Aquatic toxicity of the macrolide antibiotic clarithromycin and its metabolites

Baumann, Michaela; Weiß, Klaus; Maletzki, Dirk; Schüssler, Walter; Schudoma, Dieter; Kopf, W.; Kühnen, Ute

doi:10.1016/j.chemosphere.2014.05.089

Cited by 82 publications

(35 citation statements)

References 43 publications

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“…The estimated parameters for the log-logistic model are shown in Table 4. The alga, P. subcapitata, was highly sensitive to clarithromycin compared with the daphnid and zebrafish in the present study; and it was slightly more sensitive than the other freshwater green algae, Desmodesmus subspicatus and Anabaena flos-aquae, reported in the literature: IC50s were 37.1 mg/L and 12.1 mg/L, respectively [34]. For the algae, the rank order toxicity of the 10 pharmaceuticals for NOEC was clarithromycin > diphenhydramine > phenytoin > epinastine > crotamiton > ketoprofen > etodolac > sulpiride > bezafibrate ¼ acetaminophen.…”

Section: Individual Toxicitysupporting

confidence: 50%

“…The most toxic pharmaceutical to the algae was clarithromycin: the NOEC and IC50 were 2.45 mg/L and 6.9 mg/L as the time-weighted mean concentrations, respectively. The alga, P. subcapitata, was highly sensitive to clarithromycin compared with the daphnid and zebrafish in the present study; and it was slightly more sensitive than the other freshwater green algae, Desmodesmus subspicatus and Anabaena flos-aquae, reported in the literature: IC50s were 37.1 mg/L and 12.1 mg/L, respectively [34]. In addition, the NOEC value for the alga was only twice that of the maximum detected concentration in the effluent from WWTPs in Tokyo (1.291 mg/L; Table 1), suggesting that clarithromycin poses a high environmental risk to the alga.…”

Section: Individual Toxicitysupporting

confidence: 50%

See 1 more Smart Citation

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Watanabe

Tamura

Abe

et al. 2016

Enviro Toxic and Chemistry

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Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no-observed-effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action were nearly identical for alga, as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action.

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Section: Individual Toxicitysupporting

confidence: 50%

Section: Individual Toxicitysupporting

confidence: 50%

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Watanabe

Tamura

Abe

et al. 2016

Enviro Toxic and Chemistry

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“…Zhao et al exposed juvenile Cyprinus carpio for 28 d under semi‐static conditions to low concentrations of 6 μg SMX/L, 0.6 μg SMX/L, and 0.06 μg SMX/L; there was no mortality and no negative influence on growth rate or hepatosomatic index. Moreover, because antibiotics are not targeted against vertebrates, Baumann et al argued in a recent publication on clarithromycin that, “Although there are no data on chronic fish tests for clarithromycin, an AF [assessment factor] of 10 is justifiable, because with high probability the most sensitive species have been examined (green alga and cyanobacteria).” The same picture emerges for SMX, where the most sensitive organisms are cyanobacteria, followed by a mix of different invertebrates, marine periphyton micro‐organisms, algae, and flowering plants, whereas both vertebrate groups tested have a very high NOEC.…”

Section: Resultsmentioning

confidence: 99%

Aquatic environmental risk assessment for human use of the old antibiotic sulfamethoxazole in Europe

Straub

2015

Enviro Toxic and Chemistry

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Sulfamethoxazole (SMX) is an old sulfonamide antibiotic that was launched first in combination with trimethoprim in 1969 by F.Hoffmann-La Roche. Although sales figures for SMX have been declining over the past 20 yr, the compound is still widely used; moreover, many measured environmental concentrations (MECs) are available from Europe, the United States, Asia, Australia, and Africa. To assess aquatic risks of SMX in Europe, the exposure of European surface waters was predicted based on actual sales figures from IMS Health, incorporating environmental fate data on one side, and based on collated MECs representing more than 5500 single measurements in Europe on the other. Environmental effects were assessed using chronic and subchronic ecotoxicity data for 16 groups of aquatic organisms, from periphyton communities to cyanobacteria, algae, higher plants, various invertebrates, and vertebrates. Predicted no-effect concentrations (PNECs) were derived using both deterministic and probabilistic methodology.

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“…Such a situation revealed biotransformation as an ecotoxicologically favorable process. Baumann et al [38] indicated that some of the metabolites, notably 14-OH CLA, can be as toxic as the parent macrolides;…”

Section: Toxicity Evaluationmentioning

confidence: 99%

Biotransformation of macrolide antibiotics using enriched activated sludge culture: Kinetics, transformation routes and ecotoxicological evaluation

Terzić

Udikovic-Kolic

Jurina

et al. 2018

Journal of Hazardous Materials

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The biotransformation of three prominent macrolide antibiotics (azithromycin, clarithromycin and erythromycin) by an activated sludge culture, which was adapted to high concentrations of azithromycin (10 mg/L) was investigated. The study included determination of removal kinetics of the parent compounds, identification of their major biotransformation products (TPs) and assessment of ecotoxicological effects of biotransformation. The chemical analyses were performed by ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry, which enabled a tentative identification of TPs formed during the experiments. The ecotoxicological evaluation included two end-points, residual antibiotic activity and toxicity to freshwater algae. The enriched activated sludge culture was capable of degrading all studied macrolide compounds with high removal efficiencies (>99%) of the parent compounds at elevated concentrations (10 mg/L). The elimination of all three macrolide antibiotics was associated with the formation of different TPs, including several novel compounds previously unreported in the literature. Some of the TPs were rather abundant and contributed significantly to the overall mass balance at the end of the biodegradation experiments. Biodegradation of all investigated macrolides was associated with a pronounced reduction of the residual antibiotic activity and algal toxicity, indicating a rather positive ecotoxicological outcome of the biotransformation processes achieved by the enriched sludge culture.

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Aquatic toxicity of the macrolide antibiotic clarithromycin and its metabolites

Cited by 82 publications

References 43 publications

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Aquatic environmental risk assessment for human use of the old antibiotic sulfamethoxazole in Europe

Biotransformation of macrolide antibiotics using enriched activated sludge culture: Kinetics, transformation routes and ecotoxicological evaluation

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