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

Abstract

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.

COVID-19 drugs in aquatic systems: a review

“…To date, a number of aquatic organisms have been used to investigate the ecotoxicology of the therapeutics drugs, including freshwater and terrestrial organisms (Table 3 ). The aquatic ecotoxicology of ivermectin and niclosamide is relatively well-documented compared to other COVID-19 therapeutic drugs (Leak et al 2020 ; Mesa et al 2017 ; Montforts et al 2003 ; Hepditch et al 2021 ). The EC 50 of ivermectin in Daphnia magna was 25 ng/L while the predicted NOEC for an invertebrate was about 10 ng/L (Montforts et al 2003 ).…”

“…The EC 50 of ivermectin in Daphnia magna was 25 ng/L while the predicted NOEC for an invertebrate was about 10 ng/L (Montforts et al 2003 ). Using rainbow trout ( Oncorhynchus mykiss ) as a bioassay species, the EC50 of niclosamide was estimated to be 0.11 mg/L (Hepditch et al 2021 ).…”

Niclosamide Is a Much More Potent Toxicant of Mitochondrial Respiration than TFM in the Invasive Sea Lamprey (Petromyzon marinus)

“…49 However, earlier studies using the concentration addition model, which is based on a toxic unit approach to predict toxicity, indicate that the interactions may be synergistic, with niclosamide enhancing TFM toxicity in rainbow trout in a manner that was greater than that predicted by the toxicity of each lampricide alone. 48,56 Recent work suggests that the underlying mechanism behind the greater than additive (synergistic) effect of niclosamide on TFM toxicity in the larval sea lamprey is through the inhibition of TFM detoxification, 28 possibly due to competition between TFM and niclosamide for phase 2 enzymes of detoxification, such as the glucuronosyltransferase and/or sulfotransferase known to play a role in the detoxification of both lampricides. 25−28 Effect of Acute Temperature Changes on Mitochondrial Function and Lampricide Toxicity.…”

Variation in the Transcriptome Response and Detoxification Gene Diversity Drives Pesticide Tolerance in Fishes

“…In most treatments, TFM is applied at concentrations reaching the sea lamprey 9 h LC 99.9 of TFM, the concentration needed to kill 99.9% of the exposed population, and is co-applied with 1–2% niclosamide because these compounds interact in a greater than additive fashion . While niclosamide is broadly toxic to fishes, TFM is highly toxic to lampreys relative to jawed fishes.…”