Review of the Nonsteroidal Anti-Inflammatory Drug Consumption, Occurrence, Potential Impacts on Environmental Health, and Insights into Regulatory Decision-Making Brazilian Aquatic Ecosystems

Abstract

The ubiquitous presence of nonsteroidal anti-inflammatory drugs (NSAIDs) in aquatic compartments has been described, and recent studies reported several adverse biological effects on nontarget species after short- and long-term exposures. Despite the recent reports, integrated information related to the measurements and effects of NSAIDs on Brazilian water ecosystems is still limited, given the importance of Brazilian aquatic biodiversity. Thus, to fill these gaps, after a close literature search using scientific databases, this review aims to summarize the main scientific efforts concerning the occurrence of NSAIDs in Brazilian aquatic environments, the multiple physiological effects on native species, and the different protocols used in the research laboratories. Accordingly to the current literature data (2013-2023), a total of 32 studies were found describing the occurrence of diclofenac, ibuprofen, naproxen, and ketoprofen in Brazilian waters, with concentration ranging from 2.5 to 785,280 ng L^-1, with the majority of the studies performed in Sao Paulo state (n = 10) showing the heterogeneity of monitoring across Brazilian territory. Regarding the adverse effects on native aquatic species, a total of 3 species, including , , and , have been used to investigate the NSAIDs' adverse effects. The investigations reported endocrine disruption effects by diclofenac and ibuprofen, isolated and combined, in teleosts, oxidative stress responses, and immunotoxicity effects after NSAIDs exposure. When considering the ecotoxicological risk assessment of NSAIDs to Brazilian water bodies, the data showed a low risk quotient (RQ) for the native models across Brazilian territory. However, due to the lack of investigations using representative biological models and robust data concerning the adverse biological impacts of NSAIDs, the RQ may be underestimated, and future directions on NSAIDs investigations are suggested using an integrative approach between environmental safety standards and human health at different environmental risk evaluations.

1

Nonsteroidal anti-inflammatory drug (NSAID) detection range (ng L^–1) in the Brazilian states aquatic ecosystem.

2

Main neuroendocrine axes on teleost fish, including hypothalamus-pituitary-gonads (HPG), hypothalamus-pituitary-thyroid (HPT), and hypothalamus-pituitary-interrenal gland (HPI) pathways, and possible pathways to endocrine disruption on Brazilian teleost fish.

3

Risk Quotient (RQ) range in Brazilian territory associated with the NSAID concentration (1 to 785,280 ng L^–1). The adverse effects were observed at lower concentrations. NA indicates the lack of data in the present geographic regions.

4

Risk Quotient for the NSAIDs considering the range of maximum concentrations found in the Brazilian studies.