Title: Explanatory dictionary of terms used in toxicology
Duffus and Douglas
Completion Date: 2007 - project completed
IUPAC has the world authority on chemical nomenclature and terminology
and experience in critical evaluation of data. In order to incorporate
chemistry and merge toxicology into the terminology used in toxicokinetics
in various scientific disciplines a project was initiated to create
a glossary of terms used in toxicokinetics (project
The objective of this new project is to create an explanatory dictionary
of concepts in toxicokinetics consisting of about 40 terms chosen
from the glossary of terms used in toxicokinetics (referred to above)
with full explanations of the meaning of the terms and the underlying
concepts. Such a project will improve the IUPAC impact in a number
of scientific fields and improve the image of chemistry in society.
It will serve the needs of the chemists in the world, who increasingly
require an understanding of toxicology, and thus be of global interest.
The terms in toxicokinetics will be selected on the basis of
their importance for human health. The "Explanatory Dictionary
of Concepts in Toxicokinetics" will play an important role in
helping chemists to meet the increased requirement from society and
government for risk assessment of chemicals produced by the chemical
industry. It is designed to help chemists to understand fully the
meaning of terms used in toxicokinetics which they will met in the
literature related to risk assessment. Better risk assessment will
result helping to ensure that the practice of chemistry remains safe
and continues to benefit human health.
Two first draft examples of entries for the Dictionary are given
below to illustrate how the explanatory text may be developed from
the existing definitions. It is expected that the final versions will
be longer and include concept diagrams to illustrate the relationship
of concepts, and figures as appropriate.
volume of distribution (Vd) apparent (hypothetical) volume
of fluid required to contain the total amount of a substance in the
body at the same concentration as that present in the plasma assuming
equilibrium has been attained.
Vd = dose (mg)/plasma concentration (mg/L) = ? L
or = dose (mol)/plasma concentration(mol/L) = ? L
From this relationship, it can be seen that:
1. lower plasma concentrations imply a higher volume of distribution
of the substance
2. higher plasma concentrations imply a lower volume of distribution
of the substance
A value for the Vd for a given substance of less than 5 L would imply
the substance is primarily in the plasma. On the other hand, a Vd
of much more than 5 L implies that the substance is more widely distributed
through the body
Examples of situations which affect the volume of distribution
1. If a toxic substance is mostly bound to plasma proteins such as
albumin, the Vd will approximate to the plasma volume.
2. If a toxic substance is highly lipid soluble, and distributes
mainly to adipose tissue, the plasma concentration will be low and
the Vd will be larger than the plasma volume and may even exceed the
volume of total body water.
Limitations of the Vd
The volume of distribution is a theoretical measurement and the possibility
that it may exceed the volume of total body water emphasises this
Toxic substances have different affinities for different body tissues
and the observation of a large Vd does not indicate the location of
the relevant toxic substance in the body. Even where this is known,
it must be remembered that the main location of the substance may
not be its site of action.
For example, organochlorines accumulate in fatty tissue but their
site of action may be on the nervous system or on the reproductive
Plasma concentration and hence volume of distribution changes over
time and so a single determination of Vd gives much less information
than a time course study.
biotransformation Chemical conversion of a substance by living
organisms or enzyme preparations derived there from.
After Nagel et al. (eds), 1991
A number of chemicals are biotransformed into metabolites by the
enzyme systems in the mother, placenta, or fetus. The exact role of
genetically-determined biotransformation enzymes in influencing the
expression of teratogenicity has not been ascertained for most substances.
Important enzymes, in this respect, are localized in the endoplasmic
reticulum and constitute a family of cytochrome P-450-dependent mono-oxygenases.
Environmental chemicals that enhance or inhibit the activities of
these mono-oxygenases (and thus the rate of metabolism of certain
chemicals), are referred to, respectively, as inducers or inhibitors.
The inducers include phenobarbital, chlordane, DDT, polycyclic aromatic
hydrocarbons, flavons, dioxins, indoles, and polyhalogenated biphenyls,
many of which are combustion products, industrial chemicals, and pesticides.
The inhibitors include carbonmonoxide (in vitro), imidazole, methylene
blue, aniline, amines, and some more or less specific inhibitors.
The ability of chemicals to induce or inhibit the activity of the
microsomal enzyme systems is an important factor to be taken into
account in devising experimental protocols. (Environmental Health
Criteria 30, Principles for Evaluating Health Risks to Progeny Associated
with Exposure to Chemicals during Pregnancy)
May 2005 - At its meeting in Rottenburg, on 18-19 May 2005,
the task group agreed that the project title should be changed from
'Explanatory dictionary of concepts in toxicokinetics' to 'Explanatory
dictionary of terms used in toxicology', in order to make it clear
that the terms discussed were relevant and fundamenetal to the wider
field of toxicology.
A draft revised is being circulated among the TGMs.
Jan 2006 - A manuscript is being prepared for publication
in Pure Appl. Chem. A final document is submitted to public
review comments until 31 May 2006.
> provisional recommendations
Project completed - IUPAC Recommendations published in
Pure Appl. Chem. 79(9), 1583-1633, 2007.
> See Project Part 2
Material from part 1 and 2 will be included in a book to be published
with the Royal Society of Chemistry.
Last Update: 17 September 2007
<project announcement published
Jul-Aug 2004 issue>