Fish biomarkers for regulatory identification of endocrine disrupting chemicals.

Demonstrating chemical-induced adverse effects, endocrine mechanisms/modes of action (MOAs) and their causal link is needed for regulatory identification of endocrine disrupting chemicals (EDCs). This paper addresses critical issues over MOAs and their causal link to changes in endpoints. Vitellogenin (VTG), secondary sex characteristics (SSC), and sex ratio (also an apical endpoint) are indicative of chemicals interfering with EAS (estrogen, androgen and steroidogenesis) pathways. These biomarkers, however, can be changed by non-EAS chemicals, systemic toxicity and the stress response. Examples are shown that proving causal link between MOAs and changes in endpoints may be difficult for regulatory identification of EDCs. The paper concludes that both in vitro and in vivo data are needed to define MOAs for regulatory identification of EDCs. Further development of guidance documents for data interpretation and for defining the level of evidence is needed for regulatory identification of EDCs.