Significance of metabolites in the environmental risk assessment of pharmaceuticals consumed by human

Han, Eun Jeong; Lee, Dong Hoon

doi:10.1016/j.scitotenv.2017.03.044

Cited by 39 publications

(23 citation statements)

References 41 publications

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“…Available literature data on the harmfulness and occurrence of pharmaceuticals in the environment indicate the need for Responsible Editor: Gerald Thouand Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11356-020-08881-3) contains supplementary material, which is available to authorized users. their environmental risk assessment (Han and Lee 2017;Desbiolles et al 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, to give some examples of other drug groups: O-desmethyltramadol (O-DES-TRA), the metabolite of an opioid analgesic tramadol (TRA), was found to be a stronger inhibitor of opioid receptors, and metoprolol acid (MET-ACID), a beta-blocker TP, was also found slightly more toxic than the parent compound towards three species of fungi (Jaén-Gil et al 2019). The occurrence of pharmaceutical TPs in the environment and their potential biological activity indicate the need to extend the environmental risk assessment with ecotoxicological tests for these substances (Han and Lee 2017). Therefore, the main aim of our study was to evaluate the toxicity of selected TPs of different pharmaceuticals, which are commonly detected in many aquatic environments at relatively high concentrations in comparison to other therapeutic compounds.…”

Section: Introductionmentioning

confidence: 99%

“…They are considered safe due to the rare occurrence of side effects, mainly in children and the elderly (Sandilands and Bateman 2016;Terzi et al 2017). Diclofenac, naproxen, and ibuprofen (IBU) were selected from this drug group along with their four TPs (Table 1), due to confirmed presence in WWTP effluents at concentrations from ng L −1 to μg L −1 levels (Lonappan et al 2016;Han and Lee 2017;Wilkinson et al 2017), as well as due to the abovementioned ecotoxicological data (Isidori et al 2005b;Lonappan et al 2016). A substance of similar function (opioid analgesic), TRA, was selected because of its wide use (and apparent abuse), along with its primary metabolite O-DES-TRA.…”

Section: Introductionmentioning

confidence: 99%

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Ecotoxicity screening evaluation of selected pharmaceuticals and their transformation products towards various organisms

Grabarczyk

Mulkiewicz

Stolte

et al. 2020

Environ Sci Pollut Res

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The intensive development of medical science has led to an increase in the availability and use of pharmaceutical products. However, nowadays, most of scientific attention has been paid to the native forms of pharmaceuticals, while the transformation products (TPs) of these substances, understood herein as metabolites, degradation products, and selected enantiomers, remain largely unexplored in terms of their characterization, presence, fate and effects within the natural environment. Therefore, the main aim of this study was to evaluate the toxicity of seven native compounds belonging to different therapeutic groups (nonsteroidal anti-inflammatory drugs, opioid analgesics, beta-blockers, antibacterial and anti-epileptic drugs), along with the toxicity of their 13 most important TPs. For this purpose, an ecotoxicological test battery, consisting of five organisms of different biological organization was used. The obtained data shows that, in general, the toxicity of TPs to the tested organisms was similar or lower compared to their parent compounds. However, for example, significantly higher toxicity of the R form of ibuprofen to algae and duckweed, as well as a higher toxicity of the R form of naproxen to luminescent bacteria, was observed, proving that the risk associated with the presence of drug TPs in the environment should not be neglected.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ecotoxicity screening evaluation of selected pharmaceuticals and their transformation products towards various organisms

Grabarczyk

Mulkiewicz

Stolte

et al. 2020

Environ Sci Pollut Res

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“…Challenges in the determination of ecotoxicity posed by the diversity of PhACs to be tested are further complicated by the large number of potentially exposed wildlife species and their specific target affinity and by the variety of toxicological endpoints that might be affected (Arnold et al ; Kostich and Länge ). Pharmaceutical metabolites and their potential ecotoxic effects are even less understood, and some studies have already shown metabolites’ toxicity to wildlife species to be often similar to or even worse than that of the parent compound (Heye et al ; Han and Lee ).…”

Section: Resultsmentioning

confidence: 99%

Modeling pharmaceutical emissions and their toxicity‐related effects in life cycle assessment (LCA): A review

Emara¹,

Lehmann²,

Siegert³

et al. 2018

Integr Envir Assess & Manag

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Over the last few decades, worldwide detection of active pharmaceutical ingredients (APIs) in aquatic environments and the associated toxicological effects on wildlife and human health have become a matter of public and scientific debate. While life cycle assessment (LCA) and life cycle impact assessment (LCIA) models are increasingly used to assess the potential eco-and human-toxicological effects of chemical emissions, few studies have looked into the issue of modeling pharmaceutical emissions specifically and their toxicity-related effects in an LCA context. This paper reviews the state of the art to inventory and characterize API emissions in LCA with the goal to identify relevant gaps and challenges. A search for 208 environmentally relevant APIs in 2 life cycle inventory (LCI) databases revealed a meager representation of this group of chemicals. Similarly, the LCIA model USEtox was found to include characterization factors (CFs) for less than 60 APIs. First approaches to model API emissions in LCA were identified on the basis of an examination of 40 LCA case studies in the pharmaceutical sector and in the field of wastewater treatment. Moreover, CFs for 79 additional APIs, expressing their ecotoxicity and/or human toxicity potential, were gathered from literature. An analysis of the variability of API-CFs in different LCIA models showed a variation of about 2-3 orders of magnitude. Based on the review results, 3 main gaps in the modeling and characterization of API emissions in an LCA context were identified: (1) incomplete modeling of API flows and API emissions along the life cycle of human pharmaceuticals, especially during their use and end-of-life phase, (2) limited API coverage in existing LCIA toxicity models, and (3) missing pharma-specific impact pathways (e.g., endocrine disruption and antibiotic resistance) in existing LCIA models. Recommendations to tackle these gaps are provided, and priority action steps are discussed. Integr Environ Assess Manag 2019;15:6-18. C 2018 SETAC

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“…In order to increase abundance of blaCTX-M harbouring bacteria we added 1μg mL -1 of cefotaxime to triplicate incubations, the same used to select ESBL-bacteria (Santanirand et al, 2011) and 10 6 times higher than that found in an aquatic environment previously (Han and Lee, 2017), thus mimicking a high antibiotic release. Two different types of controls were conducted in triplicate: one enrichment without any antibiotics and one with 1μg mL -1 of ampicillin, in order to provide an antibiotic similar to cefotaxime but not specifically selecting for blaCTX-M. All enrichments were incubated at 20°C in the dark for 4 days.…”

Section: Enrichment Experimentsmentioning

confidence: 99%

Seasonality of the antibiotic resistance gene blaCTX-M in temperate Lake Maggiore

et al. 2019

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The beta lactamase gene blaCTX-M, responsible of the resistance to cephalosporins, has been detected in microbes from hospitals to open waters. We studied the seasonality and stability of blaCTX-M in Lake Maggiore over 3 years and the role of potential inputs of allochthonous bacteria and/or antibiotic pollution in promoting its occurrence. blaCTX-M was mainly present from January to July in the pelagic microbial community and the gene occurrence was significantly related to low water temperature. To evaluate its temporal stability in the bacterial community over a short period, we measured blaCTX-M daily over the course of 6 days. The gene was below the limit of quantification except for one sampling when its abundance peaked, suggesting a point contamination. The bacterial community of the lake in which blaCTX-M was detected suggests that at least two distinct bacterial populations contained the gene. The occurrence of known blaCTX-M containing genera and the occurrence of the gene, however, did not overlap. Furthermore, the experimental addition of cefotaxime to lake water incubations did not promote abundance of the gene. These data imply that blaCTX-M was present in the environmental microbial community. Increases of gene abundances were likely caused by environmental parameters other than antibiotic contamination.

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Significance of metabolites in the environmental risk assessment of pharmaceuticals consumed by human

Cited by 39 publications

References 41 publications

Ecotoxicity screening evaluation of selected pharmaceuticals and their transformation products towards various organisms

Ecotoxicity screening evaluation of selected pharmaceuticals and their transformation products towards various organisms

Modeling pharmaceutical emissions and their toxicity‐related effects in life cycle assessment (LCA): A review

Seasonality of the antibiotic resistance gene blaCTX-M in temperate Lake Maggiore

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