In Vitro Models for Endocrine Disruptor Screening

Many in vitro and in vivo assay methodologies have been utilized in assessing potential endocrine activity. The Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) convened by the EPA recommended a tiered testing approach for the evaluation endocrine disruptive effects of chemicals in commerce. The tiered testing approach allowed for a rapid initial prioritization for evaluation in mechanistically based screens at the Tier I level with more definitive in vivo Tier II testing. This Tier I battery was designed to be quick, more sensitive than specific and able to clarify and assess multiple modes of endocrine action and include, receptor binding, gene transactivation and potential effects on steroidogenesis. This presentation will focus on a discussion of the status of the current in vitro methodologies being utilized in the field as a part of this screening process.  Furthermore, interest in combined exposures to mixtures of chemicals possessing endocrine activity has become a subject of intense interest. The combined toxicity of these compounds is dependent upon whether or not they act in an additive, synergistic or antagonistic manner.  Current in vitro approaches to attempt to address the interactions of compounds in endocrine mixtures will also be discussed.