Biological monitoring in occupational and environmental toxicology

doi:10.1016/S0378-4274(99)00076-4

Toxicology Letters

Volume 108, Issues 2–3, 5 September 1999, Pages 77-89

https://doi.org/10.1016/S0378-4274(99)00076-4 Get rights and content

Abstract

Recent developments in analytical chemistry improve our ability to characterise individual exposure to environmental pollutants by measuring their levels in accessible biological media, down to the nanomolar level even for organic compounds. As useful complements for risk assessment, biomarkers of individual susceptibility are being intensively investigated in both cancer and non cancer epidemiology, acknowledging that host factors may not only play a key role in multifactorial diseases, but also affect the lower tail of the dose-response relationship for toxic outcomes. A third promising area of research is the development and validation of biomarkers of early effect. The use of more quantitative and sensitive end-points could increase our ability to identify toxic responses to chemicals polluting the workplace and the general environment. As a whole, these advances are likely to result in a better characterisation of dose-response relationships, a key step towards effective prevention. This paper provides an overview of the 4th International Symposium on Biological Monitoring.

Section snippets

Biological monitoring

Biological monitoring (BM) is the periodic measurement of a biomarker of exposure, which has been defined as ‘an exogenous substance or its metabolise or the product of an interaction between a xenobiotic agent and some target molecule or cell that is measured in a compartment within an organism’ (National Research Council., 1987).

BM is aimed at quantifying the amount of chemical absorbed, transformed into an active metabolise, or accumulated in deposit or target organs, tissues or cells as a

Technological advances

Technology and powerful software applied to mass spectrometry are greatly improving hyphenated techniques, i.e. gas chromatography, liquid chromatography and inductively coupled plasma, all relying on mass spectrometry (MS) detection. Hyphenated techniques take advantage of prior separation of analyses, but especially of: (i) the selectivity and sensitivity of MS; (ii) a wider dynamic range compared to suitable alternatives; and (iii) little sample manipulation which could give rise to

Gene-environment interactions

Most traits that vary in a population are determined by multiple factors. Although an additive effect is the most frequent situation, interactions may occur causing either potentiating or inhibiting effects. Even if each factor contributes a modest variation or affect a small proportion of the whole population, non-linear and unpredictable interactions may account for a high proportion of the etiologic fraction. Also, multiple interactions may occur, resulting in a complex trait. Many complex

Biomarkers of susceptibility

In environmental epidemiology, a great deal of efforts are being devoted to explore the lower tail of dose-response relationships in both cancer and non-cancer end-points, identifying ‘susceptible’ individuals, i.e. those subjects who biotransfonn absorbed chemicals into effective doses even at the low exposure levels shared with the vast majority of the population who do not exhibit any adverse effects.

In toxicology, the concept of susceptibility is rather ambiguous. Indeed, the identification

Interference among components of mixtures

With this respect, hexane metabolism can now be characterised with little or no manipulation of the sample (Manini et al., 1999). Co-exposure to equimolar doses of either methyl-ethyl-ketone (MEK) or toluene results in competitive inhibition of hexane biotransformation. As compared to n-hexane, both toluene and MEK probably share a higher affinity for relevant drug-metabolising enzymes, resulting in a faster excretion of metabolises and shorter half-life as compared to n-hexane. Whereas only

Biomarkers of effect

A biomarker of effect has been defined as ‘a measurable biochemical, physiological or other alteration within an organism that, depending on magnitude, can be recognised as an established or potential health impairment or disease’ (National Research Council, 1989). Research on biomarkers of effect is rapidly generating a large amount of data measuring intermediate end-points occurring probably after exposure and possibly before illness (Mutti, 1995). Such biomarkers are expected to reflect

Nephrotoxicity

Work on biomarkers of nephrotoxicity dates back to mid-century, when Friberg’s pioneering studies on cadmium nephrotoxicity lead to set-up a qualitative test identifying low molecular weight proteinuria (Friberg, 1950). It took 15 years to develop semi-quantitative methods to assess Cd-induced low molecular weight proteinuria (Piscator, 1966a, Piscator, 1966b) and 15 more years to characterise Cd-induced proteinuria on the basis of the urinary excretion of single low and high molecular weight

Neurotoxicity

Concern for the acute and long-term effects of chemicals on the nervous system has been growing because of: (i) the vulnerability of the central and peripheral nervous system to a broad spectrum of chemical pollutants; (ii) the inability of neurones to regenerate after injury, which accounts for the serious consequences of disabling conditions caused by neurotoxicity; and (iii) the unique and critical role of the nervous system in the control of body function, including that of other organs and

Acknowledgements

Support for research discussed in this paper was obtained from the European Commission (Contr. ENV-CT96-171 and ENV-CT9-173).

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