EXPERIMENTAL-DESIGNS AND RISK ASSESSMENT IN COMBINATION TOXICOLOGY - PANEL DISCUSSION

Advancing our knowledge on the toxicology of combined exposures to che micals and implementation of this knowledge in guidelines for health r isk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A prerequisite for successful research and fruitful discus sions on the toxicology of combined exposures (mixtures of chemicals) is the use of defined terminology implemented by an authoritative inte rnational body such as, for example, the International Union of Pure a nd Applied Chemistry (IUPAC) Toxicology Committee. The extreme complex ity of mixture toxicology calls for new research methodologies to stud y interactive effects, taking into account limited resources. Of these methodologies, statistical designs and mathematical modelling of toxi cokinetics and toxicodynamics seem to be most promising. Emphasis shou ld be placed on low-dose modelling and experimental validation. The sc ientifically sound so-called bottom-up approach should be supplemented with more pragmatic approaches, focusing on selection of the most haz ardous chemicals in a mixture and careful consideration of the mode of action and possible interactive effects of these chemicals. Pragmatic approaches may be of particular importance to study and evaluate comp lex mixtures; after identification of the 'top ten' (most risky) chemi cals in the mixture they can be examined and evaluated as a defined (s imple) chemical mixture. In setting exposure limits for individual che micals, the use of an additional safety factor to compensate for poten tial increased risk due to simultaneous exposure to other chemicals, h as no clear scientific justification. The use of such an additional fa ctor is a political rather than a scientific choice. Copyright (C) 199 7 Elsevier Science Ltd.