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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Integrated Screening Process for Potential Fish Toxicants

Fisheries managers use toxicants to control invasive and undesirable fish species. The U.S. Geological Survey (USGS) Upper Midwest Environmental Science Center of DOI developed a screening process to minimize and replace animal testing while developing new chemical control agents for invasive species. The goal is to identify compounds that are potentially toxic to target species while posing minimal risk to native species. The three integrated phases of the screening process include (1) identifying physical and chemical properties of compounds that affect bioavailability in fish, (2) prescreening of a publicly available chemical databank to prioritize candidate compounds, and (3) screening of selected compounds for cytotoxicity using in vitro biological assays, ecotoxicity modeling, and fish cell lines. Although in vivo testing continues to be utilized in the development of new fish toxicants, the screening process enables minimization of animal testing while developing a new chemical control agent for invasive species. 

Ecotoxicity modeling uses a QSAR modeling system that determines species-specific responses to chemical exposures using existing toxicity data and chemical properties. These in silico assessment methods can be used to prioritize candidate compounds and estimate cytotoxicity. Models can predict more than 3,000 endpoints for over 600 taxa against more than 9,000 chemicals. A user interactive prototype of the model results is available on the USGS website.

Promising novel toxicants identified in the ecotoxicity modeling step are tested using cellular assays to identify which toxicants have the biological activity required. USGS has developed multiple endpoint assays that measure cell viability based on quantitation of adenosine triphosphate. These assays use cell lines from native species including fathead minnow, bluegill sunfish, rainbow trout, lake sturgeon, and paddlefish, as well as invasive species, including silver carp and bighead carp. Six novel species-selective toxicants have been identified. Four toxicants demonstrating potent species-selective cytotoxic effects are being manufactured for in vivo toxicity screening assays. Two toxicants have completed in vivo testing and show modest selectivity for silver and bighead carp.