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Forces Comité van Aanbeveling

16. ON THE PROBLEMS OF TOXICOLOGY

M. Lotti and P. Nicotera (University of Padua, IT) discuss toxicology, the authors making the following points:

Several key advances in biology and medicine in the past were brought about by studies of poisons. The eludication of the mechanism of carbon monoxide toxicity by Claude Bernard (1813-1878), which led to the understanding of the function of hemoglobin, is a classic example. However, Jean-Pierre Changeux and colleagues, who used alpha-bungarotoxin to purify acetylcholine receptors, and William Catterall, who isolated sodium channels using scorpion toxin, probably did not consider themselves to be toxicologists. Has modern toxicology actually provided new fundamental concepts? Surprisingly, with a few notable exceptions, it has not _ it is nowadays regarded as an applied science that is devoted to minimizing environmental health risks posed by chemicals, mainly through risk assessment.
At the same time, there is an emerging crisis of confidence in toxicology as an applied science that can effectively predict risk, as illustrated by the debate about servicemen exposed to depleted uranium from weapons during the Kosovo conflict in 1999. Although there is no evidence for radiological or chemical carcinogenic risk at any conceivable level of exposure, the wide perception of this issue has been very different.
Predictions based solely upon epidemiological projections without solid scientific bases are often misleading. Examples include the debates over genetically modified foods, dioxins, measles vaccinations, and prion diseases in cattle and sheep. In the case of prion diseases, there is a remarkably uncertain and contradictory range of theoretical predictions for the size of any future epidemic of variant Creutzfeld-Jakob disease in humans.
There are surely various reasons for this failure of trust, but the authors discuss one in particular. Perhaps because of the immense scope of research into the mechanisms by which individual compounds act, basic research has, over the past two decades, become irrelevant to many toxicologists. A discipline that mostly depends on others for fresh fundamental knowledge, and is slow in acquiring it, will also be slow in its progress and weak in its conclusions. Prejudice, ideology and irrationality will undoubtedly grow. For instance, few among the public appreciate the fact that hazard and risk are different concepts. Hazard defines the potential of a compound to cause harm and is therefore associated with virtually any molecule, whereas a risk of adverse health effects relates to the level of exposure and to individual susceptibility to that molecule. Such misunderstanding may account for the generous public funds that have been allocated to the study of dioxin toxicity, despite the lack of evidence for effects on human health at current environmental exposures.
Toxicology is being shaped by worldwide political agendas, triggered by the public's desire for swift and precautionary solutions to the possible health effects of environmental chemicals. The resulting feedback loop has impoverished the discipline, because its growth has largely been driven by the demand for protocols for regulatory actions (1-5).

References (abridged):

1. Berry, C. Trends Pharmacol. Sci. 22, 277-280 (2001).

2. Golub, T. R.l. Science 286, 531-537 (1999).

3. Hoeijmakers, J. H. J. Nature 411, 366-374 (2001).

4. Smith, L. L. Trends Pharmacol. Sci. 22, 281-285 (2001).

5. Gibbons, M. Nature 402, C81-C84 (1999).

Nature 2002 416:481

ScienceWeek http://www.scienceweek.com

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16. ON THE PROBLEMS OF TOXICOLOGY

References (abridged):