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Extensive agricultural use of neonicotinoid insecticide products has resulted in the presence of neonicotinoid mixtures in surface waters worldwide. Although many aquatic insect species are known to be sensitive to neonicotinoids, the impact of neonicotinoid mixtures is poorly understood. In the present study, the cumulative toxicities of binary and ternary mixtures of select neonicotinoids (imidacloprid, clothianidin, and thiamethoxam) were characterized under acute (96-h) exposure scenarios using the larval midge Chironomus dilutus as a representative aquatic insect species. Using the MIXTOX approach, predictive parametric models were fitted and statistically compared with observed toxicity in subsequent mixture tests. Single-compound toxicity tests yielded median lethal concentration (LC50) values of 4.63, 5.93, and 55.34 μg/L for imidacloprid, clothianidin, and thiamethoxam, respectively. Because of the similar modes of action of neonicotinoids, concentration-additive cumulative mixture toxicity was the predicted model. However, we found that imidacloprid-clothianidin mixtures demonstrated response-additive dose-level-dependent synergism, clothianidin-thiamethoxam mixtures demonstrated concentration-additive synergism, and imidacloprid-thiamethoxam mixtures demonstrated response-additive dose-ratio-dependent synergism, with toxicity shifting from antagonism to synergism as the relative concentration of thiamethoxam increased. Imidacloprid-clothianidin-thiamethoxam ternary mixtures demonstrated response-additive synergism. These results indicate that, under acute exposure scenarios, the toxicity of neonicotinoid mixtures to C. dilutus cannot be predicted using the common assumption of additive joint activity. Indeed, the overarching trend of synergistic deviation emphasizes the need for further research into the ecotoxicological effects of neonicotinoid insecticide mixtures in field settings, the development of better toxicity models for neonicotinoid mixture exposures, and the consideration of mixture effects when setting water quality guidelines for this class of pesticides. Environ Toxicol Chem 2017;36:3091-3101. © 2017 SETAC.

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Assessing the persistence of chemicals in the environment is a key element in existing regulatory frameworks to protect human health and ecosystems. Persistence in the environment depends on many fate processes, including abiotic and biotic transformations and physical partitioning, which depend on substances' physicochemical properties and environmental conditions. A main challenge in persistence assessment is that existing frameworks rely on simplistic and reductionist evaluation schemes that may lead substances to be falsely assessed as persistent or the other way around—to be falsely assessed as nonpersistent. Those evaluation schemes typically assess persistence against degradation half‐lives determined in single‐compartment simulation tests or against degradation levels measured in stringent screening tests. Most of the available test methods, however, do not apply to all types of substances, especially substances that are poorly soluble, complex in composition, highly sorptive, or volatile. In addition, the currently applied half‐life criteria are derived mainly from a few legacy persistent organic pollutants, which do not represent the large diversity of substances entering the environment. Persistence assessment would undoubtedly benefit from the development of more flexible and holistic evaluation schemes including new concepts and methods. A weight‐of‐evidence (WoE) approach incorporating multiple influencing factors is needed to account for chemical fate and transformation in the whole environment so as to assess overall persistence. The present paper's aim is to begin to develop an integrated assessment framework that combines multimedia approaches to organize and interpret data using a clear WoE approach to allow for a more consistent, transparent, and thorough assessment of persistence. Integr Environ Assess Manag 2022;18:868–887. © 2021 ExxonMobil Biomedical Sciences, Inc. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Acute (96‐h) toxicities of 5 systemic insecticides (chlorantraniliprole, cyantraniliprole, flupyradifurone, flubendiamide, and sulfoxaflor) were tested on larval Chironomus dilutus and compared with the neonicotinoid imidacloprid. Three insecticides were less acutely toxic than imidacloprid (2.5–25 times lower). However, chlorantraniliprole and cyantraniliprole were 1.5 to 1.8 times more toxic to C. dilutus. Thus, these ryanodine receptor agonists could pose a higher risk to aquatic insects than their neonicotinoid predecessors, warranting further studies. Environ Toxicol Chem 2020;39:587–594. © 2019 SETAC

There are insufficient toxicity data to assess the ecological risks of many pharmaceuticals and personal care products (PPCPs). While data limitations are not uncommon for contaminants of environmental concern, PPCPs are somewhat unique in that an a priori understanding of their biological activities in conjunction with measurements of molecular, biochemical, or histological responses could provide a foundation for understanding mode(s) of action and predicting potential adverse apical effects. Over the past decade significant progress has been made in the development of new approach methodologies (NAMs) to efficiently quantify these types of endpoints using computational models and pathway‐based in vitro and in vivo assays. The availability of open‐access knowledgebases to curate biological response (including NAM) data and sophisticated bioinformatics tools to help interpret the information also has significantly increased. Finally, advances in the development and implementation of the adverse outcome pathway framework provide the critical conceptual underpinnings needed to translate NAM data into predictions of the ecologically relevant outcomes required by risk assessors and managers. The evolution and convergence of these various data streams, tools, and concepts provides the basis for a fundamental change in how ecological risks of PPCPs can be pragmatically assessed. Environ Toxicol Chem 2022;00:1–12. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Watersheds are subjected to diverse anthropogenic inputs, exposing aquatic biota to a wide range of chemicals. Detection of multiple, different chemicals can challenge natural resource managers who often have to determine where to allocate potentially limited resources. Here, we describe a weight‐of‐evidence framework for retrospectively prioritizing aquatic contaminants. To demonstrate framework utility, we used data from 96‐h caged fish studies to prioritize chemicals detected in the Milwaukee Estuary (WI, USA; 2017–2018). Across study years, 77/178 targeted chemicals were detected. Chemicals were assigned prioritization scores based on spatial and temporal detection frequency, environmental distribution, environmental fate, ecotoxicological potential, and effect prediction. Chemicals were sorted into priority bins based on the intersection of prioritization score and data availability. Data‐limited chemicals represented those that did not have sufficient data to adequately evaluate ecotoxicological potential or environmental fate. Seven compounds (fluoranthene, benzo[a]pyrene, pyrene, atrazine, metolachlor, phenanthrene, and DEET) were identified as high or medium priority and data sufficient and flagged as candidates for further effects‐based monitoring studies. Twenty‐one compounds were identified as high or medium priority and data limited and flagged as candidates for further ecotoxicological research. Fifteen chemicals were flagged as the lowest priority in the watershed. One of these chemicals (2‐methylnaphthalene) displayed no data limitations and was flagged as a definitively low‐priority chemical. The remaining chemicals displayed some data limitations and were considered lower‐priority compounds (contingent on further ecotoxicological and environmental fate assessments). The remaining 34 compounds were flagged as low or medium priority. Altogether, this prioritization provided a screening‐level (non‐definitive) assessment that could be used to focus further resource management and risk assessment activities in the Milwaukee Estuary. Furthermore, by providing detailed methodology and a practical example with real experimental data, we demonstrated that the proposed framework represents a transparent and adaptable approach for prioritizing contaminants in freshwater environments. Integr Environ Assess Manag 2023;00:1–21. © 2022 SETAC