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Ecotoxicological assessment of over-the-counter NSAID (diclofenac, ibuprofen, aspirin) and antipyretic (acetaminophen) pharmaceuticals: A review of their toxicity effects on aquatic crustaceans

Singh, Delezia S.; Pflugmacher Lima, Stephan (2025)

Integrated Environmental Assessment and Management 22(1), 47 - 83.
DOI: 10.1093/inteam/vjaf082


Open Access Peer Reviewed
 

Commonly used, over-the-counter nonsteroidal anti-inflammatory drugs (OTC NSAIDs) and antipyretic pharmaceuticals represent emerging contaminants of concern, with high global consumption attributing to their frequent detection across diverse water systems. Concerns surround their harmful impacts on aquatic biota, especially because waterbodies represent the predominant receiving matrices for drug-imbued effluents and waste disposal. To support the growing evidence of toxicity effects from emerging contaminants like OTC drugs on nontarget organisms, ecotoxicological assessments have been conducted using bioassay experiments and biological models, like crustaceans. To shed light on the scope of toxicity data on common OTC drugs available for this sensitive group while identifying research gaps and poorly studied areas that need future ecotoxicological attention, the goal focused on reviewing existing literature on toxicity studies that involved crustaceans and commonly used NSAID and antipyretic OTC medications represented by ibuprofen, diclofenac, aspirin/acetylsalicylic acid, and paracetamol/acetaminophen. Published studies were accrued from literature databases using a systematic search strategy and a four-stage protocol. A total of 814 records resulted, with 68 meeting relevance following their eligibility screening against defined criteria. Extracted data were organized according to general bibliographical identifiers, experimental design aspects, and key findings. Assimilated information revealed that most studies focused on acute toxicity testing for the chosen pharmaceuticals using largely microcrustaceans as test models (Branchiopoda, Copepoda, Isopoda, Amphipoda, Ostracoda, and Mysida), especially conventionally known groups (daphnids). Ibuprofen was the most investigated across all taxa (32.9%), but effect concentrations for caridean shrimps (Neocaridina denticulata and Atyaephyra desmarestii) and the amphipod Hyalella azteca reflected notable sensitivity toward diclofenac. Fewer studies assessed mixtures, metabolites, and long-term/sublethal effects in relation to the focus drugs. Future research efforts can supplement these information deficiencies with the aid of efficient nontraditional (ecotoxicological) methodologies within ethical frameworks to support environmental policy and risk management for NSAID and antipyretic pharmaceuticals.

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Ecotoxicology of Polystyrene microplastic fragments: Oxidative stress effects in Neonate versus adult Daphnia magna

Esterhuizen, Maranda; Lee, Sang-Ah; Järvinen, Riikka; Kim, Youngsam...

Water, Air, & Soil Pollution 235:195 / 234:713.
DOI: 10.1007/s11270-024-07011-w


Open Access Peer Reviewed
 

Polystyrene is an inert polymer; however, sublethal effects have been observed in aquatic organisms exposed to microparticles of this plastic. Information on microplastic-related oxidative stress and related antioxidative responses as adverse effects and the underlying mechanisms of toxicity are limited. Daphnids are key contributors in aquatic ecosystems, linking primary producers to consumers and predators, facilitating energy transfer and thus being considered an ideal bioindicator organism to study the adverse effects of polystyrene fragments on the oxidative stress status and subsequent enzymatic antioxidant response. In the present study, neonates (≤ 24 h) and adult daphnids were acutely exposed to polystyrene fragments sieved to three size factions (< 25 µm, 45—63 µm, and 100—500 µm), and adverse effects were evaluated after 24 and 48 h. In adults, larger particles elicited reactive oxygen species by 61%, which was met with elevated superoxide dismutase (17%) and catalase activities (98%), restoring redox homeostasis within 48 h. However, in neonates, the reactive oxygen species increased with exposure to all polystyrene sizes within 24 h, and homeostasis was regained within 48 h without eliciting the enzymatic antioxidant defense. The adverse effects were associated with size fractions that were too large to be consumed, suggesting that leached additives may be involved. Further studies are needed to determine whether nonenzymatic antioxidants were responsible for neutralizing excess reactive oxygen species in neonates.

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Phytoremediation of diclofenac using the Green Liver System: Macrophyte screening to system optimization

Esterhuizen, Maranda; Pflugmacher Lima, Stephan (2023)

New Biotechnology 76, 82 - 89.
DOI: 10.1016/j.nbt.2023.05.004


Open Access Peer Reviewed
 

Green Liver Systems employ the ability of macrophytes to take up, detoxify (biotransform), and bioaccumulate pollutants; however, these systems require optimization to target specific pollutants. In the present study, the aim was to test the applicability of the Green Liver System for diclofenac remediation considering the effects of selected variables. As a starting point, 42 macrophyte life forms were evaluated for diclofenac uptake. With the three best performing macrophytes, the system efficiency was evaluated at two diclofenac concentrations, one environmentally relevant and that other significantly higher (10 µg/L and 150 µg/L) and in two system sizes (60 L and 1000 L) as well as at three flow rates (3, 7, and 15 L/min). The effect of single species and combinations on removal efficiency was also considered. The highest internalization percentage was recorded in Ceratophyllum spp., Myriophyllum spp., and Egeria densa. Phytoremediation efficiency with species combinations was far superior to utilizing only a single macrophyte type. Furthermore, the results indicate that the flow rate significantly affected the removal efficiency of the pharmaceutical tested, with the highest remediation efficiency obtained with the highest flow rate. System size did not significantly affect phytoremediation; however, increase diclofenac concentration reduced the systems performance significantly. When planning the setup of a Green Liver System for wastewater remediation, basic knowledge about the water, i.e., pollutant types and flow, must be utilized during planning to optimize remediation. Various macrophytes show diverse uptake efficiencies for different contaminants and should be selected based on the pollutant composition of the wastewater.

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Titanium (IV) oxide anatase nanoparticles as vectors for diclofenac: assessing the antioxidative responses to single and combined exposures in the aquatic macrophyte Egeria densa

Esterhuizen, Maranda ; Lutsko, Mariia ; Kim, Youngsam ; Yoon, Hakwon; Park, Chang-Beom...

Ecotoxicology 32, 394 – 402.
DOI: 10.1007/s10646-023-02646-7


Open Access Peer Reviewed
 

Titanium dioxide, frequently used in commonplace products, is now regularly detected in aquatic environments. Understanding its toxic effects on native biota is essential. However, combined toxicity with commonly occurring pollutants, such as the pharmaceutical diclofenac, may provide more insight into environmental situations. Therefore, the present study aimed to evaluate the effects of titanium dioxide and diclofenac, individually and combined, on the macrophyte Egeria densa. Diclofenac uptake and removal by the macrophyte were assessed. Diclofenac and titanium dioxide were mixed prior to exposure to allow binding, which was assessed. Toxicity of the individual compounds and the combination was evaluated by assaying enzymes as bioindicators of biotransformation and the antioxidative system. Cytosolic glutathione S-transferase and glutathione reductase activities were increased by diclofenac, titanium dioxide, and the combination. Both enzymes’ activities were more significantly elevated by diclofenac and the combination than nanoparticles alone. Microsomal glutathione S-transferase was unaffected by diclofenac exposure but inhibited with titanium dioxide and the mixture. Diclofenac elicited the most significant response. Based on the data, the cytosolic enzymes effectively prevented damage.

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Prof. Dr. Stephan Pflugmacher Lima


Hochschule Coburg

Fakultät Angewandte Naturwissenschaften und Gesundheit (FNG)
Friedrich-Streib-Str. 2
96450 Coburg

T +49 9561 317
Stephan.Pflugmacher-Lima[at]hs-coburg.de