INTRODUCTION: The exposures to hazardous antineoplastic drugs (AD) represent serious risks for health care personnel but the exposure limits are not commonly established because of the no-threshold effects (genotoxic action, carcinogenicity) of many ADs. In this study, we discussed and derived practically applicable technical guidance values (TGV) suitable for management of AD risks. METHODS: The long-term monitoring of surface contamination by eight ADs was performed in pharmacies and hospitals in the Czech Republic and Slovak Republic in 2008-2021; in total 2,223 unique samples were collected repeatedly in 48 facilities. AD contamination was studied by LC-MS/MS for cyclophosphamide, ifosfamide, methotrexate, irinotecan, paclitaxel, 5-fluorouracil and gemcitabine and by ICP-MS for total Pt as a marker of platinum-based ADs. RESULTS: The study highlighted importance of exposure biomarkers like 5-fluorouracil and especially carcinogenic and persistent cyclophosphamide, which should be by default included in monitoring along with other ADs. Highly contaminated spots like interiors of laminar biological safety cabinets represent a specific issue, where monitoring of contamination does not bring much added value, and prevention of staff and separated cleaning procedures should be priority. Rooms and surfaces in health care facilities that should be virtually free of ADs (e.g., offices, kitchenettes, daily rooms) were contaminated with lower frequency and concentrations but any contamination in these areas should be carefully examined. DISCUSSION AND CONCLUSIONS: For all other working places, i.e., majority of areas in pharmacies and hospitals, where ADs are being prepared, packaged, stored, transported, or administered to patients, the study proposes a generic TGV of 100 pg/cm2. The analysis of long-term monitoring data of multiple ADs showed that the exceedance of one TGV can serve as an indicator and trigger for improvement of working practices contributing thus to minimizing of unintended exposures and creating a safe work environment.
- MeSH
- antitumorózní látky * MeSH
- chromatografie kapalinová MeSH
- cyklofosfamid analýza MeSH
- fluorouracil analýza MeSH
- lékárny * MeSH
- lidé MeSH
- nemocnice MeSH
- pracovní expozice * analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
Oxidative stress is an important toxicity and genotoxicity mechanism of many chronic adverse health outcomes. This study developed a sensitive extraction method for urine matrix (based on lyophilization, without the need for pre-cleaning by solid phase extraction), coupled to LC-MS/MS analysis of the biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG). The methodology was validated in urine samples from a cohort of Spanish pregnant women collected during the first, second and third trimester of pregnancy, and urine samples collected within 24 h after delivery (n = 85). A detection and quantification limit of 0.01 and 0.05 μg/L, respectively, were established. The median 8-OHdG concentration was 2.18 μg/L (range 0.33-7.79); and the corresponding creatinine-adjusted concentrations ranged from 1.04 to 13.12 with median of 4.48 μg 8-OHdG/g creatinine. The concentrations of non-adjusted 8-OHdG significantly decreased (p < 0.05) in the 3rd trimester and post-delivery urine samples when compared to the 1st trimester levels. 8-OHdG concentrations were further studied in placenta samples matching the same urine samples (n = 26), with a median value of 1.3 ng 8-OHdG/g of tissue. Placental 8-OHdG concentrations were correlated with urinary levels of non-adjusted 8-OHdG in the 3rd trimester. Considering the small cohort size, results must be interpreted with caution, however statistical analyses revealed elevated urinary non-adjusted 8-OHdG levels in the 1st trimester of mothers that delivered boys compared to those who delivered girls (p < 0.01). Increased urinary non-adjusted 8-OHdG concentrations at the time of delivery were significantly associated with clinical records (any type of clinical record during pregnancy; p < 0.05). The novel extraction and analytical method for the assessment of 8-OHdG is applicable for sensitive analysis of multiple analytes or biomarkers in urine matrix. This method could also be applied for other matrices such as blood or tissues. Our findings show that 8-OHdG in urine of pregnant women could predict oxidative stress in placenta and can be related to characteristics such as maternal obesity, mode of delivery and newborn sex.
- MeSH
- 8-hydroxy-2'-deoxyguanosin MeSH
- biologické markery moč MeSH
- chromatografie kapalinová metody MeSH
- deoxyguanosin * moč MeSH
- kreatinin moč MeSH
- lidé MeSH
- novorozenec MeSH
- oxidační stres MeSH
- placenta MeSH
- poškození DNA MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- těhotenství MeSH
- těhotné ženy * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Components of cyanobacterial water blooms were quantified in aerosols above agitated water surfaces of five freshwater bodies. The thoracic and respirable aerosol fraction (0.1-10 μm) was sampled using a high-volume sampler. Cyanotoxins microcystins were detected by LC-MS/MS at levels 0.3-13.5 ng/mL (water) and < 35-415 fg/m3 (aerosol). Lipopolysaccharides (endotoxins) were quantified by Pyrogene rFC assay at levels < 10-119 EU/mL (water) and 0.13-0.64 EU/m3 (aerosol). Cyanobacterial DNA was detected by qPCR at concentrations corresponding to 104-105 cells eq./mL (water) and 101-103 cells eq./m3 (aerosol). Lipopolysaccharides isolated from bloom samples induced IL-6 and IL-8 cytokine release in human bronchial epithelial cells Beas-2B, while extracted cyanobacterial metabolites induced both pro-inflammatory and cytotoxic effects. Bloom components detected in aerosols and their bioactivities observed in upper respiratory airway epithelial cells together indicate that aerosols formed during cyanobacterial water blooms could induce respiratory irritation and inflammatory injuries, and thus present an inhalation health risk.
- MeSH
- aerosoly MeSH
- chromatografie kapalinová MeSH
- lidé MeSH
- lipopolysacharidy analýza MeSH
- mikrocystiny toxicita MeSH
- sinice * metabolismus MeSH
- sladká voda analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- toxiny kmene Cyanobacteria * MeSH
- voda MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children. A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables. Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (-15.1% change per IQR increase, 95% CI = -23.6, -5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition. Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- lidé MeSH
- metylace DNA MeSH
- oxidační stres MeSH
- pesticidy * analýza MeSH
- pyrethriny * moč MeSH
- vystavení vlivu životního prostředí analýza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The consumption of hazardous antineoplastic drugs (ADs) used in anticancer chemotherapies is steadily increasing representing thus risks to both human health and the environment. Hospitals may serve as a contamination source, and pharmacists preparing the antineoplastic drugs (ADs) as well as nurses administering chemotherapy and caring for oncology patients are among the healthcare professionals being highly exposed. Here, we present the results of systematic monitoring (2018-2020) of surface contamination by 13 ADs in the pharmacies and hospitals in the Czech Republic (CZ; large-scale monitoring, 20 workplaces) and Slovak Republic (SK; pilot study at 4 workplaces). The study evaluated contamination by three commonly monitored ADs, i.e., 5-fluorouracil (FU), cyclophosphamide (CP), and platinum (total Pt representing cis-, carbo-, and oxaliplatin) together with ten less explored ADs, i.e., gemcitabine (GEM), ifosfamide (IF), paclitaxel (PX), irinotecan (IRI), docetaxel (DOC), methotrexate (MET), etoposide (ETOP), capecitabine (CAP), imatinib (IMAT), and doxorubicin (DOX). Floors and desktop surfaces in hospitals (chemotherapy application rooms, nurse working areas) were found to be more contaminated, namely with CP and Pt, in both countries when compared to pharmacies. Comparison between the countries showed that hospital surfaces in SK are generally more contaminated (e.g., CP median was 20 times higher in SK), while some pharmacy areas in the CZ were more contamined in comparison with SK. The newly studied ADs were detected at lower concentrations in comparison to FU, CP, and Pt, but some markers (GEM, IF, PX, and IRI) were frequently observed, and adding these compounds to routine monitoring is recommended.
- MeSH
- antitumorózní látky * analýza MeSH
- cyklofosfamid analýza MeSH
- fluorouracil analýza MeSH
- ifosfamid analýza MeSH
- kontaminace zdravotnického vybavení MeSH
- lékárny * MeSH
- lidé MeSH
- monitorování životního prostředí metody MeSH
- nemocnice MeSH
- pilotní projekty MeSH
- pracovní expozice * analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
- Publikační typ
- abstrakt z konference MeSH
Although information about the occurrence and distribution of retinoids in the environment is scarce, cyanobacterial water blooms have been identified as a significant source of these small molecules. Despite the confirmed presence of retinoids in the freshwater blooms dominated by cyanobacteria and their described teratogenic effects, reliable identification of retinoid producers and the mechanism of their biosynthesis is missing. In this study, the cultures of several taxonomically diverse species of axenic cyanobacteria were confirmed as significant producers of retinoid-like compounds. The consequent bioinformatic analysis suggested that the enzymatic background required for the biosynthesis of all-trans retinoic acid from retinal is not present across phylum Cyanobacteria. However, we demonstrated that retinal conversion into other retinoids can be mediated non-enzymatically by free radical oxidation, which leads to the production of retinoids widely detected in cyanobacteria and environmental water blooms, such as all-trans retinoic acid or all-trans 5,6epoxy retinoic acid. Importantly, the production of these metabolites by cyanobacteria in association with the mass development of water blooms can lead to adverse impacts in aquatic ecosystems regarding the described teratogenicity of retinoids. Moreover, our finding that retinal can be non-enzymatically converted into more bioactive retinoids, also in water, and out of the cells, increases the environmental significance of this process.
- Publikační typ
- tisková chyba MeSH
Cíle: Cytotoxická léčiva (CL) představují riziko pro zdravotnický personál. Povrchové dezinfekční prostředky jsou používány v nemocnicích k prevenci mikrobiální kontaminace. Není mnoho informací o jejich vlivu na povrchovou kontaminaci CL. Naše studie zkoumala účinnost vybraných dezinfekčních prostředků na odstranění kontaminace CL na podlahách v nemocnicích. Metody: Dle průzkumu ve 43 nemocnicích bylo vybráno devět nejčastěji používaných dezinfekcí, které byly testovány na účinnost odstranění devíti CL - cyklofosfamid (CP), ifosfamid (IF), kapecitabin (CAP), sunitinib (SUN), metotrexát (MET), doxorubicin (DOX), irinotecan (IRI), paklitaxel (PX) a 5-fluorouracil (FU). Výsledky: Mezi nejčastěji používané dezinfekce v nemocnicích patří činidla na bázi peroxidu vodíku, chlornanu sodného, glukoprotaminu, glutaraldehydu a také prostředky obsahující alkoholy. Podlahovou kontaminaci CL odstraňuje nejúčinněji aktivní chlór (při použití však uvolňuje dráždivé toxické látky) a peroxid vodíku. Problematické se jeví odstranění karcinogenního CP. Prostředky na bázi alkoholu mohou mobilizovat kontaminaci CL z hlubších vrstev podlahového materiálu. Závěry: Pro každodenní použití lze ve smyslu dezinfekce i dekontaminace CL doporučit zejména prostředky s oxidačními účinky. Další přípravky mají variabilní účinky vůči různým CL. V případě rizika vysoké kontaminace by měl být úklidový proces doplněn o používání prostředků například na bázi aktivního chloru, který je účinný také proti karcinogennímu a perzistentnímu CP.
Objectives: Cytotoxic therapeutics (CT) pose a risk to healthcare professionals. Surface disinfectants are used in hospitals to prevent microbial contamination. Information about their effects on removing CT is incomplete. Our study has examined the effectiveness of selected disinfectants on CT floor contamination. Methods: According to a survey in 43 hospitals, the nine most commonly used disinfectants were selected and tested for the presence of nine CTs - cyclophosphamide (CP), ifosfamide (IF), capecitabine (CAP), sunitinib (SUN), methotrexate (MET), doxorubicin (DOX), irinotecan (IRI), paclitaxel (PX) and 5-fluorouracil (FU). Results: The most commonly used disinfectants in hospitals include agents based on hydrogen peroxide, sodium hypochlorite, glucoprotamine, glutaraldehyde and alcohol. The most effective way to remove floor contamination is chlorine (which however releases irritating compounds) and hydrogen peroxide. The removal of carcinogenic CP was problematic. Alcohol-based agents can mobilize CL contamination from deeper layers of flooring material. Conclusions: For everyday disinfection and decontamination of CT it is possible to recommend products based on oxidizing agents. Other agents have variable efficiency against CT. Cleaning processes should be complemented by the regular use of strong chlorine-based disinfectants, which are also effective against carcinogenic and persistent CP.
The COVID-19 pandemic has raised the problem of efficient, low-cost materials enabling the effective protection of people from viruses transmitted through the air or via surfaces. Nanofibers can be a great candidate for efficient air filtration due to their structure, although they cannot protect from viruses. In this work, we prepared a wide range of nanofibrous biodegradable samples containing Ag (up to 0.6 at.%) and Cu (up to 20.4 at.%) exhibiting various wettability. By adjusting the magnetron current (0.3 A) and implanter voltage (5 kV), the deposition of TiO2 and Ag+ implantation into PCL/PEO nanofibers was optimized in order to achieve implantation of Ag+ without damaging the nanofibrous structure of the PCL/PEO. The optimal conditions to implant silver were achieved for the PCL-Ti0.3-Ag-5kV sample. The coating of PCL nanofibers by a Cu layer was successfully realized by magnetron sputtering. The antiviral activity evaluated by widely used methodology involving the cultivation of VeroE6 cells was the highest for PCL-Cu and PCL-COOH, where the VeroE6 viability was 73.1 and 68.1%, respectively, which is significantly higher compared to SARS-CoV-2 samples without self-sanitizing (42.8%). Interestingly, the samples with implanted silver and TiO2 exhibited no antiviral effect. This difference between Cu and Ag containing nanofibers might be related to the different concentrations of ions released from the samples: 80 μg/L/day for Cu2+ versus 15 μg/L/day for Ag+. The high antiviral activity of PCL-Cu opens up an exciting opportunity to prepare low-cost self-sanitizing surfaces for anti-SARS-CoV-2 protection and can be essential for air filtration application and facemasks. The rough cost estimation for the production of a biodegradable nanohybrid PCL-Cu facemask revealed ~$0.28/piece, and the business case for the production of these facemasks would be highly positive, with an Internal Rate of Return of 34%.
- MeSH
- antivirové látky chemie MeSH
- biokompatibilní potahované materiály chemie MeSH
- Cercopithecus aethiops MeSH
- COVID-19 prevence a kontrola přenos MeSH
- lidé MeSH
- měď chemie MeSH
- nanovlákna chemie MeSH
- polyestery chemie MeSH
- SARS-CoV-2 chemie MeSH
- titan chemie MeSH
- Vero buňky MeSH
- zlato chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
