IUPAC Glossaries of Terms Used in Toxicology

In 1973, IUPAC established a Commission on Toxicology, within the framework of the Clinical Chemistry Section.  Following the fundamental objectives of IUPAC from its very

beginning, the prime objective of the Commission was to promote world-wide “regulation, standardization, or codification” in relevant areas of chemistry.  Since 1973, the science of toxicology has developed rapidly, along with recognition of its importance in the maintenance of human health.  There have been two main driving forces.  First, the success of synthetic chemistry in producing many new substances with useful properties that contributed to better health and a better quality of life and second,  the gradual realisation that new substances might bring with them problems if not handled properly.  Unforeseen problems had arisen, for example, from excessive use of antibiotics, promoting the evolution of antibiotic resistant bacteria, and from careless disposal of waste and pesticides damaging our environment.  The awareness of such problems led to the introduction of new legislation such as the U.S. Toxic Substances Control Act (TSCA) and the European Regulation, Evaluation, Authorization and Restriction of CHemicals (REACH).   On these foundations, amongst others, the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) was built by the United Nations.  GHS defines and classifies the hazards of chemical products, communicating health and safety information via labels and safety data sheets.  It has been adopted internationally as the agreed basis for the replacement of the assortment of hazardous material classifications and labelling schemes previously used around the world.

The main driving force for the global harmonization of classification and labelling of chemicals was the need for globally agreed-upon legislation covering production, marketing, use, and disposal of chemicals.  In its absence, trade in chemicals had been seriously impeded, and even blocked, by national differences in legislation and, underlying them, in toxicity classification and labelling.  Key to the development of GHS was the action of the Organisation for Economic Cooperation and Development (OECD) in producing expert-approved toxicity tests that, if followed carefully, would provide data that were mutually-acceptable between nations and provide a basis for mutually-acceptable toxicity classifications.  Without this, international acceptance of GHS would have been impossible.

All of the developments in international harmonisation of toxicity classifications and in subsequent health and safety legislation, environmental protection legislation, and legislation covering the life cycle of chemicals from production to final disposal, had consequences for chemists.  However, at the time, few chemists were acquainted with toxicology and its terminology.  Accordingly, the IUPAC Commission on Toxicology decided to set up a project to produce a toxicology textbook written with chemists in mind.  It was clear that this book must have a glossary of toxicological terms if it were to be standalone textbook.  This project started in 1989 and resulted in a toxicology textbook for chemists and set of Powerpoint slides that are available (though not the CD listed alongside) on the IUPAC Educational Materials website* for download as a basis for teaching and learning fundamentals of toxicology. (See: http://media.iupac.org/publications/cd/essential_toxicology/index.html).

The book was subsequently published in two editions by the Royal Society of Chemistry (RSC).¹  This book carried its own glossary and this formed the basis for the first IUPAC Glossary of Terms used in Toxicology²  and, with it, a strategy for glossary preparation that underlies all succeeding toxicology glossaries.

*Note: The old IUPAC Educational Materials website has not been updated for some time, but still carries useful material such as the toxicology slides.

As a first step, the literature was thoroughly searched for existing toxicology glossaries and for terminology that was likely to cause problems, either because it was completely new or because it was being used in a new way.  Once an approximation to a final list of terms requiring definition was completed, the list was reviewed for completeness by practising toxicologists. Thereafter, definitions were drafted and these were submitted to a number of experts for review and comment.  Particular mention should be made of the kind collaboration of Professor Paolo Preziosi, then President of the International Union for Toxicology (IUTOX) and of Professor Norman Aldridge in the review stage of the first IUPAC glossary.  The Working Party for this glossary was also fortunate in having scientific support from the International Programme on Chemical Safety, the International Register of Potentially Toxic Chemicals, and the United Nations Environment Programme, allowing the use of published and unpublished material.  The Royal Society of Chemistry, London, UK, also kindly permitted the use of definitions from its books.  The Regional Office for Europe of the World Health Organization (WHO) generously permitted incorporation of definitions from Environmental Health Publication 10, “Environmental Toxicology and Ecotoxicology.” Further valuable support was given by Professor J.M. Last, the International Epidemiological Association, and Oxford University Press for permission to quote definitions from “A Dictionary of Epidemiology”, Second Edition.  In addition, The Association of Clinical Biochemists Scientific Committee reviewed a draft of the glossary and annotated it with their suggestions.  The Working Party further exchanged information with the IUPAC Commission on Biotechnology.  As a result, a number of terms may be found in both the toxicology glossary and the “Glossary of Terms Used in Biotechnology” prepared by that Commission.  In addition, helpful comments were received from the IUPAC Commission on Agricultural Chemistry and from other Commissions, such as the Commission on Water Chemistry.  Guidance was also received from members of Interdivisional Committee on Nomenclature, Terms, and Symbols (ITCNS).

The wide support enjoyed in compiling the first IUPAC Glossary of Terms Used in Toxicology is emphasised above because it established the basis of collaboration with appropriate experts and societies without which the subsequent specialised glossaries could not have been produced.  The first working party had also to learn the principles of compiling and defining terminology as it went along.  This learning process has continued throughout the production of succeeding glossaries until the present.  Aspects of the learning process are described in the article by Templeton entitled, “IUPAC Glossaries in Toxicology,”³ that appeared in Chemistry International in 2014.

The original Glossary for Chemists of Terms Used in Toxicology² was published in 1993 and a fully- revised and updated version⁴ was published in 2007.  This version contains about 1,200 fundamental terms.  It was been adopted by the U.S. National Library of Medicine and is the glossary associated with the ToxTutor modules on ToxNet (https://toxnet.nlm.nih.gov/ ).  It may be found online through ToxNet and at the U.S. National Library of Medicine web site at http://sis.nlm.nih.gov/enviro/iupacglossary/frontmatter.html.  In addition, it has been included as an Annex in the “Encyclopedia of Toxicology, 3rd Edition,” and also in “Information Resources in Toxicology, 4th Edition” (and 5th Edition in press), both edited by Philip Wexler.  Another book that has adopted many of the IUPAC definitions from the revised updated version of the original IUPAC Glossary is “A Small Dose of Toxicology: The Health Effects of Common Chemicals” by Steven Gilbert, available on the internet for download as a-free e-book ( See: http://www.toxipedia.org/display/dose/A+Small+Dose+of+Toxicology ).

A problem that has concerned those who have worked on the IUPAC toxicology glossaries over the years is that conventional definitions often seem inadequate to describe subtle nuances and underlying concepts.  The Working Group on the revised version of the original toxicology glossary attempted to solve this problem by identifying about forty terms that might benefit from something more than the normal definition with notes.  These terms were given expanded definitions in two papers in Pure and Applied Chemistry (PAC) that were called “Explanatory Dictionaries.”^5,6  Subsequently these articles were combined and published by the RSC in a book called “Concepts in Toxicology”⁷.  In this book, the relationships between the terms were shown in concept maps based on levels of organization, from molecules to organelles, to tissues and organs, and ultimately to individual organisms, populations, and ecosystems. Below, as an example, is one of these maps.

The first IUPAC glossary of terms used in toxicology contained definitions for over 1,200 terms frequently used in the relevant scientific literature and in related health and safety law and practice.  There were two annexes, one containing a list of abbreviations used in toxicology and and one containing a list of abbreviations used by international bodies and regulatory authorities.

The definitions given in the first glossary reflected identifiable current usage.  Obsolete terms such as “cytochrome P448” were included because such terms will still be found in older scientific articles of importance.  For some of the entries, alternative definitions have been given reflecting current variations in usage.

After the the first IUPAC glossary of terms used in toxicology, no further terms were considered for inclusion for some years until it became clear that toxicology was continuing to develop and to expand into a wide-range of other specialties in human medicine and biology.  The first area to get specialist attention was toxicokinetics⁸.  This glossary alone included definitions of three hundred and sixty-five terms.

Once the Glossary of Terms Used in Toxicokinetics⁷ had been published in Pure and Applied Chemistry, a review of the original glossary suggested that it needed revision to bring it up to date.  Consequently the two existing glossaries were merged and every definition was reconsidered and rewritten to clarify it where necessary.  After the normal strict PAC refereeing, the resultant extended and revised glossary³ was published⁴.

In revising the original glossary, it became clear that many terms used in ecotoxicology were missing.  Ecotoxicology was rapidly becoming a major concern of many chemists and an integration of environmental chemistry and ecotoxicology was taking place.  Accordingly, an IUPAC project to prepare a Glossary of Terms Used in Ecotoxicology⁹ was initiated.  The Glossary included terms related to chemical speciation in the environment, sampling, , and environmental analysis, as well terms related to adverse ecological effects of chemicals, ecological biomarkers, and the environmental distribution of chemicals.  In its final form, this glossary consisted of about 1,139 terms.

After the Glossary of Terms Used in Ecotoxicology was published, it was recognised that other important areas of toxicology with new and changing terminology were emerging, including immunotoxicology^10, neurotoxicology¹¹, and developmental and reproductive toxicology¹².  As before, the relevant literature was exhaustively searched in order to construct a list of new or redefined terms. Definitions were developed and refined before submitting each new glossary to the rigorous reviewing process required for acceptance for publication in PAC.  This added about 3,200 term definitions to the 1,500 already accumulated in previous glossaries.

With the publication in PAC of three new glossaries containing more than twice as many terms as the original version, it was clear that the toxicology glossary project had outgrown PAC. So it was proposed that a hard copy comprehensive IUPAC toxicology glossary should be produced as a book with the aim of eventually putting it online through the IUPAC website.  This was approved as an IUPAC project that would combine and revise the existing glossaries and prepare the resultant text for publication as a Comprehensive Glossary of Terms Used in Toxicology.¹³ The resultant book with that title was published by RSC on 1 September, 2017.

Toxicology uses terminology from chemistry, medicine, geology, botany, zoology, ecology, and veterinary medicine, as well as legal terms, many of them from fairly-recent legislation introduced to ensure chemical safety from manufacture to recycling or waste disposal.  To facilitate the continually-increasing global trade in chemicals and to manage it safely, understanding toxicology has become essential to the classification of toxicity, accurate labelling, and the production of accompanying safety data sheets.  In order to achieve this, legislation based on toxicity classification and labelling is in the process of co-ordination at the international level by the Globally Harmonized System promoted by the United Nations.

A harmonized system needs harmonized terminology, and such terminology requires rigorous definition, with a strong reviewing system to ensure that this is achieved. Chemistry has, through IUPAC, had such a system in place now for a hundred years.  The Comprehensive Glossary of Terms used in Toxicology has taken advantage of this system, and the definitions contained in it have been rigorously reviewed by IUPAC Committees, as well as by experts from the disciplines that contribute to toxicological science. Thus, the compilers are confident that this glossary will succeed in its aim of being a valuable toxicology reference book for students and researchers, as well as for those involved in chemicals legislation, regulation, management, and risk assessment.  Since Toxicology is a rapidly developing science, the compilers of the “Comprehensive Glossary” have already started on a new glossary to cover the latest developments in molecular toxicology.  This reflects the impact of molecular biology on toxicology, and will reinforce the link between toxicology and pure and applied chemistry as IUPAC starts its next hundred years.