Topic 4.9 Wildlife as models for the study of how mixtures, low doses, and the embryonic environment modulate the action of endocrine-disrupting chemicals*

This paper will review briefly the use of wildlife as models in the study of how mixtures, low doses, and the embryonic environment modulate the action of endocrine active substances (EASs). In so doing, it will show how the issue of low dosages must be considered within the context of mixtures present in the environment and the endocrine background of the exposed individual. That is, in nature, EASs usually are found in mixtures in which the constituent parts are in concentrations well below their NOAEL (no observed adverse effect level) as determined in single compound studies in the laboratory. In addition, exposure always occurs on organisms in various endocrine states. Thus, the issue of mixtures and dosages must always be considered within the context of the endocrine background. Finally, the effects of exposure are passed down through the generations. The question of exposure then at the level of the individual becomes very complicated, as it must take into account that at every life stage, the naturally occurring endocrine milieu of the organism (or tissue), any EAS burden inherited from the mother or built up over the individual’s life, and the social environment in which the individual develops and interacts as an adult, will influence the response to acute exposure.