Evidence of the Impacts of Pharmaceuticals on Aquatic Animal Behaviour (EIPAAB): a systematic map and open access database

Jake Mitchell Martin , Marcus Michelangeli, Michael Grant Bertram, Paul J. Blanchfield, Jack A. Brand, Tomas Brodin, Bryan Brooks, Daniel Cerveny, Kate N. Fergusson, Malgorzata Lagisz, Lea M. Lovin, Isaac Y. Ligocki, Shinichi Nakagawa, Dhiho Ozeki, Natalia Sandoval-Herrera, Scarlett Kendall, Josefin Sundin, Hung Tan, Eli Thoré, Bob B M Wong, Erin S. McCallum

Background
Over the last decade, pharmaceutical pollution in aquatic ecosystems has emerged as a pressing environmental issue. Recent years have also seen a surge in scientific interest in the use of behavioural endpoints in chemical risk assessment and regulatory activities, underscoring their importance for fitness and survival. In this respect, data on how pharmaceuticals alter the behaviour of aquatic animals appears to have grown rapidly. Despite this, there has been a notable absence of systematic efforts to consolidate and summarise this field of study. To address this, our objectives are twofold: (1) systematically identify, catalogue, and synthesise primary research articles on the effects of pharmaceuticals on aquatic animal behaviour; and (2) to organise this information into a comprehensive open-access database for scientists, policymakers, and environmental managers.

Methods
We systematically searched two electronic databases (Web of Science and Scopus) and supplemented these with additional article sources. The search string followed a Population–Exposure–Comparison–Outcome framework to capture articles that used an aquatic organism (population) to test the effects of a pharmaceutical (exposure) on behaviour (outcome). Articles were screened in two stages: title and abstract, followed by full-text screening alongside data extraction. Decision trees were designed a priori to appraise eligibility at both stages. Information on study validity was collected but not used as a basis for inclusion. Data synthesis focused on species, compounds, behaviour, and quality themes and was enhanced with additional sources of metadata from online databases (e.g. National Center for Biotechnology Information (NCBI) Taxonomy, PubChem, and IUCN Red List of Threatened Species).

Review findings
We screened 5,988 articles, of which 901 were included in the final database, representing 1,739 unique species-by-compound combinations. The database includes data collected over 48 years (1974–2022), with most articles having an environmental focus (510) and fewer relating to medical and basic research topics (233 and 158, respectively). The database includes 173 species (8 phyla and 21 classes). Ray-finned fishes were by far the most common clade (75% of the evidence base), and most studies focused on freshwater compared to marine species (80.4% versus 19.6%). The database includes 426 pharmaceutical compounds; the most common groups were antidepressants (28%), antiepileptics (11%), and anxiolytics (10%). Evidence for the impacts on locomotion and boldness/anxiety behaviours were most commonly assessed. Almost all behaviours were scored in a laboratory setting, with only 0.5% measured under field conditions. Generally, we detected poor reporting and/or compliance with several of our study validity criteria.

Conclusions:
Our systematic map revealed a rapid increase in this research area over the past 15 years. We highlight multiple areas now suitable for quantitative synthesis and areas where evidence is lacking. We also highlight some pitfalls in method reporting and practice. More detailed reporting would facilitate the use of behavioural endpoints in aquatic toxicology studies, chemical risk assessment, regulatory management activities, and improve replicability. The EIPAAB database can be used as a tool for closing these knowledge and methodological gaps in the future.