Use of IVIVE to characterize fish toxicants
The use of pesticides to control invasive species is a key component of integrated pest management plans. Traditionally, the development of new chemical controls required testing on numerous animals. In vitro cytotoxicity testing, which reduces animal use, is becoming more common to prioritize candidate toxicants and permits high-throughput testing. However, it remains unknown whether in vitro cytotoxicity values (i.e., effective concentrations or EC50 values) are representative of in vivo toxicity values (i.e., lethal concentration for 50% of organisms or LC50). DOI’s USGS has begun proof-of-concept studies on the use of fish cytotoxicity screening assays to prioritize new candidate pesticides to control nuisance fishes. Recent studies have quantified the cytotoxicity EC50 values of the fish toxicant Antimycin-A using a commercially available gill cell line (RTgill-W1) from rainbow trout (Oncorhynchus mykiss). This study utilized the procedure described in OECD Test Guideline 249 and the CellTiter-Glo 2.0 (Promega) cell viability assay for assessing RTgill-W1 cytotoxicity. In vitro to in vivo extrapolation (IVIVE) was applied to assay results and indicated that, for most valuable metrics, the ratio of in vitro to in vivo toxicity was approximately 1. These results demonstrate that toxicity as measured in rainbow trout gill cell lines is predictive of whole-animal toxicity and shows promise for the development of additional fish gill cell lines for screening of pesticide candidates.