Delayed toxicity of three fluoroquinolones and their mixtures after neonatal or embryonic exposure, in Daphnia magna

Tolosi, Roberta; Liguoro, Marco De

doi:10.1016/j.ecoenv.2021.112778

Cited by 11 publications

(12 citation statements)

References 36 publications

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“…Perhaps improvement is possible by (additionally) performing tests with exposure pulses (as prescribed by EFSA, 2018) or by extending the test duration (e.g., until an incipient LC50 is reached). To make the acute test more informative, a follow-up in clean medium, as used by Tolosi & De Liguoro (2021), could be particularly effective (even when using a shorter recovery period). Modeling studies with simulated data sets can shed more light on the power of various test designs to identify model parameters (Ashauer et al, 2016).…”

Section: Limitations Of Acute Toxicity Testsmentioning

confidence: 99%

“…Second, would we be able to identify (extreme) delayed toxicity from short-term standard toxicity tests by using TKTD analysis? To provide some insights into these questions, I will re-analyse recently published data for D. magna with fluoroquinolones (Tolosi & De Liguoro, 2021), which are antibacterial drugs for human and veterinary medicine. The study is interesting because of the experimental design (acute exposure with a long recovery period in clean medium), and because it shows rather severe delayed effects (scoring immobility as proxy for death).…”

Section: Introductionmentioning

confidence: 99%

“…In some cases, no further mortality will occur in the recovery period, but in other cases mortality will continue for some time. In the most extreme cases, mortality rates are even observed to increase after transfer to clean exposure medium (see Bechmann et al, 2019; Tolosi & De Liguoro, 2021). Clearly, the extent to which a compound causes delayed mortality in a species should be of substantial interest both for risk assessment applications and for scientific studies.…”

Section: Introductionmentioning

confidence: 99%

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Identifying and Predicting Delayed Mortality with Toxicokinetic–Toxicodynamic Models

Jager

2024

Enviro Toxic and Chemistry

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The prevalence of standardized toxicity testing in ecotoxicology has largely obscured the notion that toxicity is a function of time as well. The necessity of considering time is vividly demonstrated by observations of delayed mortality, that is, deaths continue to occur even when animals are no longer exposed to a toxicant. In this contribution, I explore to what extent toxicokinetic–toxicodynamic (TKTD) models from the framework of the General Unified Threshold model for Survival (GUTS) can capture delayed mortality, and to what extent this phenomenon can be predicted from short‐term standard tests. I use a previously published data set for fluoroquinolones in Daphnia magna that shows strongly delayed mortality (using immobilization as a proxy for death). The model analysis shows that the GUTS stochastic death models can capture delayed mortality in the complete data set with a long recovery phase, but that the delayed effects would not have been predicted from a 2‐day standard test. The study underlines the limited information content of standard acute test designs. Toxicokinetic–toxicodynamic modeling offers a handle on the time aspects of toxicity but cannot always be relied on to provide accurate extrapolations based on severely limited standard tests. The phenomenon of delayed toxicity requires more structured study to clarify its prevalence and impact; I discuss several avenues for further investigation. Environ Toxicol Chem 2024;00:1–6. © 2024 SETAC.

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Section: Limitations Of Acute Toxicity Testsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identifying and Predicting Delayed Mortality with Toxicokinetic–Toxicodynamic Models

Jager

2024

Enviro Toxic and Chemistry

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“…Interestingly, a safety analysis of this antibiotic on anuran amphibian larvae showed that the environmental concentration of enrofloxacin (10 µg/L) affected the development, size, shape, and growth of larvae, as well as inhibiting the activity of antioxidant enzymes [ 155 ]. It was also proposed that in Daphnia magna , enrofloxacin can cause high reproductive toxicity, as well as genetic or epigenetic changes that will only produce effects in subsequent generations [ 158 , 159 , 160 ].…”

Section: The Safety Of Enrofloxacin Usementioning

confidence: 99%

Enrofloxacin—The Ruthless Killer of Eukaryotic Cells or the Last Hope in the Fight against Bacterial Infections?

Grabowski

Gaffke

Pierzynowska

et al. 2022

IJMS

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Enrofloxacin is a compound that originates from a group of fluoroquinolones that is widely used in veterinary medicine as an antibacterial agent (this antibiotic is not approved for use as a drug in humans). It reveals strong antibiotic activity against both Gram-positive and Gram-negative bacteria, mainly due to the inhibition of bacterial gyrase and topoisomerase IV enzymatic actions. The high efficacy of this molecule has been demonstrated in the treatment of various animals on farms and other locations. However, the use of enrofloxacin causes severe adverse effects, including skeletal, reproductive, immune, and digestive disorders. In this review article, we present in detail and discuss the advantageous and disadvantageous properties of enrofloxacin, showing the benefits and risks of the use of this compound in veterinary medicine. Animal health and the environmental effects of this stable antibiotic (with half-life as long as 3–9 years in various natural environments) are analyzed, as are the interesting properties of this molecule that are expressed when present in complexes with metals. Recommendations for further research on enrofloxacin are also proposed.

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“…FQs can pose potential risks. − The median effective concentrations (EC 50 ’s) of levofloxacin (LEV), enrofloxacin (ENR), and flumequine (FLU) were 3.13, 7.18, and 15.11 mg/L based on the toxicity to the neonatal or embryonic of D. magna . Moreover, the mixed toxicity of these three FQs followed the concentration addition principle, suggesting that accumulation of FQs might pose a greater risk to human health and ecological safety. The toxicity of zwitterionic lomefloxacin (LOM) and ofloxacin (OFL) to Vibrio fischeri was reduced after photodegradation, whereas the transformation products of lomefloxacin (LOM) were much more toxic .…”

Section: Introductionmentioning

confidence: 99%

Fe(V) Dominates the Toxicity Increase Pathway during Ferrate(VI) Degradation of Fluoroquinolone Antibiotics

Wang

Jiang

et al. 2023

ACS EST Eng.

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Environmental accumulation of fluoroquinolones (FQs) has brought concerns over their potential risks to human health. This study found that ferrate (Fe(VI)) could efficiently degrade norfloxacin (NOR), ciprofloxacin (CIP), and levofloxacin (LEV). However, cytotoxicity to mammalian cells of NOR, CIP, and LEV dramatically increased from 9. 41, 8.34, and 11.05 mg phenol/L to 20.76, 26.13, and 32.45 mg phenol/L after reacting with Fe(VI) for 3 min. Intracellular oxidative stress in the mammalian cells also increased, suggesting the risk of applying Fe(VI) for FQ degradation. Fe(V) was demonstrated to play the major role in FQ degradation by kinetics investigation, probe contaminant (PMSO and 2,2′-azino-bis-(3-ethylbenzothiazoline-6sulfonate) (ABTS)), and pyrophosphate competing experiments. Density functional theory (DFT) calculation and toxicity prediction suggested that, in the CIP-ferrate system, Fe(V) increased the toxicity via oxidizing the piperazine group to −NH 2 . In the NOR-ferrate and LEV-ferrate systems, Fe(V) mainly attacked the quinolone ring. The unstable products underwent subsequent carboxylation or hydroxylation, leading to the further increased toxicity. The current research on micropollutant removal focused on applying various approaches to activate ferrate to generate high-valent iron intermediates with stronger oxidizing capacity. Our study gave a risk warning that high-valent iron intermediates might play an important role in increasing the toxicity of micropollutants.

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Delayed toxicity of three fluoroquinolones and their mixtures after neonatal or embryonic exposure, in Daphnia magna

Cited by 11 publications

References 36 publications

Identifying and Predicting Delayed Mortality with Toxicokinetic–Toxicodynamic Models

Identifying and Predicting Delayed Mortality with Toxicokinetic–Toxicodynamic Models

Enrofloxacin—The Ruthless Killer of Eukaryotic Cells or the Last Hope in the Fight against Bacterial Infections?

Fe(V) Dominates the Toxicity Increase Pathway during Ferrate(VI) Degradation of Fluoroquinolone Antibiotics

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