Tiffany M. Wolf

Fish serve as indicators of exposure to contaminants of emerging concern (CECs)—chemicals such as pharmaceuticals, hormones, and personal care products—which are often designed to impact vertebrates. To investigate fish health and CECs in situ, we evaluated the health of wild fish exposed to CECs in waterbodies across northeastern Minnesota with varying anthropogenic pressures and CEC exposures: waterbodies with no human development along their shorelines, those with development, and those directly receiving treated wastewater effluent. Then, we compared three approaches to evaluate the health of fish exposed to CECs in their natural environment: a refined fish health assessment index, a histopathological index, and high‐throughput (ToxCast) in vitro assays. Lastly, we mapped adverse outcome pathways (AOPs) associated with identified ToxCast assays to determine potential impacts across levels of biological organization within the aquatic system. These approaches were applied to subsistence fish collected from the Grand Portage Indian Reservation and 1854 Ceded Territory in 2017 and 2019. Overall, 24 CECs were detected in fish tissues, with all but one of the sites having at least one detection. The combined implementation of these tools revealed that subsistence fish exposed to CECs had histological and macroscopic tissue and organ abnormalities, although a direct causal link could not be established. The health of fish in undeveloped sites was as poor, or sometimes poorer, than fish in developed and wastewater effluent‐impacted sites based on gross and histologic tissue lesions. Adverse outcome pathways revealed potential hazardous pathways of individual CECs to fish. A better understanding of how the health of wild fish harvested for consumption is affected by CECs may help prioritize risk management research efforts and can ultimately be used to guide fishery management and public health decisions. Integr Environ Assess Manag 2024;20:846–863. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).