Untargeted Screening Research Articles

Pesticide contamination and associated ecological risks in estuarine waters of Brazil's Legal Amazon.

Pesticide contamination remains a significant environmental concern globally, with important implications for aquatic ecosystems. Despite being one of the world's largest pesticide consumers, monitoring and assessment of pesticide pollution are limited in Brazil, especially in sensitive regions like the Amazon. In this study, the occurrence and environmental risks of 8 pesticides of different classes, namely alachlor, atrazine, chlorfenvinphos, isoproturon, irgarol, simazine, diuron, and its transformation product DCPMU (1-(3,4-dichlorophenyl)-3-methyl urea) were analysed in surface water of the São Marcos Estuarine Complex (SMEC) in two consecutive years. The quantification of the target compounds was performed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Suspected and untargeted screening analyses with ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was also conducted to identify transformation products (TPs) and additional pesticides in water samples. All target pesticides, except for alachlor, were found in at least one sampling campaign. The antifouling biocides irgarol and diuron were ubiquitous in 2018 and 2019, with detection frequencies varying between 81 and 100% and maximum concentrations of 13.6ng L-1 and 17.1ng L-1, respectively. In 2019, the detection frequencies of the target pesticides were considerably higher than in 2018, with atrazine, isoproturon, and DCPMU being found in 100% of the samples. In 2019, chlorfenvinphos and isoproturon were the pesticides with the highest levels, reaching 48.6ng L-1 and 44.6ng L-1, respectively. The UHPLC-HRMS analysis showed the presence of the pesticides DEET (N,N-diethyl-meta-toluamide), octhilinone (2-Octyl-4-isothiazolin-3-one), and cyprodinil (4-cyclopropyl-6-methyl-N-phenylpyrimidin-2-amine) in water samples. Additionally, the TPs 2-hydroxy-atrazine, didemethylisoproturon (1-(4-isopropylphenyl)urea) and M1 (2-methylthio-4-tert-butylamino-6-amino-s-triazine) were found. The environmental risk assessment showed that irgarol was the primary contributor to the global risk quotient in the SMEC region. Similarly, chlorfenvinphos also showed a high risk to the local aquatic biota, especially in 2019. This research not only highlights the urgent need for improved pesticide monitoring in Brazil but also establishes a baseline for future studies and environmental management efforts in SMEC. We emphasize the importance of prioritising pollutants and implementing effective mitigation strategies to protect the fragile aquatic ecosystems of the Brazilian Amazon.

The limited clinical utility of a routine creatine kinase (CK) on admission to a psychiatric inpatient unit

BackgroundCreatine kinase (CK) is an intracellular enzyme expressed most commonly in tissues such as skeletal muscle. CK can be used as an investigation to support the diagnosis of conditions such as neuroleptic malignant syndrome (NMS), a rare idiosyncratic drug reaction – classically to antipsychotic medications – which can be fatal. Routine screening of CK in psychiatric inpatients is a known practice, but its value is uncertain. We aimed to ascertain whether such screening resulted in new diagnoses of NMS or other conditions, and changes in clinical management.MethodsUsing an electronic case register, we conducted a descriptive retrospective cohort study, identifying all psychiatric inpatient admissions in a South London mental health trust over a four-year period where a CK test was conducted within 48 h of admission. We extracted the demographic and clinical characteristics (e.g., diagnosis) of those who met inclusion criteria. Free-text review was performed on all those with a CK potentially suggestive of NMS (CK ≥ 4x upper limit of normal reference range (ULN)) to determine the impact of this abnormal result on subsequent management and diagnosis (including NMS if identified).ResultsOf 14,236 inpatient episodes in the specified window, 2358 (16.6%) had a CK test within 48 h of admission. This was ≥ 4x ULN in 327 (13.8%) cases (free-text successfully reviewed in 318). There were no cases of NMS identified. An abnormal CK result led to a new alternative diagnosis, such as dehydration or catatonia, in only 14 patients (4.4% raised CK sample, 0.6% total CK sample). Impact on subsequent management appeared limited, with the most common adjustment being an increase in frequency of physical observations in 47 instances (14.8%).ConclusionsThe clinical utility of untargeted screening using a serum CK for psychiatric inpatients appears limited, with poor specificity in detection of NMS and a minimal impact on subsequent clinical management.

Development and evaluation of statistical and artificial intelligence approaches with microbial shotgun metagenomics data as an untargeted screening tool for use in food production.

We evaluated the feasibility of using untargeted metagenomic sequencing of raw milk for detecting anomalous food ingredient content with artificial intelligence methods in a study specifically designed to test this hypothesis. We also show through analysis of publicly available fluid milk microbial data that our artificial intelligence approach is able to successfully predict milk in different stages of processing. The approach could potentially be applied in the food industry for safety and quality control.

Application of a molecular networking approach using LC-HRMS combined with the MetWork webserver for clinical and forensic toxicology

Backgrounds and aimsIn toxicology, LC-HRMS for untargeted screening yields a great deal of high quality spectral data. However, there we lack tools to visualize/organize the MS data. We applied molecular networking (MN) to untargeted screening interpretation. Our aims were to compare theoretical MS libraries obtained in silico with our experimental dataset in patients to broaden its application, and to use the MetWork web application for metabolite identification. MethodsSamples were analyzed using an LC-HRMS system. For MN, data was generated using MZmine, and analyzed and visualized using MetGem. MetWork annotations were filtered and this file was used for annotation of the previously obtained MN. Results155 compounds including drugs found in patients were recorded. Using this dataset, we confirmed in 60 patients intake of tramadol, amitriptyline bromazepam, and cocaine. The results obtained by the reference methods were confirmed by MN approaches. Eighty percent of the compounds were common to both conventional and MN approaches. Using MetWork, metabolites and parent drugs such as amitriptyline, its metabolite nortriptyline and amitriptyline glucuronide phase 2 metabolites were anticipated and proposed as putative annotations. ConclusionThe workflow increases confidence in toxicological screening by highlighting putative structures in biological matrices in combination with CFM-ID (Competitive Fragmentation Modeling for Metabolite Identification) and MetWork to extend the annotation of potential drugs even without a reference standard.

Targeted and untargeted screening of a plant extract library established from raw materials originating from Upper Austria

Plant extracts rich in phytochemicals are known for their health benefits. Plant extract library from edible plants obtained from the region of Upper Austria was prepared. Food grade extraction procedures were applied, and relevant physico-chemical parameters measured. A focus on polyphenolic compounds revealed a significant correlation between the total phenolic content (measured by a colorimetric assay) and the cumulated concentration of main individual polyphenols (measured by HPLC-DAD), demonstrating the comparability of these parameters. Targeted screening was performed by HPLC-FLD and −MS for the presence of phytomelatonin. 20 extracts were identified with concentrations of up to 1.4 µg/mL of this phytochemical, which attracts much attention from the food industry. Finally, chemometric methods were employed to cluster extracts based on their phenolic compound profile. This approach allows for an informed preselection of extracts without the need for comprehensive chemical analysis.

Targeted and untargeted screening for impurities in losartan tablets marketed in Germany by means of liquid chromatography/high resolution mass spectrometry

Technical advances in the field of quality analysis allow an increasingly deeper look into the impurity profile of drugs. The ability to detect unexpected impurities in addition to known impurities ensures the supply of high-quality drugs and can prevent recalls due to the detection of harmful unexpected impurities, as has happened recently with the N-nitrosamine and azido impurities in losartan (LOS) drug products. In the present study, the LC-MS/HRMS approach described by Backer et al. was applied to an even more complex system, being the investigation of 35 LOS drug products and combination preparations purchased in 2018 and 2022 in German pharmacies. The film-coated tablets were analysed by means of four LC-MS/HRMS method variants. For the separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and for mass spectrometric detection a qTOF mass spectrometer with electrospray ionization in positive and negative mode was used. An information-dependent acquisition method was applied for the acquisition of high-resolution mass spectrometry data. The combination of an untargeted and a targeted screening approach revealed the finding of eight impurities in total. Beside the five LOS related compounds, LOS impurity F, J, K, L, M, and related compound D from amlodipine besilate, LOS azide and an unknown derivative thereof were detected. Identification and structure elucidation, respectively, were successfully performed using in silico fragmentation. Differences in the impurity profiles of drug products from 2018 and 2022 could be observed. This study shows that broad screening approaches like this are applicable to the analysis of drug products and can be an important enhancement of the quality assurance of medicinal products.

Screening for Forensically Relevant Drugs Using Data-Independent High-Resolution Mass Spectrometry.

Forensic and clinical laboratories are expected to provide a rapid screening of samples for a wide range of analytes; however, the ever-changing landscape of illicit substances makes analysis complicated. There is a great need for untargeted methods that can aid these laboratories in broad-scope drug screening. Liquid chromatography hyphenated with high-resolution mass spectrometry (LC-HRMS) has become a popular technique for untargeted screening and presumptive identification of drugs of abuse due to its superior sensitivity and detection capabilities in complex matrices. An untargeted extraction and data acquisition method was evaluated for the broad screening of high-priority drugs of abuse in whole blood. A total of 35 forensically relevant target analytes were identified and extracted at biologically relevant low and high (10× low) concentrations from whole blood using supported liquid extraction. Data-independent acquisition was accomplished using ultraperformance liquid chromatography and a quadrupole time-of-flight mass spectrometry. Results were acceptable for screening assays, with limits of detection at or below the recommended low-concentration cutoffs for most analytes. Analyte ionization varied from 30.1 to 267.6% (average: 110.5%) at low concentrations and from 8.6 to 383.5% (average: 93.6%) at high concentrations. Extraction recovery ranged from 8.5 to 330.5% (average: 105.3%) at low concentrations and from 9.4 to 127.5% (average: 82.7%) at high concentrations. This variability was also captured as precision, ranging from 4.7 to 135.2% (average: 36.5%) at low concentrations and from 0.9 to 59.0% (average: 21.7%) at high concentrations. The method described in this work is efficient and effective for qualitative forensic toxicology screening, as demonstrated by analysis of 166 authentic suspected impaired driver and postmortem specimens. That said, it is critical that laboratories establishing untargeted LC-HRMS screening assays be aware of the strengths and limitations across diverse drug categories and chemical structures.

Development and validation of a versatile non-invasive urinary steroidomics method for wildlife biomonitoring

Wildlife conservation is often challenged by a lack of knowledge about the reproduction biology and adaptability of endangered species. Although monitoring steroids and related molecules can increase this knowledge, the applicability of current techniques (e.g. immunoassays) is hampered by species-specific steroid metabolism and the requisite to avoid invasive sampling. This study presents a validated steroidomics method for the (un)targeted screening of a wide range of sex and stress steroids and related molecules in urine using ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). In total, 50 steroids (conjugated and non-conjugated androgens, estrogens, progestogens and glucocorticoids) and 6 prostaglandins could be uniquely detected. A total of 45 out of 56 compounds demonstrated a detection limit below 0.01 ng μL−1. Excellent linearity (R2 > 0.99), precision (CV < 20 %), and recovery (80–120 %) were observed for 46, 41, and 39 compounds, respectively. Untargeted screening of pooled giant panda and human samples yielded 9691 and 8366 features with CV < 30 %, from which 84.1 % and 83.0 %, respectively, also demonstrated excellent linearity (R2 > 0.90). The biological validity of the method was investigated on male and female giant panda urine (n = 20), as well as pooled human samples (n = 10). A total of 24 different steroids were detected with clear qualitative and quantitative differences between human and giant panda samples. Furthermore, expected differences were revealed between female giant panda samples from different reproductive phases. In contrast to traditional biomonitoring techniques, the developed steroidomics method was able to screen a wide range of compounds and provide information on the putative identities of metabolites potentially important for reproductive monitoring in giant pandas. These results illustrate the advancements steroidomics brings to the field of wildlife biomonitoring in the pursuit to better understand the biology of endangered species.

Gas and Liquid Chromatography Mass Spectrometry as a Tool for Elucidating Volatile Organic Compounds (VOCs) and Metabolites in Maternal Milk: A Perspective on Infants’ Health Risk Assessment

Maternal milk is pivotal for infants’ nutrition. It also portrays the chemical burden to which the mother has been exposed. One of the chemical families that is prevalent and related to potential toxic effects are volatile organic compounds (VOCs). In the present study, motivated by the scarcity of works dealing with concomitant VOC and metabolite determination in maternal milk, two new gas/liquid chromatography tandem mass spectrometry (GC-MS/MS, LC-MS/MS) methods for the simultaneous measurement of 25 VOCs and 9 of their metabolites, respectively, in maternal milk were developed and applied to 20 maternal milk samples collected from mothers in Greece. In parallel, a headspace solid-phase microextraction (HS-SPME)–GC-MS method was employed for the untargeted screening of chemicals. Low detection rates for benzene, toluene, styrene and p,m-xylenes, and three of their metabolites, namely N-acetyl-S-(benzyl)-L-cysteine (BMA, metabolite of toluene), 3-methylhippuric (3-MHA, metabolite of xylenes) and mandelic acid (MA as DL and R isomers, metabolites of styrene and ethylbenzene), were evidenced in concentrations varying from &lt;lower limit of quantification (LLOQ) to 0.79 ng mL−1. HS-SPME–GC-MS disclosed the presence of common maternal milk constituents such as fatty acids. Nevertheless, bisphenol-A, bisphenol derivatives and phthalates were also detected. The infants’ health risk assessment demonstrated a low risk and negligible carcinogenic risk, yet the detection of these compounds should not be underestimated.

Safety profile of ZnO active packaging PBAT based biomaterial for food packaging. First tier evaluation

Materials produced with polybutylene adipate terephthalate (PBAT) and starch are raising great interest for packaging and food contact applications, including as support for active antimicrobial agents such as zinc oxide nanoparticles (ZnO). Studies focusing on the safety of these materials as evaluated with the current reference rules for food contact materials, are lacking. A commercially available PBAT/starch-based material was incorporated with ZnO and the overall and specific migration of the films were studied at different conditions of simulants and temperature. The overall migration (OM) limit is exceeded due to the release of starch as confirmed by infrared spectroscopy. The impact of temperature on the OM was higher for the ethanol 10%. The incorporation of ZnO particles reduced the OM, for both temperatures tested for ethanol 10%. The impact of incorporating ZnO in the migration into acetic acid was relevant at 20 °C only. Beside starch, most relevant migrants were PBAT oligomers made of butanediol and two different kinds of diacids, terephthalic acid or adipic acid. The cyclic diester of 1,4-butanediol and adipic acid, butenyl butanediol adipate in either cyclic and linear form and oligomers terephthalic acid, but-3-enyl hexadecyl ester were detected in an untargeted screening with GC-MS. A second TPA oligomer was not fully identified. The specific migration was in several cases, depending on the simulant and on the temperature, higher than 50 μgkg−1 (semi-quantification), the threshold value for requiring additional toxicity test (genotoxicity tests applied to oligomers below 1000 Da). This indicates the need for more detailed studies with more precise quantification to verify the need for toxicity tests.

LC-MS/MS platform-based serum untargeted screening reveals the diagnostic biomarker panel and molecular mechanism of breast cancer

BackgroundBreast cancer (BC), the most common form of malignant cancer affecting women worldwide, was characterized by heterogeneous metabolic disorder and lack of effective biomarkers for diagnosis. The purpose of this study is to search for reliable metabolite biomarkers of BC as well as triple-negative breast cancer (TNBC) using serum metabolomics approach. MethodsIn this study, an untargeted metabolomics technique based on ultra-high performance liquid chromatography combined with mass spectrometry (UHPLC-MS) was utilized to investigate the differences in serum metabolic profile between the BC group (n = 53) and non-BC group (n = 57), as well as between TNBC patients (n = 23) and non-TNBC subjects (n = 30). The multivariate data analysis, determination of the fold change and the Mann-Whitney U test were used to screen out the differential metabolites. Additionally, machine learning methods including receiver operating curve analysis and logistic regression analysis were conducted to establish diagnostic biomarker panels. ResultsThere were 36 metabolites found to be significantly different between BC and non-BC groups, and 12 metabolites discovered to be significantly different between TNBC and non-TNBC patients. Results also showed that four metabolites, including N-acetyl-D-tryptophan, 2-arachidonoylglycerol, pipecolic acid and oxoglutaric acid, were considered as vital biomarkers for the diagnosis of BC and non-BC with an area under the curve (AUC) of 0.995. Another two-metabolite panel of N-acetyl-D-tryptophan and 2-arachidonoylglycerol was discovered to discriminate TNBC from non-TNBC and produced an AUC of 0.965. ConclusionThis study demonstrated that serum metabolomics can be used to identify BC specifically and identified promising serum metabolic markers for TNBC diagnosis.

Screening DNA Damage in the Rat Kidney and Liver by Untargeted DNA Adductomics.

Air pollution, tobacco smoke, and red meat are associated with renal cell cancer (RCC) risk in the United States and Western Europe; however, the chemicals that form DNA adducts and initiate RCC are mainly unknown. Aristolochia herbaceous plants are used for medicinal purposes in Asia and worldwide. They are a significant risk factor for upper tract urothelial carcinoma (UTUC) and RCC to a lesser extent. The aristolochic acid (AA) 8-methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-I), a component of Aristolochia herbs, contributes to UTUC in Asian cohorts and in Croatia, where AA-I exposure occurs from ingesting contaminated wheat flour. The DNA adduct of AA-I, 7-(2'-deoxyadenosin-N6-yl)-aristolactam I, is often detected in patients with UTUC, and its characteristic A:T-to-T:A mutational signature occurs in oncogenes and tumor suppressor genes in AA-associated UTUC. Identifying DNA adducts in the renal parenchyma and pelvis caused by other chemicals is crucial to gaining insights into unknown RCC and UTUC etiologies. We employed untargeted screening with wide-selected ion monitoring tandem mass spectrometry (wide-SIM/MS2) with nanoflow liquid chromatography/Orbitrap mass spectrometry to detect DNA adducts formed in rat kidneys and liver from a mixture of 13 environmental, tobacco, and dietary carcinogens that may contribute to RCC. Twenty DNA adducts were detected. DNA adducts of 3-nitrobenzanthrone (3-NBA), an atmospheric pollutant, and AA-I were the most abundant. The nitrophenanthrene moieties of 3-NBA and AA-I undergo reduction to their N-hydroxy intermediates to form 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) adducts. We also discovered a 2'-deoxycytidine AA-I adduct and dA and dG adducts of 10-methoxy-6-nitro-phenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-III), an AA-I isomer and minor component of the herbal extract assayed, signifying AA-III is a potent kidney DNA-damaging agent. The roles of AA-III, other nitrophenanthrenes, and nitroarenes in renal DNA damage and human RCC warrant further study. Wide-SIM/MS2 is a powerful scanning technology in DNA adduct discovery and cancer etiology characterization.

Application of advanced high resolution mass spectrometric techniques for the analysis of losartan potassium regarding known and unknown impurities

Recalls of medicinal products can cause supply bottlenecks. This is often due to the findings of unexpected impurities that pose a health risk to patients. A recent example is losartan potassium which was contaminated with azido-impurities. The choice of the analytical method determines which substances can be detected and thus controlled. In this study a combination of an untargeted screening approach for impurities and a targeted evaluation of high-resolution mass spectrometry data was applied to search for impurities not described so far, leaving out a precise quantification. Six losartan potassium samples were studied regarding known and unknown impurities and hence highlight the applicability and capability of the approach. For separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and an electrospray ionization in positive and negative mode for mass spectrometric detection was used. An information-dependent acquisition method was applied for the measurement of losartan potassium samples. The untargeted data evaluation using general unknown comparative screening revealed the presence of N-methyl-2-pyrrolidone (NMP) and another impurity from synthesis. The identity of NMP was corroborated by a spiking experiment and the amount was estimated by means of standard addition. A targeted data evaluation by generating extracted ion chromatograms resulted in finding of four additional impurities. Combined approaches like this are needed to detect and respond to changes in the quality of drugs precociously.

Embedding Mixed Sorbents in Binder: Solid-Phase Microextraction Coating with Wide Extraction Coverage and Its Application in Environmental Water Analysis.

Solid-phase microextraction (SPME) is a simple and highly effective sample-preparation technique for water analysis. However, the extraction coverage of a given SPME device with a specific coating can be an issue when analyzing multiple environmental contaminants. Therefore, instead of synthesizing one sorbent material with dual or multiple functions, we investigated a new strategy of preparing SPME blades using a homogeneous slurry made by mixing three different sorbent particles─namely, hydrophobic/lipophilic balanced (HLB), HLB-weak cationic exchange (HLB-WCX), and HLB-weak anionic exchange (HLB-WAX)─with a polyacrylonitrile (PAN) binder. The developed coating is matrix compatible, as the binder functions not only as a glue for immobilizing the sorbent particles but also as a porous filter, which only allows small molecules to enter the pores and interact with the particles, thus avoiding contamination from large elements. The results confirmed that the proposed mixed-coating SPME device provides good extraction performance for polar and nonpolar as well as positively and negatively charged compounds. Based on this device, three comprehensive analytical methodologies─high-throughput SPME-LC-MS/MS (for the quantitative analysis of targeted drugs of abuse and artificial sweeteners), in-bottle SPME-LC-high resolution MS (HRMS) (for the untargeted screening of organic contaminants), and on-site drone sampling SPME-LC-HRMS (for on-site sampling and untargeted screening)─were developed for use in environmental water analysis. The resultant data confirm that the proposed strategies enable comprehensive water quality assessment by using a single SPME device.

Untargeted screening of NIAS and cyclic oligomers migrating from virgin and recycled polyethylene terephthalate (PET) food trays

Polyethylene terephthalate is considered one of the most used and approved recycled plastic polymer as food contact materials (FCM); however, the fundamental details arising from the recycled content of PET trays in relation to processing conditions or extent of recycling are not well understood. In the present work, the presence and migration of different series of PET cyclic oligomers from industrially recycled trays were investigated using official food simulant D1 at 40 °C for 10 days. The trays were produced in two different facilities, using different extrusion processing technology, namely single and twin-screw extruder. Tested food packaging trays were produced from different ratios of virgin (vPET) and recycled PET (rPET), varying from 0% up to 100% w/w content. Analysis of the trays using MALDI-TOF-MS revealed a decrease in the molecular weight distribution (Mw) in rPET compared to virgin PET plastic. Untargeted screening with UHPLC-QTOF-MS, revealed the presence and migration of several intentionally added substances (IAS) as well as non-intentionally added substances (NIAS). The results demonstrated differences of the cyclic oligomers migration into the selected food simulant, depending on the rPET/vPET ratios as well as among the applied extrusion technology applied. Following multivariate analysis, marker compounds found to be benzyl butyl phthalate (BBP), butyl lactate, dodecenamide, 2-methyl-1,3-dioxolane, PET 2nd series cyclic dimer as well as PET 1st series cyclic dimer can be considered as marker compounds.

Degradation of pharmaceuticals in UV/H2O2 process: EEM-based kinetic model, transformation products and corresponding toxicity evaluation

Advanced oxidation process (AOP) by UV/H2O2 presented excellent performance on removing trace pharmaceuticals in wastewater. Monitoring the removal efficiency of pharmaceuticals rapidly can evaluate the effectiveness of UV/H2O2 process. And evaluating the potential risks of this technology is essential to facilitate its engineering application. In this study, diclofenac, ibuprofen, naproxen, carbamazepine and citalopram, which have potential biological effect to ecological environment, were degraded by UV/H2O2 in wastewater. Results suggested that UV/H2O2 could degrade 5 pharmaceuticals effectively. An EEM-based degradation kinetic model was constructed by combining pseudo first-order kinetic patterns of pharmaceuticals degradation and multiple exponential decay pattern of fluorescence degradation. This model could estimate the removal of pharmaceuticals rapidly and exhibited excellent predictive capability (R2 values > 0.90). Based on suspect and untargeted screening, 40 transformation products (TPs) were identified, with hydroxylation, (de)methylation and decarboxylation being the dominant pathways. Among them, 20 TPs were newly discovered. Furthermore, the predicted toxicity results from Ecological Structure-Activity Relationship (ECOSAR) model suggested that 37.5%− 42.5% of TPs exhibited higher toxicity than parent compounds. The increased toxicity of TPs of DCF and IBP could be attributed to decarboxylation. This study provides a promising and rapid method for monitoring the degradation of pharmaceuticals and estimating the toxicity of TPs. These findings facilitate further evaluation of the practicality and risks associated with the UV/H2O2 process for pharmaceutical removal in wastewater.

Dynamic changes to the plant cuticle include the production of volatile cuticular wax-derived compounds.

The cuticle is a hydrophobic structure that seals plant aerial surfaces from the surrounding environment. To better understand how cuticular wax composition changes over development, we conducted an untargeted screen of leaf surface lipids from black cottonwood (Populus trichocarpa). We observed major shifts to the lipid profile across development, from a phenolic and terpene-dominated profile in young leaves to an aliphatic wax-dominated profile in mature leaves. Contrary to the general pattern, levels of aliphatic cis-9-alkenes decreased in older leaves following their accumulation. A thorough examination revealed that the decrease in cis-9-alkenes was accompanied by a concomitant increase in aldehydes, one of them being the volatile compound nonanal. By applying exogenous alkenes to P. trichocarpa leaves, we show that unsaturated waxes in the cuticle undergo spontaneous oxidative cleavage to generate aldehydes and that this process occurs similarly in other alkene-accumulating systems such as balsam poplar (Populus balsamifera) leaves and corn (Zea mays) silk. Moreover, we show that the production of cuticular wax-derived compounds can be extended to other wax components. In bread wheat (Triticum aestivum), 9-hydroxy-14,16-hentriacontanedione likely decomposes to generate 2-heptadecanone and 7-octyloxepan-2-one (a caprolactone). These findings highlight an unusual route to the production of plant volatiles that are structurally encoded within cuticular wax precursors. These processes could play a role in modulating ecological interactions and open the possibility for engineering bioactive volatile compounds into plant waxes.

Associated factors with mycotoxin exposure in Spanish population

Human exposure to mycotoxins is a global concern since filamentous fungi can contaminate food and feed from crops to ready-to-eat meals. Human urine biomonitoring is a widely used technique to evaluate mycotoxins exposure, as an alternative to food correlation studies. The aim of this study is to describe human exposure to mycotoxins and to investigate the associated sociodemographic, lifestyle and dietary variables. Participants were 540 women from the Valencia (Spain) cohort of the Spanish Childhood and Environment Project (INMA). A validated multi-mycotoxin method using HPLC-Q-TOF-MS was applied to determine the concentration of ten selected mycotoxins: Enniatin A, Enniatin B, Enniatin A1, Enniatin B1, Beauvericine, Aflatoxin B1, Aflatoxin B2, Aflatoxin G1, Aflatoxin G2 and Ochratoxin A. A simultaneous untargeted screening of mycotoxins and their metabolites has been performed. Mycotoxins associations were assessed by bivariate and multivariate regression models using participants' sociodemographic, lifestyle and dietary data collected through questionnaires. Mycotoxins were detected in 81% of urine samples. The method quantified mycotoxins concentrations in up to 151 samples. Most quantified mycotoxins were: Enniatin B [% of detection (concentration range)] = 26% (1.0–39.7 ng/mg) and Enniatin B1 = 7% (0.5–14.4 ng/mg). Besides the ten-targeted mycotoxins, other mycotoxins and metabolites were studied, and higher incidence was observed for Deepoxy-deoxynivalenol (45%), Ochratoxin B (18%) and Ochratoxin α (17%). Higher mycotoxins concentrations were associated with rural areas as well as with participants belonged to lower social class, beer, light sodas and fruit juice consumers. On the contrary, higher processed meat intake was related to lower mycotoxins’ levels. Studies are required to better evaluate the exposure to mycotoxins from food and their environmental relationships.

Untargeted Screening of Per- and Polyfluoroalkyl Substances (PFASs) in Airborne Particulate of Three Italian E-Waste Recycling Facilities

Poly- and perfluorinated alkyl substances (PFASs) are widely used in the electrical and electronic appliance industry to the point that waste of electrical and electronic equipment (WEEE), also known as e-waste, creates significant potential for PFAS exposure (by inhalation, ingestion, or dermal exposure) for people handling and recycling e-waste. The aim of this work was the development of an untargeted analytical approach in order to detect the presence of possible unknown PFASs in particulate matter collected in three Italian e-waste facilities through liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HR-MS/MS) in negative ionization mode. By means of three acquisition experiments, nine compounds were detected as candidate PFASs, and three were definitively confirmed by comparison with their authentic standards. Among these, bistriflimide (bis (trifluoromethylsulfonyl) imide), an ionic liquid with several promising technological applications, was the most abundant compound detected in all three recycling plants. This is the first study associating the presence of fluorinated ionic liquids with e-waste, and as these chemicals are not only toxic and persistent but also highly mobile, our results indicate the need to include them in future PFAS research. Only further data on their actual environmental diffusion will determine whether they are emerging pollutants or not.

Interactions between sulfonamide homologues and glycosyltransferase induced metabolic disorders in rice (Oryza sativa L.)

Sulfadiazine and its derivatives (sulfonamides, SAs) could induce distinct biotoxic, metabolic and physiological abnormalities, potentially due to their subtle structural differences. This study conducted an in-depth investigation on the interactions between SA homologues, i.e. sulfadiazine (SD), sulfamerazine (SD1), and sulfamethazine (SD2), and the key metabolic enzyme (glycosyltransferase, GT) in rice (Oryza sativa L.). Untargeted screening of SA metabolites revealed that GT-catalyzed glycosylation was the primary transformation pathway of SAs in rice. Molecular docking identified that the binding sites of SAs on GT (D0TZD6) were responsible for transferring sugar moiety to synthesize polysaccharides and detoxify SAs. Specifically, amino acids in the GT-binding cavity (e.g., GLY487 and CYS486) formed stable hydrogen bonds with SAs (e.g., the sulfonamide group of SD). Molecular dynamics simulations revealed that SAs induced conformational changes in GT ligand binding domain, which was supported by the significantly decreased GT activity and gene expression level. As evidenced by proteomics and metabolomics, SAs inhibited the transfer and synthesis of sugar but stimulated sugar decomposition in rice leaves, leading to the accumulation of mono- and disaccharides in rice leaves. While the differences in the increased sugar content by SD (24.3%, compared with control), SD1 (11.1%), and SD2 (6.24%) can be attributed to their number of methyl groups (0, 1, 2, respectively), which determined the steric hindrance and hydrogen bonds formation with GT. This study suggested that the disturbances on crop sugar metabolism by homologues contaminants are determined by the interaction between the contaminants and the target enzyme, and are greatly dependent on the steric hindrance effects contributed by their side chains. The results are of importance to identify priority pollutants and ensure crop quality in contaminated fields.