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The toxic unit and additive index approaches were used to understand how 2 pesticides, 3‐trifluoromethyl‐4‐nitrophenol (TFM) and 2,5‐dichloro‐4‐nitrosalicylanilide (niclosamide; Nic), interact in mixtures. Our first objective was to determine whether the interaction was strictly additive or greater than additive at doses comparable to those used to control invasive sea lamprey ( Petromyzon marinus ) in the Laurentian Great Lakes, and our second was to compare the utility of the toxic unit and additive index models for determining how TFM and Nic interacted. Typically, TFM is mixed with Nic (1–2%, w/v) to increase its potency and reduce TFM use. However, there is little information on how the 2 chemicals interact. Using a well‐studied, resident nontarget fish, the rainbow trout ( Oncorhynchus mykiss ), we conducted toxicity tests with TFM, Nic, and TFM:Nic (100:1, w/v; TFM/1% Nic) mixtures over 12 h to determine if the interaction was strictly additive, less than additive (antagonistic), or greater than additive (synergistic). The toxic unit and additive index approaches indicated synergistic interactions at environmentally relevant concentrations, suggesting that both are valid approaches for predicting how TFM and Nic interact. The toxic unit approach was simpler to conceptualize and to calculate, and we recommend that it be used when describing how TFM and Nic, and other similar organic compounds, interact with each other in aquatic ecosystems.  Environ Toxicol Chem  2021;40:1419–1430. © 2021 The Authors.  Environmental Toxicology and Chemistry  published by Wiley Periodicals LLC on behalf of SETAC.

environmental toxicology and chemistry

A Toxic Unit and Additive Index Approach to Understanding the Interactions of 2 Piscicides, 3‐Trifluoromethyl‐4‐Nitrophenol and Niclosamide, in Rainbow Trout