IRPTC
The International Register of Potentially
Toxic Chemicals
Challenges of Data Collection in the Field of Toxicology
S e r g i o Caroli, Antonio Menditto, Ferdinando Chiodo
Istituto Superiore di Sanitfi., Viale Regina Elena 299, 00161 Roma, Italy
Abstract
The benefits and drawbacks consequent to the widespread use of
chemicals are inextricably interwoven. According to recent esti-
mates, more than 8 million substances are presently known, 70,000
of which are in common use as industrial compounds, pesticides,
pharmaceuticals, food additives, cosmetics and the like. It is esti-
mated that substances used as such will increase annually by 1000
in number. The deleterious consequences deriving from their ex-
ploitation pose tremendous challenges to the scientific community
for the protection of human health and the environment. Therefore
it is of utmost priority to appropriately select valid information gen-
erated in this investigation area and to convey it correctly to users.
Here, the adoption of the principles of good laboratory practice in
experimental activities is essential, as well as the creation of global
networks for data exchange on the safe use of chemicals. The struc-
ture and goals of the International Register of Potentially Toxic
Chemicals (IRPTC, the database of the United Nations Environ-
ment Programme) are detailed to give an example of such an un-
dertaking. Seventeen fields are covered, i.e. identifiers, properties
and classification, production/trade, production processes, use,
pathways into the environment, concentrations, environmental fate
tests, environmental fate, chemobiokinetics, mammalian toxicity,
special toxicity studies, effects on organisms in the environment,
sampling/preparation/analysis, spills, treatment of poisoning, waste
management and recommendations/legal mechanisms.
Key words: International Register of Potentially Toxic Chemicals;
IRPTC; data collection; data exchange; information,
selected; United Nations Environment Programme;
UNEP
1 Introduction
An effective protection of h u m a n health and environment
is nowadays based on three main pillars, namely reliability
of experimental information, harmonization of research
activities at a national and international level and adequate
diffusion of critically evaluated data. This applies even
more so in the case of chemical substances given their
worldwide increasing production, use, storage, transport,
handling and disposal. More than 8 million chemicals are
in fact presently known, 70,000 of which are in c o m m o n
use as industrial compounds, pesticides, pharmaceuticals,
food additives, cosmetics and the like. Benefits and draw-
backs consequent to this ubiquitous presence are inextrica-
104
Policy and Legislation
bly interwoven. It would certainly be preposterous to en-
visage a massive reduction in the manufacturing of chemi-
cals without at the same time significantly affecting the
quality of life achieved so far.
In response to increasing awareness of public opinion, the
1970s saw a complete reversal of approaches and general
policy followed by the more industrialized countries to ex-
ert an effective control in the environmental dispersion of
chemicals and ultimately on their possible noxious conse-
quences. This led primarily to give priority to preventive
strategies instead of undertaking after-emergency curative
steps to minimize the deleterious follow-up of unforesee-
able events. This new attitude, on the other hand, was not
at all in conflict with technological progress, which in turn
benefited from the added knowledge of the negative side ef-
fects of indiscriminate use of chemical substances. In this
context the role played by international organizations,
such as O E C D and W H O , definitely, triggered the concep-
tion and introduction of operative mechanisms to verify
whether, and how, products not yet on the market could
endanger m a n k i n d and ecosystems. The US Toxic Sub-
stances Control Act (better k n o w n as TOSCA) and the suc-
cessive EC Directive No. 79/831 (called the Sixth Amend-
ment, later replaced by the Seventh Amendment, i.e. EC
Directive No. 92/32) adopted by all member states, are two
milestones in this field [1, 2]. Such a dramatic change in the
environmental policy of various countries caused an imme-
diate surge forward in the task of systematic and critical
collection of data on toxic effects and other properties of
the multiplicity of substances already on the market and
more or less in general useage [3-5].
From this standpoint, the intrinsic characteristics of the
substance, namely its physical-chemical properties, are of
p a r a m o u n t importance. These account for the substance's
environmental behaviour and interaction with living or-
ganisms. They also fingerprint the c o m p o u n d in an un-
equivocal manner, backed up by all possible types of spec-
tral data (UV, IR, N M R , mass and other). Such a set of pa-
rameters is vital for the univocal identification of the chem-
ical and consequently its detection in whatever matrix. By
the same token, proper analytical methodologies of highest
precision and, above all, accuracy are the cornerstone of any
proper evaluation of the substance pattern and impact, as
ESPR - Environ. Sci. & Pollut. Res. 3 (2) 104-107 (1996)
9 ecomed publishers, D-86899 Landsberg, Germany
Policy and Legislation
it is only through them that reliable quantitative dose-effect
relationships can be attained.
The establishment in the late 1970s of the International
Register of Potentia]ly Toxic Chemicals (IRPTC) under the
aegis of the United Nations Organization (UNO) and as a
part of the United Nations Environment Programme
(UNEP) is the most valid answer presently conceivable to
satisfy such a need at planetary level without interfering
with or overlapping other databanks, be they national or
international. These in turn meet more specific and diversi-
fied exigencies, although they are one of several potential
sources of information of undeniable importance for the
Register itself.
This paper focuses mainly on the role played to date by the
IRPTC to accomplish such goals. On the other hand, the
evolution of this programme and the prospects open by ac-
tivities presently being launched are the subject of another
article following this one.
2 Organizationand Purpose of the Register
More than twenty years have elapsed since the date that
can be considered the official birthday of the Register
[6-8]. During the United Nations Conference on Man and
Environment held in 1972 in Stockholm, in fact, it was
recommended that the United Nations Environment Pro-
gramme be established and, within this framwork, plans be
developed for an international register of data on chemicals
in the environment. Thus, the main objective of the Regis-
ter is that of evaluating, predicting and reducing the risk
caused by the presence of chemicals in the environment.
For this purpose the Register provides the most up-to-date,
reliable and complete information to authorities responsi-
ble for the safeguard of health and environment. This is an
extremely challenging task with a number of targets:
1. easier access to data already available in the global net-
work on the effects of chemical products in order to
achieve better useage of national and international re-
sources;
2. identification of the sectors where present knowledge is
poor or merely nonexistent with the ensuing promotion
of research suited to fill these gaps;
3. emphasis on the risks inherent in the various substances
and stimulation of competent authorities on preventive
measures to minimize their indiscriminate use;
4. information on legal provisions, monitoring and con-
trol activities and existing reliable recommendations,
for the control of potential toxic chemicals.
The structure used by the Register to attain these goals is
outlined in Table 1 and is based on four main components.
The network of collaborating units mentioned also in-
cludes the National Correspondents, as well as national
and international institutions, industrial centers and exter-
nal contractors. Table 2 summarizes the main goals of the
Register.
ESPR- Environ. Sci. & Pollut. Res. 3 (2) 1996
IRPTC
Table 1: Structural elementsfor the IRPTC activities
- The Programme Activity Centre (PAC), i,e. the operative and c o o r -
dinating headquarters located in Geneva.
- The network of collaborating units with the function of receiving
and forwarding to PAC the queries addressed to IRPTC by users.
- Information sources which put their databases at the IRPTC's dis-
posal.
- The National Correspondents acting as coordination centres for
the interaction with the IRPTC, with an acitve role in the exchange
of information.
Table 2: Objectivesof IRPTC
1. To make it easier to obtain the existing information on production,
distribution, release, disposal and adverse effects of chemicals.
2. To identify the important gaps in present knowledge of the effects
of chemicals and call attention to the need for research to fill those
gaps.
3. To help identify potential hazards from chemicals and wastes and
t o improve awareness of the dangers.
4. To provide information about national, regional and global policies,
controls and recommendations on potentially toxic chemicals.
5. To help implement policies for the exchange of information on
chemicals in international trade.
3 T o w h o m I R P T C is Addressed
To decide which information and to what extent it should
be dealt with by the Register necessitates clearly identifying
possible categories of users. Four classes of potential ad-
dressees have been envisaged, each obviously in part over-
lapping the others:
1. member states of the United Nations, in particular of
UNEP, as well as of all other international organiza-
tions involved in environmental management and pol-
icy;
2. authorities responsible for the protection of public
health and control of chemical production, transport,
import-export and use of substances containing nox-
ious components;
3. the scientific community at large;
4. industries and analogous establishments, the activities
of which imply the introduction and the dispersion of
chemicals into the environment.
At the present stage of development of the Register, infor-
mation on many thousands of substances is available at
various degrees of complexity. The goal in each case is the
accomplishment of a so-called profile, i.e. a collection of
factual information, accurately selected and unequivocally
traceable to the sources from which qualitative and quan-
titative data were extracted. It is not conceivable, however,
that reliable and exhaustive information can be had
quickly and throughly for all substances. Thus, the prepa-
ration of profiles is focused on a relatively small number of
compounds, considered high priority from an impartial
scrutiny of lists already in existence, as well as on the basis
of accidents and emergencies. This led to the completion of
105
IRPTC
about one thousand profiles, a good percentage of which
are pesticides; the overall process is never-ending as each
dossier is continuously updated and revised in the light of
new knowledge accrued in the meanwhile. New profiles,
on the other hand, are added as soon as a minimum
amount of reliable information can appropriately be set up.
4 How the Register Works
A long preliminary effort was made at the onset of IRPTC
to select the type of information most suited to compile a
profile, in order to fully meet the needs of extremely diver-
sified users, guaranteeing at the same time an entirely de-
pendable and flexible system of consistent data. The pre-
sent structure of a profile encompasses ten main categories,
namely identifiers, bibliographic sources, physical-chemi-
cal properties, analysis, environment, toxicity, exposure,
production, treatment and legal aspects. These reflect the
sectors in which one can effectively and logically distribute
the information necessary to assess the impact of chemicals
and measures to be adopted for an effective control. All
this material is re-allocated, for the sake of practicality, into
seventeen categories, one or more of them forming part of
the topics listed above. Finally, several of these categories
are further subdivided into sections for more effective re-
trieval of a specific subject matter. The overall structure is
detailed in Table 3. Within this context it is worth recalling
that no quantitative figure should be viewed singularly. In-
stead, it is a fragment of the entire fabric of knowledge and
scientific evidence put together in a highly consistent way,
and therefore capable of providing competent authorities
with sound and reliable elements of information when de-
ciding on qualified actions to be taken.
Table 3: IRPTCdata profile structure
1. Identifiers, Properties and Classification
2. Production/Trade
3. Production Process
4. Use
5. Pathways into the Environment
6. Concentrations (loss/persistence, concentrations, human intakes)
7. Environmental Fate Tests (biodegratation/biotransformation, pho-
todegradation, hydrolysis, sorption, evaporation, oxidation, model
ecosystem studies)
8. Environmental Fate
9. Chemobiokinetics (absorption, distribution, bioconcentration fac-
tor, metabolism, excretion)
10. Mammalian Toxicity
11. Special Toxicity Studies (biochemical interactions, carcinogenici-
ty, mutagenicity, neurotoxicity, behaviour, sensitization, interacting
agents, primary irritation, immunotoxicity, reproduction, terato-
genicity)
12. Effects on Organisms in the Environment (aquatic toxicity, terres-
trial toxicity)
13. Sampling, Preparation, Analysis
14. Spills
15. Treatment of Poisoning
16. Waste Management
17. Recommendations/Legal Mechanisms
106
Policy and Legislation
5 T h e Problem of Sources
One of the first difficulties to overcome was encountered in
the strategy necessary to extract reliable and complete in-
formation from the enormous mass of papers, books, doc-
uments, reports and other published literature. The criteria
that have been adopted for this are based on the widest
possible exploitation of information, carefully evaluated by
international panels of experts and summarized in mono-
graphs, working documents and the like, for which the
term "secondary literature" is used. It is quite understand-
able, however, that these critical reports are not always
available. A sequence of priorities has thus been established
for bibliographic material, so that when certain informa-
tion is lacking, the next step is followed. The hierarchy in-
spiring this modus operandi is illustrated in Table 4. This
is an expedient compromise between the preservation of
the quality standards already touched upon and the possi-
bility of having at one's disposal more or less valid infor-
mation where the only alternative would be no data at all.
Table 4: Prioritysequence of information sources as adopted by
IRPTC
1. Monographs and guidance documents whose contents were sub-
jected to critical revision at an international level (secondary litera-
ture).
2. Monographs and guidance documents whose contents were sub-
jected to critical revision at national level.
3. Surveys, monographs and reports at national level not evaluated
critically by a panel of experts.
4. Papers published in scientific journals, reports supplied by indus-
tries and the like (primary literature).
This strategy can be considered acceptable only if that kind
of data are clearly labeled as provisional. Furthermore, it is
important to stress that research workers will rarely find a
detailed description of procedural aspects in the Register,
and consequently more often than not will need to consult
the published work. This aspect is in fact outside the scope
of the Register which instead aims at pointing out, for the
benefit of the scientific community, the substances which
apparently show wide gaps in experimental research in
spite of their considerable potential for toxic effects. The
inadequacy of presently available budgetary resources
compared to the gravity of the issue makes it even more
manifest that such evaluations play a vital role for both
competent authorities and industrial sectors for effective
and rational coordination of research in this field. The con-
stant updating of the Register ensures that all relevant in-
formation (or any significant alterations to data already
possessed) can be included upon becoming available. The
major phases of a profile compilation are set forth in Table 5.
Among the users of IRPTC, developing countries deserve
special attention considering the general inadequacy and
paucity of structures, and the ensuing higher vulnerability
in the battle for the protection of man and the environ-
ment. With the purpose therefore of obviating the lack of
ESPR -Environ. Sci. & Pollut. Res. 3 (2) 1996
Policy and Legislation
Table 5: Main steps of the compilation of a data profile for the
Register
1. Formation of the database of bibliographic information (through
collection of documents and evaluation of literature, with active
participation of the network of collaborative units).
2. Screening and presentation of data (inclusive of preparation of
texts, of working sheets of the Register and of their computerized
version, again with the active participation of the network of collab-
orative units).
3. Revision and correction of drafts.
4. Definitive profiles.
essential facilities in these countries (certainly with the
keenest necessity of proper information on the deleterious
effects of chemicals), profiles are also supplied in the
printed version as well as computerized.
6 D i f f u s i o n of Information
The Register exploits two powerful channels for the diffu-
sion of data and information in general. The first is a
query-response service. Requests of the most diversified na-
ture are continually addressed to the Central Unit of the
Register in Geneva, either through the network of national
correspondents or directly. Queries range from very spe-
cific questions on particular compounds to the delivery of
whole profiles. There are also general questions concerning
categories of compounds, mathematical relationships be-
tween structure and activity and similar things. To comply
with the requests the Register calls on, if necessary, other
international organizations such as W H O and ILO who
will provide assistance.
The second means of spreading information is the IRPTC
Bulletin. The purpose of this publication is not only that of
illustrating the Register activities, but also to keep the
reader informed on what is being accomplished by other
agencies. News regarding scientific and technological
progress and legal updating on a global scale is reported.
Published in English, Spanish, Russian and French, this
quarterly publication now serves as a rapid and flexible in-
formation tool. Nor should the primary importance of
IRPTC in implementing the Londong Guidelines be over-
looked [9]. According to a voluntary agreement reached in
1987, trade of chemicals banned or severely restricted in
the exporting country should take place only with the in-
formed consent of the recipient. Thus, a summary of the
most updated knowledge on the detrimental effects of a
substance should be forwarded to the authorities of the im-
porting country before the actual sale be approved. The
Register, thanks to its very nature, is the ideal mechanism
to properly manage this activity.
ESPR- Environ. Sci. & Pollut. Res. 3 (2) 1996
IRPTC
7 The Foreseeable Future
The Register is now well established and is gaining wide
popularity. The progress made so far fully reflects the ini-
tially set goals, but at the same time poses certain prob-
lems, such as the need to improve the format for loading of
data. This aspect is extremely important, as it has direct
consequences on the efficiency of data retrieval. Other cru-
cial points are the treatment of nonpublished information
as well as of data qualified as confidential. A more and
more extensive and flexible expansion of the links between
the Register and the other components mentioned above
complete the scenario of top priorities.
The awareness acquired in the recent past of the global na-
ture of problems inherent in the control of chemical sub-
stances, and of the needs that ensue to adopt planetary
strategies for their solution, does not allow interests and
considerations at a national level to be taken into account.
The dependence of today's society on the availability and
dispersion of countless chemical substances does not con-
sent their use to be substantially reduced without an unac-
ceptable diminution in welfare. The only choice is therefore
a systematic and unitary approach to identify and limit (or
erase where possible) the noxious consequences deriving
from the improper use of chemicals. The Register thus con-
stitutes an additional weapon in the arsenal of the task
force for a more effective control of chemical substances
and, ultimately, for the achievement of a better quality of
life.
Acknowledgments
The skills and patience of Mr. Massimo DELLEFEMMINEand Mr. Marco
MOZZICAFREDDOin dealing with the various drafts of this manuscript
are gratefully acknowledged.
8 References
[I] G. W. INGLE(Ed.): TSCA'sImpact on Society and Chemical Indus-
try. ACS Symposium Series 213, American Chemical Society,
Washington, D.C. 1983, pp. 244
[2[ EEC Directive 79/831: Off. J. Eur. Comm. 22 (1979) 1259, 10
[3] The United Nations Environment Programme (UNEP) 1979
(Nairobi, Kenya)
[4] M. GILBERT;J. W. HUISMANS~in: Education and Safe Handling in
Pesticide Application. E. A. H. VAN HEEMSTRA,W. E TORDOIR
(Eds.), Elsevier Scientific Publishing Company (Amsterdam) 1982
[5] S. CAROLI;E CHIODO;A. MENDITTO(Eds.): Chemicals in Interna-
tional Trade: Information and Control. Special Issue of the Annali
dell'Istituto Superiore di Sanitfi 30 (1994) 361-47I
[6] J.W. HUISMANS:The International Register of Potentially Toxic
Chemicals. Ecotox. Environm. Safety 4 (1980) 393-403
[7] J.W. HUISMANS:Ambio 7 (1978) 275
[8] IRPTC:Instructions for the Selection and Presentation of Data for
the International Register of Potentially Toxic Chemicals with
Sixty Illustrative Chemical Data Profiles. Register Attribute Series
No. 2, Geneva, 1979
[9] EnvironmentalLaw Guidelines and Principles: London Guidelines
for the Exchange of Information on Chemicals in International
Trade. Decision 14/27 of the Governing Council of UNEP, 17 June
1987, 1987 (Nairobi, Kenya)
107