Paracelsus Revisited: The Dose Concept in a Complex World

Abstract

At the time that Paracelsus coined his famous dictum, 'What is there that is not poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison', embryonic toxicology was a fairly focused discipline that mainly dealt with occupational poisonings and side effects of pharmaceuticals, such as mercury. While Paracelsus paved the way for the modern threshold concept and the no-adverse effect level, modern-day toxicology is now tussling with highly complex issues, such as developmental exposures, genetic predisposition and other sources of hypersusceptibility, multiple causes of underestimated toxicity, and the continuous presence of uncertainty, even in regard to otherwise well-studied mercury compounds. Further, the wealth of industrial chemicals now challenges the 'untested-chemical assumption', that the lack of documentation means that toxic potentials can be ignored. Unfortunately, in its ambition to provide solid evidence, toxicology has been pushed into almost endless replications, as evidenced by the thousands of toxicology publications every year that focus on toxic metals, including mercury, while less well-known hazards are ignored. From a public health viewpoint, toxicology needs to provide better guidance on decision-making under ever-present uncertainty. In this role, we need to learn from the stalwart Paracelsus the insistence on relying on facts rather than authority alone to protect against chemical hazards.

Fig. 1

Paracelsus, at age 45, three years before he died in 1541 (contemporary copper engraving). Note Paracelsus’ motto on top.

Fig. 2

With time, better knowledge allows appreciation that lower exposures must be ensured in order to avoid adverse health effects, and it is also realized that very small doses are tolerated without any risk of adverse effects. However, only with near-perfect knowledge will the two curves meet. It is the purpose of modern toxicology to responsibly interpret science so that adverse effects are avoided, although with due recognition that some low-level exposures must be allowed. Redrawn from (63).