Approaches to assessing combination effects of oestrogenic environmental pollutants.

Concerns about possible combination effects of environmental chemicals with estrogenic activity have motivated the search for synergisms between such agents. However, much published work has taken no account of the concepts and methods for analysing combination effects, which were developed in toxicology and pharmacology. In the present communication, we draw attention to conceptual frameworks relevant for a sound analysis of the effects of mixtures of oestrogenic compounds. A model calculation is presented demonstrating that it is conceivable that weakly oestrogenic compounds may be able to act together to produce significant effects, even when they are present at concentrations below their individual effect thresholds. Our results suggest that it may not be necessary to invoke synergisms in order to explain the discrepancy between the high concentrations of these agents required to produce effects in in vitro assay systems and their low concentrations in the environment.