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Additive effects on the androgen signaling pathway by chemicals with different modes of action-COW2015
Citation:
Hotchkiss, A., J. Furr, V. Wilson, AND E. Gray. Additive effects on the androgen signaling pathway by chemicals with different modes of action-COW2015. COWS 2015, COPENHAGEN, DENMARK, April 26 - 30, 2015.
Impact/Purpose:
TO PRESENT DATA AND STATISTICAL MODELS OF HOW TO PREDICT THE LONG TERM INTERACTIONS OF CHEMICALS WITH DIFFERENT MODES OF ACTION THAT DISRUPT FETAL ANDROGEN SIGNALING ON REPRODUCTIVE DEVELOPMENT-presented at the 8th Copenhagan Workshop on Endocrine Disrupters COW2015
Description:
Risk assessments have traditionally been developed on a chemical-by-chemical basis. However, regulatory agencies recently have been considering cumulative effects of chemicals that act via a common mechanism of toxicity. Here we present data on several mixture studies of chemicals that affect various aspects of the androgen signaling pathway during male rat sex differentiation. Disruption of the androgen signaling pathway during this time may include interference with binding to the androgen receptor, inhibition of steriodogenic enzyme activity, inhibition of steroid transport, or alteration of normal Leydig cell development via an unknown mechanism. These disruptions manifest in a number of different reproductive alterations including malformations of the genitalia or reproductive tract. Our results show that mixtures of chemicals impacting the same pathway had a dose-additive effect in terms of altering male sex differentiation despite operating via different mechanisms of toxicity. Further, dose addition models, and not response addition models, appropriately predicted the observed effects. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policies of the US EPA.