Larval fathead minnow exposed to organophosphate pesticides

New approach methods (NAMs) can reduce the need for chronic, animal studies. We applied benchmark concentration (BMC) response modeling to transcriptomic changes in whole fathead minnow larvae after 1-day exposure to several concentrations of three organophosphate pesticides (OPPs): fenthion, methidathion, and parathion. The fathead minnow larvae transcriptional points of departure were 0.007, 0.115, and 0.046 mg/L, respectively. transcriptional points of departure reflected the relative potencies from traditional, chronic studies with fenthion identified as the most potent. Moreover, the fathead minnow larvae transcriptional points of departure were within 18-fold of the chronic apical points of departure for fish species. Short-term exposure to OPPs significantly impacted acetylcholinesterase mRNA abundance (FDR p-value 2) and canonical pathways (IPA, z-score>|2|) associated with organism death and neurological/immune dysfunctions, indicating the conservation of key events related to OPP toxicity. Together, these results build confidence in using short-term, molecular-based assays for the characterization of chemical toxicity and risk, thereby reducing reliance on chronic, animal studies.