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 #2000-034-2-700).
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.
> project announcement published in Chem. Int. Jul-Aug 2004 issue
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 fact.
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 system.
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.
Project completed – IUPAC Recommendations published in Pure Appl. Chem. 79(9), 1583-1633, 2007.
> See Project Part 2 (#2006-020-1-700)
Material from part 1 and 2 will be included in a book to be published with the Royal Society of Chemistry.