Fish Short-term Reproduction Assay Peer Review – EPA Response

RDG/ The Fish Short-Term Reproductive Assay described in the Integrated Summary Report (ISR) and supported by ample supporting materials is overall an excellent approach for Tier 1 screening for chemicals that might perturb the hypothalamic-pituitary-gonadal (HPG) axis. The rationale for the design of the 21 day test, the endpoints selected, and approaches for analyzing data clearly have been carefully thought through, and are very well described is this ISR. Chemicals selected for developing and optimizing the assay are diverse and cover major known mechanisms of HGP interference, as well as chemicals whose mechanisms are unknown and chemicals not thought to interfere with the HPG (i.e., negative controls). Thus, the studies and data supporting this assay are very impressive, and lead to the conclusion, by this reviewer at least, that this assay will be highly effective for its intended purpose. Responses to specific charge questions are provided below.