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)
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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
Annex 5
INTOX communication record and miniform
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.