EcoToxChip provides insights into pathway perturbation upon chlorantraniliprole exposure to larval fathead minnow.

Chlorantraniliprole (CHL), a diamide insecticide, has been detected in surface waters around the world, raising concern for aquatic organism exposures. Diamide insecticides interfere with calcium release during muscle contraction in target and nontarget organisms through binding of the ryanodine receptor (RyR). Limited studies have shown that chronic exposure to CHL can cause toxicity to larval fish, but acute responses across larval fish have been under-studied, especially sublethal effects. Further, biological pathways perturbed by CHL binding to the RyR have yet to be explored. Therefore, the EcoToxChip, a 384-feature quantitative polymerase chain reaction (qPCR) array, was used to characterize altered pathways in larval (24 hr post-hatch) fathead minnows (Pimephales promelas) following a 96-h static exposure to 6 concentrations of CHL, ranging 10-250 µg/L. Using EcoToxXplorer, several genes were identified as responsive to increasing CHL concentrations, including genes involved in calcium-mediated processes, cellular communication, immune system, and nervous system pathways. Additionally, although results from the EcoToxChip focus on an individual fish species, the U.S. Environmental Protection Agency's Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool allows for the extrapolation of toxicity knowledge across fish species. Here, SeqAPASS was employed to explore the conservation of the CHL-RyR interaction, which highlighted the conserved interaction in over 100 fish species. This study demonstrates the utility of multiple predictive toxicology tools to enhance understanding of the toxicity of a widely used insecticide.