How to assess risk from combined exposures to radiation and other agents?

Efforts to assess and quantify deleterious effects from toxicants concentrate mainly on single agents whereas real world environmental and occupational exposures to natural and anthropogenic agents entail quite often the concomitant presence of several toxicants. For occupational important exposure situations, combined exposures to physical and chemical agents such as radon and smoking or asbestos and smoking, respectively, were shown to produce over-additive effects at exposure levels typical for earlier workplaces. Already the elucidation of possible health risks from a single agents, its dependence on exposure level, exposure rates, age at exposure and its expression in time is a complex endeavour. Therefore in the past and the present the main emphasis in radiation protection, toxicology, and public health is on the study and assessment of single toxicants. The existing data base on combined effect is rudimentary, mainly descriptive and rarely covers exposure ranges large enough to make direct inferences to present day low dose exposure situations. In view of the multitude of possible interactions between the large number of potentially harmful agents in the human environment, descriptive approaches will have to be substitutes by the use of mechanistic models for critical health endpoints such as cancer. To generalize and predict the outcome of combined exposures, agents will have to be grouped depending on their physical or chemical mode of action on the molecular (genotoxic/non-genotoxic) and cellular level. As a basic requirement, clear concepts and definitions are needed to give the terms interaction, additivity, synergism and antagonism unambiguous meanings. (authors)