needed for diagnosis and treatment of poisoning collected
    and recorded in a standardized manner, toxicovigilance and poison
    prevention programmes developed, mechanisms for exchanging experience
    of dealing with major chemical accidents established, and specialized
    training in poison control encouraged.

         A consultation of experts from poison information centres, from
    developed and developing countries, was held in London, England, from
    24 to 25 February 1986, to advise on the structure and content of the
    proposed guidelines on poison control. It was agreed that the
    guidelines would be in two parts, the first concerned with national
    policy, and the second with technical aspects of establishing and
    running the various elements of a poison control programme. A drafting

              

    1  Hereafter referred to simply as the World Federation.

    group was established and charged with the preparation of the
    guidelines. This group met twice - from 25 to 26 November 1986 in
    Brussels, Belgium, and from 16 to 20 February 1987 in London, England
    - and concentrated on the drafting of the policy overview.

         The initial draft was examined by an extended editorial group,
    meeting from 9 to 14 November 1987 in Salvador, Bahia, Brazil, during
    the Fifth Congress of the Brazilian Society of Toxicology. Work on the
    drafting of Part II was also initiated at that time.

         Additional contributions were made by a number of experts,
    acknowledged below. Besides the extensive experience of poison control
    published in the literature, the results of the following activities
    were used in assembling material: the Joint IPCS/EC/World Federation
    survey on poison control centres and related toxicological services;1
    the Joint IPCS/EC Project on Antidotes; the IPCS Poisons Information
    Package project - IPCS INTOX - being undertaken jointly with the
    Canadian Centre for Occupational Health and Safety (CCOHS) and the
    Centre de Toxicologie du Québec (CTQ), with financial assistance from
    the International Development and Research Centre of Canada (IDRC);
    the joint WHO (EURO)/IPCS/EC meetings held in Munich, 16 to 20
    December 1985, on public health response to acute poisonings2 and in
    Munster, 8 to 12 December 1986, on prevention of acute chemical
    poisonings;3 and the IPCS seminar on training for poison control
    programmes in developing countries,4 held in London in February 1987.

         Subsequently, a complete draft text was circulated for comment to
    members of the World Federation and selected IPCS focal points in
    various countries. The text was examined at a joint IPCS/EC
    secretariat meeting with the General Assembly of the World Federation,
    held at WHO headquarters in Geneva, 31 October to 2 November 1988; it
    was the opinion of the meeting that the guidelines reflected
    experience in Europe and North America, but should be tested in a
    number of other regions of the world before being finalized and
    published.

         The guidelines were first presented at the Joint IPCS/WHO/World
    Federation Workshop on Prevention and Management of Poisoning by Toxic
    Substances, held in Kuala Lumpur, Malaysia, 29 November to 2 December
    1989, in which representatives from 27 countries took part. They were
    also presented and discussed at two regional IPCS workshops on
    development of poison control programmes, held in Montevideo, Uruguay,
    in March 1991 and February 1992, organized by the Centro de
    Información y Asesoriamento Toxicológico and with partial financial
    support from the International Union of Toxicology (IUTOX). The
    guidelines were further used as the basis for national workshops on
    poison control held in Ciloto, Indonesia, in November 1992, Bangkok,
    Thailand, in November 1992, and New Delhi, India, in December 1992.

         Due account having been taken of experience of their use in
    different parts of the world, the guidelines are now issued as a WHO
    publication to encourage their wide distribution and use throughout
    the world.

         Attention is drawn to the report5 of the United Nations
    Conference on Environment and Development (UNCED), held in Rio de
    Janeiro, Brazil, in June 1992, in Agenda 21, Chapter 19, of which all
    countries are called upon to promote the establishment and
    strengthening of poison control centres to ensure prompt and adequate
    diagnosis and treatment of poisoning, including networks of centres
    for chemical emergency response.

         Following the recommendations of UNCED in relation to sound
    management of chemicals, an Intergovernmental Forum on Chemical Safety
    (IFCS) was established in April 1994. One of the priority activities
    recommended to all governments by IFCS is the establishment of poison
    centres with related clinical and analytical facilities and the
    promotion of harmonized systems for recording data in different
    countries. These guidelines provide policy and technical advice to
    those responsible for setting up poison centres and related
    facilities, and give recommended approaches for harmonized data
    recording among countries.

              

    1    Report of the survey of poison control centres and related
         toxicological services 1984-1986.  Journal de toxicologie
          clinique et expérimentale, 1988, 8(5):313-371.

    2     Public health response to acute poisonings: poison control
          programmes: report on a joint working group, Munich, 16-20
          December, 1985. Copenhagen, World Health Organization Regional
         Office for Europe, 1986 (Environmental Health Series, No. 11).

    3     Prevention of acute chemical poisonings: high-risk circumstances:
          report on a joint WHO/IPCS/CEC meeting. Copenhagen, World
         Health Organization Regional Office for Europe, 1987
         (Environmental Health Series, No. 28).

    4      Report of IPCS Seminar on Training for Poison Control Programmes
          in Developing Countries. Geneva, World Health Organization,
         1987 (unpublished document ICS/87.33, available on request from
         Programme for the Promotion of Chemical Safety, World Health
         Organization, 1211 Geneva 27, Switzerland).

    5    Adopted by the United Nations General Assembly at its 47th
         Session in New York, in December 1992, Resolution GA47/719.

    Acknowledgements

         The following are the members of the drafting group and experts
    who prepared specific sections of these guidelines:

    Dr B. Fahim, Director, Poison Control Centre, Ain Shams University,
    Cairo, Egypt

    Dr R. Flanagan, Toxicology Laboratory, Medical Toxicology Unit, Guy's
    and St Thomas's Hospital Trust, London, England

    Dr M. Govaerts, formerly Director, Belgian Poisons Centre, Brussels,
    Belgium

    Dr J.A. Haines, IPCS Secretariat, World Health Organization, Geneva,
    Switzerland (Chairman of the drafting group)

    Dr V. Murray, Honorary Consultant, Medical Toxicology Unit, Guy's and
    St Thomas's Hospital Trust, London, England (Rapporteur of the
    drafting group)

    Dr H. Persson, Director, Swedish National Poisons Information Centre,
    Karolinska Hospital, Stockholm, Sweden

    Dr J. Pronczuk de Garbino, IPCS Secretariat, World Health
    Organization, Geneva, Switzerland

    Dr E. Wickstrom, Director, Poisons Information Centre, Oslo, Norway

    Ms H. Wiseman, Medical Toxicology Unit, Guy's and St Thomas's Hospital
    Trust, London, England

         The following experts took part in consultations and review
    working groups for the guidelines:

    Dr A. Berlin, Secretariat, Directorate General V, European Commission,
    Luxembourg

    Dr I.R. Edwards, Director, WHO Collaborating Centre for International
    Drug Monitoring, Uppsala, Sweden, formerly Director, National
    Toxicology Group, University of Otago, Dunedin, New Zealand

    Dr N. Fernicola, Toxicology Consultant, Pan American Health
    Organization, Bogota, Colombia

    Dr E. Fournier, formerly Director, Toxicology Service, Fernand Widal
    Hospital, Paris, France

    Dr J. Garbino, formerly Assistant, Intensive Care Unit, Hospital de
    Clínicas Dr Manuel Quintela, Montevideo, Uruguay

    Dr A.N.P. van Heijst, formerly Director, Dutch Poisons Control Centre,
    Utrecht, Netherlands

    Dr J. Indulski, formerly Director, Nofer's Institute of Occupational
    Medicine, Lodz, Poland

    Dr A. Jaeger, Director, Poisons Centre, Strasbourg, France

    Dr J.P. Lorent, Swiss Toxicological Information Centre, Zurich,
    Switzerland

    Dr S. Magalini, Director, Poisons Centre, Rome, Italy

    Dr F. Oehme, Veterinary College, University of Kansas, Manhattan, KS,
    USA, formerly President, World Federation of Associations of Clinical
    Toxicology Centres and Poison Control Centres

    Dr M. Repetto, Director, National Toxicology Institute, Seville, Spain

    Dr L. Roche, Lyon, France, formerly Secretary General, World
    Federation of Associations of Clinical Toxicology Centres and Poison
    Control Centres

    Dr B. Rumack, formerly Director, Rocky Mountain Drug and Poisons
    Information Center, Denver, CO, USA

    Dr N.N. Sabapathy, formerly Zeneca Agrochemicals, Hazelmere, England

    Dr S. Shabeer Hussain, Director, National Poison Control Centre,
    Karachi, Pakistan

    Dr W.A. Temple, Director, National Toxicology Group, University of
    Otago, Dunedin, New Zealand

    Dr M. Thoman, Associate Editor, Veterinary and Human Toxicology, Des
    Moines, IA, USA

    Dr M.T. van der Venne, Directorate General V, European Commission,
    Luxembourg

    Dr C. Vigneaux, Anti-Poisons Centre, Lyon, France

    Dr J. Vilska, Director, Poison Information Centre, Helsinki, Finland

    Dr G. Volans, Director, Medical Toxicology Unit, Guy's and St Thomas's
    Hospital Trust, London, England

    Dr R. Wennig, Director, National Health Laboratory, Luxembourg

    Introduction

         The massive expansion in the availability and use of chemicals,
    including pharmaceuticals, during the past few decades has led to
    increasing awareness - on the part not only of the medical profession
    but also of the public and various authorities - of the risks to human
    health posed by exposure to those chemicals. Moreover, each country
    has a variety of natural toxins to which its population may be
    exposed. Authorities need only to consult local hospital accident and
    emergency departments for confirmation that toxic risks exist in every
    country and, in many cases, are increasing.

         Tens of thousands of man-made chemicals are currently in common
    use throughout the world, and between one and two thousand new
    chemicals appear on the market each year. In industrialized countries,
    there may be at least one million commercial products that are
    mixtures of chemicals, and the formulation of up to one-third of these
    may change every year. A similar situation exists in the rapidly
    industrializing developing countries. Even in the least developed
    regions, there is growing use of agrochemicals such as pesticides and
    fertilizers, of basic industrial chemicals, particularly in small-
    scale rural cottage industries, and of household and other commercial
    products, as well as pharmaceuticals.

         Every individual is exposed to toxic chemicals, usually in
    minute, subtoxic doses, through environmental and food contamination.
    In some instances, people may be subjected to massive, or even fatal,
    exposure through a chemical disaster or in a single accidental or
    intentional poisoning. Between these two extremes there exists a wide
    range of intensity of exposure, which may result in various acute and
    chronic toxic effects. Such effects clearly lie in the public health
    domain, particularly in cases of chemical contamination of the
    environment that may result in exposure of an unsuspecting public. The
    situation is similar to, but subtler than, exposure to infectious
    diseases: although chemicals may be absorbed in small quantities, they
    do not induce pathological signs until toxic concentrations are
    reached in the tissues of exposed individuals.

         The global incidence of poisoning is not known. It may be
    speculated that up to half a million people die each year as a result
    of various kinds of poisoning, including poisoning by natural toxins.
    WHO conservatively estimates that the incidence of pesticide
    poisoning, which is high in developing countries, has doubled during
    the past 10 years; however, the number of cases that occur each year
    throughout the world, and the severity of cases that are reported, are
    unknown. It was estimated in 1982 that, while developing countries
    accounted for only 15% of the worldwide use of pesticides, over 50% of
    cases of pesticide poisoning occurred in these countries and, being
    due mainly to misuse of the chemicals, were largely avoidable. The
    worldwide frequency of major incidents involving chemicals, i.e.
    incidents that could cause multiple deaths, has been rising during the
    past two decades. There is growing concern about the possible health

    consequences of chronic exposure to naturally occurring toxic
    substances and to man-made chemicals and waste. In addition,
    poisonings of domestic animals are a cause for concern in certain
    countries, because of their economic impact on animal husbandry.

         The principal toxic risks that exist in any country may be
    readily identified by surveys of hospital accident and emergency
    wards, forensic departments, and rural hospitals in agricultural
    areas. The growing incidence of poisoning from accidental exposures to
    chemicals, and recent examples of acute poisoning in local populations
    as a result of industrial and transport accidents involving chemicals
    have highlighted the importance of countries having special programmes
    for poison control and, in particular, the facilities for diagnosis,
    treatment, and prevention of poisoning.

         Although the risks of poisoning by chemicals are not yet
    universally recognized, some countries have already established poison
    control programmes that provide the framework for both prevention and
    management of poisoning. These newly emerging programmes are important
    elements of chemical safety. Such programmes will vary in their
    structure according to local circumstances, but they all need clear
    direction and coordination in order to ensure the efficient use of
    resources, appropriate patient care, and effective preventive
    measures. There is a wide variety of starting points for any country
    wishing to initiate a poison control programme, and it is essential to
    identify the existing capabilities and facilities on which a programme
    may be built. The main elements of such programmes are identification
    of the toxic hazards existing locally (in order to establish
    preventive measures), diagnosis of poisoning, and treatment of
    poisoned patients.

         These guidelines are intended to help countries that wish to
    establish or strengthen facilities for the prevention and management
    of poisoning. They are concerned with the identification of relevant
    existing facilities, of needs, of potential resources (including human
    resources), and of other bodies whose collaboration is essential to
    the implementation of successful poison control. Based on the
    experience of established poison information centres throughout the
    world, the guidelines provide advice rather than a unique model, and
    should be adapted in accordance with the socioeconomic and cultural
    conditions prevailing in each country.

         Part I is written primarily for the administrator and decision-
    maker; it provides a policy overview of the problems of poisoning and
    the types of programmes and facilities that will be effective in
    preventing and dealing with them. Particular emphasis is given to the
    key role to be played by poison information centres.

         Part II provides technical guidance for those with direct
    responsibility for the establishment and operation of specific poison
    control facilities and covers the following topics:

    *    information services

    *    clinical services (including lists of antidotes and other agents
         used in the treatment of poisoning)

    *    analytical toxicology services

    *    toxicovigilance and prevention of poisoning

    *    response to major emergencies involving chemicals

    *    antidotes and their availability

    *    standardized formats for the collection and storage of essential
         data by poison information centres

    *    documentary and library support for poison information centres.

    I.  Policy overview

    1.  Poison information centres: their role in the prevention and
        management of poisoning

    History

         Recognition of the problem of poisoning and of the need for
    specialized facilities to deal with it, as well as the existence of a
    number of health care professionals concerned with human toxicology,
    has invariably been the primary prerequisite for the establishment of
    poison information centres. The first centres were instituted in North
    America and Europe during the 1950s. Since then, numerous others have
    been created, principally in industrialized countries. The early
    poison information centres originated in a wide variety of fields,
    including paediatrics, intensive care, forensic medicine, occupational
    health, pharmacy, and pharmacology. To some extent, the original
    character of many centres has been maintained, and there is thus
    considerable heterogeneity in their structure and organization.

         A global study undertaken during the period 1984-1986 indicated
    that, while most developed countries had well established facilities
    for poison control, this was rarely the case in developing
    countries.1 Furthermore, in industrialized countries, there may be a
    number of institutions that provide different types of information on
    toxic chemicals. It must be remembered, however, that each ministry or
    agency in a developed country may have its own information services
    for its specialized needs, but that, in a developing country, the
    poison information centre - where it exists - may be the only source
    of information on toxic chemicals available 24 hours a day. Centres in
    developing countries may therefore have to provide a much broader
    toxicological information service than their counterparts in some
    developed countries.

         Poisoning of animals may have important economic consequences,
    and special veterinary poison information centres have been
    established in some countries, including Australia, France, and the
    USA. In most countries, however, many poison information centres may
    deal with toxicological problems that affect both animals and humans.

         Poison information centres may operate effectively with various
    types of organizational structure. The majority depend on a hospital
    administration and are, to some extent, connected with a university
    and with the country's public health service at national or regional
    level. Close association with units that treat poisoned patients and
    with analytical laboratories is essential to most centres, although
    the way in which this is organized depends on local conditions. Many

              

    1    Report of the survey of poison control centres and related
         toxicological services 1984-1986.  Journal de toxicologie clinique
          et expérimentale, 1988, 8(5):313-371.

    centres are multifunctional, providing an information service,
    clinical unit, and analytical laboratory. Most are at least partially
    supported by public funding, and operate as independent foundations
    with their own governing bodies on which various public authorities
    are represented. It is thus impossible to specify a single
    organizational model for a poison information centre.

    Functions

         The poison information centre is a specialized unit providing
    information on poisoning, in principle to the whole community. Its
    main functions are provision of toxicological information and advice,
    management of poisoning cases, provision of laboratory analytical
    services, toxicovigilance activities, research, and education and
    training in the prevention and treatment of poisoning. As part of its
    role in toxicovigilance, the centre advises on and is actively
    involved in the development, implementation, and evaluation of
    measures for the prevention of poisoning. In association with other
    responsible bodies, it also plays an important role in developing
    contingency plans for, and responding to, chemical disasters, in
    monitoring the adverse effects of drugs, and in handling problems of
    substance abuse. In fulfilling its role and functions, each centre
    needs to cooperate not only with similar organizations, but also with
    other institutions concerned with prevention of and response to
    poisoning.

     Provision of information and advice

         The main function of a poison information centre is to provide
    information and advice concerning the diagnosis, prognosis, treatment,
    and prevention of poisoning, as well as about the toxicity of
    chemicals and the risks they pose. As already mentioned, centres in
    some countries may be required to provide a very broad range of
    information on toxic chemicals, including data on risks to the
    environment and on safe levels in food and environmental media as well
    as in the workplace. The information should be available to all who
    may benefit from it, such as medical and other professional personnel,
    other concerned groups, various authorities, the media, and the
    public.

         Access to the information service is normally by telephone,
    especially in an emergency, but there are several other communication
    channels, including computer networks, written responses to enquiries,
    and publications. Where telephone services are inadequate, the centre
    can act through direct consultation with those who visit in person and
    by providing written material on specific topics.

         If it is to be reliable, the advice should be based on the
    continuous, systematic collection and evaluation of data by the staff
    of the centre, backed by local experience. All information and advice
    should be adapted to the specific circumstances of the suspected
    poisoning, i.e. whether exposure to the poison is acute or chronic,

    and the condition of the patient involved, taking into consideration
    the type of enquiry and the enquirer's technical understanding of the
    poisoning. While many routine enquiries may be answered by suitably
    trained nurses, pharmacists, or other specialists, supervision by a
    physician trained in medical toxicology is essential.

         The information service must be available 24 hours a day, seven
    days a week, throughout the year. Section 2 provides further details
    of the role of centres in providing information.

     Patient management

         While a poison information centre may have its own clinical
    toxicology unit or treatment facilities, poisoned patients may, be
    cared for at any of a variety of medical facilities: the centre will
    always provide information to a much larger area than that covered by
    a specific clinical toxicology unit. Many different categories of
    medical and paramedical personnel may be involved in the diagnosis and
    treatment of poisoning. Poisoning incidents frequently occur in the
    home, at work, or in rural areas and usually at some distance from
    medical facilities. The first person in contact with an individual who
    has been, or is suspected to be, poisoned may have little or no
    medical training.

         Appropriate information has therefore to be made available to
    ensure an adequate response in every situation. It is necessary to
    confirm whether poisoning has actually occurred, to ensure that the
    proper first-aid measures can be taken, and to assess what type of
    treatment, if any, is required. The centre exists to provide such
    information, giving advice on the different aspects of diagnosis and
    treatment that is appropriate to the enquirer's level of
    understanding.

         It is essential for poison information centres to be closely
    connected with facilities that provide care for poisoned patients and
    for the medical staff at each centre to be involved in the treatment
    of poisoning. This close association between poison information
    services and poison treatment services facilitates the necessary
    updating and expansion of information on the diagnosis and treatment
    of local poisoning cases, encourages detailed follow-up of patients,
    and stimulates essential research on human toxicology and patient
    management.

         It is highly desirable that each country or major population area
    should have at least one clinical toxicology service dedicated
    exclusively to the management of poisoning cases and located in a
    hospital that can provide a wide range of services, including
    intensive care. Clinical toxicology services fulfil a specialized
    medical function in the management and treatment of poisoning, helping
    to improve the identification of toxins and evaluation of their
    effects, to elucidate the mechanisms and kinetics of different kinds
    of toxic action, and to assess new diagnostic and therapeutic

    techniques. They also play an important role in evaluating the
    clinical efficacy of antidotes. Clinical facilities are described in
    more detail in Section 3.

         Rapid transport of severely poisoned persons to treatment
    facilities, or of doctors to patients who cannot be moved may be
    required. It is essential for poison information centres to be aware
    of the availability of ambulances - and possibly helicopters and
    aeroplanes - for transporting patients who need intensive care. Some
    ambulances and other means of transport may be specially equipped for
    transporting critically ill patients to the appropriate hospital
    facilities. In emergencies, coordination with the traffic police
    authorities may also be needed to help speed the transport of poisoned
    patients. Rapid delivery of antidotes and of samples for laboratory
    analysis must also be ensured, and could be coordinated by poison
    information centres.

     Laboratory services

         A laboratory service for toxicological analyses and biomedical
    investigations is essential for the diagnosis, assessment, and
    treatment of certain types of poisoning. It is especially important
    for clinical units treating poisoned patients: without analytical
    data, many toxicological problems cannot be accurately assessed. The
    data are required primarily to assist diagnosis and to back up
    decisions on the use of various therapeutic procedures to support
    prognosis. The laboratory service can also determine the kinetics of
    the toxin, particularly its absorption, distribution, metabolism, and
    elimination. Analytical facilities are also essential for research and
    for monitoring populations at risk from exposure to toxic chemicals. A
    laboratory service of the type outlined will permit the
    identification, characterization, and quantification of toxic
    substances in both biological and non-biological samples, i.e. in body
    fluids such as blood and urine, and in hair and nails, and in scene
    residues, as well as of both natural toxins and substances suspected
    of being poisonous.

         If adequate general laboratory facilities already exist, it is
    possible to give general guidelines for the development of a service,
    although the requirements for particular analyses will vary with local
    circumstances. Two levels of operation may be envisaged. The first
    would offer a relatively restricted but more widely distributed
    service based mainly on simple spot tests, immunoassays, and thin-
    layer chromatography. Field tested techniques for use at this first
    level are detailed in an IPCS manual.1 The second level would support
    the first but be more advanced, offering a full range of analyses
    using a wide variety of techniques. Laboratories operating at this

              

    1    Flanagan RJ et al.  Basic analytical toxicology. Geneva, World
         Health Organization, 1995.

    level would be capable of acting as reference laboratories, confirming
    the results of screening tests and engaging in quality control and
    method development. Links should be developed between laboratories in
    such areas as training, research, and quality assurance.

         The analyses to be developed should be selected according to
    proven clinical need and should:

    *    be backed up by a supply of appropriate pure reference compounds;

    *    be backed up by an adequate supply of consumables, such as
         reagents, and by satisfactory arrangements for maintenance; and

    *    use practical analytical techniques that can provide results
         within a reasonable time.

         It may be economical and advisable for the laboratory to
    undertake other related work, such as the provision of services for
    monitoring therapeutic drug use, dealing with occupational chemical
    exposure, and screening for drug abuse, since these services require
    similar skills and can be undertaken with the same or similar
    equipment.

         Adequate safety precautions must be taken to protect the
    laboratory staff from health risks, such as hepatitis and human
    immunodeficiency virus (HIV) infection, associated with handling
    biological samples.

         A laboratory should have adequate staff and equipment to carry
    out the analyses that are essential in cases of poisoning within the
    country or region. Thus, an analytical toxicology service will need at
    least one trained analyst and one assistant, but larger numbers of
    personnel will be needed as the range of techniques in use and the
    number of analyses being performed increases. Analyses that are
    directly concerned with the treatment of poisoned patients should be
    available 24 hours a day.

         Siting the laboratory in the same place as the poison information
    centre and treatment service has marked advantages as regards
    interdisciplinary collaboration. Many countries lack adequate
    toxicological laboratory facilities; in such cases it may be necessary
    to combine the services providing clinical analytical toxicology with
    those used in forensic medicine, occupational toxicology, monitoring
    of therapeutic drug use, food contaminants or substance abuse, and
    veterinary toxicology. Laboratory services are described in more
    detail in Section 4.

     Teaching and training

         The experience gained in a poison information centre can be an
    important source of human and animal toxicological data. The
    application and communication of this knowledge are vital for

    improving the prevention and management of poisoning. Centres thus
    have educational responsibilities that extend to the training of
    medical practitioners and other professional health workers likely to
    encounter cases of poisoning, and to communication with the local
    population and the mass media. Later sections of these guidelines
    include advice on the training needs of centres as well as on their
    teaching and training functions.

     Toxicovigilance

         Toxicovigilance is an essential function of poison information
    centres. It is the active process of identifying and evaluating the
    toxic risks existing in a community, and evaluating the measures taken
    to reduce or eliminate them. Analysis of enquiries received by centres
    permits the identification of those circumstances, populations, and
    possible toxic agents most likely to be involved, as well as the
    detection of hidden dangers. The role of a centre in toxicovigilance
    is to alert the appropriate health and other authorities so that the
    necessary preventive and regulatory measures may be taken. For
    example, the centre may record a large number of cases of poisoning by
    a specific product newly introduced to the local market; cases
    occurring in a particular population group (e.g. analgesic poisoning
    in children); or cases occurring in particular circumstances (e.g.
    carbon monoxide poisoning from faulty heating stoves) or at particular
    times of the year (e.g. mushroom poisoning in the autumn or snake
    bites in the summer). Only now is the unique role of poison
    information centres in toxicovigilance being widely recognized. This
    role enables them to make a major contribution to the prevention of
    poisoning through their collaboration with the health and other
    appropriate authorities. Section 5 gives further details on this
    aspect of their work.

     Prevention

         Drawing on its observations and experience, a poison information
    centre can contribute to the prevention of poisoning by:

    *    alerting responsible authorities to circumstances where the risk
         of poisoning is high so that appropriate preventive measures may
         be taken, including: drawing the attention of various users of
         toxic chemicals to the risks involved, introducing codes of
         practice or legislation to control the labelling of toxic
         products or special packaging to reduce the risk of exposure to
         toxic substances, and modification or withdrawal of products from
         the market;

    *    encouraging manufacturers to employ less toxic formulations and
         to improve the packaging and labelling of their products;

    *    informing the general public, as well as special groups at risk,
         about recognized or emerging risks to the community posed by the
         use, transport, storage, and disposal of specific chemicals and
         natural toxins, and giving guidance on how to avoid exposure to,
         or accidents with, these substances; means such as brochures,
         leaflets, posters, educational programmes, and campaigns in the
         media may be employed, but should not arouse unjustified false
         anxieties and should take due account of local psychosocial and
         cultural circumstances;

    *    giving special warnings to professional health care workers
         concerning specific toxic risks.

         The role of poison information centres in prevention of poisoning
    is described further in Section 5.

     Drug information and pharmacovigilance

         The medical profession must have access to advice on the
    therapeutic and adverse effects of pharmaceutical agents; some
    countries have drug information centres that provide this specialized
    information. Poison information centres are automatically concerned
    with problems of adverse drug reactions and side-effects, and may be
    contacted by physicians and the public for advice on both drug
    overdoses and the adverse effects of therapeutic doses. Enquiries may
    also relate to contraindications, for instance whether a drug should
    be prescribed in pregnancy or to a patient with a history of hepatic
    or renal disease. Poison information centres thus have the
    responsibility of contributing to pharmacovigilance in collaboration
    with other institutions established for that purpose. In a developing
    country, a combined drug and poison information service may be a
    logical use of resources.

     Substances of abuse

         All poison information centres receive enquiries about substances
    of abuse, including substances of natural origin such as cocaine,
    chemicals with a specific use such as solvents, pharmaceutical agents
    such as amfetamines, and illicit drugs designed for abuse. There are
    also increasing demands on analytical laboratories to identify
    substances of abuse. As many as 10% of patients seen at clinical
    toxicology facilities may be people poisoned by such substances; in
    some cases a mixture of substances may be involved, and in others the
    effects of one substance may be masked by those of another.

         It is part of the task of a poison information centre to provide
    information relating to substances of abuse and, when necessary, to be
    able to refer enquiries or patients to institutions or authorities
    dealing with other aspects of substance abuse. Centres must know how
    to recognize the signs and symptoms of substance abuse, how to treat
    an overdose in an emergency, and how to deal with withdrawal
    syndromes. They must know what facilities are available for patients

    needing rehabilitation and for those who wish to give up substance
    abuse. Advice must be available for the families and friends of
    substance abusers on how to identify signs of intoxication and the
    substances involved.

     Environmental toxicology

         There is growing anxiety among the general public about the
    possible deleterious effects on health of toxic chemicals found in
    food, in consumer goods such as cosmetics, and in the environment
    (air, water, and soil). People are uncertain about whether pollution
    is giving rise to chronic poisoning among those exposed to it, whether
    the effects are cumulative, and whether there are long-term sequelae.
    Furthermore, the harmful effects on non-human species, and whether
    they may be acute or chronic, are of growing concern to both the
    scientific community and the public. Poison information centres,
    particularly in countries where there is no other readily accessible
    source of information on toxic chemicals, are being asked to provide
    information on the effects of environmental contaminants, on the risks
    associated with toxic wastes, and on safe levels of chemicals in the
    environment and in food and other consumer goods.

         Poison information centres could play an important role in
    quantifying the relationship between exposure to toxic chemicals and
    observed clinical features of poisoning, including long-term sequelae.
    They should work closely with the medical profession, particularly
    general practitioners and occupational health physicians, hospital
    outpatient departments and pre- and postnatal clinics, who may be well
    placed to observe the possible clinical features and sequelae of
    exposure to chemicals. Medical practitioners must also be provided
    with data on the possible effects of exposure to environmental
    contaminants, and information on the types of biological and other
    samples that should be collected and analysed. Mechanisms for the
    systematic collection, validation, and follow-up of data should be
    established; it is also essential that the data are comparable, both
    nationally and internationally, so that they may be used for the
    benefit of all.

     Contingency planning for chemical incidents and disasters

         Poison information centres can contribute to the handling of
    major chemical incidents and disasters by providing appropriate
    information in the event of an emergency and by taking an active part
    in contingency planning and in education and training. They should
    also take part in epidemiological follow-up studies and other research
    initiatives, where appropriate, collaborating and acting in concert
    with other bodies involved in accident prevention and control. A
    national or regional poison information centre can serve to centralize
    and coordinate such activities. The role of centres in responding to
    chemical incidents and disasters is further described in Section 6.

     Cooperation and interrelationships

         To provide an effective information service and help in the
    prevention and management of the deleterious effects of toxic
    chemicals on human health and the environment, it is essential for
    centres to cooperate closely with a wide range of partners,
    particularly medical experts. Relationships should be fostered with
    other professional and social institutions that can contribute to the
    effective provision of information by poison information centres. For
    example, specialists in fields such as botany and zoology can assist
    in the rapid identification of toxic plants or animal species.
    Cooperation must also be established with industrial and commercial
    enterprises that manufacture, import, or handle chemicals, various
    research institutions, and consumer organizations and trade unions.

         Contacts are needed with ministries of health and the full range
    of health services and institutions, including different hospital
    departments, general practitioners, paediatricians, pharmacists,
    coroners and medico-legal experts, occupational physicians,
    epidemiologists, experts in information technology, scientific
    societies, and local and central health authorities. It is also
    important for poison information centres to cooperate with other
    government bodies, such as ministries of agriculture, the environment,
    labour, industry, trade, and transport, and with consumer protection
    agencies.

         Good relationships with newspapers, radio, and television are
    valuable, since the media have a key role in bringing information to
    the public. The publishing or broadcasting of educational messages on
    the prevention of poisoning can form part of a general process of
    health education; poison information centres should provide the media
    with appropriate information and material. In the event of a major
    chemical incident the media have an even more significant part to
    play: they must be kept fully and properly briefed by poison
    information centres and the emergency services so that all essential
    information can be given to the public without causing undue panic and
    alarm. In either role, the media have a responsibility to check the
    accuracy of the information they disseminate, so that any tendency to
    speculate or exaggerate is avoided. Regular contact between the media
    and poison information centres will lay the foundation for mutual
    confidence in the relationships.

         Of equal importance is contact between the poison information
    centres themselves, both nationally and internationally. This may be
    established directly or through national and regional scientific and
    professional associations, as well as through the World Federation.
    Other means of contact include national and international congresses
    and meetings. Important areas for international collaboration are:
    exchange of case data and product and substance data in comparable
    formats, evaluation of antidotes, quality control, training, response
    to major accidents, and research.

    Benefits

         The service provided by poison information centres offers
    considerable direct health benefits by reducing morbidity and
    mortality from poisoning and enabling the community to make
    significant savings in health care costs. Cases of exposure to
    chemicals that carry no toxic risk can be rapidly identified, and
    unnecessary medical care and transport are thus avoided. Mild
    poisoning cases that can be treated by first-aid measures alone or by
    non-hospital medical personnel are quickly recognized, and physicians
    can be provided with advice on the management of moderately severe
    cases that can be treated in general health facilities. Severe
    poisoning cases, which may need very special facilities and equipment
    for treatment, are sent directly to hospitals where these facilities
    are available, thus avoiding delays and wastage of resources at
    general treatment facilities. Specific antidotes, therapeutic agents,
    and medical equipment can be made more easily available through
    coordination of stocks, so reducing costs and saving lives. Centres
    can also help to prevent the unnecessary use of special antidotes and
    of sophisticated and expensive treatments.

         Access to information and advice at poison information centres
    stimulates the interest of local communities and makes them more
    committed to the prevention of poisoning. Centres help promote
    awareness of special requirements concerning the control and
    regulation of chemicals, including the labelling and packaging of
    products. Through active observation and evaluation of toxic risks and
    phenomena in the community, they are in a position to recognize
    sudden, unexpected rises in the incidence of poisoning and to alert
    authorities capable of taking the necessary action. Particular
    occupational settings may be involved, as well as the community in
    general. Indirectly, through improved prevention, the cost of
    poisoning to the whole community is reduced. Advice provided by
    centres in the event of major chemical disasters will help to minimize
    the effects on human health, maximize the effective use of limited
    medical resources, and prevent a recurrence of similar accidents. The
    education and training provided by poison information centres enable
    professional health workers and the general public to recognize and
    avoid the dangers of poisoning and to take effective action when
    poisoning incidents occur.

         The case data collected by centres provide an epidemiological
    basis for local toxicovigilance and contribute to the international
    fund of knowledge about human toxicology and management of poisoned
    patients. Through its contacts with centres in other countries and
    regions, a poison information centre may obtain information, notably
    on antidotes, that has already been evaluated, thus enabling it to
    respond to emergencies and other needs in a cost-effective manner. It
    may also identify toxic risks evaluated elsewhere, so that timely
    preventive action may be taken.

    Conclusions and recommendations

         In accordance with WHO's definition of health and its goal of
    "Health for All by the Year 2000", everyone should have access to
    relevant information on how to prevent and deal with poisoning. Poison
    information centres provide such information and are an essential part
    of a country's capacity for ensuring the safety of chemical
    substances. Moreover, the United Nations, through its Conference on
    Environment and Development, has called upon all countries to promote
    the establishment of poison information centres with related chemical
    and analytical facilities to ensure prompt and adequate diagnosis and
    treatment of poisoning, including networks of centres for chemical
    emergency response.

     Establishing a poison information centre

         A poison information service should be available in  every
     country, irrespective of its size or population. Ideally, there
    should be one national centre with, if necessary, a series of regional
    satellite centres. In a large country, or one with a large population
    or several different language groups, a number of regional centres may
    be needed, with close collaboration between them. Generally speaking,
    a poison information centre should serve a population of 5-10 million,
    but a proliferation of centres should be avoided. Depending on the
    availability of other services that provide information on toxic
    chemicals, a poison information centre may have to advise on a wide
    range of problems, and its associated facilities, e.g. laboratory
    services, may have to be multifunctional.

     Location

         When a poison information centre is established, especially in a
    developing country, existing medical facilities should be surveyed to
    determine where the centre can best be located and operate most
    effectively, bearing in mind that it is essential for a centre to have
    a number of health care professionals interested in human toxicology.
    Where feasible, the centre should be located at a leading hospital
    with emergency and intensive care services, as well as a medical
    library and a laboratory. If possible it should be linked directly
    with a hospital department where poisoned patients are treated: this
    may make it easier to recruit staff who already have experience and
    interest in the problems of poisoning. The laboratory facilities of
    such a hospital can usually be expanded to allow toxicological
    analysis to be undertaken and appropriate quality control to be
    exercised. Location at a university teaching hospital or in a
    toxicological or public health institution may also have advantages.
    Whatever the location chosen, it should be the aim of the facility to
    operate 24 hours a day all year round.

     Potential for development

         A poison information centre needs certain minimum facilities and
    resources to function optimally, but a modest establishment that can
    be expanded in the future is preferable to no service at all.
    Initially, it may be impossible for the centre's own staff to provide
    a round-the-clock service, and arrangements may have to be made for an
    existing service, such as a hospital emergency ward, to help out at
    certain times. The aim, however, should be to provide a 24-hours-a-
    day, 7-days-a-week information service throughout the year, with
    continuous access to a physician trained in toxicology, and to achieve
    this as quickly as possible. The treatment and laboratory facilities
    at a hospital may be further developed to deal with poisoning cases.
    The information section of the centre should work closely with the
    clinicians and laboratory specialists but should remain an independent
    unit since it will serve a much larger community than the hospital -
    possibly the whole country.

     Staff

         A poison information centre needs a multidisciplinary team of
    poison information specialists1 led by physicians with toxicological
    experience. The team may include physicians, nurses, analysts,
    pharmacists, veterinarians, and other scientists representing a wide
    variety of disciplines including biology, chemistry, medicine, and
    pharmacology. This team needs the support of documentalists and such
    experts in information science and informatics as the circumstances
    and functions of the centre may warrant. A poison information
    specialist helps to prepare and provide expert information and advice
    on preventing and dealing with poisoning. While the scientific or
    technical background of this specialist may vary, the work demands
    appropriate training, which in some countries carries a certificate or
    other qualification. A poison information specialist should work under
    the supervision of a medical toxicologist. Those members of the team
    who answer enquiries must have adequate knowledge of toxicology and
    related scientific disciplines and should also be in regular contact
    with analytical and treatment facilities. The medical members of the
    team should themselves treat poisoned patients.

              

    1    The term "poison information specialist" is used in these
         guidelines to include all personnel at poison information centres
         who are involved in providing the poison information service.

         Medical personnel from emergency, intensive care, and treatment
    units may work part-time in the information unit, thus adding to their
    experience. There is growing recognition of the need for centres to
    have access to expert psychiatric advice, which is especially helpful
    in dealing with attempted suicide, the psychopathic use of poisons,
    and substance abuse, and in the management of some poisoned patients.
    Psychiatry may also provide guidance on dealing with emergency
    situations without causing panic, e.g. in the event of a major
    chemical disaster.

         Good administration is of course essential. In some established
    centres, an administrative director is responsible for all
    administrative matters including funding, which allows the medical
    director to concentrate on the scientific supervision of the centre.
    Some form of administrative assistance is required at all centres, as
    well as adequate secretarial support.

         Numbers of staff in the various categories must be sufficient to
    provide an adequate, continuous service at all times. While the
    enquiry load may vary according to the time of day, it would be
    desirable always to have a minimum of two poison information
    specialists on duty to answer calls. To provide continuous medical
    advice throughout the year, at least three trained physicians are
    needed.

         Since highly experienced staff are essential, independent
    official recognition of the professional status of poison centre staff
    is desirable. Pay, working conditions, and incentives must be
    sufficiently attractive to keep staff turnover to a minimum. Further
    advice on staff requirements is provided in Section 2.

     Equipment and facilities

         If a poison information centre is to function effectively,
    certain basic equipment is essential, including suitable office
    furniture and facilities for the storage of confidential data.
    Specific areas should be set aside for answering telephone enquiries,
    consultation with patients, preparation of documents, staff meetings,
    and secretarial and administrative work. Staff on duty should have
    comfortable, suitably furnished rest areas. Additional desk space is
    needed at centres using computer equipment and on-line databases, and
    air-conditioning and humidity control may also be necessary. Centres
    themselves should be secure.

         Equipment and facilities for the information service are
    described in detail in Section 2; equipment for treatment units is
    described in Section 3 and equipment for laboratory services in
    Section 4.

         Poison information centres should have their own libraries and
    facilities for handling and reproducing documents. Reserved telephone
    lines are essential, and other means of national and international
    communication are highly desirable, such as telex, short-wave radio,
    and - in particular - fax. A fax machine is a recognized means of
    communicating information rapidly among centres and hospitals,
    particularly during emergencies, and should therefore be regarded as
    essential. Growing use is now being made of electronic mail for
    communication among poison control centres and other partners in
    poison control.

         A list of handbooks and journals that are more or less essential
    for the information unit of a centre is given in Section 9, although
    each centre should add to and adapt this list in developing its own
    documentation and ensure that it is updated periodically.

     Legal status and financing

         Poison information centres should be officially recognized by
    government authorities. They should have independent status,
    stability, and neutrality to enable them to carry out their functions
    effectively. A centre may have a governing body, including
    representatives of various government and other authorities, to
    provide policy guidance and assist in fund-raising. This body should
    not, however, interfere with the daily operation of a centre or
    compromise its independence. The legal status of a centre should
    enable it to maintain the confidentiality of the data it handles. Its
    main source of financial support, which is a government
    responsibility, should respect its independent and neutral status.
    Information should be provided free of charge to enquirers,
    particularly in emergencies, although charges may be levied in certain
    circumstances.

     Twinning arrangements

         Twinning arrangements between centres in developing and developed
    countries can be very valuable, permitting exchanges of documentation,
    including case data on unusual types of poisoning, exchanges of staff
    for teaching and training, and the provision of antidotes, especially
    in emergencies. As a means of technical cooperation between developing
    countries, twinning should also be encouraged between new and
    established centres in these countries. For effective twinning it is
    important that centres have facilities for rapid communication
    (telephone, telex, and fax), and that arrangements are made to enable
    the rapid importation of antidotes and other essential supplies in
    times of emergency, without bureaucratic hindrance.

     Action by national and local authorities

         The prevention and control of poisoning could be made more
    effective through a number of appropriate actions by national and
    local authorities, where these have not yet been taken. These measures
    include:

    *    official recognition by government authorities of the role of
         poison information centres in carrying out toxicovigilance and of
         their contribution to prevention through the provision of
         information services, together with adequate financial support
         for the centres providing these services;

    *    ensuring that the community has ready access to the services
         provided by poison information centres;

    *    establishment of channels of communication providing prompt
         access for poison information centres to organizations (including
         the media) that can be alerted, outside normal working hours if
         necessary, to toxic hazards and advised on appropriate ways of
         dealing with them;

    *    ensuring that centres have access to adequate information on the
         composition of commercial and other products on the local market,
         on the understanding that the confidentiality of the information
         will be respected;

    *    ensuring that the information on patients gathered by a poison
         information centre remains confidential at all times;

    *    establishment of clinical toxicology services wherever needed;

    *    establishment of services for toxicological analysis wherever
         needed;

    *    provision of educational facilities and courses in toxicology,
         and establishment of certificates or other appropriate
         qualifications for information specialists at poison information
         centres, as well as for nursing and paramedical staff working in
         treatment units and analysts in toxicological laboratories;

    *    official recognition of medical toxicology as a discipline in its
         own right, and encouragement of academic institutions to develop
         the discipline by providing appropriate teaching units or
         departments;

    *    promotion of national and international exchanges of staff and
         experts;

    *    facilitating the exchange of biological and other samples for
         analysis, and the import and export of equipment and chemical
         reagents;

    *    provision of antidotes and essential supplies for the treatment
         of poisoned patients, and arrangements for their rapid
         importation in the event of an emergency;

    *    provision of transport facilities for patients where existing
         facilities are inadequate;

    *    improvement of the communications infrastructure in countries
         where it is inadequate; and

    *    establishment of mechanisms and facilities for the systematic
         recording and long term follow-up of patients exposed to toxic
         chemicals.

     Action at the international level

         Cooperation at the international level between poison information
    centres, their national and regional associations, relevant
    professional bodies, governments, and international organizations in
    the following areas could do much to improve the prevention and
    control of poisoning:

    *    improving international communication and exchange of information
         and experience in the field of poison control, as well as
         exchange of personnel, particularly for purposes of education and
         training;

    *    harmonizing definitions of and criteria for clinical signs,
         symptoms, and sequelae of poisoning, including severity grading;

    *    establishing comparability between methods of collecting,
         storing, transporting, and analysing biological and other
         samples, and monitoring exposure to toxic chemicals and relating
         these to observed features of toxicity and sequelae;

    *    establishing internationally agreed mechanisms for the
         collection, validation, and analysis of data relating to exposure
         to toxic chemicals and observed features of poisoning, including
         long-term sequelae;

    *    undertaking collaborative research projects using agreed
         protocols, e.g. for evaluating new antidotes, elucidating the
         mechanisms of poisoning, and improving treatment regimens;

    *    establishing channels of communication between countries whereby
         antidotes, other therapeutic agents, and medical equipment can be
         made rapidly available on request in the event of a chemical
         incident or emergency, and samples for analysis can be imported
         and exported as necessary;

    *    establishing channels of communication between countries for
         rapid access to information about chemical incidents or
         emergencies that may be of value in deciding whether a toxic
         alert should be called.

    II.  Technical guidance

    2.  Information services

    Organization and operation

         The roles and functions of a poison information centre are
    briefly described in Section I of these guidelines. This section aims
    to provide more detailed guidance, principally on the establishment
    and operation of new centres, but also on the improvement of existing
    centres. It is additionally concerned with the location, facilities,
    and equipment of such centres and their staffing. Certain financial
    aspects are also considered.

         The effective functioning of a poison information centre depends
    on the availability of an adequate volume of evaluated data to furnish
    a basis for the advice given. Two categories of data are collected:
    those derived from various external sources, including other centres,
    as well as scientific journals, textbooks, reports, and data sheets;
    and those obtained in the course of the centre's information work and
    its follow-up of reported poisoning cases.

         It is essential for centres to have data on local commercial
    products, including pharmaceuticals, as well as on natural toxins
    produced by local poisonous plants and poisonous and venomous animals.
    Centres may be expected to identify tablets, capsules, plants, fungi,
    and insects and other animals. Each centre uses data culled from the
    various sources in compiling its own documentation for use by the
    staff of the centre. This documentation enables staff to provide
    information that is appropriate for the particular enquirer and
    adapted to local and national conditions. It is thus unique to the
    centre and essential for the information service that the centre
    provides.

         Centres should establish a mechanism for obtaining access to
    adequate data on commercial products from manufacturers and importers;
    such data should be regularly updated and its confidentiality
    protected. A system of rapid access to data on foreign products is
    also essential. Information on the composition, packaging, and form of
    each product must be available and sufficiently detailed to allow the
    product to be identified, its toxicity evaluated, and its long-term
    effects assessed.

         The documentation prepared by the centre itself on aspects of
    poisoning by chemicals and products, including evaluation of toxicity,
    symptoms, and treatment, is of particular importance. Past experience
    of poisoning cases involving specific chemicals and products plays an
    important role in this. Data on clinical cases, covering circumstances
    of poisoning, relevant medical histories, and the full evolution of
    each case, should be included in this documentation. Data on enquiries

    to the centre, as well as clinical data, should be systematically
    collected: they provide unique toxicological information that can be
    extremely valuable in diagnosis and treatment. To be of maximum value,
    case data must be fully recorded and followed up. Exchanges of such
    data between poison information centres, both nationally and
    internationally, could greatly enhance the effectiveness of the
    services they provide. A standard format for reporting case data and a
    mechanism for their collection and analysis are essential (see
    Annex 5).

         Centres should also collect (and regularly update) information on
    health and other relevant resources and facilities in the region or
    country. This information should cover services that provide diagnosis
    and treatment, including specialized treatment facilities, such as
    dialysis units, hyperbaric oxygen chambers, and clinical toxicology
    services; analytical facilities and the types of analyses they
    provide; facilities for emergency transport of patients; antidotes and
    their availability; and other medical and non-medical services with
    related areas of responsibility.

         A poison information centre should have its own library, which
    could be associated with a university or medical library. Certain
    books and publications should be accessible at all times at the centre
    itself; others could be kept at a local medical library but must be
    immediately accessible. Section 9 lists a selection of the books and
    journals that may provide library support for a poison information
    centre.

         Poison information centres would benefit greatly from more
    efficient collection, storage, retrieval, and analysis of the data
    they require. Computerization is one tool for this purpose, and most
    established centres have their own computers. The IPCS has developed a
    computerized information package, known as IPCS INTOX, to help centres
    in developing their own poison information systems. A summary
    description of the package is given in Annex 1.

     Planning a poison information centre

         Identification of the principal toxic risks in the local
    community helps in determining the activities on which the efforts of
    a poison information centre should initially be concentrated (e.g.
    poisoning by pesticides). Available facilities should be reviewed to
    allow the selection of locations that best meet the criteria outlined
    in these guidelines. However, it must be stressed that primary
    prerequisites for the success of a centre are enthusiasm and interest
    in human toxicology on the part of a group of health care
    professionals who recognize the problem of poisoning in their country
    and are committed to dealing with it.

         During the planning of a poison information centre, the following
    questions should be carefully considered:

    *    To whom will the service be offered initially, e.g. the medical
         profession only, the public, veterinarians? Will it be a
         24-hours-a-day service from the outset? How will it be expanded
         subsequently? How will its existence be advertised to the user
         population?

    *    What are the initial and subsequent staffing requirements? How
         will the centre contact and recruit the necessary expertise?

    *    Are the telephone and other communication systems adequate?

    *    How will the centre collect the full range of data needed to
         operate the information service?

    *    How will the reliability, accuracy, and usefulness of the data be
         evaluated?

    *    How will the data be compiled, recorded, and stored for rapid
         retrieval?

    *    How will the data be managed and updated? Who will have access to
         what type of data, and who will have the authority to modify data
         files?

         Before a centre becomes operational it is also necessary to:

    *    obtain certain essential literature (see section 9);

    *    provide basic training for the staff who will work in the centre

    *    print forms (in the local language) for collecting information
         on local commercial products and for recording enquiries to the
         centre, with provision for follow-up of calls and cases (see
         Section 8); and

    *    on the basis of local information, begin compiling files on the
         chemicals used in local commercial products, including
         pharmaceuticals, on local natural toxins, and on relevant medical
         and analytical services available in the country (see below and
         Section 8).

     Operating a poison information centre

         Once a poison information centre becomes operational, i.e. is
    able to offer an emergency response service, it should function around
    the clock. In the initial period, before the centre is fully staffed,
    the service may, at certain times, rely on the assistance of
    established emergency or intensive care services.

         For ethical and commercial reasons, much of the information
    handled by poison information centres, notably that relating to
    manufactured products and to patients, must be considered as
    confidential. Responsibility for the correct handling of such
    information rests essentially with the medical director and eventually
    with the other staff of the centre, particularly the information
    specialists who need the information on an emergency basis.

         Rapid identification of the poisons or types of poison involved
    in an emergency is one of a centre's main tasks. The constitution,
    origin, uses, and toxicity of the pharmaceuticals, chemicals, plants,
    or animals involved need to be identified immediately to permit the
    appropriate action to be taken.

     Information on commercial products

         Most existing poison information centres began by organizing card
    indexes of basic information on each of the toxic substances or
    natural toxins used or occurring in the area or country concerned.
    Although this type of information can now be stored in rapidly
    accessible computer files, the use of card indexes may still be
    recommended in a newly established centre for the initial
    identification of poisons. A computerized system can be added later,
    and the card index system should therefore contain as much information
    as is needed, recorded in such a way that it can later be transferred
    to a computerized system. The recommended format for collecting and
    storing information on commercial products for use in the IPCS INTOX
    Package is given in Annex 4.

         The card index or computer file should contain entries on  all 
    commercial products, such as pharmaceuticals, household products, and
    pesticides, commonly used in the country concerned. Although files
    from other (e.g. neighbouring) countries may be useful, every poison
    information centre will have to organize and maintain its own files.
    Information for these may be extracted from local pharmacopoeias and
    government registries, or obtained from pharmaceutical firms,
    manufacturers of household products, importers of chemicals, etc.

         A similar card index or computerized file system should be
    organized for natural toxins, poisonous plants, and poisonous and
    venomous animals.

     Information on enquiries

         Systematically collected data on enquiries form an essential part
    of the database at a centre. They must cover not merely the enquiries
    that pertain to clinical cases but every kind of enquiry received at
    the centre, including toxicological consultations registered by the
    clinical services.

         Standardized recording of enquiries, including those relating to
    clinical cases, will allow the centre to:

    *    maintain its own clinical and other data registry

    *    implement toxicovigilance activities

    *    support epidemiological and statistical studies

    *    perform self-audit and continuously evaluate the quality and
         efficiency of its services

    *    back up its clinical and legal responsibilities

    *    validate new techniques of patient management

    *    provide data for scientific reports

    *    exchange information with other poison information centres

    *    contribute to the fund of knowledge on human toxicology.

         Computer facilities for recording data on enquiries and cases
    offer enormous advantages, and the IPCS INTOX package provides a
    framework for this purpose. Further work is needed on,  inter alia, 
    the classification of agents involved in poisoning, the
    standardization of analytical data, and the harmonization of severity
    grading of case data; much is being done at present by IPCS in
    collaboration with poison centres and experienced toxicologists. The
    format used in the IPCS INTOX Package for recording communications is
    given in Annex 5.

         All poison information centres should prepare annual reports of
    their activities; a suggested layout for an annual report for a poison
    information centre is given in Annex 6. This layout provides a
    comprehensive format, which should be adapted to local circumstances.

    Location, facilities, and equipment

     Location

         General criteria for the location of a poison information centre
    are given in Section 1 of these guidelines, but the final choice of
    location will depend on local circumstances. Certain conditions,
    however, should be respected, namely that:

    *    the centre is regarded as neutral and independent, and security
         for all the information stored at the centre is ensured;

    *    there is rapid and ready communication with other organizations
         concerned with poisoning, particularly clinical and analytical
         services;

    *    access to the centre within the building in which it is located
         is easy, but restricted for unauthorized persons; and

    *    the centre is centrally situated within the geographical and
         demographic area it serves.

         The poison information centre should ideally be located within,
    or closely associated with, a hospital. Location within a hospital has
    the advantage of providing ready access to a network of medical
    disciplines that will support and enhance the work of the centre,
    enabling staff to deepen their knowledge of the clinical aspects of
    poisoning. If also located within a university, the centre will have
    easier access to, among other things, libraries, research facilities,
    and educational activities. Location within a public health institute
    or ministry permits more activities relating to prevention of
    poisoning and a closer relationship with decision-making authorities,
    but it is still essential for the medical staff of a centre to be
    involved in the care of poisoned patients, and for the information
    service to operate round the clock.

         To some extent, the location may also be determined by the number
    of enquiries received. For example, if more than 5000 emergencies are
    registered each year, a full-time staff will be required to provide a
    24-hours-a-day service, and the centre should then be an independent
    facility, though preferably situated in a hospital. However, some
    centres are run effectively from other locations. If fewer than 5000
    calls are received annually, outside support may be required to
    maintain a 24-hour service. In this case also, the centre may be
    located in a hospital but should be situated where regular hospital
    staff, notably from emergency and intensive care wards, are available
    to assist in maintaining the service.

     Facilities

         A poison information centre should be accommodated in suitable
    rooms or working areas, equipped with basic furniture (desks, tables,
    chairs) and such other facilities as are essential for its principal
    functions. Additionally it should have immediate access to the
    relevant literature and other sources of information.

         The rooms should be large enough to permit the efficient storage
    and retrieval of documents and the holding of necessary meetings. One
    room should be allocated to the "answering" service and should contain
    the telephones assigned to it, plus the basic files, protocols, and
    books needed by the information specialists and physicians on duty. An
    area should be set aside as a library where scientific work can be
    undertaken. Another area is required for working groups and staff or
    other meetings; this should be at least large enough to allow the
    assembly of all the staff of the centre, together with a number of
    advisers or visitors.

         Staff on duty should have a private area providing the basic
    facilities for personal hygiene and rest. Food and drink should also
    be available, as well as vehicle parking space outside the building.

         The medical director should have an office or suitable private
    area for specific work, interviews, and consultations; similar
    facilities should be available to other staff receiving patients. A
    separate area should also be assigned for administrative and
    secretarial work. As a centre develops new functions, additional space
    may be required and the location should therefore allow for this
    future expansion. Experience has demonstrated that, as more
    information is gathered and new activities or responsibilities
    assumed, bigger working areas rapidly become necessary.

     Furniture

         The minimum furniture needed for a new centre consists of desks
    and chairs, a large work table, lockable filing cabinets, and
    bookshelves. As the service develops and the working area grows,
    further appropriate office and library furniture should be provided.
    When the service starts functioning on a round-the-clock basis, the
    medical toxicologists and information specialists on duty must have a
    private area with suitable furniture and an adequate degree of
    comfort. It may also be necessary to provide a bed for rest between
    duty periods. Optimally, there could be specially designed work
    stations incorporating computer terminals where appropriate.

     Equipment

         It is particularly important that a poison information centre
    should have equipment for fast and reliable communication, and for the
    storage and retrieval of information.

         Communication with enquirers must be through reliable telephones
    reserved for the purpose and covering the whole area served by the
    centre. Two telephones are a minimum. In some countries the poison
    information centre is automatically connected with the emergency
    telephone services, and all calls concerned with toxicological
    emergencies are directed straight to the centre. The emergency number
    of the centre should be easy to remember and accessible from all
    telephones in the region served by the centre. In developing regions
    of the world, the radio telephone can be useful in reaching distant
    areas and remote populations. Other rapid methods of communication
    include the telex and, for documents, the fax, now considered a "must"
    at most centres. Electronic mailing systems (e-mail) are now being
    established at some centres. Fast and reliable communication will be
    valuable not only for the information service but also for the
    necessary contacts with other centres and access to international
    databanks. These systems must be well maintained and financially
    supported by the appropriate authorities or government ministry. The
    importance of worldwide communication networks for toxicology has been
    recognized: ideally, the centre should be equipped with the most
    practical advanced communication system appropriate to the country and
    to the centre's functions.

         The storage of case records, files, and documentation requires,
    at the least, sufficient bookshelves and filing cabinets to permit
    systematic collection and easy retrieval. A lockable section should be
    available for confidential data.

         With the development of the service, additional space, furniture,
    and storage facilities should be made available for the growing
    collection of books, published material, and files. If circumstances
    permit, automated systems may replace manual storage, retrieval, and
    processing systems, and computers must consequently be recognized as
    important items of equipment for a poison information centre. A
    microfiche system may also be a useful means of storing documentation.

         A poison centre often has to stock antidotes and other substances
    used in the treatment of poisonings and therefore requires a
    refrigerator; a lockable cabinet for storing pharmaceutical agents
    should be provided.

         From the outset, a centre should be adequately equipped with
    typewriters, a word processor with a good quality printer, and
    photocopying equipment or other suitable means of reproducing
    documents. The role of a centre in education and training may require
    it to have its own slide, overhead, and video projection equipment.

    Staff

         A poison information centre should be headed by a director
    experienced in toxicology and have sufficient personnel to perform the
    duties of the centre on a 24-hours-a-day, 7-days-a-week basis. The
    director is wholly responsible for the operation of the centre and
    should ideally be employed on a full-time basis. He or she should have
    personal leadership qualities, together with the ability to supervise
    other staff and maintain good relations with colleagues and other
    collaborators in the poison control programme. The director should
    also be able to promote research, raise funds, and undertake the
    further development of the information service. The medical functions
    of the centre must be the responsibility of a medical toxicologist. It
    may also be desirable to have an administrative director responsible
    for the financial, administrative, and other non-medical aspects of
    the centre. In addition, full-time - and possibly also part-time -
    medical toxicologists, poison information specialists, and
    administrative and support staff are required. Ultimately, centres
    also need advisers in various medical and non-medical fields, few of
    whom would normally be on the staff of the centre at the outset. The
    work of the centre may eventually call for the services of a number of
    full-time or part-time experts in particular fields such as psychiatry
    and veterinary medicine.

         In Part I of these guidelines it was pointed out that a fully
    operational centre, providing a round-the-clock service and adequate
    medical advice, requires a minimum of three full-time medical
    toxicologists (or the part-time equivalent) and a sufficient number of

    poison information specialists to ensure at least one person being on
    duty at any given time. The frequency of enquiries is likely to vary
    during the course of the day, and it may be necessary to have
    additional staff on duty at certain times. In this respect, patterns
    vary throughout the world, and it is up to the individual centre to
    ensure that its service is adequate for local needs. In practice, at
    least 6-8 dedicated, trained, full-time poison information specialists
    are required: this allows for coverage of staff absences for illness,
    holidays, and professional training.

     The medical toxicologist

         Medical toxicology is the discipline concerned with the harmful
    effects of chemicals, including natural substances, on humans,
    although its scope is broader than simply the clinical aspects of the
    subject. A medical toxicologist is a qualified physician with several
    years' experience in the treatment of cases of poisoning and a
    grounding in such areas as emergency medicine, paediatrics, public
    health, internal medicine, intensive care, and forensic medicine.
    Clinical experience in occupational diseases and in diseases caused by
    pollutants and other chemicals of environmental origin is particularly
    relevant. Experience in clinical toxicology is essential, and
    experience in toxicological research is also valuable.

         The medical toxicologist may provide expert advice to national
    decision-making bodies, and is often responsible for training at
    hospitals and medical faculties, and takes part in the
    multidisciplinary teaching of toxicology at university level. He or
    she must keep abreast of the latest developments in all areas of the
    discipline, including analytical and experimental toxicology.

         In the specific field of information, the medical toxicologist
    must be able to organize and compile a comprehensive dossier on
    poisons and their effects, based on the available material and
    personal experience, to train junior toxicologists and the centre's
    information specialists in collecting and interpreting data, and to
    give appropriate information in response to enquiries.

         It is particularly important for medical toxicologists to
    undertake the systematic collection and evaluation of clinical
    observations, as these constitute a major source of information for
    the poison information centre.

         The medical director of a poison information centre should be the
    most experienced of its medical toxicologists and the best equipped to
    take responsibility for medical decisions, treatment protocols, and
    the promotion of research.

     The poison information specialist

         For the purpose of these guidelines, the personnel directly in
    charge of the round-the-clock response to enquiries are termed poison
    information specialists. They must be appropriately trained and able
    to carry out the basic functions of a poison centre, with the support
    of a medical toxicologist, preferably a clinician treating poison
    victims. They should be able to give information to all types of
    enquirer on the basis of duly evaluated data available at the centre
    and in accordance with agreed patient management protocols. In cases
    where information is not available at the centre, they should know how
    it may be obtained. They must also know when to consult a medical
    toxicologist or adviser in a special area and should be able to record
    details of enquiries, cases, or consultations, using a standardized
    method. In many situations, poison information specialists will help
    evaluate the data used at the centre. With additional qualifications
    or experience in information management and computing, they can play a
    useful role in the organization and management of records kept at the
    centre.

         Poison information specialists may be drawn from many different
    disciplines, including various branches of medicine, pharmacy,
    nursing, chemistry, biology, and veterinary science. In each case,
    training for the specialized work of a poison information centre is
    essential and should be a continuing process so that they all remain
    abreast of new developments in toxicology. Information specialists
    should have the opportunity to participate in appropriate scientific
    meetings in their own countries and elsewhere. Training should lead to
    an officially recognized certificate or other qualification: there is
    a need for universally recognized qualifications in this field.

         All members of the information team should take part in the
    different activities of the centre, e.g. answering enquiries,
    preparing documentation and reports, operating computer programs, and
    making regular searches of the literature. Regular discussions among
    the team on interesting cases and various toxicological problems
    should be encouraged as a means of making each member aware of new
    developments and promoting a harmonized approach to poisoning and
    patient management. Periodic meetings among poison information centres
    within a country, or from the various countries of a region, should
    also be encouraged in order to discuss similar topics.

     Veterinary expertise

         The widespread use of veterinary drugs and the addition of
    chemicals to animal feedstuffs, unless carried out under veterinary
    supervision, can lead to contamination of human food. The effects of
    toxic substances on animals are often unique, and their diagnosis and
    appropriate management require the expertise of trained veterinarians.
    Furthermore, cases of exposure of animals to environmental chemicals

    may provide early warning of the potential exposure of humans. It
    would be highly desirable for poison information centres to have
    access to specialist veterinary knowledge in order to be able to
    recognize and respond to problems of animal poisoning as well as to
    advise on the risks of human exposure to drugs used for animals.

     Administrative and support staff

         A centre should have at least one secretary and, if possible,
    clerical staff to assist in the establishment, maintenance, and
    updating of the information system. Provision should be made for the
    maintenance and cleaning of equipment and facilities at the centre;
    this is often the responsibility of the administration of the building
    where the centre is located.

         The administrative staff of a poison information centre should be
    qualified to manage and supervise its financial resources, equipment
    needs, and operational requirements, as well as dealing with routine
    personnel matters. Ideally, there should be a senior administrator or
    administrative director in charge of all these activities, with
    suitable support staff and clearly defined responsibilities that do
    not overlap with those of the medical director.

         If a centre has its own library it will require a librarian or an
    information specialist/documentalist, or both.

     Advisers in special areas

         When a poison information centre is being established, a variety
    of specialist help and advice is essential. This may be medical or
    non-medical and may come from independent experts or from
    representatives of specialized organizations and local agencies. As
    the centre acquires more experience and the scope and volume of its
    work expand, it may become necessary to employ extra staff with some
    of the various kinds of expertise indicated below, on a part-time or
    full-time basis.

         Specialists collaborating with the centre should be able to
    provide, whenever necessary, specific information on subjects within
    their recognized fields of expertise. The toxicology-related areas
    where the information might be needed will depend on local
    circumstances. Advice from the medical profession may be required in
    such areas as public health, psychiatry, occupational medicine,
    paediatrics, nephrology, teratology, anaesthesiology, veterinary
    medicine, pharmacy, epidemiology, and environmental health.
    Consultation with representatives of medical associations and
    government or local medical organizations may be of value whenever
    specific problems arise. In non-medical areas, advice might be needed
    from specialists in agronomy, botany, zoology, herpetology,
    entomology, mycology, ecology, statistics, computer sciences,
    industry, engineering, law, and information technology and other areas
    of information management.

         A close relationship should be established, once those
    specialists able and willing to collaborate with the centre have been
    identified. An agreement should be made as to what is expected of the
    specialists, and how and when advice is to be provided to the centre.
    No special training is required for these collaborators, but they
    should be introduced to the work of the centre and the way it
    functions. Periodic joint scientific meetings and activities may be
    very helpful in cementing the relationships between the centre and its
    special advisers, who may also help in training the staff of the
    centre in their specific areas of competence.

     Development of human resources

         The evolution of the poison information centre will depend on
    local circumstances, needs, and resources. Ideally, there should be
    career opportunities for all the staff of a centre, each of whom
    should have the chance of additional training and advancement within
    his or her own area of competence. Contacts with other agencies
    dealing with various aspects of the prevention and treatment of
    poisoning should be stimulated both within the country and abroad.
    Where appropriate, professional staff should be encouraged to
    undertake relevant research and contribute to the literature.

    Financial aspects

         Since poison information centres can be considered as part of the
    public health service, government resources are the most appropriate
    source of financial support. However, each centre must remain neutral,
    independent, and preferably autonomous in order to carry out its
    functions effectively, and these conditions must be respected,
    whatever the principal source of financing.

         Governments should recognize the cost-effectiveness of the
    service provided by poison information centres to the community, and
    therefore make every effort to sustain their financial support. It may
    be difficult for a centre to produce direct evidence of its cost-
    effectiveness, but it should be stressed that:

    *    it discourages the excessive use of medical resources

    *    it reduces the adverse effects of poisoning on health, as well as
         mortality from poisoning

    *    it helps to reduce the risks of occupational poisoning.

         Other sources of funding may be acceptable, if they are available
    and if the autonomy of the centre is guaranteed. Social groups in the
    community, fund-raising campaigns, philanthropic groups, and
    associations of industry and commerce may all be sources of support.
    Funds for specific projects received from national and international
    organizations concerned with chemical safety may be very useful for
    investigating areas of joint interest. Private funding initiatives
    have proved to be effective in many countries and should not be
    discouraged, particularly in the case of new services.

         It is an important principle that information should be provided
    free of charge, at least in an emergency. However, some payment to the
    centre may be appropriate when special reports or expertise are
    requested by private institutions or individuals.

         Although the bulk of a centre's budget will be devoted to
    salaries, it should be remembered that adequate funding for the
    maintenance of up-to-date information is essential. Significant
    portions of the budget should also be devoted to the operation and
    maintenance of equipment, for example the telephones, telex, fax,
    photocopying, and computer systems, as well as to the development of
    appropriate educational material.

    Research

         Poison information centres are important sources of information
    on human toxicology; in particular, they may be able to signal the
    approach of new toxicological hazards. They also have enormous scope
    for broadening the scientific database on human toxicology through
    regional and international cooperation. Their research function should
    be recognized and encouraged by the relevant authorities.

    3.  Clinical services

    Introduction

         Cases of poisoning may be treated in many places, e.g. at the
    scene of the accident, during transport, in a hospital. The type of
    care that can be given will depend on whoever makes the initial
    contact with the patient and in what circumstances. Certain members of
    the community, such as firemen, policemen, and teachers, may
    frequently be the first to be faced with poisoning cases. In rural
    areas, nurses and primary health care workers, and even agronomists
    and veterinarians, may have to deal with poisoned persons. They all
    need at least some basic training in first aid as well as in
    decontamination and measures for their own protection. An IPCS
    handbook on this first level of response to poisoning is in
    preparation.1

              

    1     Management of poisoning. A handbook for health care workers.
         Geneva, World Health Organization (in preparation).

         General practitioners or family doctors are often the first
    medically qualified persons consulted. They must be able to give
    appropriate initial treatment and may need to contact their local
    poison information centre. Most patients with serious poisoning, if
    they survive, will sooner or later reach a hospital, ideally one with
    a wide range of medical facilities, including intensive care. In some
    places, specialized treatment services have been established offering
    the best possible conditions for the management of poisoning. These
    services also have the advantage of ready access to a wide range of
    related medical facilities.

         Most cases of poisoning, however, will be treated through a
    country's normal health service facilities, usually at a general
    hospital, far from a poison information centre and without access to a
    specialized clinical toxicology unit. According to patients' needs,
    treatment may be given by different services within the hospital,
    including the following:

    *     Emergency services. In practice, emergency services receive a
         relatively high number of poisoning cases, as they function on a
         round-the-clock basis and are provided with trained personnel and
         basic equipment for decontamination and life-support measures.

    *     Intensive care units. Intensive care units are usually well
         provided with highly specialized personnel and equipment for
         resuscitation, life-support measures, and care of critical
         poisoning cases.

    *     General medical units. Basic medical care of non-critical
         poisoning cases can be provided within general medical units in
         which staff have received some training in, or information on,
         clinical toxicology and which are in close contact with poison
         information centres.

    *     Specialized services. Specialized services offer the advantage of
         well trained medical staff and appropriate equipment for the
         management of poisoning cases in which specific organs or
         physiological functions are affected; they include nephrology,
         gastroenterology, neurology, cardiology, and haematology
         services.

    *     Paediatric departments. Poisoned children are frequently treated
         in paediatric departments.

         To be able to treat poisoned patients, general hospitals need
    equipment for:

    *    gastrointestinal, cutaneous, and ocular decontamination (e.g.
         equipment for gastric lavage)

    *    immediate, and often longer-term, life-support measures (e.g.
         endotracheal intubation, assisted and controlled ventilation,
         parenteral fluid therapy, pharmacological treatment, cardiac
         pacing, defibrillation)

    *    continuous cardiac and circulatory monitoring (through ECGs,
         blood pressure measurements, etc.) and monitoring of other vital
         functions

    *    X-ray examinations

    *    initial and repeated general biomedical laboratory analyses (e.g.
         acid-base balance, blood gases, electrolytes, blood glucose,
         liver and kidney function, and coagulation)

    *    initial and repeated specific toxicological analyses of body
         fluids such as blood, urine, and stomach contents (the choice of
         analyses will vary according to local patterns of poisoning)

    *    haemodialysis, peritoneal dialysis, haemoperfusion

    *    administration of appropriate antidotes (some of which may be
         specific to local needs and all of which should be stored in
         accordance with WHO recommendations1.

         In an emergency, it is essential that the relevant medical
    personnel at general hospitals and other health service facilities
    where poisoning cases are treated have rapid access to toxicological
    information and experience. Here, the poison information centre plays
    a key role through its telephone advice service. Ideally, centres
    should circulate information to general hospitals and other health
    service facilities on a regular basis. This information should be
    adapted to suit local needs and should include general advice on the
    diagnosis and management of poisoning cases commonly expected to be
    treated at the particular hospital or facility, as well as information
    on new developments in patient management and on new types of
    poisoning.

         The information flow should be a two-way process. General
    hospitals and health science facilities should be encouraged to
    maintain close contact with national and regional poison information
    centres and to furnish these centres with regular reports on cases of
    poisoning, particularly the more unusual ones. Such reporting helps to
    maintain an up-to-date national database on poisoning and is important
    for toxicovigilance.

              

    1     The International Pharmacopoeia, Third edition. Vol. 2, Quality
          specifications. Geneva, World Health Organization, 1981.

         The training of medical personnel in relevant aspects of
    toxicology for their work in managing poisoned patients is another
    important task for the poison information centre. For this purpose, it
    is essential that the centre itself is closely involved in the
    management of poisoning cases.

         Some countries have found it valuable to have one or more
    specialized clinical toxicology units where the most important cases
    of poisoning in a region are treated. In some cases an intensive care
    unit is associated with, or forms part of, a clinical toxicology unit.
    The latter would normally be associated with a national or regional
    poison information centre.

    Clinical toxicology units

     Roles and functions

         While general clinical wards and various specialized services
    that treat both poison victims and other types of patient are
    potential participants in poison control programmes, clinical
    toxicology units deal exclusively with the management of poisoning.
    These independent specialized units may have three principal functions
    besides patient management, namely toxicovigilance, education, and
    research. Locating a poison information service and analytical
    facilities in the same department or building as a clinical toxicology
    unit is an advantage and may be of benefit to patients. However, where
    there is no common location, highly reliable communications between
    the unit, the information service, and the laboratory are essential in
    order to establish a partnership between them in the diagnosis and
    management of poisoning.

         Ideally, a specialized clinical toxicology unit should be part of
    national or regional medical facilities for the management and
    treatment of poisoning. It provides for:

    *    optimal treatment of poisoned patients

    *    identification of the effects of chemicals and natural toxins on
         health

    *    evaluation of the cause-effect relationship in a case of
         poisoning

    *    assessment of new developments in clinical and analytical methods
         of diagnosis and in treatment

    *    development of specific therapeutic management

    *    appropriate follow-up and surveillance of cases for
         identification and assessment of sequelae, and

    *    study of the circumstances of the poisoning and predisposing
         factors (data can then be used for planning preventive action).

         Clinical toxicology units should record data on poisoning cases
    and toxicological consultations in a standardized format, preferably
    compatible with that used by poison information centres. Full case
    data, including follow-up, should be recorded.

     Location and facilities

         The minimum requirements for setting up a clinical unit for the
    treatment of acute poisoning are:1

    *    availability of methods, equipment, and areas for the
         resuscitation, decontamination, and initial management of
         poisoning cases

    *    good communication links with a poison information centre

    *    well established protocols for the treatment of common cases of
         acute poisoning

    *    availability of antidotes for immediate use, in quantities
         appropriate to the frequency of the main forms of poisoning (see
         Section 7)

    *    laboratory facilities for standard biological analyses and for
         toxicological screening (see Section 4)

    *    availability of emergency transport for patients

    *    an emergency plan for dealing with disasters and major chemical
         accidents.

              

    1    See also Table 1.

        Table 1

    Facilities for clinical toxicology

                                                                                                                            

                              Minimal facilities                          Optimal facilities
                                                                                                                            

    Location                  Emergency department; internal              Separate specialized unit within a
                              medicine ward; or intensive care            multifunctional poison centre, or
                              unit with ready access to a poison          closely associated with such a centre
                              information centre                          with two-way links
    Equipment for:

    Resuscitation             Devices for: suction; airway control;       Additionally: mechanical ventilator;
                              and IV administrations                      ECG; oscilloscope; defibrillator;
                                                                          pacemakers; haemodynamic
                                                                          monitoring equipment

    Decontamination           Separate area for decontamination,          Additionally: facilities for dialysis
                              with gastric lavage equipment,              and haemoperfusion
                              shower, and facilities for skin and
                              eye washing

    Diagnosis and                                                         EEG; fibroscopic devices, e.g.
    prognosis                                                             oesophagoscope, bronchoscope

    Antidotes and other       Selection made from the list in             Full selection, including agents still
    agents                    Annex 2, according to local needs           under development

    Laboratory:

    Biological                Blood typing; cross-matching; blood         Comprehensive analysis of blood,
                              gases; pH; electrolytes; standard           urine, and other body fluids;
                              uring analysis; cerebrospinal fluid         functional studies
                              analysis
                                                                                                                            

    Table 1  (contd.)

    Facilities for clinical toxicology

                                                                                                                            

                              Minimal facilities                          Optimal facilities
                                                                                                                            

    Toxicological             Screening test equipment for thin-          Equipment for more specific
                              layer chromatography                        quantitative and qualitative analyses,
                                                                          including those for toxicokinetic
                                                                          and various research studies (see
                                                                          Section 4)

    Other facilities          Normal facilities for transport of          Transport facilities (e.g. ambulances,
                              patients                                    aircraft) equipped with life-saving
                                                                          systems
                                                                          Access to a specialized centre, e.g.
                                                                          for psychiatric and social rehabilitation

    Personnel                 Emergency room physicians and               Clinical toxicologists; anaesthetist;
                              intensive care physicians, available        paediatrician; psychiatrist; social
                              24 hours a day                              worker
                                                                                                                            
             To function to the best advantage, a clinical toxicology service
    should be located as a separate department within an advanced
    multifunctional hospital and within or next to the poison information
    centre, preferably on the ground floor in order to facilitate rapid
    access. It should have:

    *    full facilities for prolonged life support, stabilization of
         vital signs, and correction of acid-base and fluid and
         electrolyte abnormalities (see Table 1)

    *    equipment for decontamination and the elimination of poisons,
         including dialysis and haemoperfusion

    *    the appropriate range of antidotes and medicaments used in the
         treatment of poisoning (see Section 7)

    *    protocols for the assessment and management of poisoning cases

    *    access to an analytical laboratory with appropriate equipment for
         qualitative and quantitative biological and toxicological assays
         on a round-the-clock basis (see Section 4)

    *    protocols for recommended analytical tests, including collection
         of specimens and interpretation of results (see Section 4)

    *    established systems for the collection and analysis of data on
         all clinical cases for epidemiological records, toxicovigilance
         assessment, and preventive action

    *    psychiatric rehabilitation and social assistance services.

         There should be sufficient space for all levels of patient care,
    and for the activities of the staff on duty, including administration,
    small conferences, education activities, and storage of clinical
    records.

         Consideration should also be given to such practical matters as a
    comfortable rest area, personal hygiene facilities, parking space, and
    the provision of food and beverages round the clock for duty staff.

    Staff

         Initially, the staff may consist of emergency-room physicians to
    provide resuscitation and first aid, plus paediatricians,
    anaesthetists, and intensive-care staff to look after severely
    poisoned patients. However, in developing countries or in newly
    established clinical units, there may be a shortage of sufficiently
    well qualified medical personnel, in which case medical officers or
    adequately trained paramedical personnel have an important part to
    play in the initial evaluation, transfer, and referral of poisoning
    cases. They should be capable, for example, of recognizing a case of,

    poisoning, of identifying the main toxic syndromes (e.g.
    anticholinergic, cholinergic, opioid), and especially of recognizing
    situations that require the immediate application of life-saving
    measures.

         Ideally, therefore, the staff should consist of:

    *    The medical director of the clinical toxicology service, who
         should be qualified to:

         -    organize the care of poisoned patients, both directly and
              through case consultation

         -    implement, review, and update protocols for the evaluation
              and treatment of poisoning cases

         -    supervise staff performance

         -    promote toxicological research

         -    identify those programmes or agencies that might provide
              funding for research or the further development of the
              service.

    *    Trained specialist(s) in clinical toxicology with practical
         experience and, ideally, with a professional qualification.

    *    Physician(s) with competence in the care of critically ill
         patients.

    *    Psychiatrist(s).

    *    Advisers from other medical disciplines, e.g. pharmacology, and
         from non-medical areas of interest.

    *    Social workers.

    *    Supporting paramedical staff (e.g. nurses, medical officers).

    *    Administrative staff and record-keepers.

     Training

         While the need for clinical toxicology services is becoming
    increasingly obvious, the growing demand for adequate, trained
    personnel is not being met. Physicians from countries with no
    appropriate facilities should be sent for training in toxicology to
    established centres where poisoned patients are treated. The objective
    in each case should be for the trainee to obtain experience of every
    aspect of the work of a centre, so as to be able to initiate or
    develop poison control activities in his or her own country. It is
    important for trainees to know the problems and special "risk
    profiles" associated with poisoning in their own countries before
    starting their courses.

         Physicians from developing countries where facilities for
    training in some aspects of clinical toxicology are available could be
    trained in their own countries if appropriate programmes were
    organized, with visiting experts invited to teach those subjects for
    which training facilities are lacking. Alternatively, trainees could
    be sent to centres abroad to supplement or enlarge experience gained
    at home.

         A training programme for clinical toxicologists should include
    education in the theoretical aspects of human toxicology, preparation
    for a dissertation, and teaching activities. Trainees should also gain
    experience of work in:

    *    a poison information centre (including training in preparing
         documents, collecting information, replying to enquiries,
         recording case data, and follow-up of cases);

    *    a clinical toxicology unit, emergency department, or intensive
         care unit where poisoned patients are treated; and

    *    a toxicological laboratory, where a practical understanding of
         sampling and analytical methods and of the medical interpretation
         of the results of analyses is provided.

         There should also be opportunities to attend or participate in
    seminars, courses, lectures, conferences, and meetings within and
    outside the centre.

         This training programme would be expected to take two years and
    should be undertaken preferably by physicians with some experience in
    related disciplines and some knowledge of chemistry, biochemistry,
    statistics, epidemiology, pharmacology, and information technology. It
    should cover all the main areas of toxicology in general, while
    stressing those in which local cases or risks of poisoning are
    frequent or severe. The basic contents of such a training programme
    are indicated in Table 2.

         Although the basic professional training of clinical staff is
    supplemented by experience obtained in the course of their work, the
    rapid development of toxicology makes continuing education and
    updating of knowledge a professional and ethical responsibility. Means
    of achieving this include the reading of scientific literature,
    participation in local, regional, and national seminars, meetings, and
    workshops, or attendance at training courses of several days' or
    weeks' duration. The continued updating of expertise can be stimulated
    by, for example, making participation in scientific meetings a
    condition of certification. In the USA, where professional
    certification is controlled by the American Board of Medical
    Toxicology, the American Board of Veterinary Toxicology, and the
    American Board of Toxicology, evidence of active interest in new
    developments is necessary in order to maintain expert status in
    toxicology. This system not only encourages continuing education but
    also contributes to career advancement by boosting professional
    status.

    Table 2

    Contents of training programme on clinical toxicology
                                                                            

    Part 1

     1.  General principles of medical toxicology

    *    Type and circumstances of poisoning:

         --   type of poisoning (acute, subacute, chronic)
         --   deliberate (suicidal, criminal, dependence, abortion)
         --   accidental (at work, at home, environmental)
         --   poisoning epidemics
         --   groups at risk (children, the elderly, pregnant women,
              workers)

    *    Basic principles of toxicology:

         --   experimental data and evaluation
         --   toxicity testing
         --   routes of exposure
         --   toxicokinetics (metabolism)
         --   toxicodynamics (mechansims of toxic action)
         --   carcinogenesis
         --   teratogenesis
         --   genetic toxicology

    *    Clinical diagnosis:

         --   clinical aspects
         --   toxic syndromes, differential diagnosis
         --   role of analytical services

    *    General principles of treatment of poisoning:

         --   first aid and decontamination
         --   prevention of absorption
         --   enhancement of elimination
         --   symptomatic and supportive treatment
         --   antidotal therapy

    *    Organizations and groups with a role in poison control
         programmes:

         --   governmental and regulatory authorities
         --   poison control centres
         --   universities
         --   experimental toxicologists
         --   other research groups concerned with assessment of human
              toxicity
                                                                        

    Table 2 (contd.)

                                                                        

     2.  Human toxicology of specific substances

    *    Systematic study of the most common and important causes of, and
         substances involved in, human poisoning:

         --   medical products
         --   industrial products
         --   pesticides/agricultural products
         --   household products
         --   poisonous plants and fungi
         --   poisonous and venomous animals
         --   environmental pollutants
         --   food poisoning

    *    For each substance, the following should be considered:

         main use; physicochemical properties; kinetics; metabolism; mode
         of toxic action; toxicity data; laboratory data (toxic levels,
         etc.); pathology; symptomatology; diagnosis; treatment;
         carcinogenicity; teratogenicity; legal aspects; prevention;
         particular aspects of acute and chronic toxicity; long-term
         effects

    Part II

    *    Human toxicology: an extended study, including coverage of less
         commonly encountered substances

    *    Prediction of toxicity

    *    Statistical and epidemiological programmes for evaluation of
         acute and chronic toxicity of specific substances

    *    Critical evaluation of literature sources

    *    Medico-legal aspects

    *    Research: an appreciation of the methods used in experimental
         toxicology, toxicovigilance, and epidemiology

    *    Different areas of toxicology: ecotoxicology, occupational
         toxicology, immunotoxicology, genotoxicity, forensic toxicology,
         etc.
                                                                        
    
         Nurses and paramedical personnel working in clinical units where
    cases of poisoning are treated should also be given special training
    in toxicology. This is especially important in countries where
    qualified physicians are scarce or are overwhelmed by crowded
    emergency rooms and outpatient consultations.

         Nurses, paramedical personnel, and clinical officers will need a
    concise and more practical training course than that given to
    physicians, perhaps based on the training programme on clinical
    toxicology outlined in Table 2. For example, the principles of quick
    clinical diagnosis, first-aid measures, decontamination techniques,
    and recognition of life-threatening symptoms are of primary
    importance. Other more theoretical aspects of toxicology may be
    omitted altogether or considered only briefly.

    Recommendations

         Clinical toxicology is still not acknowledged as a separate
    medical discipline in most countries. Its full acceptance as such by
    medical schools and the public health service is therefore desirable,
    and the importance of active collaboration among scientists and
    professionals in this area has now been internationally recognized.
    Every effort must be made to ensure that the relevant human resources
    are developed as quickly and effectively as possible. Measures to
    harmonize approaches to clinical toxicology throughout the world and
    to coordinate the work of international organizations and other
    international bodies in this area should be reinforced.

         At the national level, the following measures should be taken to
    support and promote clinical toxicology:

    *    Clinical toxicology services should be established wherever the
         need for them is identified.

    *    The discipline of clinical toxicology should be given official
         recognition, as should the trained professionals who may be
         already working in this field.

    *    Academic institutions should be encouraged to develop clinical
         toxicology as a discipline in its own right, e.g. by establishing
         a department within a teaching hospital with an intensive care
         unit, outpatient clinic, laboratory for toxicological analysis,
         etc. This would be a step towards the institution of an academic
         career structure for clinical toxicologists.

         Additional, internationally coordinated measures that would be
    useful in promoting clinical toxicology include the establishment of:

    *    mechanisms for ensuring unimpeded communication and exchange
         information and experience

    *    collaborative research projects on clinical toxicology

    *    international collaboration in establishing protocols for the
         treatment of poisoned patients and for the evaluation of
         antidotes

    *    international mechanisms for ensuring the adequate availability
         of antidotes and early warning of toxic hazards

    *    appropriate international educational programmes and exchanges.

    4.  Analytical toxicology and other laboratory services

    Introduction

         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

     Location

         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.

     Equipment

         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

    Conway apparatus

    Gutzeit apparatus

    direct-reading spectrophotometer

    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

    capillary electrophoresis

    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)

    fluorescence immunoassay

    enzyme-linked immunosorbent assay

    fluorimetry

    infrared spectrometry

     Reference materials

         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.

     Reference works

         A list of reference books on laboratory investigations is given
    in Section 9.

     Quality assurance

         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

     Safety measures

         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

    Staff

         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

    *    thin-layer chromatography

    *    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

    *    mass spectrometry

    *    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.

    Table 3

    Criteria for laboratories providing training in clinical
    analytical toxicology
                                                                        

    Staff

    *    The laboratory should be headed by a toxicologist with at least 5
         years' experience in clinical analytical toxicology. In addition,
         he or she should have suitable academic qualifications (e.g. a
         doctorate), have published original research, and have teaching
         experience.

    *    At least two experienced analytical toxicologists should also
         work in the laboratory to ensure comprehensive coverage.

    Organization

    *    The laboratory should offer a 24-hour emergency service and
         should be associated with a multifunctional poison centre
         providing an information service and patient care, so as to
         facilitate contact between the clinical and analytical services.

    *    A wide range of analyses should be available on a regular basis
         and it should be possible to undertake special investigations
         according to needs (e.g. occupational exposure to toxic metals
         and certain pesticides; monitoring of drug use).

    Techniques

    *    Instruction in the following techniques should be readily
         available:

         -  qualitative colour tests

         -  thin-layer chromatography

         -  scanning ultraviolet/visible spectrophotometry

         -  immunochemical assays (radioimmunoassay, enzyme-multiplied
            immunoassay, fluorescence polarization immunoassay)

         -  gas-liquid chromatography (flame ionization, electron
            capture, nitrogen/phosphorus detection)

         -  high-performance liquid chromatography (ultraviolet,
            fluorescence, electrochemical detection)

         -  flame and electrothermal atomic absorption spectrophotometry

         -  liquid- and solid-phase extraction techniques.
                                                                        

         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.

    5.  Toxicovigilance and prevention of poisoning

    Introduction

         Poison information centres have a fundamental role, in
    partnership with others, in toxicovigilance and prevention.
    Toxicovigilance consists of the active observation and evaluation of
    toxic risks and phenomena in the community - an activity that should
    result in measures aimed to reduce or remove risks. Thus its main goal
    is prevention.

         The role of poison information centres in toxicovigilance
    includes:

    *    identifying serious poisoning risks in the local community, and
         the substances, circumstances, and population groups involved;

    *    identifying changes in the incidence of poisoning, e.g. different
         substances of abuse, application of new pesticides, and seasonal
         variations in the incidence of poisoning, such as carbon monoxide
         poisoning from heating appliances;

    *    monitoring the toxicity of commercial products, such as
         household, industrial, and agricultural chemicals, as well as
         pharmaceuticals (by any route of administration), for acute,
         medium-term, and chronic effects, with particular regard to new
         products and formulations (e.g. overuse of analgesics,
         occupational exposure to solvents);

    *    monitoring the toxic effects of drug overdosage;

    *    identifying substances that cause significant morbidity and
         mortality, and specific effects on target organs (e.g. high
         incidence of renal insufficiency, fetal malformations);

    *    reporting to health authorities and other relevant bodies
         situations that demand preventive or corrective action, and,
         where appropriate, calling an alert;

    *    monitoring the effectiveness of preventive measures.

         Where new or altered patterns of poisoning are identified by
    centres, the data should be strictly verified and evaluated before
    they are reported to those in charge of community health and
    regulatory actions and/or to the manufacturers or users of the
    chemicals involved. Sometimes, this information should also be
    disseminated at the international level, notably to other poison
    information centres, professional bodies concerned with toxicology,
    and organizations such as WHO.

         Preventive measures for both individual and multiple cases of
    poisoning should be established on the basis of the available data on
    high-risk factors, particularly the circumstances, the substances
    involved, and the potential victims.

         A centre could initiate its preventive activities by reporting
    information on toxic hazards, identified by toxicovigilance, to those
    with the authority to take appropriate action, and by giving
    information and advice to those involved in health education. Further
    preventive activities could include educational campaigns, producing
    educational material, and planning, in partnership with others, the
    implementation and evaluation of preventive measures.

         The principal types of preventive action that should be initiated
    by poison information centres are:

    *    education, which is a most important part of any action and
         should be aimed at particular groups at risk, as well as the
         general public and professional health care workers;

    *    reports to, and collaboration with, various organizations and
         institutions on such matters as the development of safer
         products, safety measures relating to the packaging, design,
         labelling, transport, and handling of hazardous products, and
         withdrawing or limiting the availability of selected toxic
         substances.

         Collaboration among all partners in a poison control programme
    should be strengthened in order to enhance the efficacy of
    toxicovigilance and preventive actions. The essential partners are:

    *    poison information centres, facilities for toxicological
         analysis, and clinical toxicology services, which have a key role
         in identifying and studying toxicological risks and problems;

    *    medical and paramedical professionals, such as hospital
         physicians, general practitioners, occupational physicians,
         coroners and medico-legal experts, psychiatrists, and
         pharmacists, all of whom are in a position to collect data that
         supplement and complement those generated by poison information
         centres;

    *    government and local authorities, which have the power to ban or
         control the use of high-risk chemicals;

    *    industries, including manufacturers, transporters, and users of
         chemicals, who should provide the necessary data on the chemicals
         they handle and cooperate in the implementation of preventive
         measures;

    *    universities and research institutions, particularly those
         concerned with experimental clinical toxicology, which may
         provide valuable data on chemicals and contribute to their
         identification and control;

    *    specialists in mass communications and sociologists, who, in the
         event of a toxicological emergency, should advise on the
         appropriate message to the public and its dissemination in a
         manner that will avoid misunderstandings and alarmism.

    Toxicovigilance and prevention programmes

         Depending on the facilities that exist in a particular country,
    minimum programmes for toxicovigilance and prevention should be
    established initially, with the aim of expanding them later. Such
    programmes require good basic information about the local situation,
    including details of acute and chronic poisoning cases, problems of
    environmental contamination, drug abuse, and circumstances in which
    there is a high risk of exposure.

         Priority should be given to collecting this minimum basic data,
    which can be done cheaply and reasonably quickly by using:

    *    data from enquiries received by the poison information centre,
         which may provide valuable qualitative and quantitative
         information on cases of poisoning and be used for the evaluation
         of preventive activities;

    *    case data from accident and emergency wards, forensic
         departments, and local hospitals or occupational health clinics;

    *    technical information on toxic products and their effects, which
         can be obtained from the literature and other direct sources such
         as manufacturers and importers of chemicals.

         The data collected should permit the identification of local
    populations at risk and of harmful substances and dangerous
    circumstances that are likely to play a part in local poisoning cases.
    This should be helpful for planning appropriate preventive measures.

     Documentary resources and other facilities

         The minimum documentary resources and physical facilities
    required are the following:

    *    textbooks, reviews, manuals, periodicals, and other scientific
         publications, which would normally be available in poison
         information centres and which are mostly supplied by medical
         libraries, manufacturers, importers, and health authorities;

    *    selected references and periodicals concerning the local
         situation and needs;

    *    analysed data on enquiries received by the poison information
         centre;

    *    reports of surveys and monitoring carried out by other poison
         information centres;

    *    educational material produced by other poison information
         centres;

    *    suitable space for conferences and educational events;

    *    office supplies and equipment;

    *    simple means for reproducing leaflets and hand-outs.

         For maximum effectiveness, however, a programme for
    toxicovigilance and prevention of poisoning must have comprehensive
    data on all chemical substances and natural toxins found in the
    country concerned and appropriate evaluated case data on poisoning
    (with specific and detailed treatment procedures). Among the
    additional facilities required are the following:

    *    statistical and epidemiological data

    *    a specialized library

    *    communication facilities, with equipment for monitoring and
         recording calls

    *    access to computerized databases

    *    computers for storage and retrieval of data

    *    facilities for microfilming

    *    educational and instructional materials (brochures, posters,
         slides, videotapes) and facilities for producing them

    *    space for information resources, data storage, staff
         administration, and public and professional education.

     Staff

         A minimum programme for toxicovigilance and the prevention of
    poisoning requires staff with toxicological training and experience.
    For a full-scale programme, the poison information centre would need,
    in addition to those running the telephone enquiry service and dealing
    with patients, a sufficient number of people to follow up enquiries,
    write reports, and design and implement preventive activities.
    Training in epidemiology and the use of statistics is highly valuable
    in view of the type of studies required for toxicovigilance. Staff
    involved should be familiar with the legislation and regulations
    concerning the safety of chemical products and be aware of local
    toxicological problems related to the environment and to veterinary
    medicine. They should also be taught how to deal with the public, the
    mass media, and professionals from other fields in order to
    communicate the message of prevention.

         The director of the centre should also:

    *    have some knowledge of other disciplines relevant to
         toxicovigilance and the prevention of poisoning;

    *    be able to supervise the analysis of data and promote
         epidemiological research;

    *    ensure that a periodic (at least annual) assessment is made of
         the evolution of poisoning problems in the country or region
         concerned and that the relevant authorities are kept informed
         about preventive measures;

    *    utilize available data to call an alert on toxicological problems
         when necessary, enlist the cooperation of relevant partners, and
         plan effective action;

    *    ensure that adequate educational material on the prevention of
         poisoning is prepared for both health care professionals and the
         public, including material for use in paediatric outpatient
         clinics, by teachers and children at school, and by doctors in
         rural hospitals;

    *    identify sources of funding for preventive activities (e.g. for
         the publication of colourful, easily understood brochures or
         posters, and for financing campaigns and educational courses).

         Besides the staff of poison information centres, other
    specialists who should be involved in toxicovigilance and prevention
    include:

    *     health educators to design programmes, contact the mass media,
         and supervise effective continuous distribution of educational
         material;

    *     primary health workers to promote prevention at community level;

    *     psychiatrists to evaluate the incidence and severity of certain
         types of poisoning (e.g. in suicide attempts) in order to study
         the possibilities of preventing or minimizing them;

    *     social workers to evaluate the social conditions that may be
         determinants in some types of poisoning case, and to advise on
         ways of getting clear messages to target populations;

    *     experimental toxicologists to provide experimental data on
         chemicals and their properties.

         Toxicovigilance and poisoning prevention programmes also need the
    support of adequate administrative and secretarial personnel.

    Recommendations

         The efficacy of toxicovigilance and of measures for the
    prevention of poisoning could be considerably enhanced by the
    implementation of a number of measures at both national and
    international level.

     Recommended action at national level

         Efficient communication and coordination between all partners in
    a poison control programme are primary ingredients for the development
    of effective national plans for toxicovigilance and prevention. As
    part of a long-term strategy, adequate knowledge of local poisoning
    cases should be assembled through data collection and epidemiological
    investigations. Computerization should facilitate the storage,
    handling, and rapid analysis of the data. It is therefore essential to
    promote:

    *    a system for the centralized registration of poisoned patients
         treated in hospitals (with diagnostic codes), together with
         mechanisms for the follow-up of patients in order to identify and
         evaluate possible medium- and long-term sequelae;

    *    regulations for the notification of poisoning incidents (e.g.
         obligatory anonymous reporting of all cases);

    *    the collection of sound morbidity and mortality statistics with
         precise certification of death by cause (e.g. from public health
         systems and forensic departments);

    *    the pooling of information collected from related areas of mutual
         interest, e.g. experimental toxicology, analytical toxicology,
         occupational medicine;

    *    contacts with industry for the exchange of information on
         chemical products manufactured and used, and the circumstances
         and effects of poisoning by these chemicals.

         Official support for, and recognition of, the role of poison
    information centres in toxicovigilance and prevention of poisoning
    would add weight to the preventive actions instituted by a centre and
    make it easier for a centre to obtain complete data on the composition
    of toxic and potentially toxic products. In some cases, legislation
    providing for the confidential disclosure of the chemical composition
    of products to poison information centres would be of great value.
    Legislative authorities should seek the recommendations and advice of
    poison information centres concerning control measures and legislation
    to prevent poisoning.

         Preventive and educational action may be aimed at the whole
    community (for example, campaigns for the prevention of poisoning,
    posters demonstrating the dangers of poisoning by household products
    and how to avoid them, booklets showing how to recognize poisonous
    fungi and plants) or specific groups at risk (e.g. on such subjects as
    pharmaceuticals and pregnancy, the safe use of pesticides by rural
    workers, and the risks of self-medication in the elderly). Media and
    communications experts have a vital role in preventive action, since
    the messages employed should be concise, clearly understandable, and
    attractive.

         The methods employed for preventing, and generating awareness
    about, poisoning should be adapted to suit national situations and
    circumstances.

     Recommended action at international level

         In any country, the problems arising from chemical poisoning are
    closely linked to geographical, climatic, demographic, economic, and
    sociocultural conditions. However, tens of thousands of chemicals are
    in commercial use, and the same chemicals, drugs, or natural toxins
    may be found in quite different domestic or working environments in
    different countries, and as contaminants of air, soil, and water.
    Products containing these chemicals are widely traded throughout the
    world, and the movement of environmental contaminants does not respect
    national frontiers.

         Many chemicals "travel" when carried by people (e.g. as medicines
    obtained on holidays, drugs of abuse, insect repellents), and, if
    unavailable or not in commercial use in a particular country, may be
    unknown to the local poison information centre. Cooperation between
    poison information centres in different countries, and with
    international organizations, may be of value to both national and
    international programmes for toxicovigilance and the prevention of
    poisoning.

         Poison information centres may arrange to share data on toxic
    risks, which would permit early warning of potential problems. Pooling
    of information and expertise in respect of case data on rare, limited,
    or new phenomena, and of substance data on new hazardous products may
    enable preventive measures to be taken at an early stage. For the
    useful exchange of information, it is also essential for collaborators
    to standardize terminology, agreeing on matters of format and content
    as well as on the procedures involved in the exchange.

         The following are recognized as areas in which international
    collaboration, through organizations such as IPCS and the World
    Federation, is needed:

    *    the exchange between poison information centres and the relevant
         authorities of bibliographies and documentation on
         internationally traded formulated products, or on products found
         outside their country of origin;

    *    the establishment of centralized or regional systems for the
         collection and exchange of data on poisoning cases, including
         their follow-up, and for the assessment, validation, analysis,
         and storage of these data;

    *    the establishment of a mechanism for the rapid notification of
         toxic alerts called in any country and the exchange of experience
         in dealing with such alerts;

    *    the exchange of experience of education and training programmes
         in the field of toxicovigilance and prevention of poisoning;

    *    the production and dissemination of educational materials on the
         prevention of poisoning, including material targeted at specific
         high-risk groups, to be adapted by each centre for local use.

    6.  Response to major emergencies involving chemicals1

    Introduction

         The accidental discharge of chemicals during industrial
    operations, as well as during transport by land, sea, and inland
    waterways, is a growing problem throughout the world. Chemical
    accidents do not always involve cases of poisoning. However, people
    exposed to a major release of chemicals may, in some instances, be
    seriously contaminated and require emergency treatment. Chemical
    discharge may pollute the environment and give rise to poisoning in
    populations some distance from the accident itself. Major incidents
    involving many cases of poisoning may also be caused by the accidental
    or deliberate contamination of food, water, medicines, or consumer
    goods by synthetic chemicals or natural toxins. In some cases, these
    incidents may not be immediately associated with chemical
    contamination but are identified through the toxicovigilance
    activities of poison information centres.

         Many countries have emergency plans covering the fullest possible
    range of natural and technological disasters. The fire and rescue
    services, together with the police, are usually the first to be
    involved in the response to a major chemical accident. By providing
    appropriate information, poison information centres have an important
    contribution to make to the handling of major incidents involving
    chemicals, and clinical toxicology services may also be involved in
    the treatment of victims. Centres should take an active part in
    contingency planning, education, and training for chemical accidents.
    They should also initiate research and follow-up studies when
    appropriate. A poison information centre often has the advantage of
    being the only centre of its kind in a country or a region providing a
    24-hours-a-day service and may therefore play a central role in
    chemical emergencies.

         The staff of the poison information centre should receive
    specific instructions on how to act in the case of a chemical
    disaster. They should be prepared to provide relevant information on
    the chemicals involved to those responsible for handling the emergency
    or alert procedures, as well as to decision-makers and the mass media.
    They should know how to recognize the magnitude or level of the
    accident (whether it is operational, local, regional, or
    international) and should alert the centre's director, other staff,
    and health and other authorities, according to established procedures.

              

    1    See also:  Health aspects of chemical accidents. Guidance on
          chemical accident awareness, preparedness and response for
          health professionals and emergency responders. Paris,
         Organisation for Economic Co-operation and Development, 1994
         (OCDE/GD (94)1).

         Staff must also be trained to deal with the general public,
    either directly or, preferably, through the mass media. They should be
    instructed on how to avoid creating panic and how to communicate
    calmly with others involved in responding to the disaster and also
    with the community, providing reassurance and a clear message.
    Retrospective studies of chemical incidents that have occurred in the
    area or examination of hypothetical disaster situations may form a
    good basis for the training of staff and for contingency planning with
    other concerned bodies.

    Information

         The poison information centre may act as the focal point for
    action in case of chemical accidents and should be prepared to provide
    adequate information rapidly in the acute phases. When building up
    toxicological data banks, centres should therefore include information
    on all chemicals likely to be involved in accidents in the region, not
    forgetting the less frequently used industrial chemicals and reactive
    intermediates. It is important to have information on:

    *    toxic chemicals and their effects

    *    high-risk areas and processes and/or activities involving risk

    *    which chemical(s) might be released, in what forms and quantities

    *    possible protective and remedial measures.

         The exact location, capabilities, and capacities of treatment and
    toxicological analytical services and of facilities for emergency
    transport must be known. Centres must also be aware of the
    responsibilities and roles of all bodies involved in contingency
    planning, and establish close communication links with rescue services
    and the police. The information may have to be gathered by the poison
    information centre itself if emergency contingency planning has not
    yet been organized in the country or may be requested from the
    authorities when such plans exist and are operative. There is often a
    legal requirement for authorities to be notified of highly hazardous
    activities involving the use of chemicals and of the location of
    stored chemicals; such information could valuably be made available to
    poison information centres as well. In some countries, poison
    information centres, identified as focal points for chemical
    disasters, are informed when dangerous cargoes are being transported
    or high-risk manoeuvres involving toxic chemicals are to be undertaken
    in the areas they serve.

         Experience with industrial accidents involving chemicals is often
    available at the plants concerned but not always elsewhere. It is of
    vital importance for poison information centres to have access to this
    experience, and for activities that encourage exchanges of information
    and experience between different occupational health services and
    poison information centres to be established.

         In the event of a major chemical accident, poison information
    centres may expect a flood of telephone calls. They should be prepared
    to deal with this type of situation, avoiding panic and providing
    advice rapidly to all concerned parties.

    Treatment

         Staff at clinical toxicology services may be involved in the
    treatment of victims of chemical incidents or disasters. They need to
    provide guidance to the medical rescue teams on the triage of poisoned
    patients, on their initial treatment procedures before they reach
    hospital, and on decontamination at the site of the incident. Any
    hospital that treats patients may need to provide decontamination
    facilities outside its emergency admission area in order to prevent
    contamination of the hospital by toxic chemicals.

    Contingency planning

         Poison information centres should cooperate with other agencies
    in contingency planning for chemical accidents. Some countries,
    especially the more highly industrialized, have coordinated
    contingency plans in which a number of specific activities are
    demanded of poison information centres. In the many countries that
    lack an established emergency response system the responsibility of
    poison information centres may be even greater: they may suddenly be
    obliged to assume responsibility for the handling of an emergency. If
    contingency plans have already been established, a poison information
    centre may become an emergency control centre in the event of a
    chemical disaster. New centres should therefore have the foresight to
    consider what chemical disasters could occur within their region and
    be prepared to provide fast, accurate advice and orientation.

         Emergency medical plans must be extended to cover chemical
    accidents, and close collaboration should be established between the
    planners and the poison information centre. The centre should provide
    the planners with guidelines on: measures for risk assessment;
    decontamination  in situ and within hospitals; first-aid measures;
    general and specific therapy; and measures to ensure the availability
    of antidotes. At the medical level, poison information centres should
    also be aware of the facilities available for dealing with large
    numbers of victims in terms of number of beds, pharmaceutical
    supplies, and availability of specific antidotes.

    Education and training

         Poison information centres should play an active role in the
    education and training of all members of rescue teams for their role
    in the event of chemical accidents. This education and training should
    be geared to the educational level of each group being trained (e.g.
    firemen, field commanders, supervisors, telephone and radio operators,
    doctors). Training should cover decontamination techniques and
    protective measures for medical staff treating contaminated patients,
    as well as triage techniques.

    Follow-up studies

         Close follow-up studies of both major and minor chemical
    accidents may yield much valuable information on their handling. In
    the event of a major incident involving chemicals, poison information
    centres should be ready to mobilize competent personnel. Appropriate
    data on the accident should be collected to enable exposure to be
    related to clinical features of poisoning. This requires preparation
    in advance. A staff member from the centre may need to go to the scene
    of the incident, or to the place where the patients are being treated,
    in order to take an active part in evaluation and risk assessment,
    coordinate advice to health care personnel on site, and organize
    analytical tests. This would also provide an opportunity to collect
    human toxicological data, valuable for advice on future occasions and
    for further planning in respect of chemical accidents.

    Financial support

         If poison information centres are to respond adequately to major
    incidents involving chemicals, financial support may be required from
    the government. Personnel from the centres should have the opportunity
    to participate in educational activities and visit the sites of
    accidents outside their own areas in order to gather relevant
    information and experience. This is important not only during the
    acute phase of an incident but also at later stages when conclusions
    can be drawn from the incident and recommendations made.

    Collaboration between centres

         The need for close national and international collaboration
    between poison information centres is recognized. The hazards arising
    from the manufacture, storage, and transport of chemicals are
    sometimes shared by neighbouring countries, in which case concerted
    action should be taken to prevent or reduce the likelihood and impact
    of chemical accidents. Poison information centres should therefore
    undertake periodic exchanges of information on high-risk circumstances
    for chemical accidents, and be consulted concerning relevant
    international or intergovernmental agreements.

         To assist in the identification of chemicals to which an
    individual may have been exposed, it is essential for a poison
    information centre to build up a database of relevant information on
    commercial and other local products found in the area it serves. A
    simple card file can be used for this purpose. Alternatively, if a
    centre is contemplating computerization of its database, the IPCS
    INTOX format for standardizing product information is recommended.

    7.  Antidotes and their availability

    Introduction

         Antidotes may play an important role in the treatment of
    poisoning. While good supportive care and elimination techniques may,
    in many cases, restore a poisoned patient to good health and stabilize
    his or her body functions, the appropriate use of antidotes and other
    agents may greatly enhance elimination and counteract the toxic
    actions of the poison. In certain circumstances they may significantly
    reduce the medical resources otherwise needed to treat a patient,
    shorten the period of therapy, and, in some cases, save a patient from
    death. Thus, antidotes may sometimes reduce the overall burden on the
    health service of managing cases of poisoning. In areas remote from
    good hospital services, and particularly in developing countries that
    lack adequate facilities for supportive care, antidotes may be even
    more essential in the treatment of poisoning.

         Physicians frequently express concern about the difficulty of
    obtaining certain antidotes in an emergency. The IPCS and the EC, in
    consultation with the World Federation, are undertaking a project
    designed to evaluate the efficacy of antidotes and to encourage their
    availability. In a preparatory phase of this project an antidote was
    defined as a therapeutic substance used to counteract the toxic
    action(s) of a specified xenobiotic. A preliminary list of antidotes,
    and of other agents used to prevent the absorption of poisons, to
    enhance their elimination, and to counteract their effects on body
    functions, was established; preliminary classification of these agents
    was based on urgency of treatment and efficacy in practice. Agents
    that correspond to the WHO concept of an essential drug were
    designated as such, and some have already been incorporated into the
    WHO List of Essential Drugs1.  Antidotes and substances for
    veterinary use were also listed. Methods and principles for the
    evaluation of antidotes and other agents used in the treatment of
    poisoning were drafted and are being used as a framework for preparing
    monographs on specific antidotes, which are being published in a
    special series.2

              

    1     The use of essential drugs. Model List of Essential Drugs (ninth
          list). Seventh report of the WHO Expert Committee. Geneva,
         World Health Organization, 1997 (WHO Technical Report Series,
         No. 867).

    2     IPCS/EC Evaluation of antidotes. Cambridge, Cambridge University
         Press.

         Early in the course of this preparatory work, it became apparent
    that the availability of antidotes differed from one country to
    another. A survey of selected poison information centres was
    undertaken in order to identify the specific difficulties experienced
    in obtaining antidotes. Results showed that poison centres in
    industrialized countries generally have few problems in obtaining most
    antidotes, although administrative difficulties and the lack of
    suitable preparations and of importers and manufacturers hinder access
    to certain antidotes. Centres in developing countries, however,
    reported many problems in obtaining even the common antidotes that are
    readily available elsewhere. Problems generally arose in the following
    three interrelated areas:

    *    scientific, technical, and economic considerations

    *    regulatory and administrative requirements

    *    considerations of time and geography

    Scientific aspects

         The efficacy of a substance used as an antidote must be
    scientifically validated, initially through animal experiments,
    preferably using species that exhibit a pattern of toxicity similar to
    that in humans. The clinical efficacy of an antidote in humans may be
    mare difficult to ascertain and document than that of other
    pharmaceutical agents, since there is little opportunity for clinical
    trials. The potential toxicity of an antidote is important in deciding
    its use, and the possibility of adverse reactions should always be
    considered. An antidote known to be non-toxic may be used in cases of
    poisoning even if its efficacy is uncertain; a toxic antidote,
    however, should be used only if its therapeutic effect is known and
    the diagnosis certain. Adverse effects and chronic toxicity may be
    less important than in the case of an ordinary pharmaceutical agent,
    since an antidote is likely to be used only once. It is important that
    increased toxicity does not result from mobilization of the toxic
    substance from tissue stores or from changes in tissue distribution,
    as in the case of the transient rise in blood levels of lead, and
    precipitation of acute encephalopathy, after inappropriate use of
    antidotes in children.

         The importance of full validation of the efficacy of substances
    to be used as antidotes must be emphasized.

         Improved knowledge of the mechanisms of toxicity of different
    poisons and of the kinetics of toxic substances may also facilitate
    the development and use of specific antidotes. Once an effective
    antidote has been identified, there remains the problem of its
    manufacture as a pharmaceutical substance suitable for use in humans.
    The formulation of a preparation for oral use will, in many cases,
    make it easier to administer the antidote, for example in ambulatory
    patients.

         The scientific study of antidotes thus has implications for drug
    regulation authorities and governments, for the commercial sector, and
    for poison information centres.

    *     Drug regulation authorities and governments. Comprehensive
         scientific studies will enable regulatory authorities to
         facilitate the registration of useful, effective antidotes.
         Governments are responsible for ensuring the availability of
         antidotes and should recognize the importance of this group of
         therapeutic agents and the need to support their scientific
         study.

    *     The commercial sector. The manufacture and supply of antidotes
         are usually the responsibility of the commercial sector, which
         may also need to support appropriate studies. Industries involved
         in the manufacture and supply of potentially toxic agents must
         consider their possible effects on users and on others who may be
         exposed; they should ensure that appropriate antidotes are
         available on the local market.

    *     Poison information centres. Poison information centres, and
         especially the treatment units, have an essential role in
         monitoring the use of antidotes. Ideally, data on antidote use
         should be collected in an internationally standardized manner to
         allow results to be compared and recommendations made.
         International exchange of information should be encouraged to
         allow critical assessment of the efficacy and side-effects of
         antidotal agents. Health care professionals should be aware that
         the data required at the time certain antidotes were registered
         may have been quite limited and may therefore need updating in
         the light of more recent findings.

         Even an effective and readily available antidote will be useless
    if the attending physician is unable to establish a correct diagnosis
    or is uninformed about the availability or indications for use of the
    antidote. Information programmes should be arranged by toxicological
    and poison information centres in order to familiarize clinical
    personnel with the proper use of antidotes, particularly for
    individuals in high-risk groups, such as those exposed to hazardous
    chemicals in the course of their work.

    Technical aspects

     Registration

         Registration of a pharmaceutical for use as an antidote would
    seem a satisfactory means of dealing with problems of distribution and
    availability. However, some pharmaceutical manufacturers are
    disinclined to register antidotes because of the small volume of
    production required to meet market demand. It is therefore suggested
    that a means should be found of encouraging industries that market

    potentially toxic drugs or chemicals to provide information on
    antidotal treatment, and to facilitate the provision and registration
    of appropriate antidotes. Pharmaceutical companies that produce
    antidotes should be encouraged to register them in their countries of
    use. It would also be helpful to ease the administrative procedures
    required to permit the use of an antidote - for example by making it
    an "orphan drug"1 or a "common drug" for which the registration
    procedure is less complicated.

     Chemicals as antidotes

         Some chemical substances with antidotal properties, for example
    calcium chloride, sodium nitrite, and methylene blue, are marketed as
    chemicals but are not available in appropriate formulations for use as
    drugs. It is therefore important to ensure that the quality and purity
    of these chemicals will permit their administration as antidotes.
    Pharmacopoeia commissions should consider issuing monographs on such
    chemicals.

     Formulation of antidotes

         Certain pharmaceutical agents may be registered for uses other
    than as antidotes and are thus not available in appropriate
    formulations, or in adequate quantities, to meet the needs of poisoned
    patients. Additional authorization for use of these agents as specific
    antidotes should not present a major problem, but the necessary
    procedures need to be facilitated.

     National distribution of antidotes

         Demographic, geographical, and economic factors sometimes hinder
    the availability of antidotes. In addition, the high cost that results
    from infrequent demand and short shelf-life may prevent their
    widespread distribution. A central "bank" of antidotes could be an
    economic and effective means of ensuring distribution, and this should
    be organized by health authorities in such a way that any poison
    victim may be assured of receiving an antidote within the appropriate
    period of time.

              

    1    Orphan drugs: drugs for diseases or conditions that occur so
         infrequently that there is no reasonable expectation of the costs
         of developing and marketing being recovered through revenues from
         sales. The United States Government provides incentives for the
         production of such drugs, including tax credits, seven-year
         exclusive rights, facility in the Food and Drug Administration
         registration process, and a financial grant to cover part of the
         clinical research.

    Economic aspects

         When considering the cost of antidotes, governments should take
    into account the social and medical consequences of failure to treat
    poisoned patients in an appropriate manner and the continued economic
    burden on local or national resources that may ensue.

         In general, pharmaceutical companies will manufacture and supply
    antidotes only if they are encouraged by adequate economic returns for
    their investment and by simple registration procedures. To this end,
    governments should consider recent WHO recommendations1 concerning
    products for export and facilitate the registration of antidotes
    already evaluated and registered elsewhere.

         If antidotes cannot be supplied by the pharmaceutical industry,
    other means of ensuring their availability should be considered. These
    could include the establishment of government manufacturing
    facilities, a manufacturing pharmacy laboratory, or a system that
    allows the importation of antidotes registered elsewhere.

         Other ways of using resources efficiently, such as rationalizing
    the purchase and distribution of antidotes, should also be considered
    by health authorities and should take into account the time within
    which antidotes need to be available for use in treatment. Local
    transport conditions should also be considered.

    Registration and administrative requirements

         Antidotes are pharmaceutical products, and almost all countries
    have an official body concerned with the registration and approval of
    pharmaceutical substances. Many antidotes are drugs that have
    undergone a full range of tests before registration and are authorized
    for distribution and use in many countries. Such tests usually cover
    the physicochemical properties, stability of the formulation, and
    toxicity as determined by animal experiments, pharmacological studies,
    and clinical trials. However, certain pharmaceutical agents that have
    been evaluated for other uses may require additional authorization for
    antidotal use. This type of registration should present no major
    problem and could follow the procedure for a new antidote referred to
    in the next paragraph. There may, however, be a need to develop
    special formulations to allow sufficient quantities to be available
    for administration as an antidote.

              

    1     WHO Expert Committee on Specifications for Pharmaceutical
          Preparations. Thirty-fourth report. Geneva, World Health
         Organization, 1996 (WHO Technical Report Series, No. 863):
         Section 6.2, The WHO Certification Scheme on the Quality of
         Pharmaceutical Products Moving in International Commerce.

         For a new pharmaceutical substance to be used  only as an
    antidote, the registration procedure could be modified so that it is
    less comprehensive than that for a normal drug. Authorities often
    accept different criteria for the registration of certain
    pharmaceutical substances, for example anticancer drugs, because of
    the special conditions that apply to their use. A new antidote could
    be considered in a similar light, thereby facilitating its
    registration and encouraging manufacturers to make it more widely
    available.

         As already mentioned, a number of chemical substances that are
    not strictly pharmaceutical products, such as calcium chloride, sodium
    nitrite, and methylene blue, may be used as antidotes. If they are to
    be made available for administration to poisoned patients, their
    quality and purity become important considerations.

         Some antidotes that have been registered and approved in
    individual countries, after extensive testing, are faced with trade or
    administrative barriers when their importation into other countries is
    considered; examples include activated charcoal, syrup of ipecacuanha,
    and oximes. Countries should select from the list of essential
    antidotes those agents that are most appropriate to their needs; in
    some cases, these drugs are already listed in the WHO List of
    Essential Drugs.1

         In some countries, existing regulations may inhibit the use of
    certain substances - for example, antidotes still undergoing clinical
    trial and not yet registered - in the treatment of poisoning, even
    when these substances would be of value in clinically oriented poison
    control centres. Special legal provision should be made for practising
    physicians in clinical toxicology and poison control centres to use
    these agents - particularly in "life-saving" circumstances - on the
    basis of their own judgement. In addition, it should be possible to
    stock these substances under controlled conditions at poison control
    centres and to exchange them between such centres. These measures
    would encourage the interchange of experience and improve the database
    for subsequent registration. It is important, though, that a mechanism
    be established to ensure the purity and sterility of unregistered
    antidotal agents.

              

    1     The use of essential drugs. Model List of Essential Drugs (ninth
          list). Seventh report of the WHO Expert Committee. Geneva;
         World Health Organization, 1997 (WHO Technical Report Series,
         No. 867).

    Considerations of time and geography

         The availability of an antidote is highly dependent on its
    distribution within a country as well as its source, particularly if
    it has to be imported from another country. The best way of ensuring
    the importation of antidotes into a country might be to entrust it
    entirely to a central organization or institution. The establishment
    of a central agency responsible for the importation and distribution
    of antidotes is therefore recommended; alternatively, the task could
    be entrusted to clinically oriented poison control centres.

         Many countries already have such centralized systems for the
    importation of pharmaceutical agents. It is essential for the
    institutions concerned to consult and cooperate with national poison
    control and clinical toxicology centres, or associations of such
    centres, so that the importation of antidotes reflects local needs.
    Where certain antidotes are not available, either from local
    manufacturers or as imports, the central institution may cooperate
    with poison centres in recommending their local manufacture by
    hospital pharmacies or through pharmaceutical associations.
    Furthermore, in the event of an emergency or chemical disaster, an
    exchange arrangement between poison centres in different countries
    might make it possible to obtain a supply of some antidotes that are
    commercially available elsewhere.

         Since many antidotes are expensive, infrequently used, and have a
    limited shelf-life, central stocking of antidotes makes sound economic
    sense; it makes inspection easier and ensures a supply of products
    that have not lost their effectiveness. However, any such centralized
    system must be able to guarantee that a poisoned patient will receive
    an antidote within the time required for treatment. Certain agents
    used in the treatment of poisoning, for example, syrup of ipecacuanha
    and activated charcoal, are used frequently; others are required for
    use immediately, e.g. those used in the treatment of cyanide
    poisoning. Antidotes have been classified as those needed:

    *    immediately (within 30 minutes)

    *    within 2 hours

    *    within 6 hours.

         Antidotes needed immediately must be stocked at all hospitals, as
    well as in health centres or doctors' surgeries if the nearest
    hospital is some distance away. It may also be necessary to have
    certain antidotes available at places of work for use under medical
    supervision (e.g. in factories using cyanide). Antidotes needed within
    2 hours can be stocked at certain main hospitals; patients can be
    taken to these hospitals for treatment or the antidotes can be
    transported - within the time limit - to the health facilities at

    which treatment is provided. Antidotes needed within 6 hours may be
    stocked at central regional depots, provided that there are adequate
    facilities for transporting them within the time limit. For all
    categories of antidotes, there is the further option of keeping a
    small amount, sufficient to start treatment, in stock locally, further
    supplies being obtained from a central source as required.

         Where certain types of poisoning are frequent, or in areas where
    certain chemicals are heavily used, the appropriate antidotes may be
    kept in ambulances, operated by physicians, that are sent out to treat
    cases of poisoning. Poisoning by natural toxins may be seasonal and
    may be specific to certain regions (e.g. snake-bites in rural areas
    during planting and harvesting seasons). Antivenoms may be sent to
    rural areas during these seasons to be readily available in case of
    need. The rapid transport of antidotes may be needed in certain
    cirumstances, and appropriate advance arrangements should be made,
    e.g. for the use of official cars, aircraft, or trains. In certain
    situations, arrangements for the rapid transport of patients to
    hospitals with appropriate facilities and antidotes may be necessary.
    Comprehensive instructions on interim treatment measures should be
    given to first-aid workers or other medical or paramedical
    professionals.

         In deciding where antidotes should be stocked, a number of
    factors should be taken into consideration, notably the following:

    *    the size of the country and the area to be covered by a depot

    *    the density of the population

    *    the incidence of poisonings that require special therapeutic
         measures and/or antidotes

    *    the social and economic activities of the region that may be
         associated with a high risk of poisoning

    *    the distances of hospitals and health centres from the depot

    *    communications (road, air services, etc.) between the depot and
         the hospitals or health centres

    *    the cost of antidotes and of the wastage caused by expiry of
         effectiveness compared with the cost of transport in case of
         emergency.

         The most logical location for a regional central depot is a
    poison information centre or central hospital pharmacy. The economic
    management of the supply of antidotes could be improved by a central,
    preferably computerized, record system, regularly updated. The need to

    hold contingency stocks of antidotes for response to chemical
    disasters should be considered, especially in areas where large
    amounts of potentially hazardous chemicals are being manufactured,
    used, transported or stored. There, regional cooperation between
    centres, permitting the exchange of information on the availability of
    antidotes, is highly desirable.

         The conditions under which antidotes are stored are important
    determinants of their maximum shelf-life and an essential
    consideration when storage depots are chosen.

         Greater efforts should be made to find antidotes with longer
    shelf-lives and improved stability under harsh conditions,
    particularly of temperature and humidity, for use in areas where
    proper storage cannot be achieved.

    Special problems of developing countries

         In addition to the general problems of availability discussed
    above, it is recognized that developing countries may have special
    problems as regards antidotes. Many of these countries do not have
    poison information centres and lack the facilities available in
    developed countries for supportive treatment of poisoning.
    Consequently, they may have a greater need for certain antidotes, for
    example naloxone. It is important that these countries should
    establish centres to provide the relevant information, to recommend,
    whenever appropriate, the use of antidotes, and to coordinate the
    distribution of antidotes.

         Health authorities are sometimes unable or reluctant to
    facilitate the import of antidotes, since the procedures involved may
    be cumbersome and lengthy. Economic problems, including a shortage of
    convertible currency, are liable to worsen the situation. The pattern
    of poisoning in any given country should indicate the extent of the
    need to facilitate registration procedures and to acquire particular
    antidotes.

         Good first-aid procedures and the appropriate use of antidotes
    may be not only lifesaving but also economically sound. Although
    antidotes are sometimes expensive, their use may prevent death,
    prolonged hospitalization, or permanent sequelae. The benefits of
    their use thus outweigh the costs. International agencies may be
    helpful in enabling some countries to acquire the antidotes they need.

         Lack of adequate communication systems and transport
    infrastructure in certain countries may make it impossible to
    transport antidotes sufficiently quickly in an emergency. Measures to
    ensure the rapid transport of antidotes to affected areas, or,
    alternatively, the transport of poisoned patients to appropriate

    treatment facilities, are therefore of the greatest importance. It may
    be difficult to find adequate facilities for emergency storage depots;
    furthermore, local conditions and climate may make routine storage of
    antidotes difficult in certain areas of the country. Nevertheless, it
    is essential to ensure correct storage, and due account should be
    taken of expiry dates and the necessary conditions of temperature,
    light, and humidity. Proper storage conditions are also essential
    during the transportation of antidotes from the point of importation
    to local depots, and in transitional storage areas.

    Antidotes for veterinary use

         Poisoning in animals is a serious problem in many parts of the
    world, and poison information centres often receive enquiries
    regarding the treatment of poisoned animals. The use of antidotes in
    veterinary medicine poses a number of special problems as regards
    choice, dosage, route of administration, and availability. It is
    therefore recommended that each country should make separate
    arrangements for the examination of various aspects of veterinary use
    of antidotes by a working group with the necessary expertise, which
    should include poison specialists, veterinarians, and registration
    authorities.

    Improving availability

         The difficulties experienced in obtaining antidotes for the
    treatment of poisoned patients vary from country to country. While
    research in certain areas by industry, and at the international level,
    could improve the general availability of antidotes, each country will
    need to identify its own particular problems and take specific action
    to solve them. A combination of measures will be required, and
    collaboration will be necessary between the various individuals and
    organizations involved.

     Research and development

         Understanding of the metabolism, toxicodynamics, and
    toxicokinetics of chemicals that cause toxicity in humans can be
    improved to some extent through animal studies. However, human data
    are essential and should be obtained from properly conducted clinical
    studies, ideally using internationally agreed protocols. Better
    knowledge of the mechanism of action of toxic substances would enable
    more specific antidotes to be developed.

         Appropriate research on antidotes is also essential and should
    include kinetic, toxicological, and pharmacodynamic studies in both
    animals and humans. Carefully controlled clinical evaluations of
    antidotes are often difficult to organize and execute, because of the
    diversity and relative rarity of poisoning incidents. Proper control

    of the variables involved is complicated by many factors. For all
    these reasons, financial support for clinical research should be
    increased and facilitated, and collaborative studies at both national
    and international level should be promoted. A concerted effort by the
    scientific and clinical communities, as well as the pharmaceutical
    industry, could encourage the development of new antidotes and
    approval of existing ones for use in humans. This is clearly a long-
    term process.

         Specific studies are also necessary to develop more stable
    preparations with longer shelf-lives and the ability to withstand a
    wider range of physical conditions, particularly temperature, light,
    and humidity. It is important to develop simpler methods of testing
    the chemical stability and degradation of antidotes under unfavourable
    physical conditions. Research on more readily usable antidotes is
    needed, particularly because administration in field conditions by
    non-medical personnel may be necessary in the event of an emergency.
    Finally, research could also be directed to the possible inclusion of
    antidotes with commercial preparations of potentially toxic agents, as
    has already been done in some countries for paracetamol and
    methionine.

     Action by industry and commerce

         The pharmaceutical and chemical industries have an important part
    to play in the research and development activities referred to above.
    The pharmaceutical industry could explore ways and means of ensuring
    the manufacture and distribution of antidotes, including formulations
    for human and veterinary use which would not normally be made
    available if commercial criteria alone prevailed. Those industries
    that use or manufacture toxic chemicals could ensure the availability
    of, or ready accessibility to, appropriate antidotes at sites used by
    their workers and at nearby hospitals. This applies also to
    agricultural activities in which workers may be exposed to both
    agrochemicals and natural toxins (for example, through the bites of
    venomous animals) at certain times of the year, such as the planting,
    crop-spraying, and harvesting seasons. Industrial and commercial
    enterprises should ensure the proper training of their health
    personnel in the emergency use of antidotes. Importers and
    distributors of toxic chemicals should also ensure the availability of
    specific and effective antidotes for the substances in which they
    trade.

     Action at national level

         Poison information centres play a key role in the implementation
    of a national antidote programme. In general, they are in the unique
    position of having an overall picture of local poisoning incidents
    that will enable them to identify the need for specific antidotes in
    the country as a whole, as well as in particular areas. It is

    therefore a primary task of these centres to draw attention to the
    need for making appropriate antidotes available. They should review
    and evaluate the relevant literature, keep appropriate authorities
    informed, and facilitate any necessary activities.

         Poison information centres should also stimulate the creation of
    a national network for the supply of antidotes, which will require
    their close collaboration with the responsible authorities and with
    hospital pharmacies.

         The primary task of authorities at the national level is to
    ensure that the relevant legislation permits the availability of
    antidotes, especially those included in the WHO List of Essential
    Drugs),1 for purposes of evaluation. Machinery should be set up for
    the rapid importation, without bureaucratic hindrance, of antidotes
    for emergency use. Special arrangements may also be needed to permit
    the controlled clinical use of antidotes that are still under
    development.

         National health authorities should encourage the manufacture and
    distribution of antidotes not yet available on the local market and
    could even provide incentives to local pharmaceutical manufacturers,
    hospital pharmacies, and service laboratories. The export of these
    antidotes could then also be encouraged. Incentives may be of a
    financial, fiscal, or similar nature, or provided through the
    development of human resources and training. National health
    authorities could also help with, or encourage the organization of,
    depots for antidotes and systems for the distribution of antidotal
    agents.

     Action at international level

         It has been suggested that the establishment of international
    machinery for the purchase, storage, and distribution of certain
    antidotes might alleviate the problems of availability in some
    countries, though it is recognized that this may be difficult to
    organize and will demand considerable economic resources and political
    will. If a regional cooperative group could be formed for the supply
    and storage of antidotes, many of the existing obstacles could be
    overcome. To this end, regional meetings could be held under the joint
    auspices of IPCS and WHO Regional Offices to determine a plan of
    action and to improve cooperation in this area in the various WHO
    regions.

              

    1     The use of essential drugs. Model List of Essential Drugs (ninth
          list). Seventh report of the WHO Expert Committee. Geneva,
         World Health Organization, 1997 (WHO Technical Report Series,
         No. 867).

         There is strong support for the suggestion that a list be made of
    the type and quantities of antidotes immediately available throughout
    the world. Such a list would allow authorities to locate rarely used
    antidotes and would also enable large quantities of antidotes to be
    obtained in the event of a major accident. It would be very difficult,
    however, to keep the list up to date.

         As a result of the IPCS/EC project on antidotes, the WHO List of
    Essential Drugs has been updated and broadened to include a wider
    range of antidotes and other substances used in the treatment of
    poisoning, and it is hoped that this will make national health
    authorities less reluctant to facilitate the importation of these
    substances. The preparation of internationally evaluated monographs on
    each of these substances should also be helpful in this respect. In
    the same way, the exchanges of information that take place at
    international meetings are of great benefit to all those involved.

         By making resources and experience available through their
    development assistance programmes, developed countries could encourage
    the establishment of storage depots for antidotes in developing
    countries. With appropriate support, poison information centres in
    both developed and developing countries could serve as channels for
    passing on experience, bearing in mind that this is a two-way process.
    The poison information centres of developing countries could thus gain
    expertise in the treatment of forms of poisoning that no longer occur
    commonly in the developed countries, e.g. poisoning by
    organophosphates.

         Where suitable hospital pharmacy facilities exist in developing
    countries, some antidotes could be prepared locally in cooperation
    with local poison information centres. Education grants and training
    courses for pharmaceutical staff in this area would be of value and
    could be encouraged through international exchange programmes for the
    development of human resources.

    8.  Model formats for collecting, storing, and reporting data

         It is an essential function of poison information centres to
    collect data on chemical substances, on commercial and other products,
    and on communications (i.e. on enquiries to the centre, requests for
    information, and reports on poisoning cases). Both the operation of
    the centre and regular activity reports will be simplified if these
    data are recorded in standardized formats.

    Substance records

         To provide advice on management of a patient poisoned by a
    specific substance, centres must have information on the physical,
    chemical, and toxicological properties of the substance, its effects
    on various organ systems and body functions, and diagnostic
    observations, including results of laboratory tests. The IPCS INTOX

    Package includes formats for the systematic recording of such
    information on chemicals, pharmaceuticals, poisonous plants, and
    poisonous and venomous animals. An example is given in Annex 3.

    Product records

         A very simple format for recording data on commercial chemical
    and pharmaceutical products may be adequate, but a more comprehensive
    format, such as that designed for the IPCS INTOX Package and shown in
    Annex 4, is recommended.

    Communications records

         Poison information centres are encouraged to keep systematic
    records of all their communications, i.e. incoming and outgoing
    enquiries by telephone, fax, telex, letter, etc., and of personal
    consultations. Collection of these data is of the utmost importance:
    they should contain a complete record of any poisoning incident and of
    any individual poisoned or exposed to poison who has consulted the
    centre personally or about whom there has been a consultation. The
    amount of data that should be recorded may vary according to the needs
    and resources of the centre, as well as the scientific background of
    the staff in charge of the information service, but records should in
    any case be as complete as possible. Annex 5 shows the harmonized
    format developed for use in the IPCS INTOX system. The number of
    fields used on the record would be decided by the centre concerned, on
    the basis of its needs and resources, and would depend, among other
    considerations, on whether data are to be registered on paper or
    computerized (for which additional items or codes could be included in
    the form). A harmonized form for case data is valuable in many
    circumstances but particularly for epidemiological studies and
    clinical research.

         It is not usually possible to complete the clinical case-record
    fully on a single occasion, and some mechanism should be established
    for communicating with the responsible treating physician, or even
    with the patient, in order to collect more data on the evolution and
    outcome of the case. One such mechanism might be a "follow-up" call or
    a letter from the centre, asking the physician who treated a poisoned
    patient to complete the missing information or send a copy of the full
    record, if this is possible and confidentiality can be guaranteed.

         In the case of a regional or global system for the collection of
    clinical data to permit more extensive epidemiological and clinical
    research, the model form should be brief and concise. Many of the
    items that are appropriate to local studies may be irrelevant for
    global surveys. Further developments in this area are being undertaken
    by the IPCS.

    Annual reports

         Centres are encouraged to prepare annual reports of their
    activities, again using a standardized reporting format. A number of
    countries have their own annual report formats. In North America, the
    American Association of Poison Control Centers' Toxic Exposure
    Surveillance System (TESS) is used. The format prepared by the
    European Association of Poisons Centres and Clinical Toxicologists
    (EAPCCT) was subsequently adopted by the European Commission,1 and
    consideration is being given to its revision. The proposed format,
    developed through the IPCS INTOX Project, is given in Annex 6. Further
    work is being done on this to establish an internationally harmonized
    format with controlled vocabulary and defined terms.

    9.  Library requirements for poison information centres

         Books, journals, and other published literature are indispensable
    for the work of a poison information centre. There are a number of
    basic documents that are considered essential for establishing a
    centre; in addition, specialized literature is needed by staff
    responsible for patient management or for toxicological analysis. Each
    centre should have at its disposal documentation that is relevant to
    the national or regional situation and written, whenever possible, in
    the local language(s). The main literature requirements include the
    following:

    *    indexes, guides, and listings relating to medicines and to
         agricultural and other chemical products on the local market,
         plus the local pharmacopoeia

    *    books or other publications on the animal and plant toxins of the
         region

    *    standard textbooks of medicine (general and paediatric),
         chemistry, pharmacology, and analytical toxicology

    *    journals of medicine and toxicology

    *    dictionaries relating to the main areas covered by the
         documentation in the centre.

              

    1     Official journal of the European Communities, No. C329/13, 31
         December 1990.

         It is most important for toxicological data to be kept up to date
    and maintained in a rational, readily accessible filing system or in a
    computerized archive. The Microisis System - software developed by the
    International Development Research Centre of Canada - has proved to be
    very valuable in this connection, and is generally available through
    UNESCO or the libraries of local medical schools.

         While the volume and complexity of both bibliographical and non-
    bibliographical data relating to toxicology have greatly increased,
    the computer can expedite access to them. Many databases may be
    accessed on-line by telephone, and a growing number of databases are
    now available on compact disk (CD-ROM) using disk-players that operate
    in conjunction with relatively inexpensive desk-top computers. The use
    of computers is thus of enormous value for a centre's information
    work.

         The remainder of this section is devoted to lists of relevant
    books and journals (most of which are published in English and other
    major European languages) and to details of other information sources
    and educational material; these are recommended on the understanding
    that any centre will have to make its selection in the light of local
    resources, types of activity, and the principal poisoning problems
    that occur in the area.

    BOOKS

     Medical and general toxicology

     In English

    Baselt RC, Cravey RH.  Disposition of toxic drugs and chemicals in man,
         3rd ed. Chicago, Year Book Medical, 1989.

    Dreisbach RH, Robertson WO.  Handbook of poisoning: prevention,
          diagnosis and treatment, 12th ed. Los Altos, CA, Appleton &
         Lange, 1982.

    Ellenhorn MJ, Barceloux DG.  Medical toxicology: diagnosis and
          treatment of human poisoning. New York, Elsevier, 1988.

    Goldfrank LR et al., eds.  Goldfrank's toxicologic emergencies, 5th ed.
         Norwalk, CT, Appleton & Lange, 1994.

    Gossel TA, Bricker JD.  Principles of clinical toxicology, 3rd ed. New
         York, Raven Press, 1984.

    Gosselin RE, Smith RP, Hedge HC.  Clinical toxicology of commercial
          products, 5th ed. Baltimore, MD, Williams & Wilkins, 1984.

    Haddad LM, Winchester JF, eds.  Clinical management of poisoning and
          drug overdose, 2nd ed. Philadelphia, Saunders, 1990.

    Klaassen CD, ed.  Casarett and Doull's toxicology: the basic science of
          poisons, 5th ed. New York, McGraw-Hill, 1996.

    Noji EK, Kelen GD, eds.  Manual of toxicologic emergencies. Chicago,
         Year Book Medical, 1989.

     In French

    Baud F, Barriot P, Riou B.  Les antidotes. Paris, Masson, 1992.

    Bismuth C et al.  Toxicologie clinique, 4th ed. Paris, Flammarion,
         1987.

     In Italian

    Bozza-Marrubini ML, Laurenzi RG, Uccelli P.  Intossicazioni acute:
          meccanismi, diagnosi e terapia, 2nd ed. Milan, Organizzazione
         Editoriale Medico Farmaceutica, 1987.

     In Spanish

    Astolfi E et al.  Toxicologia de pregrado, 3rd ed. Buenos Aires, Lopez,
         1986.

    Dreisbach RH, Robertson WO.  Manual de intoxicaciones: prevención,
          diagnosis y tratamiento, 12th ed. Los Altos, CA, Appleton &
         Lange, 1987.

    Fogel de Korc E.  Patología toxicológia. Oficina del Libro, 1992.

    Repetto M.  Toxicológia fundamental. Madrid, Cientifico Medica, 1987.

     In German

    Krienke EG et al.  Vergiftungen im Kindesalter, 2nd ed. Stuttgart,
         Enke, 1986.

    Lindner E.  Toxikologie der Nahrungsmittel. Thieme, Stuttgart, 1991.

    Ludewig R, Lohs KH.  Akute Vergiftungen, 6th ed. Stuttgart, Fischer,
         1981.

    Moeschlin S.  Klinik und Therapie der Vergiftungen, 7th ed. Stuttgart,
         Thieme, 1986.

    Späth G.  Vergiftungen und akute Arzneimittelüberdosierungen, 2nd ed.
         Berlin, De Gruyter, 1982.

    Velvart J.  Toxikologie der Haushaltprodukte, 2nd ed. Berne, Huber,
         1988.

    Wirth W, Gloxhuber C.  Toxikologie, 4th ed. Stuttgart, Thieme, 1985.

     Pharmaceuticals

     In English

     American Hospital Formulary Service drug information. Bethesda, MD,
         American Society of Hospital Pharmacists (annual publication).

    Briggs GG, Freeman RK, Yaffe JS.  Drugs in pregnancy and lactation: a
          reference guide to fetal and neonatal risk, 3rd ed. Baltimore,
         MD, Williams & Wilkins, 1990.

    Davies DM, ed.  Textbook of adverse drug reactions, 4th ed. Oxford,
         Oxford University Press, 1991.

    Dukes MNG, ed.  Meyler's side effects of drugs: an encyclopedia of
          adverse reactions and interactions. 11th ed. Amsterdam,
         Elsevier, 1989.

    Gilman AG et al., eds.  Goodman & Gilman's The pharmacological basis of
          therapeutics, 9th ed. New York, Pergamon, 1996.

    Hansten PD.  Drug interactions: clinical significance of drug-drug
          interactions, 5th ed. Philadelphia, Lea & Febiger, 1985.

    Olson KR.  Poisoning and drug overdose, 2nd ed. Norwalk, CT, Appleton &
         Lange, 1994.  Physicians' desk reference. Oradell, NJ, Medical
         Economics (published annually).

    Reynolds JEF, ed.  Martindale: the extra pharmacopoeia, 31st ed.
         London, Pharmaceutical Press, 1996.

    Stockley IH.  Drug interactions, 3rd ed. Oxford, Blackwell Scientific,
         1994.

     Occupational and industrial toxicology

     In English

    Ash M, Ash I.  Thesaurus of chemical products, Vols 1 & 2, 2nd ed.
         London, Edward Arnold, 1992.

    Budavari S, ed.  Merck index: an encyclopedia of chemicals, drugs and
          biologicals, 12th ed. Rahway, NJ, Merck & Co., 1996.

    Clayton GD, Clayton FE, eds.  Patty's industrial hygiene and
          toxicology. Vol. 1, General principles, 3rd ed. New York,
         Wiley, 1981.

    Clayton GD, Clayton FE, eds.  Patty's industrial hygiene and
          toxicology, Vols 2A, 2B, 2C, 2D, 2E, 2F, 4th ed. New York,
         Wiley, 1993-1994.

    Hayes WJ, Laws ER, eds.  Handbook of pesticide toxicology. San Diego,
         Academic Press, 1991 (3 volumes).

    Lenga RE, Votoupal KL, eds.  The Sigma Aldrich library of chemical
          safety data. Milwaukee, Aldrich Chemical Co., 1992.

    Proctor NH, Hughes JP, Fischman ML, eds.  Chemical hazards of the
          workplace, 3rd ed. Philadelphia, Lippincott, 1991.

    Plestina R.  Prevention, diagnosis and treatment of insecticide
          poisoning. Geneva, World Health Organization, 1984 (unpublished
         WHO document WHO/VBC/84.889, obtainable on request from Programme
         for the Promotion of Chemical Safety, World Health Organization,
         1211 Geneva 27, Switzerland).

    Rom WN, ed.  Environmental and occupational medicine. Boston, MA,
         Little, Brown, 1992.

    Sax NI, Lewis RJ, eds.  Dangerous properties of industrial materials,
         8th ed. New York, Van Nostrand Reinhold, 1992.

    Sax NI.  Hazardous chemicals desk reference, 3rd ed. New York, Van
         Nostrand Reinhold, 1993.

    Sax NI.  Rapid guide to hazardous chemicals in the workplace, 3rd ed.
         New York, Van Nostrand Reinhold, 1993.

    Snyder JR, ed.  Ethel Browning's toxicity and metabolism of industrial
          solvents. 2nd ed. Amsterdam, Elsevier, Vol. 1 1987, Vols 2 & 3
         1990.

    Tomlin C, ed.  The pesticide manual - a world compendium, 10th ed.
         Farnham, British Crop Protection Council, 1994.

     In French

    Encyclopédie Medico-Chirurgicale.  Toxicologie-pathologie
          professionelle. Paris, Editions Techniques, 1991.

    Lauwerys R.  Toxicologie industrielle et intoxications professionelles,
         3rd ed. Paris, Masson, 1990.

     In Spanish

    Quer-Brossa S.  Toxicológia industrial. Barcelona, Salvat Editores,
         1983.

     In German

     Wirkstoffe in Pflanzenschutz und Schädlingsbekämpfungsmitteln, 2nd
         ed. Frankfurt, Industrieverband Agrar, 1990.

     Analytical toxicology

    Baselt RC, Cravey RH.  Disposition of toxic drugs and chemicals in man,
         4th ed. Foster City, CA, Chemical Toxicology Institute, 1995.

    Curry AS, ed.  Analytical methods in human toxicology, Part 1.
         Deerfield Beach, FL, VCH, 1985.

    Curry AS, ed.  Analytical methods in human toxicology, Part 2.
         Deerfield Beach, FL, VCH, 1986.

    Curry AS.  Poison detection in human organs, 4th ed. Springfield, IL,
         Charles C. Thomas, 1988.

    De Zeeuw RA et al., eds.  Gas-chromatographic retention indices of
          toxicologically relevant substances on packed or capillary
          columns with dimethylsilicone stationary phases, 3rd ed.
         Deerfield Beach, FL, VCH, 1992.

    Eller PM, ed.  NIOSH manual of analytical methods, Vol. 1, 3rd ed.
         Cincinnati, OH, National Institute of Occupational Safety and
         Health, 1984.

     Environmental health criteria. Geneva, World Health Organization
         (series).

    Feigl F.  Spot tests in organic analysis, 7th ed. Amsterdam, Elsevier,
         1966.

    Flanagan RJ et al.  Basic analytical toxicology. Geneva, World Health
         Organization, 1995.

    Moffat AC et al., eds.  Clarke's isolation and identification of drugs
          in pharmaceuticals, body fluids, and post-mortem material, 2nd
         ed. London, Pharmaceutical Press, 1986.

    Stewart CP, Stolman A.  Toxicology: mechanism and analytical methods,
          Vol. 1. New York and London, Academic Press, 1960.

    Stewart CP, Stolman A.  Toxicology: mechanism and analytical methods,
          Vol. 2. New York and London, Academic Press, 1961.

    Sunshine I.  Methodology for analytical toxicology. Cleveland, OH,
         Chemical Rubber Company Press, 1975.

    United Nations Division of Narcotic Drugs.  Recommended methods for
          testing: manuals for use by national narcotics laboratories.
         New York, United Nations, 1984-1989.1

    World Health Organization/Food and Agriculture Organization.  Data
          sheets on pesticides (unpublished WHO documents, available on
         request from Programme for the Promotion of Chemical Safety,
         World Health Organization, 1211 Geneva 27, Switzerland).

     Natural poisons

         Books on natural poisons should be selected according to the real
    incidence of risks of poisoning by animals or plants in the
    geographical area concerned. Illustrated guides, with drawings,
    photographs, or even specimens, are very useful for the identification
    of local plants and animals (fungi, snakes, spiders, scorpions,
    insects, marine animals, etc.). Most of the valuable literature will
    therefore come from the geographical area itself, but certain books
    can be recommended, since natural toxins are distributed worldwide.

    Bresinsky A, Besl  H. A colour atlas of poisonous fungi: a handbook for
          pharmacists, doctors and biologists. London, Wolfe, 1990.

    Frohne D, Pfändner HJ.  A colour atlas of poisonous plants: a handbook
          for pharmacists, doctors, toxicologists, and biologists.
         London, Wolfe, 1984.

    Halstead BW.  Poisonous and venomous marine animals of the world, 2nd
         ed. Princeton, NJ, Darwin Press, 1988.

    Lampe KF, McCann MA.  American Medical Association handbook of
          poisonous and injurious plants. Chicago, American Medical
         Association, 1985.

    Lincott G, Mitchel DH.  Toxic and hallucinogenic mushroom poisoning.
         New York, Van Nostrand Reinhold, 1977.

     Specialized toxicology

         Publications specializing in toxicology of the eye, central
    nervous system, heart, lung, kidney, liver, and skin, as well as books
    on toxins and cancer, on effects of drugs in pregnancy and lactation,
    and on drugs of abuse, may be required whenever information is needed
    on specific target organs or systems. Examples include the following:

              

    1    Separate publications for testing different substances.

    Barken RM. Rosen P, eds.  Emergency paediatrics: a guide for emergency
          and urgent care, 4th ed. St Louis, MO, CV Mosby, 1993.

    Briggs GG, Freeman RK, Yaffe SJ.  Drugs in pregnancy and lactation: a
          reference guide to fetal and neonatal risk, 4th ed. Baltimore,
         MD, Williams & Wilkins, 1994.

    Descotes J.  Immunotoxicology of drugs and chemicals, 2nd ed.
         Amsterdam, Elsevier, 1988.

    Fisher AA.  Contact dermatitis, 3rd ed. Philadelphia, Lea & Febiger,
         1986.

    Grant WM, Schuman JS.  Toxicology of the eye, 4th ed. Springfield, IL,
         Charles C. Thomas, 1993.

         Books dealing with veterinary toxicology may be helpful in some
    cases. Examples include the following:

     In English

    Bartik M, Piskac A.  Veterinary toxicology. New York, Elsevier, 1981.

    Booth NH, McDonald LE.  Veterinary pharmacology and therapeutics, 6th
         ed. Ames, IA, Iowa State University Press, 1988.

    Garner RJ et al.  Veterinary toxicology, 3rd ed. London, Balliere
         Tindall, 1988.

    Howard J.  Current veterinary therapy: food animal practice.
         Philadelphia, Saunders, 1986.

    Kirk RW.  Current veterinary therapy: small animal practice.
         Philadelphia, Saunders/Harcourt-Brace Jovanovich, 1989.

    Osweiler GD et al.  Clinical and diagnostic veterinary toxicology, 3rd
         ed. Dubuque, IA, Kendall/Hunt, 1985.

    Robinson NE.  Current therapy in equine medicine, 2nd ed. Phildelphia,
         Saunders, 1987.

     In German

    Hapke HJ.  Toxikologie für Veterinärmediziner. Stuttgart, Ferdinand
         Enke, 1988.

         Books on eco-toxicology and environmental toxicology are also
    important, as poison information centres are frequently involved in,
    or consulted about, the management and assessment of environmental
    problems and their effects on health.

         Bearing in mind that the information requested from a centre can
    sometimes involve highly specialized branches of medicine, it is
    recommended that the centre - or other readily accessible libraries -
    have well known, up-to-data textbooks on paediatrics, nephrology,
    hepatology, lung diseases, gastroenterology, cardiology,
    ophthalmology, gynaecology and obstetrics, dermatology, psychiatry,
    etc.

    Journals

         A list of some of the numerous periodicals that deal essentially
    with toxicology or closely related areas is given below. It should be
    noted that, in many countries, there are local journals on toxicology,
    usually published by national scientific associations. It is
    recommended that any poison information centres should also have
    access to journals devoted to more general clinical, industrial,
    chemical, and ecological topics.

     In English

    Adverse drug reactions and toxicological reviews. Published by Oxford
         University Press, Oxford, England.

     American journal of industrial medicine. Published by Wiley, New York,
         NY, USA.

     Annals of occupational hygiene. Published by Pergamon, Elmsford, NY,
         USA.

     Archives of environmental contamination and toxicology. Published by
         Springer Verlag, New York, USA.

     Archives of environmental health. Published by Heldref (Helen Dwight
         Reid Educational Foundation), Washington, DC, USA.

     Archives of toxicology. Published by Springer Verlag, Berlin, USA.

     Biochemical pharmacology. Published by Pergamon, Elmsford, NY, USA.

     British journal of industrial medicine. Published by British Medical
         Association, London, England.

     Drug safety (formerly  Medical toxicology). Published by ADIS Press,
         Auckland, New Zealand.

     EHP (Environmental health perspectives). Published by US Department of
         Health and Human Services, National Institute of Environmental
         Health Sciences, Research Triangle Park, NC, USA.

     Human and experimental toxicology. Published by Macmillan,
         Basingstoke, England.

     Journal of the American Industrial Hygiene Association. Published by
         American Industrial Hygiene Association, Akron, OH, USA.

     Journal of toxicology - clinical toxicology. Published by Marcel
         Dekker Inc., New York, NY, USA.

     Neurotoxicology. Published by Raven Press, New York, USA.

     Pharmacology and toxicology. Published by Munksgaard, Copenhagen,
         Denmark.

     Scandinavian journal of work, environment and health. Published by
         Finnish Institute of Occupational Health, Helsinki, Finland.

     Toxicology. Published by Elsevier, Limerick, Ireland.

     Toxicology and applied pharmacology. Published by Academic Press, San
         Diego, CA, USA.

     Toxicology letters. Published by Elsevier, Amsterdam, Netherlands.

     Toxicon. Published by Pergamon, Elmsford, NY, USA.

     Veterinary and human toxicology. Published by Comparative Toxicology
         Laboratories, Manhattan, KS, USA.

     In French

     Archives belges de médecine sociale et d'hygiène (formerly  Archives
          belges de médecine sociale, hygiène, médecine du travail et
          médecine légale). Published by Archives belges de médecine
         sociale et d'hygiène, Brussels, Belgium.

     Archives des maladies professionnelles de médecine du travail et de
          sécurité sociale. Published by Masson, Paris, France.

     Thérapie. Published by Doin, Paris, France.

     In Italian

     Medicina del lavoro. Published by Istituti Clinici di Perfezionamento,
         Milan, Italy.

     In Spanish

     Toxicología. Published by Sociedad Uruguaya de Toxicología y
         Ecotoxicología del Uruguay, Montevideo, Uruguay.

         Access to other medical journals that may contain reports of
    relevance to the work of the centre is recommended, notably those
    dealing with emergency medicine, epidemiology, intensive care,
    occupational medicine, pharmacology and adverse drug reactions,
    clinical medicine, paediatrics, public health, and psychiatry.
    Journals and newsletters published by agencies dealing with accident
    prevention or associations that undertake research in this area may
    also be useful.

         Current awareness publications, abstracts, and bibliographical
    indexes are useful for updating information. Although they are
    expensive, they are usually available at teaching hospitals and in
    university libraries. They include:

    *     Medline

    *     Toxline

    *     Reactions

    *     Current contents

    *     Toxicology abstracts

    *     Excerpta medica

    *     Index medicus

    Publications of international organizations

         The Environmental Health Criteria series published by WHO
    provides valuable data on priority chemicals  (see Annex 7).

         Poison information centres may also derive useful information
    from certain publications produced by the Food and Agriculture
    Organization of the United Nations, the International Labour
    Organisation, the International Register of Potentially Toxic
    Chemicals, and the United Nations Environment Programme. Centres
    should ask the local representatives or national correspondents of
    these agencies for lists of their publications.

         Monographs from the International Agency for Research on Cancer
    on the evaluation of the carcinogenic risk of chemicals to humans
    provide reliable, up-to-date information on a large number of
    chemicals (contact IARC, 158 Cours Albert-Thomas, 69372 Lyon Cedex 08,
    France).

    Computerized databases

         Computerized databases provide easy, on-line access to a wide
    range of useful information, but may be expensive to maintain. Some
    databases (e.g. Dialog, CIS, Medline, Toxline) have already been
    adopted by the more experienced poison information centres, but the
    more specific ones should be carefully chosen according to local needs
    and resources. A comprehensive list of databases can be provided on
    request from IPCS, World Health Organization, 1211 Geneva 27,
    Switzerland.

    Educational material

         Educational material is sometimes produced by government
    agencies, nongovernmental organizations, manufacturers' associations,
    scientific societies, accident prevention agencies, and other
    institutions interested in the prevention and correct management of
    poisoning. Such material can also be produced by the staff of poison
    information centres for the training of professional health care
    workers and others or for the information of the community.

         For example, the library at a poison information centre may have,
    for distribution, a government-produced poster on the safe use of
    pesticides; it may design and print a leaflet on the safe storage of
    medicines at home; it may distribute a booklet on the recognition of
    poisonous fungi; or it may develop, for distribution to clinicians,
    highly specialized protocols for the treatment of the most common
    types of poisoning.

         Posters, booklets, leaflets, bulletins, video cassettes, or
    audiovisual displays relevant to the local situation should also be
    available at the centre's library.

    Annex 1

    Summary description of the IPCS INTOX Package1

         The essential component of the IPCS INTOX Package is a computer
    software system for data management of poisons information. Although
    it is aimed primarily at the needs of the information services of
    poison centres in developing countries, the Package is also very
    suitable for use in developed countries with well established centres.
    It is designed to be operated in English, French, and Spanish, but
    versions for other languages can easily be developed. Moreover, the
    system can be operated on a stand-alone personal computer, a network
    of computers within a single centre, a network of centres within a
    country, and internationally. The software system is delivered with a
    CD-ROM containing Poisons Information Monographs and various other
    publications designed to be useful to poison centres, as well as the
    electronic versions of the system documentation. The software and the
    CD-ROM constitute the IPCS INTOX Package. The Package is the result of
    a continuing IPCS INTOX project carried out under the aegis of IPCS.

    Definitions

         The following paragraphs provide definitions of a number of terms
    employed in the IPCS INTOX Package:

    *    An "entity" is something that can enter the body of a human or
         animal; it is either a substance or a product, or a class of
         substances or of products. Any chemical to which an individual is
         exposed may be termed an entity. Substances and products are
         classified either by their scientific group (or family for a
         plant or animal) or by their function.

    *    A "substance" is a chemical or pharmaceutical of natural or
         synthetic origin, or produced by the biological processes of an
         organism such as a poisonous plant or a poisonous or venomous
         animal.

    *    A "product" is a substance or preparation (i.e. mixture of
         substances) placed on the market, normally with a unique
         designation or brand name.

              

    1    Developed by IPCS in association with the Canadian Centre for
         Occupational Health and Safety (CCOHS) and the Centre de
         Toxicologie du Québec (CTQ), with financial assistance from the
         International Development Research Centre (IDRC) of Canada and
         Member States of WHO. Further information about the Package and
         its availability can be obtained from the Director, IPCS, World
         Health Organization, 1211 Geneva 27, Switzerland.

    *    An "agent" is a specific instance of an entity and is the linkage
         between the substance, product components of the Package, and the
         communications component. The agent is the poison or supposed
         toxic substance or class thereof to which a communication refers.

    *    A "communication" is any interaction between a poison information
         centre and its interlocutors or clients. It usually takes the
         form of a telephone call, incoming or outgoing, but may also be a
         fax, letter, telex, or face-to-face contact.

    *    An "interlocutor" or "client" is the individual or institution
         with whom the poison information centre is communicating.

    *    An "authority list" is a series of controlled or harmonized terms
         used for data entry into, and data retrieval from, the IPCS INTOX
         Package. In some cases the authority list is fixed by the project
         and cannot be altered, e.g. Sex - Male, Female, Unknown. In some
         cases there is a proposed list of terms to which a centre can add
         its own terms, but from which it cannot delete existing terms; in
         other cases the centre is free to develop its own authority list.

    Databases

         The IPCS INTOX system maintains two interrelated databases, each
    of which uses standardized formats - the "entity" database and the
    "communications" database. The entity database contains details of
    substances and commercial and other products (including their
    synonyms). There are standardized formats for information on
    substances - chemicals and pharmaceuticals, plus the toxic substances
    contained in poisonous plants and in poisonous and venomous animals -
    and on commercial and other products that contain substances. Classes
    of substances and of products, classified either by scientific group
    or by function, are also part of the entity database and have their
    own standardized formats.

         The communications database contains records of the interactions
    between the poison information centre and its interlocutors or
    clients. The names and synonyms of all the entities, including
    classes, held by the system constitute the authority list for
    inclusion in the communications records of the names of agents. The
    use of entity names as agent names forms the link between the two
    databases.

         As far as possible data are entered using controlled or
    harmonized terms chosen from authority lists. These authority lists
    are either generated globally by the project through consensus, or
    locally by the centre itself. This comprehensive use of controlled
    vocabularies is a prerequisite for the storage of high-quality
    information which can be reliably retrieved and analysed. The use of
    controlled terms facilitates data entry and retrieval, as well as
    permitting the user to "navigate" the database.

    Substance records

         The format on substances enables a "substance record" to be
    created, containing data on the physico-chemical and toxicological
    properties of a substance, on the medical features of the effects
    produced by various routes of exposure to the substance, on management
    of patients, and on supporting laboratory investigations. Most of the
    data on substances are globally valid and may be found in the
    scientific literature or are generated as a result of the overall work
    of IPCS on risk assessment of chemicals. In order to assist poison
    information centres, particularly new centres, to develop their own
    databases on substances, a series of Poisons Information Monographs
    (PIMs) is being prepared on priority substances selected because of
    their importance as causes of poisoning or as subjects of enquiries to
    poison information centres, particularly in developing countries. The
    PIMs are issued as IPCS documents and are also made available to the
    IPCS INTOX project on a CD-ROM which is produced for the IPCS by the
    Canadian Centre for Occupational Health and Safety. PIMs can be
    imported from the CD-ROM into the IPCS INTOX database on the computer
    at the centre.

         While the formats of the PIMs are the same as those for the
    substance records in the IPCS INTOX database, it is not necessary to
    have a completed PIM in order to have a substance record. The only
    essential part of the substance record for the operation of the IPCS
    INTOX Package is the substance name, which is important, since it
    means that the database at a poison information centre using the IPCS
    INTOX Package is not limited only to information for which there is a
    PIM. Each centre may build up its own database containing substances
    of relevance to its own situation, adding the essential data from the
    PIMs as they become available or as they are subsequently revised or
    updated.

         The format for PIMs and substance records is given in Annex 3.
    The formats for chemicals, pharmaceuticals, poisonous plants, and
    poisonous and venomous animals are, with some small modifications to
    the contents, more or less identical. Guidelines are provided in the
    User's Manual for the IPCS INTOX Package on preparing PIMs and
    substance records.

    Product records

         The format on commercial products enables a product record to be
    created containing data on the manufacturer, distributor, or importer
    of a commercial product, on how the product is presented (packaging),
    on its characteristics (form and physico-chemical properties), and
    composition, on relevant toxicological data, and on patient
    management.

         The format is adapted for both commercial products containing
    chemicals and commercial preparations of pharmaceuticals. It remains
    to be seen in practice whether it is fully adaptable to non-commercial
    products, such as traditional medicines and locally fabricated
    products of variable composition found in bazaars and markets. The
    format for the product record is given in Annex 4. Guidelines on
    completing a product record are provided in the User's Manual for the
    IPCS INTOX Package.

    Classes of substances

         In a case of poisoning it is not always possible to identify the
    specific substance(s) or product(s) involved, but rather a class or
    group - an organophosphate, a benzodiazepine, a pesticide, a rat-
    killer, a dish-washing liquid, a solvent, a painkiller, etc. Any such
    class or group could be the name of the agent (poison) given by an
    enquirer (interlocutor) in a call (communication) to a poison
    information centre. The IPCS INTOX Package enables class records to be
    created so that classes and groups and their synonyms may be included
    in the entity database. The "Category of Use" or function field in the
    product record and the "Group" or "Family" fields in the substance
    record are made from the list of classes and their synonyms. Class
    structures may be complex, with a substance or product being a member
    of more than one class. Furthermore, a class record may pertain to
    more than one type of substance or product. The IPCS INTOX Package
    enables one class record to be linked to another. Each class record
    may have zero or any number of links created in it.

    Communications record

         The format on communications enables a poison information centre
    to record and retrieve information on any incoming or outgoing
    telephone call, fax, telex, letter or face-to-face contact: the person
    or institution (interlocutor) with whom the centre is interacting; an
    incident (single or multiple), and the type, location, and
    circumstances involved; a patient or patients and various related
    details; and various agent(s)/ route(s). One contact with the poison
    information centre defines one communication which may, for example,
    involve several different types of enquiry. One or more contact or
    communication dealing with the same incident/patient combination
    defines the basis of a case. The cumulative data at a poison
    information centre on a case may or may not constitute a full clinical
    case record. International work being undertaken in the context of the
    IPCS to define and harmonize medical features of effects of poisoning
    and their severity, as well as descriptions of treatment procedures,
    is at a preliminary stage and it will be a number of years before it
    is possible to consider establishing a fully harmonized hospital case
    data record for global use. Likewise, much work remains to be done on
    harmonizing the description of laboratory investigations associated
    with diagnosis, prognosis, and management of poisoned patients. The
    available version of the IPCS INTOX Package incorporates the current

    consensus on clinical features and severity grading. The format for
    recording a communication is given in Annex 5. Guidelines on recording
    a communication are available in the User's Manual for the IPCS INTOX
    Package.

    Other types of record

         A number of auxiliary databases are also provided with the IPCS
    INTOX Package. These enable centres to record the names, addresses,
    and functions of various individuals and medical and other
    institutions with which the poison information centre is in frequent
    contact.

    Interaction with other packages

         It is intended that future versions of the IPCS INTOX Package
    will be able to interface with other packages, such as plant and
    tablet identification packages, as well as packages for performing
    mathematical computations, e.g. transforming one set of units into
    another (pounds to kilograms, feet to metres, etc.).

    Hardware and software specifications

         The IPCS INTOX software system will operate on a personal
    computer with the Microsoft Windows1 operating system (version 3.1 or
    later); MS-DOS 5.0 or later is also necessary. The recommended
    hardware arrangement is an 80486 processor, running at a minimum of
    33 MHz, 8 Mb of RAM, a colour display capable of handling SVGA
    resolution (800 x 600), a 3.5" floppy disk drive, a CD-ROM drive, and
    a mouse. The required capacity of the hard disk will depend on the
    amount of information that will be collected by the centre: 120Mb
    should be considered the absolute minimum. The CD-ROM player is
    required to access the database of PIMs and other material. A printer
    of any type that is compatible with the system described is also
    recommended, depending on the quality of the output required by the
    centre. The preferred informatics specifications for the IPCS INTOX
    Package are given in the User's Manual.

         With future versions of the IPCS INTOX Package it will be
    possible to incorporate colour pictures and drawings, which are of
    particular value in the identification of poisonous plants and
    poisonous and venomous animals. This capability may also be useful in
    illustrating clinical features such as rashes and bites, as well as
    packaging materials and characteristics of commercial products.

              

    1    Microsoft is a registered trademark and Windows is a trademark of
         the Microsoft Corporation.

    Support to users of the IPCS INTOX Package

         The IPCS INTOX system development staff and other informatics
    experts in various parts of the world are accessible by fax,
    electronic mail, and telephone. In addition, the

         IPCS INTOX project operates a twinning arrangement among poison
    centres that wish to participate in such an arrangement, so that they
    can give each other mutual support, and "discussions" between members
    of the project can take place on the Internet network using electronic
    mail.

    Annex 2

    Classified lists of antidotes and other agents

    Group 1        List of antidotes

    Group 2        Agents used to prevent the absorption of poisons, to
                   enhance their elimination, or to treat symptomatically
                   their effects on body functions

    Group 3        Other useful therapeutic agents for the treatment of
                   poisoning

    Group 4        List of antidotes and related agents considered
                   obsolete

    The antidotes listed in Groups 1 and 2 are considered useful in the
                   treatment of acute human poisoning, and their
                   availability in terms of urgency of use may be
                   classified as follows:

    A              Required to be immediately available (within
                   30 minutes).

    B              Required to be available within 2 hours.

    C              Required to be available within 6 hours.

    Their effectiveness in practice may be classified as follows:

    1              Effectiveness well documented, e.g. reduction of
                   lethality in animal experiments and reduction of
                   lethality or of severe complications in human
                   poisoning.

    2              Widely used but not yet universally accepted as
                   effective, owing to lack of research data, and
                   requiring further investigation concerning
                   effectiveness or indications for use.

    3              Questionable usefulness; as many data as possible
                   regarding effectiveness should be collected.

    The classification in terms of urgency of availability (A, B, C) or
    proven effectiveness (1, 2, 3) is given next to the main indication
    for the antidote. The classification is also given in the right-hand
    column of the Group 1 list when an antidote has other possible
    applications. If there is doubt as to the classification of an
    antidote, the lower score is always given, e.g. B2 instead of A1.

        Group 1.  Antidotes

                                                                                                                               

    Antidote                      Main indication or                                Other possible
                                  pathological condition                            applications
                                                                                                                               

    acetylcysteine                paracetamol (B1)

    N-acetyl penicillamine        mercury (inorganic and vapour) (C3)

    amyl nitrite                  cyanide (A2)

    atropinea,b                   organophosphorus compounds
                                  and carbamates (A1)

    benzylpenicillina             amanitins (B3)

    ß-blockers (ß1 and ß2,        ß-adrenergic agonists (A1)                        theophylline (B1)
    preferably short-acting)

    calcium gluconate or other    HF, fluorides, oxalates (A1)                      calcium antagonists (B3)
    soluble calcium saltsa

    dantrolene                    drug-induced hyperthermia (A2)                    malignant neuroleptic
                                                                                    syndrome (A2)

    deferoxaminea,b               iron (B1)                                         aluminium (C2)

    diazepama                     organophosphates (A2)                             chloroquine (A2)

    dicobalt edetate              cyanide (A1)

    digoxin-specific antibodies   digoxin/digitoxin, other digitalis glycosides
    (Fab fragments)               (A1)
                                                                                                                               

    Group 1. Antidotes (contd.)

                                                                                                                               

    Antidote                      Main indication or                                Other possible
                                  pathological condition                            applications
                                                                                                                               

    dimercaprola,b                arsenic (B3)                                      gold (C3), mercury
                                                                                    (inorganic) (C3)

    4-dimethylaminophenol         cyanide (A1)
    (4-DMAP)

    edetate calcium disodium      lead (C2)
    (CaNa2-EDTA)

    ethanol                       methanol, ethylene glycol (A1)

    flumazenil                    benzodiazepines (B1)

    folinic acid                  folinic acid antagonists (B1)                     methanol (B3)

    glucagon                      ß-blockers (A1)

    glucose (hypertonic)          insulin (A1)

    hydroxocobalamina             cyanide (A1)

    isoprenalinea                 ß-blockers (A1)

    methioninea,b                 paracetamol (B1)

    4-methylpyrazolec             ethylene glycol (A1)                              methanol, coprin,
                                                                                    disulfiram (B2)

    methylthioninium chloride     methaemoglobinaemia (A1)
    (methylene blue)a,b 
                                                                                                                              

    Group 1. Antidotes (contd.)

                                                                                                                               

    Antidote                      Main indication or                                Other possible
                                  pathological condition                            applications
                                                                                                                               

    dimercaprola,b                arsenic (B3)                                      gold (C3), mercury
                                                                                    (inorganic) (C3)

    naloxonea                     opiates (A1)

    neostigminea                  neuromuscular block (curare type), peripheral
                                  anticholinergic efects (B2)

    obidoxime                     organophosphorus insecticides (B2)

    oxygena                       cyanide, carbon monoxide, hydrogen sulfide
                                  (A1)

    oxygen, hyperbaric            carbon monoxide (C2)                              cyanide, hydrogen
                                                                                    sulfide, carbon
                                                                                    tetrachloride

    penicillaminea,b              copper (Wilson disease) (C1)                      lead, mercury
                                                                                    (inorganic) (C2)

    pentetic acid (DTPA)          cobalt (C3)                                       radioactive metals

    phentolamine                  alpha-adrenergic poisoning (A1)

    physostigmine                 central anticholinergic syndrome from             central anticholinergic
                                  atropine and derivatives (A1)                     syndrome from other
                                                                                    drugs
                                                                                                                               

    Group 1. Antidotes (contd.)

                                                                                                                               

    Antidote                      Main indication or                                Other possible
                                  pathological condition                            applications
                                                                                                                               

    phytomenadione                coumarin derivatives (C1)
    (vitamin K1)a

    potassium ferric              thallium (B2)
    hexacyanoferrate
    (Prussian blue
    C177520)a,b

    pralidoxime                   organophosphorus compounds

    prenalterol                   ß-blockers (A1)

    propranolol (see ß-blockers)

    protamine sulfatea            heparin (A1)

    pyridoxinea                   isoniazid, hydrazines (A2)                        ethylene glycol (C3),
                                                                                    gyrometrine (B2)

    silibinin                     amanitin (B2)

    sodium nitritea,b             cyanide (A1)

    sodium nitroprussidea         ergotism (A1)

    sodium thiosulfatea,b         cyanide (A1)                                      bromate, chlorate, iodate
                                                                                                                               

    Group 1. Antidotes (contd.)

                                                                                                                               

    Antidote                      Main indication or                                Other possible
                                  pathological condition                            applications
                                                                                                                               

    succimer (DMSA)               antimony, arsenic, bismuth, cadmium, cobalt,      mercury (elemental),
                                  copper, gold, lead, mercury (organic and          platinum, silver (C3)
                                  inorganic) (B2)

    trientine (triethylene        copper (Wilson disease) (C2)
    tetramine)

    unithiol (DMPS)               cobalt, gold, lead, mercury (inorganic),          cadmium, mercury
                                  nickel (C2)                                       (organic) (C3)
                                                                                                                               

    a    Listed in the WHO Model List of Essential Drugs (see:  The use of essential drugs. Model List of Essential Drugs
          (ninth list). Seventh report of the WHO Expert Committee. Geneva, World Health Organization, 1997 (WHO Technical
         Report Series, No. 867)).
    b    Evaluated or under evaluation by group of experts on behalf of IPCS/CEC.
    c    Available only in France.
        Group 2.  Agents used to prevent the absorption of 
    poisons, to enhance their elimination, or to treat
    symptomatically their effects on body functions

    Emetics
         apomorphine
         ipecacuanha

    Cathartics and solutions for whole gut lavage
         magnesium citrate/sulfate/hydroxide (B3)
         mannitol/sorbitol/lactulose (B3)
         sodium sulfate/phosphate/bicarbonate (B3)
         polyethylene glycol electrolyte lavage solution (B2)

    Agents to alkalinize urine or blood
        sodium bicarbonate (A1)

    Agents to prevent absorption of toxic substances
    in the gastrointestinal tract
        activated charcoal (A1)            -- for adsorbable poisons
        starch (A3)                        -- for iodine

    Agents to prevent skin absorption and/or damage
        calcium gluconate gel (A1)         -- for hydrofluoric acid
        polyethylene glycol (Macrogol 400) -- for phenol

    Anti-foaming agent
        dimethiconea                       -- for soaps, shampoos

              

    a    To be evaluated.

    Group 3.  Other therapeutic agents useful for the treatment
    of poisoning

        Listed below are certain therapeutic agents that are not
    antidotes according to the accepted definition; however, because of
    their established value and sometimes specific role in the management
    of poisoning, they border on the concept of antidotes. In practice,
    these agents are used frequently in cases of poisoning and in other
    medical circumstances. Most of them are considered to be essential
    drugs and should therefore be available for immediate use.

                                                                             

    Agent                    Indications/symptoms arising from poisoning
                                                                         

    benztropine              dystonia

    chlorpromazine           psychotic states with severe agitation

    corticosteroids          acute allergic reactions, laryngeal oedema
                             (systemic/topical) bronchoconstriction,
                             mucosal oedema (inhaled)

    diazepam                 convulsions, excitation, anxiety, muscular
                             hypertonia

    diphenhydramine          dystonia

    dobutamine               myocardial depression

    dopamine                 myocardial depression, vascular relaxation

    epinephrine              anaphylactic shock, cardiac arrest
     (adrenaline)

    furosemide               fluid retention, left ventricular failure

    glucose                  hypoglycaemia

    haloperidol              hallucinatory and psychotic states

    heparin                  hypercoagulability states

    magnesium sulfate        cardiac arrhythmias

    mannitol                 cerebral oedema, fluid retention

    oxygen                   hypoxia
                                                                         
    Group 3.  (contd.)

                                                                         

    Agent                    Indications/symptoms arising from poisoning
                                                                         

    pancuronium              muscular rigidity, convulsions

    promethazine             allergic reactions

    salbutamol               bronchoconstriction (systemic/inhaled)

    sodium bicarbonate       acidosis, some cardiac disturbances
                                                                         


    Group 4.  List of antidotes and related agents now
    considered obsolete

                                                                       

    Antidote                      Indicated for
                                                                       

    acetazolamide                 modification of urinary pH

    ascorbic acid                 methaemoglobinaemia

    aurintricarboxylic
    acid (ATA)                    beryllium

    ß-aminopropionitrile          caustics

    castor oil                    as cathartic

    copper sulfate                as emetic

    cyclophosphamide              gold-paraquat

    cysteamine                    paracetamol

    diethyldithiocarbamate        thallium

    fructose                      ethanol

    guanidine precursors          botulism

    levallorphan                  opiates

    nalorphine                    opiates
                                                                       

    Group 4.  (contd.)

                                                                       

    Antidote                      Indicated for
                                                                       

    potassium permanganate        fluorides

    sodium chloride               as emetic

    sodium salicylate             beryllium

    strychnine                    central nervous system depressants

    sulfadimidine                 amanitine

    tannins                       alkaloids

    thioctic acid                 amanitine

    tocopherol (vitamin E)        paraquat

    tolonium chloride             methaemogiobinaemia

    universal antidote            ingested poisons
                                                                       
    
    Annex 3

    Example of a substance record: chemical

    1. Name

         1.1   Substance
         1.2   Group
         1.3   Synonyms
         1.4   Identification numbers
               1.4.1   Chemical Abstracts Service (CAS)
               1.4.2   Other numbers
         1.5   Main brand names/main trade names
         1.6   Main manufacturers and/or importers

    2. Summary

         2.1   Main risks and target organs
         2.2   Summary of clinical effects
         2.3   Diagnosis
         2.4   First-aid measures and management principles

    3. Physico-chemical properties

         3.1   Origin of the substance
         3.2   Chemical structure
         3.3   Physical properties
         3.4   Other characteristics

    4. Uses/high-risk circumstances of poisoning

         4.1   Uses
         4.2   High-risk circumstance of poisoning
         4.3   Occupationally exposed populations

    5. Routes of entry

         5.1   Oral
         5.2   Inhalation
         5.3   Dermal
         5.4   Eye
         5.5   Parenteral
         5.6   Others

    6. Kinetics

         6.1   Absorption by route of exposure
         6.2   Distribution by route of exposure
         6.3   Biological half-life by route of exposure
         6.4   Metabolism
         6.5   Elimination by route of exposure

    7. Toxicology

         7.1   Mode of action
         7.2   Toxicity
               7.2.1   Human data
                       7.2.1.1   Adults
                       7.2.1.2   Children
               7.2.2   Relevant animal data
               7.2.3   Relevant  in-vitro data
               7.2.4   Workplace standards
               7.2.5   Acceptable daily intake (ADI) and other guideline
                       levels
         7.3   Carcinogenicity
         7.4   Teratogenicity
         7.5   Mutagenicity
         7.6   Interactions

    8. Toxicological analyses and biomedical investigations

         8.1   Material sampling plan
               8.1.1   Sampling and specimen collection
                       8.1.1.1   Toxicological analyses
                       8.1.1.2   Biomedical analyses
                       8.1.1.3   Arterial blood-gas analyses
                       8.1.1.4   Haematological analyses
                       8.1.1.5   Other (unspecified) analyses
               8.1.2   Storage of laboratory samples and specimens
                       8.1.2.1   Toxicological analyses
                       8.1.2.2   Biomedical analyses
                       8.1.2.3   Arterial blood-gas analyses
                       8.1.2.4   Haematological analyses
                       8.1.2.5   Other (unspecified) analyses
               8.1.3   Transport of laboratory samples and specimens
                       8.1.3.1   Toxicological analyses
                       8.1.3.2   Biomedical analyses
                       8.1.3.3   Arterial blood-gas analyses
                       8.1.3.4   Haematological analyses
                       8.1.3.5   Other (unspecified) analyses

         8.2   Toxicological analyses and their interpretation
               8.2.1   Tests on toxic ingredient(s) of material
                       8.2.1.1   Simple qualitative test(s)
                       8.2.1.2   Advanced qualitative confirmation
                                 test(s)
                       8.2.1.3   Simple quantitative method(s)
                       8.2.1.4   Advanced quantitative method(s)
               8.2.2   Tests for biological specimens
                       8.2.2.1   Simple qualitative test(s)
                       8.2.2.2   Advanced qualitative confirmation
                                 test(s)
                       8.2.2.3   Simple quantitative method(s)
                       8.2.2.4   Advanced quantitative method(s)
                       8.2.2.5   Other dedicated method(s)

               8.2.3   Interpretation of toxicological analyses

         8.3   Biomedical investigations and their interpretation
               8.3.1   Biochemical analyses
                       8.3.1.1   Blood, plasma or serum:
                                 -- basic analyses
                                 -- dedicated analyses
                                 -- optional analyses
                       8.3.1.2   Urine:
                                 -- basic analyses
                                 -- dedicated analyses
                                 -- optional analyses
                       8.3.1.3   Other fluids
               8.3.2   Arteria blood-gas analyses
               8.3.3   Haematological analyses:
                                 -- basic analyses
                                 -- dedicated analyses
                                 -- optional analyses
               8.3.4   Interpretation of biomedical investigations

         8.4   Other biomedical (diagnostic) investigations and their
               interpretation

         8.5   Overall interpretation of all toxicological analyses and
               biomedical investigations

         8.6   References

    9. Clinical effects

         9.1   Acute poisoning
               9.1.1   Ingestion
               9.1.2   Inhalation
               9.1.3   Skin exposure
               9.1.4   Eye contact
               9.1.5   Parenteral exposure
               9.1.6   Others
         9.2   Chronic poisoning
               9.2.1   Ingestion
               9.2.2   Inhalation
               9.2.3   Skin exposure
               9.2.4   Eye contact
               9.2.5   Parenteral exposure
               9.2.6   Others
         9.3   Course, prognosis, cause of death
         9.4   Systematic description of clinical effects
               9.4.1   Cardiovascular
               9.4.2   Respiratory
               9.4.3   Neurological
                       9.4.3.1   Central nervous system
                       9.4.3.2   Peripheral nervous system
                       9.4.3.3   Autonomic nervous system
                       9.4.3.4   Skeletal and smooth muscle

               9.4.4   Gastrointestinal
               9.4.5   Hepatic
               9.4.6   Urinary
                       9.4.6.1   Renal
                       9.4.6.2   Others
               9.4.7   Endocrine and reproductive systems
               9.4.8   Dermatological
               9.4.9   Eyes, ears, nose, throat: local effects

               9.4.10  Haematological
               9.4.11  Immunological
               9.4.12  Metabolic
                       9.4.12.1  Acid-base disturbances
                       9.4.12.2  Fluid and electrolyte disturbances
                       9.4.12.3  Others
               9.4.13  Allergic reactions
               9.4.14  Other clinical effects
               9.4.15  Special risks: pregnancy, breast-feeding, enzyme
                       deficiencies
         9.5   Others

    10. Management

         10.1  General principles
         10.2  Relevant laboratory analyses and other investigations
               10.2.1  Sample collection
               10.2.2  Biomedical analyses
               10.2.3  Toxicological analyses
               10.2.4  Other investigations
         10.3  Life-supportive procedures and symptomatic treatment
         10.4  Decontamination
         10.5  Elimination
         10.6  Antidote treatment
               10.6.1  Adults
               10.6.2  Children
         10.7  Management discussion: alternatives, controversies, and
               research needs

    11. Illustrative cases

         11.1  Case reports from literature
         11.2  Internally extracted data on cases (from the writer of
               the monograph)
         11.3  Internal cases (added by the poison centre using
               monograph)

    12. Additional information

         12.1  Availability of antidotes and sera
         12.2  Specific preventive measures
         12.3  Other

    13. References

    14. Author(s), reviewer(s), date (including each update),
        complete addresses

    Annex 4

    INTOX product record

    FIGURE 1

    FIGURE 2

    Annex 5

    INTOX communication record and miniform

    FIGURE 3

    FIGURE 4

    FIGURE 5

    FIGURE 6

    FIGURE 7

    Annex 6

    Proposed format for a poison centre annual report1

    Period covered by the report:   from .. / .. / .... to .. /.. /....
                                          D   M     Y       D  M    Y
    1. Centre

    Name:

    Address:

    Telephone:

    Fax:

    E-mail:

    Geographical area (officially) covered by centre:

    Population served (officially) by centre  (number):

    Time of coverage:.... hours/day, from..:.. to..:..... days/week

    User profile:
        General public
        Medical professionals

    Type of service of centre:
        Poison information service
        Analytical
        Patient care
        Training
        Other

              

    1   This is a suggested and somewhat comprehensive outline, which
        centres may wish to adapt for their own situation. Work is in
        progress in IPCS to establish an internationally agreed format
        with harmonized definitions of terms used in each section,
        following those used in the IPCS INTOX Package.

     Staff:

    Name of Technical/Medical Director:
    Name of Administrative Director:
    Professional:  (number) (indicate whether full-time or part-time)
        Physicians
        Pharmacists
        Nurses
        Laboratory staff
        Other

    Administrative  (number):

    General service  (number):

    External experts/advisers  (number):

        Fields of expertise  (e.g. agronomy, environment, botany,
                                   entomology):
        Date centre established  (date when service started operating):
                                   .. / .. / ....
                                   D    M    Y

        Location of centre  (e.g. ministry, hospital, medical school,
                                   university, other):
        Administrative affiliation (e.g. Ministry of Health, university
                                   hospital, private sector, other):

    2. Statistical data on communications1

    (a) Number of incoming, outgoing and other communications during
        reporting period  (communications by telephone, fax/telex,
         letter, personal contacts), for example:

                                                                       

    Telephone    Letter     Fax/Telex   Questionnaire  Personal   Other
      call                                             contacts
                                                                       

    In     Out   In    Out  In     Out    In     Out
                                                                       

    (b)  Number of incoming communications including "personal
         contacts" that are requests for information only (NB: no exposure
         and no patient involved; all items that start with "Request for
         ..... ")

              

    1    A "communication" is any interaction between a centre and its
         interlocutors or clients.

    (c)  Number of incoming communications including "personal
         contacts" concerning incidents only (NB: no patient involved)

    (d)  Number of incoming communications including "personal
         contacts" concerning incidents with patients

    (e)  Number of incoming communications per category of interlocutor
         (all)

    (f)  Number of incoming communications by location of interlocutor
         (all)

    (g)  Number of incoming communications including "personal
         contacts" per main category of use of agent

    (h)  Number of incoming communications including "personal
         contacts" by class of agent

    (i)  Number of incoming communications by month  (graphic
          presentation):

    (j)  Number of incoming communications by hour of the day (yearly
         average)  (graphic presentation)

    (k)  Comments

    3.  Statistical data on incidents reported2

         (a)  Total number of incidents reported

         (b)  Number of incidents involving more than one patient

         (c)  Number of incidents by type  (intentional, unintentional,
               adverse reaction, other, unknown)

         (d)  Number of incidents by location (all)

         (e)  Number of incidents per main category of plant, fungus,
              or animal, or of agent (by use).

         (f)  Number of incidents per class of agent  (e.g. pharmaceutical;
               veterinary product; industrial/commercial product;
               household/leisure product; cosmetic/personal hygiene
               product; pesticide; agricultural product; abuse;
               food/beverage; warfare/anti-riot agent; environmental
               contaminant; other)

         (g)  Comments

              

    2    An incident relates to an event or episode in which an
         exposure or poisoning may or may not have taken place.

    4.  Statistical data on patients involved in communications1

    (a)  Total number of patients about whom communications are received

         -- human (NB: this number should be the same as 2(d))
         -- animal2

    (b)  Number of human patients by type of incident and agents by main
         category of use, e.g.

    (c)  Number of human patients by type of incident and by class of 
         agent

    (d)  Number of human patients by type of incident and age groups
         and sex of patients

    (e)  Number of pregnant human patients

    (f)  Number of human patients by age group and main category of use
         of the agent

    (g)  Number of human patients by age group and class of agent (NB:
         second or other level of the existing classification)

    (h)  Number of human patients by risk assessment

    (i)  Number of human patients by final severity grading

    (j)  Number of human patients by final outcome

    (k)  Number of human patients by treatment recommended by centre

    (l)  Number of human patients by location of treatment given before
         the enquiry

    (m)  Number of human patients by age group where outcome is death
         and type of incident

    (n)  Number of human patients by sex where outcome is death and
         main category of use of agent

    (o)  Number of human patients by sex where outcome is death and
         class of agent

              

    1    This refers to data on humans or animals that have been exposed
         to or poisoned by an agent.
    2    Animal information given here.

                                                                                                                    
                                              Intentional   Unintentional   Adverse   Other   Unknown    Total
                                                                            reaction
                                                                                                                

    Pharmaceuticals

    Veterinary products

    Industrial/commercial chemicals

    Household/leisure products

    Cosmetics/personal
    hygiene products

    Pesticides

    Agrochemicals, other
    than pesticides

    Abuse

    Food and beverages

    Warfare/anti-riot agents

    Environmental
    contaminants

    Other/unknown

    Total
                                                                                                                
        (p)  Comments  (e.g. summary of main observations, trends, general
          problems in relation to each main category of agent and specific
          problems with each category, such as cases with unusual
          symptomatology)

    5.  Data on analytical and other laboratory investigations

    (a)  Type and quantity of analytical equipment operational in the
         laboratory1

    (b)  Total number of toxicological analytical investigations
         undertaken

    (c)  Total number of other laboratory investigations undertaken

    (d)  Main agents investigated and techniques used, in decreasing
         order of frequency

    (e)  Other investigations carried out by the laboratory:
         --   identification of poisonous plants
         --   identification of poisonous or venomous animal
         --   analysis of water for chemical pollutants
         --   analysis of food for chemical pollutants
         --   analysis of food/water for microbiological pollutants
         --   identification of controlled/abused drugs (seizures)
         --   urine screening of drug abusers
         --   forensic toxicology
         --   occupational toxicology
         --   environmental toxicology
         --   therapeutic drug monitoring
         --   clinical microbiology
         --   others (specify)

    (f)  Comments  (e.g. availability of supplies and reagents)

              

    1    For list of equipment and techniques for the analytical
         toxicology laboratory.

    6.  Data on facilities for the management of patients

    (a)  List number of beds  (e.g. in the centre itself, emergency
          room, intensive care unit, medical ward, other)

    (b)  Outpatient clinic  (e.g. number of consultations)

    (c)  Access to specialized treatment  (e.g. haemodialysis)

    (d)  Access to specialized diagnostic facilities  (e.g. nuclear
          magnetic resonance)

    (e)  Comments

    7.  Antidotes and antivenoms available at centre

    (a)  Antidotes and antivenoms available, used and distributed
         during the year1

    (b)  Comments  (e.g. new formulations and developments)

    8.  Prevention activities

    (a)  Community poisoning prevention activities, including material
         prepared  (e.g. mass media activities, public education
          campaigns, other)

    (b)  Partners in prevention activities  (e.g. ministries, hospitals,
          community groups, nongovernmental organizations, other)

    (c)  Toxicovigilance activities:
         --   number of investigations of toxic situations thought to
              require alert
         --   number of alerts called
         --   summary of reports to authorities and other actions taken
         --   material prepared

    (d)  Results/outcome of prevention activities

    (e)  Comments

    9.  Advisory roles to governmental and other bodies

          (e.g. Advice given on registration of pesticides, on safety
          measures, regulatory activities, other)

              

    1    For classified list of antidotes.

    10. Training and education activities for professionals

    (a)  Training courses organized by centre  (e.g. title, objectives,
          place, dates, type of audience, sponsorship, other)

    (b)  Training activities organized by others where members of the
         centre took an active part  (e.g. title, objective, place, dates,
          type of audience, sponsorship, other)

    (c)  Curricular studies organized by centre:
         --   undergraduate level
         --   postgraduate level

    (d)  Comments

    11. Research activities of the centre

          (e.g. titles, objectives, partners, duration, source of
          funding specifically for research, other)

    (a)  Clinical

    (b)  Analytical

    (c)  Epidemiological

    (d)  Projects

    (e)  Other

    (f)  Comments

    12. Publications

    (a)  Publications/reports/brochures issued by the centre  (e.g.
          title, brief summary, reference)

    (b)  Publications  (e.g. case reports, articles, monographs, theses,
          books) written by the staff of the centre  (title, brief summary,
          and reference)

    (c)  Comments

    13. Informatics facilities at centre

    (a)  Computer hardware
         --   type and number of computers
         --   number of printers, CD-ROM drivers, tape drivers

    (b)  Computer software:
         --   commercially available software (name and uses)
         --   custom-built software (name and uses)

    (c)  Comments

    14. National and international meetings and cooperative
         activities of centre

    (a)  Organized by the centre
         --   national meetings/congresses/workshops  (e.g. title, place,
               dates, whether summary of meeting is available, number of
               members of the centre involved)
         --   international meetings/congresses/workshops  (e.g. title,
               place, dates, whether summary of meeting is available,
               number of members of the centre involved)

    (b)  Participation of the centre
         --   in national meetings/congresses/workshops  (e.g. title,
               place, dates, whether summary of meeting is available,
               number of members of the centre involved)
         --   in international meetings/congresses/workshops  (e.g. title,
               place, dates, whether summary of meeting is available,
               number of members of the centre involved)

    (c)  Cooperative projects/activities  (e.g. title, brief description,
          partners, duration)

    (d)  Support to other centres (e.g. setting up)  (brief description
          of activities, centre supported, dates, staff of the centre
          involved)

    (e)  Training activities for other centres  (brief description,
          centre, dates)

    (f)  Regional activities  (free-text description of activities in
          chronological order)

    (g)  Comments

    15. Budget for the period of the report
          (local currency = US$ = other)

    (a)  Overall annual budget

    (b)  Staff costs

    (c)  Operating costs

    (d)  Overall increase/decrease on previous year's budget

    (e)  Fund allocations for specific new activities  (e.g. activity,
          duration, amount)

    16. Library resources at centre

    (a)  Number of subscriptions  (list to be produced only for the
          first annual report)

    (b)  List of new acquisitions in reporting period

    (c)  Comments

    17. Main needs of the centre

         This section is intended to present briefly the needs the
         centre has identified where technical, financial, or other
         support would be desirable, or where interaction with other
         centres would be fruitful.

    Annex 7

    The Environmental Health Criteria Series

    The Environmental Health Criteria Series is published by WHO and may
    be obtained from Distribution and Sales, World Health Organization,
    1211 Geneva 27, Switzerland.

    Acetaldehyde (No. 167, 1995)
    Acetonitrile (No. 154, 1993)
    Acrolein (No. 127, 1991)
    Acrylamide (No. 49, 1985)
    Acrylonitrile (No. 28, 1983)
    Aged population, principles for evaluating the effects of chemicals   
    on (No. 144, 1992)
    Aldicarb (No. 121, 1991)
    Aldrin and dieldrin (No. 91, 1989)
    Allethrins (No. 87, 1989)
    Aluminium (in preparation)
    Aluminosilicates (bentonite, etc.) (in preparation)
    Amitrole (No. 158, 1994)
    Ammonia (No. 54, 1986)
    Anticoagulant rodenticides (No. 175, 1995)
    Arsenic (No. 18, 1981)
    Asbestos and other natural mineral fibres (No. 53, 1986)
    Barium (No. 107, 1990)
    Benomyl (No. 148, 1993)
    Benzene (No. 150, 1993)
    Beryllium (No. 106, 1990)
    Biomarkers and risk assessment: concepts and principles
      (No. 155, 1993)
    Biotoxins, aquatic (marine and freshwater) (No. 37, 1984)
    Brominated diphenylethers (No. 162, 1994)
    Butanols -- four isomers (No. 65, 1987)
    Cadmium (No. 134, 1992)
    Cadmium -- environmental aspects (No. 135, 1992)
    Camphechlor (No. 45, 1984)
    Carbamate pesticides: a general introduction (No. 64, 1986)
    Carbaryl (No. 153, 1994)
    Carbendazim (No. 149, 1993)
    Carbon disulfide (No. 10, 1979)
    Carbon monoxide (No. 13, 1979)
    Carcinogens, summary report on the evaluation of short-term
       in vitro tests (No. 47, 1985)
    Carcinogens, summary report on the evaluation of short-term
       in vivo tests (No. 109, 1990)
    Chemical exposures, principles for assessment of risks from
      (Part A) (in preparation)
    Chlordane (No. 34, 1984)
    Chlordecone (No. 43, 1984)
    Chlorendic acid and anhydride (No. 185, 1996)
    Chlorinated flame retardants (in preparation)

    Chlorinated paraffins (No. 181, 1996)
    Chlorine and hydrogen chloride (No. 21, 1982)
    Chlorobenzenes other than hexachlorobenzene (No. 128, 1991)
    Chlorofluorocarbons, fully halogenated (No. 113, 1990)
    Chlorofluorocarbons, partially halogenated
       (ethane derivatives) (No. 139, 1992)
       (methane derivatives) (No. 126, 1991)
    Chloroform (No. 163, 1994)
    Chlorophenols (No. 93, 1989)
    Chlorothalonil (No. 183, 1996)
    Chromium (No. 61, 1988)
    Community noise (in preparation)
    Cresols (No. 168, 1995)
    Cyhalothrin (No. 99, 1990)
    Cypermethrin (No. 82, 1989)
    Cypermethrin, alpha- (No. 142, 1992)
    DDT and its derivatives (No. 9, 1979)
    DDT and its derivatives -- environmental aspects (No. 83, 1989)
    Deltamethrin (No. 97, 1990)
    Diaminotoluenes (No. 74, 1987)
    1,2-Dibromoethane (No. 177, 1996)
    1,2-Dichloroethane (No. 62, 1987) (No. 176, 1995, 2nd ed.)
    2,4-Dichlorophenoxyacetic acid (2,4-D) (No. 29, 1984)
    2,4-Dichlorophenoxyacetic acid -- environmental aspects
       (No. 84, 1989)
    1,3-Dichloropropene, 1,2-dichloropropane and mixtures
       (No. 146, 1993)
    Dichlorvos (No. 79, 1988)
    Diesel fuel and exhaust emissions (No. 171, 1996)
    Diethylhexyl phthalate (No. 131, 1992)
    Diflubenzuron (No. 184, 1996)
    Dimethoate (No. 90, 1989)
    Dimethylformamide (No. 114, 1991)
    Dimethyl sulfate (No. 48, 1985)
    Diseases of suspected chemical etiology and their prevention,
      principles of studies on (No. 72, 1987)
    Dithiocarbamate pesticides, ethylenethiourea, and
      propylenethiourea: a general introduction (No. 78, 1988)
    Electromagnetic fields (No. 137, 1992)
    Endosulfan (No. 40, 1984)
    Endrin (No. 130, 1992)
    Environmental epidemiology, guidelines on studies in (No. 27, 1983)
    Epichlorohydrin (No. 33, 1984)
    Ethylbenzene (No. 186, 1996)
    Ethylene dibromide (in preparation)
    Ethylene oxide (No. 55, 1985)
    Extremely low frequency (ELF) fields (No. 35, 1984)
    Fenitrothion (No. 133, 1992)
    Fenvalerate (No. 95, 1990)
    Fluorines and fluorides (No. 36, 1984)
    Food additives and contaminants in food, principles for the safety
      assessment of (No. 70, 1987)

    Formaldehyde (No. 89, 1989)
    Genetic effects in human populations, guidelines for the study of
      (No. 46, 1985)
    Glyphosate (No. 159, 1994)
    Guidance values for health-based exposure limits (No. 170, 1994)
    Heptachlor (No. 38, 1984)
    Hexachlorobutadiene (No. 156, 1994)
    Hexachlorocyclohexanes, alpha- and beta- (No. 123, 1992)
    Hexachlorocyclopentadiene (No. 120, 1991)
    n-Hexane (No. 122, 1991)
    Hydrazine (No. 68, 1987)
    Hydrogen sulfide (No. 19, 1981)
    Hydroquinone (No. 157, 1994)
    Immunotoxicity associated with exposure to chemicals: principles
      and methods for assessment (No. 180, 1996)
    Infancy and early childhood, principles for evaluating health risks
      from chemicals during (No. 59, 1986)
    Inorganic lead (No. 165, 1995)
    Isobenzan (No. 129, 1991)
    Isophorone (No. 174, 1995)
    Kelevan (No. 66, 1986)
    Lasers and optical radiation (No. 23, 1982)
    Lead (No. 3, 1977)1
    Lead -- environmental aspects (No. 85, 1989)
    Lead, inorganic (No. 165, 1995)
    Lindane (No. 124, 1991)
    Linear alkylbenzene sulfonates and selected related compounds
      (No. 169, 1995)
    Magnetic fields (No. 69, 1987)
    Man-made mineral fibres (No. 77, 1988)
    Manganese (No. 17, 1981)
    Mercury (No. 1, 1976)1
    Mercury -- environmental aspects (No. 86, 1989)
    Mercury, inorganic (No. 118, 1991)
    Methomyl (No. 178, 1996)
    2-Methoxyethanol, 2-ethoxyethanol, and their acetates
       (No. 115, 1990)
    Methyl bromide (No. 166, 1995)
    Methylene chloride (No. 32, 1984, 1st ed.) (No. 164, 1996, 2nd ed.)
    Methyl ethyl ketone (No. 143, 1992)
    Methyl isobutyl ketone (No. 117, 1992)
    Methyl isocyanate (in preparation)
    Methylmercury (No. 101, 1990)
    Methyl parathion (No. 145, 1992)
    Mirex (No. 44, 1984)
    Morpholine (No. 179, 1996)
    Mutagenic and carcinogenic chemicals, guide to short-term tests
      for detecting (No. 51, 1985)
    Mycotoxins (No. 11, 1979)
    Mycotoxins, selected: ochratoxins, trichothecenes, ergot
       (No. 105, 1990)

    Nephrotoxicity associated with exposure to chemicals, principles
      and methods for the assessment of (No. 119, 1991)
    Neurotoxicity associated with exposure to chemicals, principles and
      methods for the assessment of (No. 60, 1986)
    Nickel (No. 108, 1991)
    Nitrates, nitrites, and N-nitroso compounds (No. 5, 1978)1
    Nitrogen, oxides of (NOx) (No. 4, 1977)1 (No. 188, 1997, 2nd ed.)
    2-Nitropropane (No. 138, 1992)
    Noise (No. 12, 1980)1
    Organophosphorus flame retardants (in preparation)
    Organophosphorus insecticides: a general introduction
      (No. 63, 1986)
    Paraquat and diquat (No. 39, 1984)
    Pentachlorophenol (No. 71, 1987)
    Permethrin (No. 94, 1990)
    Pesticide residues in food, principles for the toxicological
      assessment of (No. 104, 1990)
    Petroleum products, selected (No. 20, 1982)
    Phenol (No. 161, 1994)
    d-Phenothrin (No. 96, 1990)
    Phosgene (in preparation)
    Phosphine and selected metal phosphides (No. 73, 1988)
    Photochemical oxidants (No. 7, 1978)
    Platinum (No. 125, 1991)
    Polybrominated biphenyls (No. 152, 1994)
    Polychlorinated biphenyls and terphenyls (No. 2, 1976)1
      (No. 140, 1992, 2nd ed.)
    Polychlorinated dibenzo-p-dioxins and dibenzofurans (No. 88, 1989)
    Progeny, principles for evaluating health risks associated with
     exposure to chemicals during pregnancy (No. 30, 1984)
    1-Propanol (No. 102, 1990)
    2-Propanol (No. 103, 1990)
    Propachlor (No. 147, 1993)
    Propylene oxide (No. 56, 1985)
    Pyrrolizidine alkaloids (No. 80, 1988)
    Quintozene (No. 41, 1984)
    Quality management for chemical safety testing (No. 141, 1992)
    Radiofrequency and microwaves (No. 16, 1981)
    Radionuclides, selected (No. 25, 1983)
    Resmethrins (No. 92, 1989)
    Selenium (No. 58, 1986)
    Styrene (No. 26, 1983)
    Sulfur oxides and suspended particulate matter (No. 8, 1979)
    Synthetic organic fibres, selected (No. 151, 1993)
    Tecnazene (No. 42, 1984)
    Tetrabromobisphenol A and derivatives (No. 172, 1995)
    Tetrachloroethylene (No. 31, 1984)
    Tetradifon (No. 67, 1986)
    Tetramethrin (No. 98, 1990)
    Thallium (No. 182, 1996)

    Thiocarbamate pesticides: a general introduction (No. 76, 1988)
    Tin and organotin compounds (No. 15, 1980)
    Titanium (No. 24, 1982)
    Toluene (No. 52, 1986)
    Toluene diisocyanates (No. 75, 1987)
    Toxicity of chemicals (Part 1), principles and methods for
      evaluating (No. 6, 1978)
    Toxicokinetic studies, principles of (No. 57, 1986)
    Tributyl phosphate (No. 112, 1991)
    Tributyltin compounds (No. 116, 1990)
    Trichlorfon (No. 132, 1992)
    1,1,1-Trichloroethane (No. 136, 1992)
    Trichloroethylene (No. 50, 1985)
    Tricresyl phosphate (No. 110, 1990)
    Triphenyl phosphate (No. 111, 1991)
    Tris- and bis(2,3-dibromophenyl) phosphate (No. 173, 1995)
    Ultrasound (No. 22, 1982)
    Ultraviolet radiation (No. 14, 1979) (No. 160, 1994, 2nd ed.)
    Vanadium (No. 81, 1988)
    Vinylidene chloride (No. 100, 1990)
    White spirit (No. 187, 1996)
    Xylenes (No. 190, 1997)

              

    1    Out of print.