Evaluating non-monotonic dose-response relationships in ecotoxicological risk assessment: A case study based on a systematic review of data on fluoxetine.

Autor: van der Most MA; Division of Toxicology, Wageningen University and Research, the Netherlands. Electronic address: merel.vandermost@wur.nl., Rietjens IMCM; Division of Toxicology, Wageningen University and Research, the Netherlands. Electronic address: Ivonne.rietjens@wur.nl., van den Brink NW; Division of Toxicology, Wageningen University and Research, the Netherlands. Electronic address: nico.vandenbrink@wur.nl.
Jazyk: angličtina
Zdroj: Chemosphere [Chemosphere] 2024 Sep; Vol. 363, pp. 142819. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1016/j.chemosphere.2024.142819
Abstrakt: The environmental presence of pharmaceuticals, including the antidepressant fluoxetine, has become a subject of concern. Numerous studies have revealed effects of fluoxetine at environmental concentrations. Some of these studies have reported non-monotonic dose-response curves (NMDRs), leading to discussion because of the inconsistent detection of subtle effects and lack of mechanistic understanding. Nevertheless, investigating NMDRs in risk assessment is important, because neglecting them could underestimate potential risks of chemicals at low levels of exposure. Identification and quantification of NMDRs in risk assessment remains challenging, particularly given the prevalence of single outliers and the lack of sound statistical analyses. In response, the European Food Safety Authority (Beausoleil et al., 2016) presented a framework delineating six checkpoints for the evaluation of NMDR datasets, offering a systematic method for their assessment. The present study applies this framework to the case study of fluoxetine, aiming to assess the weight-of-evidence for the reported NMDR relationships. Through a systematic literature search, 53 datasets were selected for analysis against the six checkpoints. The results reveal that while a minority of these datasets meet all checkpoints, a significant proportion (27%) fulfilled at least five. Notably, many studies did not meet checkpoint 3, which requires NMDRs to be based on more than a single outlier. Overall, the current study points out a number of studies with considerable evidence supporting the presence of NMDRs for fluoxetine, while the majority of studies lacks strong evidence. The suggested framework proved useful for analysing NMDRs in ecotoxicological studies, but it is still imperative to develop further understanding of their biological plausibility.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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